Thyroid protocol

Jacob Schor ND, FABNO

Jan 5 2011



I learned a simple trick back in the 1980s at National College of Naturopathic Medicine. Dr. Jack Dougherty taught us a simple way to screen for thyroid disease; look at how many supplements a patient takes regularly. He taught us that, “The more supplements a patient needs to take to feel ok, the more likely they are hypothyroid.”  To this day, if a patient brings in a heavy bag of pills, I still think of Dr. Dougherty and write in my notes, “rule out hypothyroid.”


That’s kind of a scary thought when writing for the ---- members who probably take more supplements than pretty much anyone they know.  Thus writing about hypothyroidism for this readership is somehow appropriate.


Thyroid dysfunction is common.  Many people live with either undiagnosed overactive or underactive thyroid function.  Even more people probably live with diagnosed but inadequately treated disease. A December 2010 survey retested 1,037 people in the UK being treated for hypothyroidism and rechecked their hormone levels.  About 37.2% were taking the incorrect hormone doses; 19.8% too much hormone and 17.4% too little.   In recent years there is a new category called subclinical thyroid disease in which lab work and symptoms point to early disease, which is even more common.   In this article we will focus on low thyroid function, commonly called hypothyroidism, and discuss symptoms and treatment options.


If a patient’s body doesn’t produce enough thyroid hormone, then nothing else in their body will work well either.  This is the first lesson in understanding the symptom picture of low thyroid function.


The thyroid gland is a small butterfly shaped organ located in the neck just above one’s upper collar button, kind of miniature bowtie, narrow in the middle and wide on either wing.    Leonardo DaVinci is given credit for being the first to draw an anatomical illustration of the thyroid. In healthy people the gland is faint or imperceptible to the touch.  If enlarged and easy to feel, it is called a goiter. The hormones produced by the thyroid control the metabolic rate of the body, so perhaps imagine it as a thermostat. The more active the thyroid gland is, that is the more thyroid hormone it produces, the more active the body metabolism. 


When the body’s metabolism slows down when hypothyroid, it’s as if it was in a refrigerator.  Hypothyroid people feel chilly and all of their chemistry slows down.  Their digestion slows down, their brain slows down, all the chemical reactions moderated by enzymes slow down. 


Although this is an oversimplification of thyroid function, almost everything we read about the thyroid is a simplification.  The most detailed explanations of chemical mechanism that we though true just a few years back seem to be simplifications today.



About 1% of the population has hyperthyroidsism, an overactive thyroid; hypothyroidism affect fives times as many people, or more. In NHANES-III, the third National Health & Nutrition Examination Survey, a population-based survey conducted by the National Center for Health Statistics in the late 1980s through early 1990s, the overall prevalence of hypothyroidism was 4.6% while prevalence of hyperthyroidism was about 1.3%.

Hollowell reported reported similar percentages of undetected thyroid disease in 2002.  Blood samples from 13,344 people who were supposedly disease-free were tested for thyroid disease. “Hypothyroidism was found in 4.6% …. and hyperthyroidism in 1.3% ….”

A 2005 article in the American Family Physician estimated that 4.5 to 8% of the US population is hypothyroid but that possibly as many as 20% of women over 60 years old are hypothyroid. 

Many alternative health practitioners feel that these numbers still underestimate the true number of people with undiagnosed or subclinical hypothyroid disease. An August 2010 study reported that 8.3% of supposedly ‘healthy’ women who participated in a study suffered from subclinical hypothyroidism.

A 2004 Danish study that surveyed 12,012 men sought to establish a link between subclinical hypothyroidism and heart disease classified just under 20% of their cohort as having subclinical hypothyroidism.

Control Loop:

Thyroid hormone action is tightly regulated in the body through a number of mechanisms, some better and some less well understood. Basic regulation of hormone production is accomplished through a classic control loop.  When the hypothalamus in the brain senses inadequate thyroid hormone levels, it releases a hormone called thyrotropin releasing hormone (TRH) that triggers the pituitary gland, also in the brain.  The pituitary releases thyroid stimulating hormone (TSH).  TSH leaves the brain, enters the general circulation and when it reaches the thyroid gland triggers the release of thyroid hormone. This is a control loop:  high or low thyroid hormones in the blood trigger the brain to lower or increase TSH release in order to lower or increase thyroid hormone. 


Thyroid dysfunction can start in the brain through either damage or tumor activity.  If the pituitary makes no or inadequate TSH, the thyroid gland will not produce enough T4 hormone.  With inadequate amounts of T4, there will be low amounts of T3 and the patient will be hypothyroid. Luckily, such situations are rare.  In such a situation lab work would reveal a low TSH, low T4 and low T3.   To test pituitary function, the hypothalamic hormone TRH is injected into the blood stream and a blood sample is drawn to measure TSH levels a short time later.


Thyroid Gland:

When triggered by TSH, the thyroid gland releases a thyroid hormone called thyroxine, (T4) into the blood system.  Technically T4 is a pre-hormone although everyone, calls it thyroid hormone probably because most prescription thyroid medications are T4 and are called thyroid hormone. The active cellular form of thyroid hormone is triiodothyronine (T3).  The T4 must be converted to T3 to have an effect on the body. Hypothyroidism that starts in the thyroid gland is called primary hypothyroidism. In such a situation TSH will be elevated and T4 and T3 levels possibly below normal.


Raw materials:

The thyroid gland needs iodine and l-tyrosine to make T4. A dietary deficiency of iodine can limit how much thyroxine the thyroid gland can produce and lead to hypothyroid function. Worldwide, iodine deficiency is still the most common cause of hypothyroidism though this continues to decrease with the more widespread use of iodized salt. Iodine supplements, including various seaweeds, were and continue to be useful in treating hypothyroidism that is caused by iodine deficiency.  These days, in the United States, the situation is different; with salt nearly universally enriched with iodine, most researchers consider iodine deficiency to be a rare.


There are certainly those individuals who bypass these sources of iodine, either because they choose non-enriched salt or avoid salt altogether because of concern over blood pressure.



The thyroid gland produces mostly T4, a pre-hormone that must be converted to its active form, T3.  Unfortunately this conversion isn’t guaranteed.  Various factors including numerous nutrient deficiencies, drugs, chemicals and even foods interfere with conversion. This conversion is accomplished via selenoenzymes, named such because they contain selenium. In such a situation free T3 levels will be low while T4 levels may be normal.  High blood lead levels are one example of a factor that inhibits conversion.


Autoimmunity and Thyroid disease:

Most cases of thyroid disease in the United States are now caused by autoimmune disease.  That is they are the result of the body’s immune system mistakenly attacking the thyroid.  Examples of other autoimmune diseases are rheumatoid arthritis, in which the immune system attacks the joints, or juvenile diabetes where the pancreas is the target of attack.

An autoimmune disease called Hashimoto’s disease is the most common cause of low thyroid function.  This condition is characterized by an overactive immune system response that attacks the thyroid gland. Hashimoto’s disease is more common in women than in men. [The disease may actually be triggered by iodine.]  It is linked to other immune diseases such as childhood diabetes and celiac disease both of which increase risk of Hashimoto’s.  While Hashimoto’s is usually associated with hypothyroidism it can also trigger hyperthyroid symptoms.

Hyperthyroid disease is associated with Grave’s Disease in which antibodies are produced that bind to TSH receptors in the thyroid gland, stimulating excess hormone production. This distinction between diseases may not be as important as once thought.  In a 2009 paper, Paknys et al wrote:

Hashimoto's and Graves' disease are different expressions of a basically similar autoimmune process, and the clinical appearance reflects the spectrum of the immune response in a particular patient.…..”

Sometimes the two diseases overlap causing both thyroid gland stimulation and thyroid gland destruction by the immune system simultaneously or in sequence.   So even though the symptoms are dissimilar, clinicians may consider the two diseases, “… as two subsets of a single pathologic process.” About 4% of those with Hashimoto’s disease will eventually develop Grave’s disease.  

The antibodies that define the immune response in both Grave’s and Hashimoto’s disease can now be measured and the diseases more reliably diagnosed than in the past. The amount of antibodies present provides a measure of disease intensity and provides an easy tool for monitoring treatment. 

In Hashimoto’s disease Thyroid peroxidase antibody (TPOAb) and or Thyroglobulin antibody (TgAb) may be high.

Chronic Urticaria: As a side note, elevated thyroid antibodies are often associated with un-explained or chronic urticaria (hives) and should be checked for in people who have hives that appear without obvious triggers or continue over extended periods of time. A paper published in 2009 reported that 30% of chronic urticaria patients have thyroid antibodies. Even higher percentages were found in a March 2010 report. An August 2010 paper tells us that treatment with T4 improves the itching associated with urticaria but did not advise treatment with T4 unless the patient was hypothyroid.

Binding Globulin and Carrier Proteins: The vast majority of the thyroid hormones in the body, both T4 and T3 are bound to carrier proteins in the blood making the hormones unavailable to be converted, in the case of T4, or trigger a cellular reactions in the case of T3. The amount of thyroid hormone carrier proteins in the blood can change thyroid function.  Hormones do not float around free in the blood stream.  Most are bound to carrier proteins that circulate in the blood, which buffer the effect of the hormones.  Only a small percentage of hormones will detach from these proteins and be free to act.  Less than 1% of thyroid hormones are free, that is not bound to carrier proteins; more than 99% of circulating thyroid hormones are bound to either thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA) or albumin.  T4 is held in tighter control than T3.  Only about 0.04% of total T4 if free while 0.4% of total T3 is free.  Very small changes in the amount of any of these carrier proteins will thus have a large effect on the percentage of unbound hormones. Even small increases in carrier proteins will decrease the ability of T3 to stimulate the metabolism. This provides yet another level of control of thyroid hormone action.

Many things will change the level of carrier proteins in the blood.  Oral contraceptives, pregnancy, and estrogen replacement therapy are probably the most common things to increase the levels and thus lower the amount of free hormone available.

It is possible to measure and compare the amounts of total T4 and total T3 versus the free T4 and free T3 circulating in the blood. Astute practitioners will measure and compare these levels to gauge how much hormone effect is being blunted or exaggerated by high or low levels of carrier proteins.  High T3 uptake suggests high levels of carrier protein.


T4 is converted to active T3 hormone by a selenium containing enzyme called 5-deiodinase.  How efficiently the T4 is converted is yet another level controling thyroid action.  T4 can also be converted to a stereoisomer of active T3 called Reverse T3 (RT3) by a related enzyme called 5’deiodinase.  The RT3 hormone does not trigger an increase in metabolic activity as does the active T3 hormone.  Instead it ‘gets in the way’ blocking the hormone receptors in the cell and actually prevents action.

Hormone resistance

There are certain individuals with apparently normal thyroid hormone levels who still display all the classic symptoms of low thyroid function.  Typically, thyroid hormone resistance is considered to be, “… a rare autosomal dominant inherited syndrome ...” and so rare that it affects less than one in 40,000 newborns.   Yet there is a growing acceptance of other theories to explain these presentations as an acquired hormone resistance, similar to adult diabetes.  While some of these theories focus on the ratio of regular T3 hormone and reverse T3 (R-T3) there are other mechanisms also under consideration. A 2007 article in Medical Hypotheses  reports an, “….  extensive list of mutations, drugs, toxins, metabolites and autoimmune antibodies that may impair … [thyroid hormone] action in the cell…” and suggests that, “… different conditions, for example, chronic fatigue syndrome (CFS), chronic renal failure (CRF) and nonthyroidal illness, can be accompanied by…” thyroid hormone resistance and, “…reduced sensitivity to [thyroid hormone] in peripheral tissues.”



Normal Thyroid Function Requires Normal Adrenal Function:

Cortisol levels affect thyroid function.  Either low or high cortisol levels can interfere. For example the chronic stress of physical exercise lowers thyroid hormone action by suppressing T3 and elevating RT3 levels.   The high cortisol levels seen in Cushing’s disease suppress TSH production. Many practitioners feel that low cortisol conditions also need to be addressed prior to initiating thyroid hormone replacement therapy.


Thyroid and Heart Disease: A December 2010 issue of JAMA reminds us that the risk of heart disease increases with increasing TSH even in subclinical hypothyroidism.   Elevated TSH levels cause the arteries to stiffen, thickening the intima of the blood vessels.  Lowering TSH levels with supplemental thyroid maintains the elasticity and functional properties of the vessels. 


The most common symptoms of hypothyroid disease:


  • Fatigue
  • Weakness
  • Weight gain or increased difficulty losing weight
  • Dry, rough pale or yellow skin
  • Hair loss or coarse dry hair
  • Cold intolerance (you can't tolerate cold temperatures like those around you)
  • Myalgias: Muscle cramps and frequent muscle aches
  • Constipation
  • Depression
  • Irritability
  • Memory loss
  • Abnormal menstrual cycles: Irregular or heavy menses and infertility
  • Decreased libido
  • Facial puffiness
  • Fluid retention, nonpitting edema
  • Slow speech
  • Bradycardia: slow heart rate
  • Hoarse voice
  • Macroglossia – enlarged tongue
  •  Reflex delay in the relaxation phase, typically tested on Achilles tendon reflex
  • Ataxia
  • Hyperlipidemia: elevated triglycerides and cholesterol

[consider deleting this section or moving it to a second document:  869 words]

Symptoms: In Depth

  • Gastrointestinal problems:  Low thyroid function almost always causes a person to be constipated.  In fact, hypothyroidism is the most common systemic disease to cause constipation.

       Hypothyroidism is also associated with esophageal motility disorders presenting as dysphagia, heartburn, dyspepsia, nausea, or vomiting.  Abdominal discomfort, flatulence, and bloating occur in those with bacterial overgrowth secondary to poor digestion. Reduced acid production may be due to autoimmune gastritis or low gastrin levels. Constipation may result from diminished motility, leading to an ileus, megacolon, or rarely pseudo-obstruction.

  • Intellectual disabilities:

    People with low thyroid function seem to think slowly, it takes them too long to process information, gather their thoughts, recall names, where they were going, what they were doing.  Their thoughts move in slow motion. These patients are often misdiagnosed as depressed.   In a 2008 study, treating the hormone deficiency and lowering TSH below 2.15 improved mood and cognitive function.

  • fatigue and weakness: These symptoms are more common in elderly hypothyroid patients while chilliness, weight gain, paresthesiae and cramps are more common complaints in younger patients.

If untreated, chronic hypothyroidism can result in myxedema, a rare, life-threatening condition. Mental dysfunction, stupor, cardiovascular collapse, and coma can develop after the worsening of chronic hypothyroidism. Patients may pass into a hypothermic stuporous coma and die.

Additional possible complications of chronic hypothyroidism include the following:

  • Depression and psychiatric disorders. Panic attacks, anxiety, depression, phobias, and obsessive compulsive disorders are commonly encountered in hypothyroidism and hyperthyroidism.


      The signs and symptoms of hypothyroidism are often confused with depression.   A paper published in 2002 tells that that thyroid function is particularly important in bipolar patients: “…patients with bipolar disorder are particularly sensitive to variations in thyroid function within the normal range. Our results suggest that nearly three-quarters of patients with bipolar disorder have a thyroid profile that may be suboptimal for antidepressant response. It remains to be seen whether pharmacological enhancement of thyroid function will facilitate recovery from bipolar depression.”

  • Reduced cardiac output. In overt hypothyroidism, cardiac contractility and cardiac output are decreased, and vascular resistance is increased. These changes also affect people with subclinical hypothyroidism, but to a lesser degree. “The phenotype of the failing heart resembles that of the hypothyroid heart, both in cardiac physiology and in gene expression. Changes in serum T(3) levels in patients with chronic congestive heart failure are caused by alterations in thyroid hormone metabolism suggesting that patients may benefit from T(3) replacement in this setting.
  • High blood pressure. Hypothyroidism is often accompanied by diastolic hypertension that, in conjunction with elevated cholesterol, may promote atherosclerosis. Hypertension is relatively common among patients with hypothyroidism; in a 1983 study, 14.8% of patients with hypothyroidism were hypertensive, compared with 5.5% of people with normal thyroid function.
  • High cholesterol and artherosclerosis. “… lipoproteins are seriously disturbed in thyroid diseases. Overt hypothyroidism is characterized by hypercholesterolaemia and a marked increase in low-density lipoproteins (LDL) and apolipoprotein B (apo A)

    Hypothyroidism is associated with an increased risk of coronary artery disease. …. hypothyroidism are commonly associated with an atherogenic lipid profile, which improves with replacement of thyroid hormone….. Subclinical hypothyroidism (SH) is associated with lipid disorders that are characterized by normal or slightly elevated total cholesterol levels, increased LDL, and lower HDL. Moreover, SH has been associated with endothelium dysfunction, aortic atherosclerosis, and myocardial infarction.”  

In addition, patients with low thyroid hormone may be deficient in DHEA, a vital hormone that serves as a precursor of sex hormones such as estrogen and testosterone (Tagawa N et al 2000). A normal beginning dose is 15 to 75 mg, followed by blood testing.


Thyroid Deficiency Safety Caveats

An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:


  • Do not take copper supplements if you have Wilson's disease.
  • Consult your doctor if you take copper supplements and have chronic liver failure and/or chronic kidney failure.
  • Do not take high doses of copper. High doses of copper are extremely toxic.
  • Copper can cause gastrointestinal symptoms such as nausea and diarrhea.

Potassium iodide

  • Potassium iodide can cause hyperthyroidism in older people with nodular goiters.
  • Potassium iodide may exacerbate symptoms of autoimmune thyroiditis.
  • Potassium iodide may cause rashes, arrhythmias, central nervous system effects (confusion, numbness, tingling, weakness in the hands or feet), hypothyroidism, hyperthyroidism (Jod-Basedow phenomenon), parotitis (iodide mumps), thyroid adenoma and small bowel lesions.
  • Potassium iodide may cause hypersensitivity reactions including angioedema, symptoms resembling serum sickness (fever, arthralgia, eosinophilia, lymphadenopathy), cutaneous and mucosal hemorrhages, urticaria, thrombotic thrombocytopenia purpura (TTP), and fatal periarteritis.
  • Enteric-coated potassium iodide may cause nonspecific small bowel lesions manifested by stenosis with or without ulcerations. These lesions may cause hemorrhage, obstruction, perforation and death.
  • Chronic intake of pharmacological doses of iodides (>2 mg) can lead to iodism characterized by frontal headache, pulmonary edema, coryza (head cold), eye irritation, skin eruptions, gastric disturbances, as well as inflammation of the tonsils, larynx, pharynx, and submaxillary and parotid glands.


  • High doses of selenium (1000 micrograms or more daily) for prolonged periods may cause adverse reactions.
  • High doses of selenium taken for prolonged periods may cause chronic selenium poisoning. Symptoms include loss of hair and nails or brittle hair and nails.
  • Selenium can cause rash, breath that smells like garlic, fatigue, irritability, and nausea and vomiting.

Vitamin C

  • Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.
  • Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E

  • Consult your doctor before taking vitamin E if you take warfarin (Coumadin).
  • Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.
  • Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.
  • Discontinue using vitamin E 1 month before any surgical procedure.


  • High doses of zinc (above 30 milligrams daily) can cause adverse reactions.
  • Zinc can cause a metallic taste, headache, drowsiness, and gastrointestinal symptoms such as nausea and diarrhea.
  • High doses of zinc can lead to copper deficiency and hypochromic microcytic anemia secondary to zinc-induced copper deficiency.
  • High doses of zinc may suppress the immune system.

For more information see the Safety Appendix





[we need to delete this famous line: Subclinical hypothyroidism is the most commonly encountered organic cause of depression (Saddock BJ 2000 ] as I am unable to find support for this statement in this book, having searched the entire text online….).]

QJM. 2010 Nov 24. [Epub ahead of print]

Adequacy of thyroid hormone replacement in a general population.

Okosieme OE, Belludi G, Spittle K, Kadiyala R, Richards J.

From the Endocrinology and Diabetes Department, Prince Charles Hospital, Pharmacy Department, Prince Charles Hospital, Cwm Taf Local Health Board, Merthyr Tydfil, Mid Glamorgan, CF47 9DT and Morlais Medical Practice, Ty Morlais, Berry square, Dowlais, Merthyr Tydfil, Mid Glamorgan, CF48 3AL, UK.


BACKGROUND: Suboptimal thyroid hormone replacement may carry harmful health consequences.

AIMS: Our objectives were to determine the prevalence and factors associated with inadequate replacement in patients receiving treatment with levothyroxine.

DESIGN: Retrospective general practice audit.

METHODS: We identified levothyroxine users through electronic searches of primary care records in all 11 practices within a county borough. The adequacy of thyroid hormone replacement was determined from the current serum, serum thyrotropin (TSH) as: (i) adequate replacement (normal TSH; 0.4-4.0mU/l); (ii) over replacement (low TSH; <0.4mU/l); and (iii) under replacement (high TSH; >4.0mU/l).

RESULTS: Out of a registered patient population of 58 567, we identified 1037 patients who were first included in the hypothyroidism disease register between January 2004 and December 2009 (mean age 62.4±15.9 years; female 85.9%, male 14.1%). Inadequate replacement was seen in 385 patients (37.2%), comprising 205 patients (19.8%) with over replacement and 180 patients (17.4%) with under replacement. Step-wise logistic regression showed that the factors associated with under replacement were male gender [odds ratio (OR) 2.85, confidence interval (CI) 1.86-4.38; P<0.001 and younger age (OR 0.88, CI 0.80-0.98; P=0.02 per 10 year increase in age) while longer duration of treatment was associated with over-treatment (OR 1.06, CI 1.01-1.10). A thyroid function test was performed in the preceding 12 months in 914 patients (88.1%) and appropriate dose adjustments had been made in 81.0% (312/385) of patients with abnormal results.

CONCLUSION: Despite frequent monitoring and dose adjustment activities, inadequate thyroid hormone replacement remained a problem in over a third of levothyroxine users in this population.

PMID: 21109503 [PubMed - as supplied by publisher]


Clin Anat. 2011 Jan;24(1):1-9.

Historical vignettes of the thyroid gland.

Lydiatt DD, Bucher GS.

Division of Head and Neck Surgical Oncology, University of Nebraska Medical Center and Methodist Estabrook Cancer Center, Omaha, Nebraska, USA.


Although "glands" in the neck corresponding to the thyroid were known for thousands of years, they were mainly considered pathological when encountered. Recognition of the thyroid gland as an anatomical and physiological entity required human dissection, which began in earnest in the 16th century. Leonardo Da Vinci is generally credited as the first to draw the thyroid gland as an anatomical organ. The drawings were subsequently "lost" to medicine for nearly 260 years. The drawings were probably of a nonhuman specimen. Da Vinci vowed to produce an anatomical atlas, but it was never completed. Michelangelo Buonarroti promised to complete drawings for the anatomical work of Realdus Columbus, De Re Anatomica, but these were also never completed. Andreas Vesalius established the thyroid gland as an anatomical organ with his description and drawings in the Fabrica. The thyroid was still depicted in a nonhuman form during this time. The copper etchings of Bartholomew Eustachius made in the 1560s were obviously of humans, but were not actually published until 1714 with a description by Johannes Maria Lancisius. These etchings also depicted some interesting anatomy, which we describe. The Adenographia by Thomas Wharton in 1656 named the thyroid gland for the first time and more fully described it. The book also attempted to assign a function to the gland. The thyroid gland's interesting history thus touches a number of famous men from diverse backgrounds.

© 2010 Wiley-Liss, Inc.


Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002 Feb;87(2):489-99.


PMID: 11836274 [PubMed - indexed for MEDLINE]Free Article



Wilson GR, Curry RW Jr. Subclinical thyroid disease. Am Fam Physician. 2005 Oct 15;72(8):1517-24.


Department of Community Health and Family Medicine, University of Florida Health Science Center, Jacksonville, Florida 32209, USA.


Subclinical thyroid dysfunction is defined as an abnormal serum thyroid-stimulating hormone level (reference range: 0.45 to 4.50 microU per mL) and free thyroxine and triiodothyronine levels within their reference ranges. The management of subclinical thyroid dysfunction is controversial. The prevalence of subclinical hypothyroidism is about 4 to 8.5 percent, and may be as high as 20 percent in women older than 60 years. Subclinical hyperthyroidism is found in approximately 2 percent of the population. Most national organizations recommend against routine screening of asymptomatic patients, but screening is recommended for high-risk populations. There is good evidence that subclinical hypothyroidism is associated with progression to overt disease. Patients with a serum thyroid-stimulating hormone level greater than 10 microU per mL have a higher incidence of elevated serum low-density lipoprotein cholesterol concentrations; however, evidence is lacking for other associations. There is insufficient evidence that treatment of subclinical hypothyroidism is beneficial. A serum thyroid-stimulating hormone level of less than 0.1 microU per mL is associated with progression to overt hyperthyroidism, atrial fibrillation, reduced bone mineral density, and cardiac dysfunction. There is little evidence that early treatment alters the clinical course.

PMID: 16273818 [PubMed - indexed for MEDLINE]Free Article




Eur J Endocrinol. 2010 Aug;163(2):273-8. Epub 2010 Jun 1.

TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects.


Garduño-Garcia Jde J, Alvirde-Garcia U, López-Carrasco G, Padilla Mendoza ME, Mehta R, Arellano-Campos O, Choza R, Sauque L, Garay-Sevilla ME, Malacara JM, Gomez-Perez FJ, Aguilar-Salinas CA.


Departamento de Endocrinologia y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.



OBJECTIVE: To examine the association between thyroid function and the components of the metabolic syndrome and insulin resistance in an Hispanic population.


DESIGN: Cross-sectional study.


METHODS: Subjects with no history of thyroid disease or diabetes were included. Thyroid function was stratified as euthyroid or subclinical hypothyroidism (SCH) status and subsequently by free thyroxine (FT(4)) and TSH tertiles. The association of the metabolic syndrome components (defined by 2004 Adult Treatment Panel III criteria) and insulin resistance with thyroid status, TSH, and FT(4) were examined.


RESULTS: A total of 3148 subjects were analyzed. The prevalence of SCH was 8.3%. The prevalence of the metabolic syndrome was similar in euthyroid and SCH patients (31.6 vs 32.06%, P=0.89). Total cholesterol was higher in patients with SCH (5.51+/-1.19 vs 5.34+/-1.05 mmol/l, P<0.032). Serum TSH values showed a positive correlation (adjusted for age and sex) with total cholesterol, triglycerides, and waist circumference. In contrast, FT(4) showed a positive correlation with high-density lipoprotein cholesterol, and an inverse correlation with waist circumference, insulin, and HOMA-IR.


CONCLUSION: SCH is not associated with an increased risk for the metabolic syndrome (as conceived as a diagnostic category defined by the National Cholesterol, Education Program, Adult Treatment Panel III criteria). Despite this, low thyroid function (even in the euthyroid state) predisposes to higher cholesterol, glucose, insulin, and HOMA-IR levels. The combined use of TSH and FT(4), compared with the assessment based on only FT(4), is a more convenient approach to evaluate the association between thyroid function and metabolic variables.



Clin Endocrinol (Oxf). 2004 Aug;61(2):232-8.

Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years.


Kvetny J, Heldgaard PE, Bladbjerg EM, Gram J.


Section of Endocrinology, Department of Internal Medicine, Esbjerg County Hospital, Oerum Health Centre, University of Southern Denmark, Esbjerg, Denmark.



OBJECTIVE: Mild thyroid failure is associated with an increased risk for development of atherosclerosis, but whether subclinical hypothyroidism is related to risk for cardiovascular disease is controversial. The purpose of the present study was to examine a possible association between subclinical hypothyroidism and cardiovascular disease.


DESIGN: Cross-sectional study of a general population.


PATIENTS: Twelve hundred and twelve subjects, men and women, between 20 and 69 years old without thyroid disease not treated with drugs interfering with thyroid function or analysis of TSH were included.


MEASUREMENTS: Clinical signs of cardiovascular disease based on a questionnaire and medical records and laboratory analysis of lipids, atherothrombotic risk markers, C-reactive protein and TSH.


RESULTS: The main findings were a high incidence of subclinical hypothyroidism (19.7%) in a general population. Subclinical hypothyroidism was associated with higher concentrations of triglycerides and C-reactive protein. Below 50 years of age cardiovascular disease was more frequent in males with subclinical hypothyroidism compared to euthyroid males. Subclinical hypothyroidism was a predictor of cardiovascular disease in males below 50 years with an odds ratio of 3.4 (95% confidence interval 1.6-6.8) for developing cardiovascular disease compared to euthyroid age-matched males.


CONCLUSION: Our study demonstrates that patients with subclinical hypothyroidism have increased levels of triglycerides and signs of low-grade inflammation (raised C-reactive protein levels) and that subclinical hypothyroidism might be a risk factor for development of cardiovascular disease in younger males.


PMID: 15272919 [PubMed - indexed for MEDLINE]



Verkaik-Kloosterman J, van 't Veer P, Ocké MC. Reduction of salt: will iodine intake remain adequate in The Netherlands?  Br J Nutr. 2010 Dec;104(11):1712-8.


Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2003 Apr;21(2):111-3.

[Effects of lead on thyroid function of occupationally exposed workers].

[Article in Chinese]

Liang QR, Liao RQ, Su SH, Huang SH, Pan RH, Huang JL.



Lorini R, Gastaldi R, Traggiai C, Perucchin PP. Hashimoto's Thyroiditis. Pediatr Endocrinol Rev. 2003 Dec;1 Suppl 2:205-11; discussion 211.


Paknys G, Kondrotas AJ, Kevelaitis E. [Risk factors and pathogenesis of Hashimoto's thyroiditis]. Medicina (Kaunas). 2009;45(7):574-83.


McLachlan SM, Nagayama Y, Pichurin PN, Mizutori Y, Chen CR, Misharin A, et al. The link between Graves' disease and Hashimoto's thyroiditis: a role for regulatory T cells. Endocrinology. 2007 Dec;148(12):5724-33.

Free article:


Selenkow HA, Wyman P, Allweiss P. Autoimmune thyroid disease: an integrated concept of Graves' and Hashimoto's diseases. Compr Ther. 1984 Apr;10(4):48-56.

PMID: 6373115 [PubMed - indexed for MEDLINE]


Wasniewska M, Corrias A, Arrigo T, Lombardo F, Salerno M, Mussa A, et al. Frequency of Hashimoto's thyroiditis antecedents in the history of children and adolescents with graves' disease. Horm Res Paediatr. 2010;73(6):473-6.



Najib U, Bajwa ZH, Ostro MG, Sheikh J. A retrospective review of clinical presentation, thyroid autoimmunity, laboratory characteristics, and therapies used in patients with chronic idiopathic urticaria. Ann Allergy Asthma

Immunol. 2009 Dec;103(6):496-501.



PMID: 20084843 [PubMed - indexed for MEDLINE]


Aamir IS, Tauheed S, Majid F, Atif A. Frequency of autoimmune thyroid disease in chronic urticaria. J Coll Physicians Surg Pak. 2010 Mar;20(3):158-61.


PMID: 20392376


Kiyici S, Gul OO, Baskan EB, Hacioglu S, Budak F, Erturk E, Imamoglu S. Effect of levothyroxine treatment on clinical symptoms and serum cytokine levels in euthyroid patients with chronic idiopathic urticaria and thyroid autoimmunity.

Clin Exp Dermatol. 2010 Aug;35(6):603-7.


PMID: 19874329 [PubMed - in process]


Olateju TO, Vanderpump MP. Thyroid hormone resistance. Ann Clin Biochem. 2006 Nov;43(Pt 6):431-40.



Med Hypotheses. 2007;69(4):913-21. Epub 2007 Mar 26.

On commonness and rarity of thyroid hormone resistance: a discussion based on mechanisms of reduced sensitivity in peripheral tissues.


Tjørve E, Tjørve KM, Olsen JO, Senum R, Oftebro H.

Horm Metab Res. 2005 Sep;37(9):577-84.

Exercise as a stress model and the interplay between the hypothalamus-pituitary-adrenal and the hypothalamus-pituitary-thyroid axes.

Mastorakos G, Pavlatou M.

Endocrine Unit, Second Department of Obstetrics and Gynecology, ARETAIEION Hospital, Athens Medical School, National Kapodistriakon University of Athens, Athens, Greece.


Exercise represents a physical stress that challenges homeostasis. In response to this stressor, the autonomic nervous system and hypothalamus-pituitary-adrenal axis are known to react and participate in the maintenance of homeostasis and the development of physical fitness. This includes elevation of cortisol and catecholamines in plasma. However, physical conditioning is associated with a reduction in pituitary-adrenal activation in response to exercise. On the other hand, highly trained athletes exhibit chronic mild hypercortisolism at baseline that may be an adaptive change to chronic exercise. In addition the proinflammatory cytokine, IL-6 is also activated, probably via catecholamines. On the other hand, the stress of chronic exercise induces certain changes to the thyroid axis. Peripheral thyroid hormone metabolism suppression is observed, and the result is a hormonal status similar to that of euthyroid sick syndrome (ESS), with suppression of T3 and elevation of rT3 plasma levels. One mechanism proposed involves exercise-activated pathways participating in the pathogenesis of ESS. This is realized through norepinephrine's activation of NF-kappaB. Neuroendocrine response to exercise stress involves activation of NF-kappaB resulting in inactivation of T3-dependent 5'-deiodinase gene expression and enzyme activity. Thus, ESS is generated in the periphery. On the other hand, activation and nuclear translocation of NF-kappaB leads to increased transcription of proinflammatory genes responsible for the expression of proinflammatory cytokines such as TNF-alpha and IL-6. These cytokines could activate cortisol, which in turn inhibits NF-kappaB activation through IkappaB and finally shuts down this cycle.


Eur J Endocrinol. 2009 Nov;161(5):695-703. Epub 2009 Aug 17.

Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome.

Roelfsema F, Pereira AM, Biermasz NR, Frolich M, Keenan DM, Veldhuis JD, Romijn JA.

Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.


CONTEXT: The hypothalamus-pituitary-thyroid axis in Cushing's syndrome may be altered. Previous reports have shown diminished serum TSH concentration and decreased response to TRH.

OBJECTIVE: We analyzed serum TSH profiles in relation to cortisol profiles in patients with hypercortisolism of pituitary (n=16) or primary-adrenal origin (n=11) and after remission by pituitary surgery (n=7) in order to delineate aberrations in the hypothalamus-pituitary-thyroid system.

INTERVENTION: Patients and controls (n=27) underwent a 24-h blood sampling study. Serum TSH and cortisol were measured with precise methods, and data were analyzed with a deconvolution program, approximate entropy (ApEn), and cosinor regression.

RESULTS: Pulsatile TSH secretion and mean TSH pulse mass were diminished during hypercortisolism, independently of etiology (P<0.001). TSH secretion was increased in patients in remission only during daytime due to increased basal secretion (P<0.01). Pulse frequency and half life of TSH were similar in patients and controls. TSH ApEn (irregularity) was increased in patients with hypercortisolism (P<0.01), but was normal in cured patients. Cross-ApEn between TSH and cortisol, a measure of pattern synchrony loss, was increased in active disease, indicating (partial) loss of secretory synchrony. The TSH rhythm was phase delayed in hypercortisolemic patients, but normal in cured patients (P<0.01). Free thyroxine levels were decreased only in pituitary-dependent hypercortisolism compared with controls (P=0.003). Total 24-h TSH correlated negatively and linearly with log-transformed cortisol secretion (R=0.43, P=0.001).

CONCLUSION: Cortisol excess decreases TSH secretion by diminishing pulsatile release, whereas surgically cured patients have elevated nonpulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic/annexin-1 control.

PMID: 19687167 [PubMed - indexed for MEDLINE]Free Article


Rodondi N, den Elzen WPJ, Bauer DC, Cappola AR, Razvi S, Walsh JP, et al. Subclinical Hypothyroidism and the Risk of Coronary Heart Disease and Mortality. JAMA. 2010;304(12):1365-1374. doi: 10.1001/jama.2010.1361



Ciccone MM, De Pergola G, Porcelli MT, Scicchitano P, Caldarola P, Iacoviello M, et al. Increased carotid IMT in overweight and obese women affected by Hashimoto's thyroiditis: an adiposity and autoimmune linkage? BMC Cardiovasc Disord. 2010 May 28;10:22.


PMID: 20509904 [PubMed - indexed for MEDLINE]PMCID: PMC2885992

Free PMC Article :



Stamatelopoulos KS, Kyrkou K, Chrysochoou E, Karga H, Chatzidou S, Georgiopoulos G, et al. Arterial stiffness but not intima-media thickness is increased in euthyroid patients with Hashimoto's thyroiditis: The effect of menopausal status. Thyroid. 2009 Aug;19(8):857-62.


PMID: 19348585


Oliviero U, Cittadini A, Bosso G, Cerbone M, Valvano A, Capalbo D, et al. Effects of long-term L-thyroxine treatment on endothelial function and arterial distensibility in young adults with congenital hypothyroidism. Eur J Endocrinol. 2010 Feb;162(2):289-94.


Garber JR, Hennessey JV, Liebermann JA 3rd, Morris CM, Talbert RL. Clinical Upate. Managing the challenges of hypothyroidism. J Fam Pract. 2006 Jun;55(6):S1-8.


Endocrine Web.  Download December 30, 2010:


Camilleri M, Bharucha AE. Behavioural and new pharmacological treatments for constipation: getting the balance right. Gut. 2010 Sep;59(9):1288-96.

PMID: 20801775


Ebert EC. The thyroid and the gut. J Clin Gastroenterol. 2010 Jul;44(6):402-6.


Charlot L, Abend S, Ravin P, Mastis K, Hunt A, Deustch C. Non-psychiatric health problems among psychiatric inpatients with intellectual disabilities. J Intellect Disabil Res. 2010 Jun 8.


Samuels MH, Schuff KG, Carlson NE, Carello P, Janowsky JS. Health status, mood, and cognition in experimentally induced subclinical hypothyroidism. J Clin Endocrinol Metab. 2007 Jul;92(7):2545-51. Epub 2007 May 1.


Anjana Y, Tandon OP, Vaney N, Madhu SV. Cognitive status in hypothyroid female patients: event-related evoked potential study. Neuroendocrinology. 2008;88(1):59-66. Epub 2008 Feb 19.



Samuels MH, Schuff KG, Carlson NE, Carello P, Janowsky JS. Health status, mood, and cognition in experimentally induced subclinical thyrotoxicosis. J Clin Endocrinol Metab. 2008 May;93(5):1730-6.


PMID: 18285414 [PubMed


Doucet J, Trivalle C, Chassagne P, Perol MB, Vuillermet P, Manchon ND, et al. Does age play a role in clinical presentation of hypothyroidism? J Am Geriatr Soc. 1994 Sep;42(9):984-6.




Jordan RM. Myxedema coma. Pathophysiology, therapy, and factors affecting prognosis. Med Clin North Am. 1995 Jan;79(1):185-94.


PMID: 7808091 [PubMed - indexed for MEDLINE]


Romaldini JH, Sgarbi JA, Farah CS. [Subclinical thyroid disease: subclinical hypothyroidism and hyperthyroidism]. Arq Bras Endocrinol Metabol. 2004 Feb;48(1):147-58.


PMID: 15611827 [PubMed - indexed for MEDLINE]


J Fam Pract. 2007 Aug;56(8 Suppl Hot Topics):S31-9.

Evaluating and treating the patient with hypothyroid disease.


Hennessey JV, Scherger JE.



PMID: 18667141 [PubMed - indexed for MEDLINE]


Am J Psychiatry. 2002 Jan;159(1):116-21.

Slower treatment response in bipolar depression predicted by lower pretreatment thyroid function.

Cole DP, Thase ME, Mallinger AG, Soares JC, Luther JF, Kupfer DJ, Frank E.

Department of Psychiatry, University of Pittsburgh School of Medicine, USA.


OBJECTIVE: Because treatment of the depressed phase of bipolar disorder is a clinical challenge and hypothyroidism is known to be associated with depression, the authors examined the relationship between pretreatment thyroid values and response to antidepressant treatment. It was hypothesized that subjects with lower thyroid function, even within the normal range, would have a poorer response to initial treatment.

METHOD: The subjects were 65 patients in the depressed phase of bipolar I disorder who were enrolled in a larger ongoing study. A panel of thyroid measures, including thyroid-stimulating hormone (TSH), thyroxine, triiodothyronine resin uptake, and free thyroxine index (FTI), were determined before initiation of algorithm-guided treatment. The effect of each thyroid measurement on time to remission was estimated by using the Cox proportional hazards model.

RESULTS: Both lower values of FTI and higher values of TSH were significantly associated with longer times to remission, i.e., slower response to treatment. Outcomes were relatively poor unless patients had FTI values above the median and TSH values below the median. Patients with this optimal profile experienced remission 4 months faster than the remainder of the study group.

CONCLUSIONS: This study provides further evidence that patients with bipolar disorder are particularly sensitive to variations in thyroid function within the normal range. Our results suggest that nearly three-quarters of patients with bipolar disorder have a thyroid profile that may be suboptimal for antidepressant response. It remains to be seen whether pharmacological enhancement of thyroid function will facilitate recovery from bipolar depression.

PMID: 11772699 [PubMed - indexed for MEDLINE]Free Article


Minerva Endocrinol. 2004 Sep;29(3):139-50.

Thyroid hormone and the cardiovascular system.

Danzi S, Klein I.

PMID: 15282446 [PubMed - indexed for MEDLINE]Free Article


Hypertension. 1983 Jan-Feb;5(1):112-5.

Hypothyroidism as a cause of hypertension.

Saito I, Ito K, Saruta T.


To study whether there is an association between hypertension and hypothyroidism, measurements of blood pressure and thyroid function were determined in 477 female patients with chronic thyroiditis. Based on the blood levels of thyroxine (T4) and thyroid stimulating hormone (TSH), 308 patients were considered euthyroid and 169 were hypothyroid [T4 = 2.9 +/- 0.1 micrograms/dl and TSH = 105.8 +/- 6.8 microU/ml (mean +/- SEM)]. Diastolic, but not systolic, blood pressure in hypothyroid patients over 50 years was higher than in euthyroid patients of corresponding age groups. The prevalence of hypertension was higher in hypothyroid patients when hypertension was defined as the systolic and/or diastolic blood pressure above 160/95 mm Hg (14.8% vs 5.5%; p less than 0.01). Correlations between diastolic, but not systolic, blood pressure and either the blood level of triiodothyronine (T3) or T4 was significant (r = - 0.174, p less than 0.01, and r = 0.208, p less than 0.01, respectively) when data from both euthyroid and hypothyroid patients were combined. Adequate thyroid hormone replacement therapy for an average 14.8 months in 14 patients resulted in a normalization of thyroid function and a reduction of blood pressure (p less than 0.01). In four who showed no change in thyroid function due to inadequate replacement therapy, blood pressure remained elevated. These results suggest a close association between hypertension and hypothyroidism.

PMID: 6848458 [PubMed - indexed for MEDLINE]Free Article


Thyroid. 2002 Apr;12(4):287-93.

Thyroid disease and lipids.


Duntas LH.


Endocrine Unit, Evgenidion Hospital, University of Athens Medical School, Athens, Greece.



The composition and the transport of lipoproteins are seriously disturbed in thyroid diseases. Overt hypothyroidism is characterized by hypercholesterolaemia and a marked increase in low-density lipoproteins (LDL) and apolipoprotein B (apo A) because of a decreased fractional clearance of LDL by a reduced number of LDL receptors in the liver. The high-density lipoprotein (HDL) levels are normal or even elevated in severe hypothyroidism because of decreased activity of cholesteryl-ester transfer protein (CETP) and hepatic lipase (HL), which are enzymes regulated by thyroid hormones. The low activity of CETP, and more specifically of HL, results in reduced transport of cholesteryl esters from HDL(2) to very low-density lipoproteins (VLDL) and intermediate low-density lipoprotein (IDL), and reduced transport of HDL(2) to HDL(3). Moreover, hypothyroidism increases the oxidation of plasma cholesterol mainly because of an altered pattern of binding and to the increased levels of cholesterol, which presents a substrate for the oxidative stress. Cardiac oxygen consumption is reduced in hypothyroidism. This reduction is associated with increased peripheral resistance and reduced contractility. Hypothyroidism is often accompanied by diastolic hypertension that, in conjunction with the dyslipidemia, may promote atherosclerosis. However, thyroxine therapy, in a thyrotropin (TSH)-suppressive dose, usually leads to a considerable improvement of the lipid profile. The changes in lipoproteins are correlated with changes in free thyroxine (FT(4)) levels. Hyperthyroidism exhibits an enhanced excretion of cholesterol and an increased turnover of LDL resulting in a decrease of total and LDL cholesterol, whereas HDL are decreased or not affected. The action of thyroid hormone on Lp(a) lipoprotein is still debated, because both decrease or no changes have been reported. The discrepancies are mostly because of genetic polymorphism of apo(a) and to the differences between the various study groups. Subclinical hypothyroidism (SH) is associated with lipid disorders that are characterized by normal or slightly elevated total cholesterol levels, increased LDL, and lower HDL. Moreover, SH has been associated with endothelium dysfunction, aortic atherosclerosis, and myocardial infarction. Lipid disorders exhibit great individual variability. Nevertheless, they might be a link, although it has not been proved, between SH and atherosclerosis.


PMID: 12034052 [PubMed - indexed for MEDLINE]

Mayo Clin Proc. 1993 Sep;68(9):860-6.

Hyperlipidemia in patients with primary and secondary hypothyroidism.

O'Brien T, Dinneen SF, O'Brien PC, Palumbo PJ.

Division of Endocrinology/Metabolism, Mayo Clinic, Rochester, Minnesota 55905.


Hypothyroidism is associated with an increased risk of coronary artery disease. This observation may in part be related to the lipid abnormalities in patients with this condition. The lipid profiles of 268 patients with primary hypothyroidism and 27 with secondary hypothyroidism, who were examined in the Thyroid Clinic at the Mayo Clinic during a 1-year period, were reviewed. Hyperlipidemia was commonly associated with both primary and secondary hypothyroidism. The lipid values decreased with treatment of hypothyroidism. Type IIa hyperlipidemia was the most common lipid abnormality in patients with primary hypothyroidism, whereas type IIb was the most common in those with secondary hypothyroidism. Total/high-density lipoprotein cholesterol and low-density lipoprotein/high-density lipoprotein cholesterol ratios were increased in both male and female patients with primary and secondary hypothyroidism, and they decreased with restitution of the euthyroid state, although this decrease achieved statistical significance only in female patients. Significant associations with total thyroxine were noted for total cholesterol and triglycerides and with thyroid-stimulating hormone (thyrotropin) for total cholesterol and low-density lipoprotein cholesterol. Thus, both primary and secondary hypothyroidism are commonly associated with an atherogenic lipid profile, which improves with replacement of thyroid hormone. Even after restitution of the euthyroid state, however, the lipid profile remains atherogenic in male patients. In comparison with primary hypothyroidism, the lipid profile is more atherogenic in secondary hypothyroidism because of the lower high-density lipoprotein cholesterol levels associated with this condition.

PMID: 8371604 [PubMed - indexed for MEDLINE]


Med Pregl. 2003 May-Jun;56(5-6):276-80.

[Dyslipidemia and subclinical hypothyroidism].


[Article in Serbian]


Caparevi? Z, Bojkovi? G, Stojanovi? D, Ili? V.


Klinika za internu medicinu, KBC Dr Dragisa Misovi?, Dedinje, 11000 Beograd, Heroja Milana Tepi?a 1.



INTRODUCTION: Subclinical hypothyroidism is defined as an increased serum TSH and normal serum FT4 concentration. In subclinical hypothyroidism, thyroid peroxidase and thyroglobulin antibodies are frequently present. Subclinical hypothyroidism may have endogenous or exogenous causes. The prevalence of subclinical hypothyroidism is rather high. The number of patients progressing to overt hypothyroidism may be higher. These patients may be asymptomatic, or have only mild symptoms or a single symptom.


MATERIAL AND METHODS: We investigated 35 patients with subclinical hypothyroidism in order to establish the type and degree of dyslipidemia and effects of therapy with L-thyroxine (50 micrograms/d) during three months.


RESULTS: Serum cholesterol, LDL-cholesterol and apo B were increased. A significant reduction of serum cholesterol, LDL-cholesterol and apo B concentrations was established during thyroid hormone replacement.


DISCUSSION AND CONCLUSION: Only a few studies reported higher LDL and lower HDL-cholesterol values in subclinical hypothyroidism. Much interest was thus aroused to evaluate whether or not subclinical hypothyroidism is associated with hypercholesterolemia. Only patients with serum thyrotropin (TSH) concentration above 10 mU/L had a significant reduction of serum cholesterol concentration during thyroid hormone replacement. Most patients with subclinical hypothyroidism should be treated with thyroxine to prevent progression to overt hypothyroidism. Thyroid hormone replacement therapy may slow the progression of coronary heart disease, because of its beneficial effects on lipids. These findings and especially high rate of progression towards overt hypothyroidism suggest early thyroxine treatment.


PMID: 14565053 [PubMed - indexed for MEDLINE]


Duntas LH, Mantzou E, Koutras DA. Circulating levels of oxidized low-density lipoprotein in overt and mild hypothyroidism. Thyroid. 2002 Nov;12(11):1003-7.


Endocrine Unit, Evgenidion Hospital, University of Athens Medical School, Athens, Greece.


The increased low-density lipoprotein cholesterol (LDL-C) levels in hypothyroidism may enhance the formation of oxidized LDL (oxi-LDL) that may consequently generate foam cells by their uptake by the macrophages. The goal of this study was to investigate whether plasma circulating oxi-LDL levels are elevated in mild and in overt hypothyroidism, if the concentration of oxi-LDL is influenced in a short-term treatment period by thyroid hormone, and whether correlations exist between serum concentration of thyrotropin (TSH), thyroid hormone, and cholesterol. Thirty-nine patients with overt hypothyroidism (OH), 41 patients with mild thyroid failure (MTF), and 57 controls (CNTR) were investigated. Serum TSH concentrations were increased in OH (18 +/- 6 mU/L) and in MTF (6 +/- 2 mU/L), whereas in CNTR the levels were 1.6 +/- 0.3 mU/L. Plasma circulating levels of oxi-LDL were measured by a new enzyme-linked immunosorbent assay (ELISA) kit (normal range, 40-75 mU/L) and they were found statistically significantly increased in OH compared to MTF (86 +/- 16 mU/L vs. 73 +/- 13 mU/L; p < 0.01) and to CNTR (62 +/- 11 mU/L; p < 0.001). Smokers in all groups exhibited statistically significant higher plasma oxi-LDL levels compared to nonsmokers. The percentage of increase amounted to 17.7% in OH, to 9.8% in MTF, and to 8% in CNTR. Replacement treatment with levothyroxine over a period of 3 months in 12 of 39 patients with OH and in 14 of 41 patients with MTF resulted in a statistically significant decrease of oxi-LDL only in the OH group. Thus, plasma oxi-LDL decreased in OH from 82 +/- 12 mU/L to 73 +/- 10 mU/L (p < 0.05), to the upper normal level, and in MTF from 68 +/- 5 mU/L to 64 +/- 5 mU/L, respectively. In conclusion, we can state that circulating oxi-LDL levels are elevated in untreated overt hypothyroidism, they tend to be higher in mild thyroid failure, they are severely affected by smoking, however, they need a longer time course to decrease via thyroxine treatment.

PMID: 12490078 [PubMed - indexed for MEDLINE]


Can J Cardiol. 1997 Mar;13(3):273-6.

The effect of thyroid hormone therapy on angiographic coronary artery disease progression.


Perk M, O'Neill BJ.


Department of Medicine, Dalhousie University, Halifax, Nova Scotia.


Comment in:


    * Can J Cardiol. 1997 Aug;13(8):728-9.




OBJECTIVE: To study the effect of adequacy of thyroid hormone replacement therapy on coronary atherosclerosis.


DESIGN: Retrospective cohort study of elderly hypothyroid patients with coexisting coronary artery disease. The association between the adequacy of thyroid replacement and the progression of angiographic coronary artery disease was investigated. Fisher's exact test was used for statistical analysis.


SETTING: Coronary angiographies were performed at the Cardiac Catheterization Laboratory of the Victoria General Hospital, Halifax, Nova Scotia, the only tertiary referral centre for Nova Scotia and Prince Edward Island. Information about the past and current thyroid status of the subjects was collected from their family physicians.


PATIENTS: Of 4103 patients admitted for coronary angiography during 1992 and 1993, 25 were on thyroid replacement therapy to treat hypothyroidism. Ten patients who underwent more than one coronary arteriography were selected (seven females and three males, mean age 65 +/- 10 years).


RESULTS: Of five patients inadequately treated for hypothyroidism, all demonstrated angiographic evidence of coronary atherosclerosis progression. However, five of seven who were treated adequately did not show atherosclerosis progression (P = 0.02, OR = 0.72, 95% CI 1.36 to infinity). Decreasing or maintaining the dose of L-thyroxine at 100 micrograms or less resulted in coronary atherosclerosis progression in six of six patients, whereas five of six patients taking fixed or increasing doses of L-thyroxine 150 micrograms or higher were spared from disease progression (P = 0.015, OR = 0.41, 95% CI 2.4 to infinity).


CONCLUSIONS: Angiographic coronary artery disease progression may be prevented by adequate thyroid replacement in hypothyroidism. With the help of modern, sensitive thyroid stimulating hormone assays higher doses of L-thyroxine may be safer and more effective in the atherosclerosis management of this patient population. Thyroid hormones can protect against atherosclerosis, presumably due to their metabolic affects on plaque progression.



Clin Chem Lab Med. 2003 Mar;41(3):284-92.

Steroids, sex hormone-binding globulin, homocysteine, selected hormones and markers of lipid and carbohydrate metabolism in patients with severe hypothyroidism and their changes following thyroid hormone supplementation.


Bicíková M, Hampl R, Hill M, Stanická S, Tallová J, Vondra K.


Institute of Endocrinology, Praha, Czech Republic.



Laboratory markers of thyroid function, selected steroid hormones, sex hormone-binding globulin (SHBG), homocysteine, prolactin, major markers of lipid- and glucose metabolism and of insular-growth hormone axes were investigated in fasting sera from 16 female patients with severe hypothyroidism after thyroidectomy because of thyroid cancer. The results obtained in severe hypothyroidism within 5-6 weeks after withdrawal of thyroid substitution therapy before control scintigraphy were compared with those obtained after correction of thyroid function. Elevated levels of homocysteine and prolactin in hypothyroidism significantly decreased after correction, while SHBG concentration increased. Correction of thyroid function led to significant changes of growth hormone and immunoglobulin F1 (decrease and increase, respectively), while insulin and proinsulin increased only insignificantly. Elevated levels of total cholesterol and triglycerides in hypothyroidism were normalized, along with a significant increase in high density lipoprotein (HDL)-cholesterol. As revealed by correlation and factor analyses, different relationships characterizing both states were found in hypothyroidism and after correction of thyroid function. A strong inverse relationship between homocysteine and free thyroid hormones confirms the effect of thyroid hormones on homocysteine metabolism. No such inverse relation was found in euthyroid state, however. Similarly, in hypothyroidism only, dehydroepiandrosterone sulfate correlated positively with immunoglobulin F1 and homocysteine and negatively with thyroid hormones and SHBG.


PMID: 12705335 [PubMed - indexed for MEDLINE]


Endocr Relat Cancer. 2006 Dec;13(4):1269-77.

Human melanoma cells express functional receptors for thyroid-stimulating hormone.


Ellerhorst JA, Sendi-Naderi A, Johnson MK, Cooke CP, Dang SM, Diwan AH.


Department of Experimental Therapeutics, Unit 362, University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, USA.



We have reported a high prevalence of hypothyroidism in the cutaneous melanoma population, suggesting that the pathologic hormonal environment of hypothyroidism promotes melanoma growth. The objective of this study was to test the hypothesis that TSH, which circulates at elevated levels in hypothyroid individuals, stimulates the growth of melanoma cells. Our results show that TSH receptors (TSHR) are expressed by virtually all cutaneous melanocytic lesions, including benign nevi, dysplastic nevi, and melanomas, with higher expression found in malignant and pre-malignant lesions. The finding of TSHR expression by human tumors is confirmed in cultured melanoma cells and melanocytes, in which TSHR expression is demonstrated by immunofluorescent staining, western blotting, and reverse transcriptase-PCR. Melanoma TSHR are functional, as evidenced by the ability of TSH to induce the formation of cAMP and to activate the mitogen-activated protein kinase (MAPK) pathway. Cultured melanoma cells, but not melanocytes, are induced to proliferate at a physiologically relevant concentration of TSH. Taken together, these data support the hypothesis that TSH is a growth factor for human melanoma. Our findings have broad clinical implications for the prevention of melanoma and the management of established disease.


PMID: 17158770 [PubMed - indexed for MEDLINE]Free Article




Oncol Rep. 2003 Sep-Oct;10(5):1317-20.

High prevalence of hypothyroidism among patients with cutaneous melanoma.


Ellerhorst JA, Cooksley CD, Broemeling L, Johnson MM, Grimm EA.


Department of Bioimmunotherapy, M.D. Anderson Cancer Center, Houston, TX 77030-4095, USA.



We have previously reported a high prevalence of hypothyroidism among patients with uveal melanoma. The objectives of the present study were to determine if a similar pattern of thyroid pathology exists among patients with cutaneous melanoma as well. To address this question, the medical records of all patients registered at the University of Texas M.D. Anderson Cancer Center with a diagnosis of cutaneous melanoma during the years 1997 and 1998 were examined for a history of overt hypothyroidism, defined as a requirement for thyroid hormone replacement. Data regarding stage and site of the primary tumor were obtained for these patients and for age/gender matched euthyroid controls from the same melanoma study population. Among 1,580 cutaneous melanoma patients (948 M/632 F), 111 (7.0%) gave a history of hypothyroidism [23/948 M (2.4%) and 88/632 F (13.9%)]. The prevalences of hypothyroidism for both males and females were significantly higher than those reported for the general population. Characteristics of the primary tumor did not differ between cases and controls, although there was a trend for a lower rate of primary tumor ulceration among the hypothyroid case subjects. We conclude that hypothyroidism of varied etiologies is common among patients with cutaneous melanoma. These data suggest that melanoma may be responsive to hormones of the thyroid hormone control loop, raising many questions of clinical and biologic importance.


PMID: 12883700 [PubMed - indexed for MEDLINE]



Clin Endocrinol (Oxf). 2004 Aug;61(2):232-8.

Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years.


Kvetny J, Heldgaard PE, Bladbjerg EM, Gram J.


Section of Endocrinology, Department of Internal Medicine, Esbjerg County Hospital, Oerum Health Centre, University of Southern Denmark, Esbjerg, Denmark.



OBJECTIVE: Mild thyroid failure is associated with an increased risk for development of atherosclerosis, but whether subclinical hypothyroidism is related to risk for cardiovascular disease is controversial. The purpose of the present study was to examine a possible association between subclinical hypothyroidism and cardiovascular disease.


DESIGN: Cross-sectional study of a general population.


PATIENTS: Twelve hundred and twelve subjects, men and women, between 20 and 69 years old without thyroid disease not treated with drugs interfering with thyroid function or analysis of TSH were included.


MEASUREMENTS: Clinical signs of cardiovascular disease based on a questionnaire and medical records and laboratory analysis of lipids, atherothrombotic risk markers, C-reactive protein and TSH.


RESULTS: The main findings were a high incidence of subclinical hypothyroidism (19.7%) in a general population. Subclinical hypothyroidism was associated with higher concentrations of triglycerides and C-reactive protein. Below 50 years of age cardiovascular disease was more frequent in males with subclinical hypothyroidism compared to euthyroid males. Subclinical hypothyroidism was a predictor of cardiovascular disease in males below 50 years with an odds ratio of 3.4 (95% confidence interval 1.6-6.8) for developing cardiovascular disease compared to euthyroid age-matched males.


CONCLUSION: Our study demonstrates that patients with subclinical hypothyroidism have increased levels of triglycerides and signs of low-grade inflammation (raised C-reactive protein levels) and that subclinical hypothyroidism might be a risk factor for development of cardiovascular disease in younger males.


PMID: 15272919 [PubMed - indexed for MEDLINE]


J Postgrad Med. 1993 Jul-Sep;39(3):137-41.

Menstrual irregularities and lactation failure may precede thyroid dysfunction or goitre.


Joshi JV, Bhandarkar SD, Chadha M, Balaiah D, Shah R.


Institute for Research in Reproduction, Seth GS Medical College, Parel, Bombay, Maharashtra.


Comment in:


    * J Postgrad Med. 1993 Jul-Sep;39(3):118-9.




Menstrual and reproductive history of 178 women referred to the thyroid clinic was compared with 49 healthy controls. Cases were classified as euthyroid, hypothyroid or hyperthyroid after clinical examination and after serum T3, T4, TSH measurements. Reproductive history was related chronologically to symptoms and signs of thyroid dysfunction. Only 31.8% of hypothyroid and 35.3% of hyperthyroid women had normal menstrual pattern in contrast with 56.3% of Euthyroid and 87.8% of healthy controls (p < 0.001). Reproductive failure (infertility, pregnancy wastage, failure of lactation) occurred in 37.5% of hypothyroid and 36.5% of hyperthyroid cases against 16.3% of euthyroid and 16.7% of healthy controls (p < 0.05). Interestingly, in 45% of cases with menstrual abnormality, the anomaly was antecedent to other clinical features by a variable period of two months to ten years. Reproductive failure and lactation failure also preceded thyroid dysfunction or goitre. Reproductive dysfunction may therefore be considered as one of the presenting symptoms of thyroid disorders in women, keeping in mind both menstrual irregularities and lactation failure may also arise from other common or idiopathic origins. Especially in women with menstrual irregularities in the perimenopausal age if thyroid dysfunction is detected, pharmacotherapy may be a superior alternative to surgical interventions like hysterectomy.


PMID: 8051643 [PubMed - indexed for MEDLINE]Free Article


Clin Endocrinol (Oxf). 2007 Mar;66(3):309-21.

Thyroid disease and female reproduction.


Poppe K, Velkeniers B, Glinoer D.


Department of Endocrinology, Vrije Universiteit Brussel (AZ-VUB), Brussels, Belgium.



The menstrual pattern is influenced by thyroid hormones directly through impact on the ovaries and indirectly through impact on SHBG, PRL and GnRH secretion and coagulation factors. Treating thyroid dysfunction can reverse menstrual abnormalities and thus improve fertility. In infertile women, the prevalence of autoimmune thyroid disease (AITD) is significantly higher compared to parous age-matched women. This is especially the case in women with endometriosis and polycystic ovarian syndrome (PCOS). AITD does not interfere with normal foetal implantation and comparable pregnancy rates have been observed after assisted reproductive technology (ART) in women with and without AITD. During the first trimester, however, pregnant women with AITD carry a significantly increased risk for miscarriage compared to women without AITD, even when euthyroidism was present before pregnancy. It has also been demonstrated that controlled ovarian hyperstimulation (COH) in preparation for ART has a significant impact on thyroid function, particularly in women with AITD. It is therefore advisable to measure thyroid function and detect AITD in infertile women before ART, and to follow-up these parameters after COH and during pregnancy when AITD was initially present. Women with thyroid dysfunction at early gestation stages should be treated with l-thyroxine to avoid pregnancy complications. Whether thyroid hormones should be given prior to or during pregnancy in euthyroid women with AITD remains controversial. To date, there is a lack of well-designed randomized clinical trials to elucidate this controversy.


PMID: 17302862 [PubMed - indexed for MEDLINE]


Arq Bras Endocrinol Metabol. 2009 Nov;53(8):976-82.

Clinical implications of altered thyroid status in male testicular function.


Wajner SM, Wagner MS, Maia AL.


Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.



Thyroid hormones are involved in the development and maintenance of virtually all tissues. Although for many years the testis was thought to be a thyroid-hormone unresponsive organ, studies of the last decades have demonstrated that thyroid dysfunction is associated not only with abnormalities in morphology and function of testes, but also with decreased fertility and alterations of sexual activity in men. Nowadays, the participation of triiodothyronine (T3) in the control of Sertoli and Leydig cell proliferation, testicular maturation, and steroidogenesis is widely accepted, as well as the presence of thyroid hormone transporters and receptors in testicular cells throughout the development process and in adulthood. But even with data suggesting that T3 may act directly on these cells to bring about its effects, there is still controversy regarding the impact of thyroid diseases on human spermatogenesis and fertility, which can be in part due to the lack of well-controlled clinical studies. The current review aims at presenting an updated picture of recent clinical data about the role of thyroid hormones in male gonadal function.


PMID: 20126850 [PubMed - indexed for MEDLINE]Free Article


Publication Types, MeSH Terms, Substances

Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007752.

Interventions for clinical and subclinical hypothyroidism in pregnancy.

Reid SM, Middleton P, Cossich MC, Crowther CA.

ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, 72 King William Road, Adelaide, South Australia, Australia, 5006.


BACKGROUND: Over the last decade there has been enhanced awareness of the appreciable morbidity of thyroid dysfunction, particularly thyroid deficiency. Since treating clinical and subclinical hypothyroidism may reduce adverse obstetric outcomes, it is crucial to identify which interventions are safe and effective.

OBJECTIVES: To identify interventions used in the management of hypothyroidism and subclinical hypothyroidism in pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes.

SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2009).

SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared a pharmacological intervention for hypothyroidism and subclinical hypothyroidism in pregnancy with another intervention or placebo.

DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and quality and extracted the data.

MAIN RESULTS: We included three RCTs of moderate risk of bias involving 314 women. In one trial of 115 women, levothyroxine therapy to treat pregnant euthyroid women with thyroid peroxidase antibodies was not shown to reduce pre-eclampsia significantly (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.11 to 3.48) but did significantly reduce preterm birth by 72% (RR 0.28; 95% CI 0.10 to 0.80). One trial of 30 hypothyroid women compared levothyroxine doses, but only reported biochemical outcomes. A trial of 169 women compared the trace element selenomethionine (selenium) with placebo and no significant differences were seen for either pre-eclampsia (RR 1.44; 95% CI 0.25 to 8.38) or preterm birth (RR 0.96; 95% CI 0.20 to 4.61). None of the three trials reported on childhood neurodevelopmental delay.There was a non-significant trend towards fewer miscarriages with levothyroxine, and selenium showed some favourable impact on postpartum thyroid function and decreased incidence of moderate to advanced postpartum thyroiditis.

AUTHORS' CONCLUSIONS: Levothyroxine treatment of clinical hypothyroidism in pregnancy is already standard practice given the documented benefits from earlier non-randomised studies. Whether levothyroxine should be utilised in autoimmune and subclinical hypothyroidism remains to be seen, but it may prove worthwhile, given a possible reduction in preterm birth and miscarriage. Selenomethionine as an intervention in women with thyroid autoantibodies is promising, particularly in reducing postpartum thyroiditis. There is a probable low incidence of adverse outcomes from levothyroxine and selenomethionine. High-quality evidence is lacking and large-scale randomised trials are urgently needed in this area. Until evidence for or against universal screening becomes available, targeted thyroid function testing in pregnancy should be implemented in women at risk of thyroid disease and levothyroxine utilised in hypothyroid women.

PMID: 20614463 [PubMed - indexed for MEDLINE]


Delange F. Iodine deficiency in Europe and its consequences: an update.

Eur J Nucl Med Mol Imaging. 2002 Aug;29 Suppl 2:S404-16.


PMID: 12192540 [PubMed - indexed for MEDLINE]


DONALD G. McNEIL Jr. In Raising the World’s I.Q., the Secret’s in the Salt

The New York Times December 16, 2006


Public Health Nutr. 2007 Dec;10(12A):1554-70.

Iodine deficiency and brain development in the first half of pregnancy.

de Escobar GM, Obregón MJ, del Rey FE.




   Sante. 2007 Jan-Mar;17(1):41-50.

[Reflections on mental retardation and congenital hypothyroidism: effects of trace mineral deficiencies].

[Article in French]

Sidibé el H.


PMID: 17897901 [PubMed - indexed for MEDLINE]Free Article




Verkaik-Kloosterman J, van 't Veer P, Ocké MC. Reduction of salt: will iodine intake remain adequate in The Netherlands?  Br J Nutr. 2010 Dec;104(11):1712-8.


Increased risk of iodine deficiency with vegetarian nutrition.

Remer T, Neubert A, Manz F.

Br J Nutr. 1999 Jan;81(1):45-9.PMID: 10341675 [PubMed - indexed for MEDLINE]


Ann Nutr Metab. 2003;47(5):183-5.

Iodine deficiency in vegetarians and vegans.

Krajcovicová-Kudlácková M, Bucková K, Klimes I, Seboková E.

PMID: 12748410 [PubMed - indexed for MEDLINE]


Thyroid. 2001 May;11(5):457-69.

Environmental iodine intake affects the type of nonmalignant thyroid disease.


Laurberg P, Bülow Pedersen I, Knudsen N, Ovesen L, Andersen S.


Department of Endocrinology and Medicine, Aalborg Hospital, Denmark.



The relationship between the iodine intake level of a population and the occurrence of thyroid diseases is U-shaped with an increase in risk from both low and high iodine intakes. Developmental brain disorders and endemic goiter caused by severe iodine deficiency may seriously deteriorate overall health status and economic performance of a population. Severe iodine deficiency with a median 24-hour urinary iodine excretion of the population below 25 microg needs immediate attention and correction. Less severe iodine deficiency with median urinary iodine excretion below 120 microg per 24 hours is associated with multinodular autonomous growth and function of the thyroid gland leading to goiter and hyperthyroidism in middle aged and elderly subjects. The lower the iodine intake, the earlier and more prominent are the abnormalities. At the other end of the spectrum, severely excessive iodine intake starting at median urinary iodine excretion levels around 800 microg per 24 hours is associated with a higher prevalence of thyroid hypofunction and goiter in children. A number of studies indicate that moderate and mild iodine excess (median urinary iodine >220 microg per 24 hours) are associated with a more frequent occurrence of hypothyroidism, especially in elderly subjects. The exact mechanism leading to this has not been clarified, and more studies are needed to define the limits of excessive iodine intake precisely. Due to the frequent occurrence of thyroid disorders, proper monitoring and control of the population iodine intake level is a cost-effective alternative to diagnosing, therapy and control of the many individual cases of thyroid diseases that might have been prevented.


PMID: 11396704 [PubMed - indexed for MEDLINE]


J Pediatr Endocrinol Metab. 2009 Apr;22(4):327-34.

Excessive iodine intake and ultrasonographic thyroid abnormalities in schoolchildren.


Duarte GC, Tomimori EK, de Camargo RY, Catarino RM, Ferreira JE, Knobel M, Medeiros-Neto G.


PMID: 19554806 [PubMed - indexed for MEDLINE]



Br Med J. 1976 Feb 14;1(6006):372-5.

Thyrotoxicosis induced by iodine contamination of food--a common unrecognised condition?


Stewart JC, Vidor GI.



Br Med J. 1976 Sep 18;2(6037):701.

Thyrotoxicosis induced by iodine in food.


Stewart JC, Vidor GI.


PMID: 974560 [PubMed - indexed for MEDLINE]PMCID: PMC1688295


J Med Food. 2007 Mar;10(1):90-100.

Seaweed and soy: companion foods in Asian cuisine and their effects on thyroid function in American women.

Teas J, Braverman LE, Kurzer MS, Pino S, Hurley TG, Hebert JR.




Med J Aust. 2010 Oct 4;193(7):413-5.

Iodine toxicity from soy milk and seaweed ingestion is associated with serious thyroid dysfunction.

Crawford BA, Cowell CT, Emder PJ, Learoyd DL, Chua EL, Sinn J, Jack MM.


PMID: 20919974 [PubMed - indexed for MEDLINE]


Endocr J. 2008 Dec;55(6):1103-8. Epub 2008 Aug 9.

Suppression of thyroid function during ingestion of seaweed "Kombu" (Laminaria japonoca) in normal Japanese adults.

Miyai K, Tokushige T, Kondo M; Iodine Research Group.


Miyai K, Kondo M, Tokushige T, Takahashi M, Watanabe R.


Thyroid. 2003 Jun;13(6):561-7.

Effect of iodine restriction on thyroid function in patients with primary hypothyroidism.

Kasagi K, Iwata M, Misaki T, Konishi J.



J Gen Intern Med. 2006 Jun;21(6):C11-4.

Iodine-induced thyrotoxicosis after ingestion of kelp-containing tea.

Müssig K, Thamer C, Bares R, Lipp HP, Häring HU, Gallwitz B.


PMID: 16808731 [PubMed - indexed for MEDLINE]PMCID: PMC1924637Free PMC Article


    Endocr Metab Immune Disord Drug Targets. 2009 Sep;9(3):277-94. Epub 2009 Sep 1.

Role of iodine, selenium and other micronutrients in thyroid function and disorders.

Triggiani V, Tafaro E, Giagulli VA, Sabbà C, Resta F, Licchelli B, Guastamacchia E.

PMID: 19594417 [PubMed - indexed for MEDLINE]



Biol Trace Elem Res. 2002 Jul;88(1):25-30.

Concentration of selenium in the whole blood and the thyroid tissue of patients with various thyroid diseases.


Kucharzewski M, Braziewicz J, Majewska U, Gó?d? S.



PMID: 12117262 [PubMed - indexed for MEDLINE]

Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations.


Gärtner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW.


J Clin Endocrinol Metab. 2002 Apr;87(4):1687-91.PMID: 11932302 [PubMed - indexed for MEDLINE]Free Article


Biofactors. 2003;19(3-4):165-70.

Selenium in the treatment of autoimmune thyroiditis.


Gärtner R, Gasnier BC.



Thyroid. 2008 Jan;18(1):7-12.

No immunological benefit of selenium in consecutive patients with autoimmune thyroiditis.

Karanikas G, Schuetz M, Kontur S, Duan H, Kommata S, Schoen R, Antoni A, Kletter K, Dudczak R, Willheim M.



Biol Trace Elem Res. 2008 Summer;123(1-3):1-7. Epub 2008 Mar 6.

Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism.


Erdal M, Sahin M, Hasimi A, Uckaya G, Kutlu M, Saglam K.




Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT.

 Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society. J Clin Endocrinol Metab. 2005 Jan;90(1):581-5; discussion 586-7.

PMID: 15643019 [PubMed - indexed for MEDLINE]Free Article


Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III).


Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE.


J Clin Endocrinol Metab. 2002 Feb;87(2):489-99.PMID: 11836274 [PubMed - indexed for MEDLINE]Free Article

The spectrum of thyroid disease in a community: the Whickham survey.


Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG, Young E, Bird T, Smith PA.


Clin Endocrinol (Oxf). 1977 Dec;7(6):481-93.

Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease.


Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruf J, Smyth PP, Spencer CA, Stockigt JR; Guidelines Committee, National Academy of Clinical Biochemistry.


Thyroid. 2003 Jan;13(1):3-126.

American Association of Clinical Endocrinologists.  Subclinical thyroid disease.


Thyroid. 2005 Sep;15(9):1035-9.

Optimal thyrotropin level: normal ranges and reference intervals are not equivalent.


Dickey RA, Wartofsky L, Feld S.


PMID: 16187911 [PubMed - indexed for MEDLINE]


J Clin Endocrinol Metab. 2005 Sep;90(9):5483-8.

The evidence for a narrower thyrotropin reference range is compelling.


Wartofsky L, Dickey RA.



Arch Intern Med. 2007 Jul 23;167(14):1533-8.

Serum thyrotropin measurements in the community: five-year follow-up in a large network of primary care physicians.


Meyerovitch J, Rotman-Pikielny P, Sherf M, Battat E, Levy Y, Surks MI.


Research & Health Planning Department, Health Planning and Policy Wing, Clalit Health Services, 101 Arlozorov St, PO Box 16250, Tel Aviv 62098, Israel.



PMID: 17646608 [PubMed - indexed for MEDLINE]Free Article


Clin Endocrinol (Oxf). 2002 Nov;57(5):577-85.

Psychological well-being in patients on 'adequate' doses of l-thyroxine: results of a large, controlled community-based questionnaire study.


Saravanan P, Chau WF, Roberts N, Vedhara K, Greenwood R, Dayan CM.



Thyroid. 2002 May;12(5):421-5.

Risk factors for cardiovascular disease in women with subclinical hypothyroidism.

Luboshitzky R, Aviv A, Herer P, Lavie L.



  Br Med J. 1920 Mar 13;1(3089):359-360.


Murray GR.

PMID: 20769820 [PubMed - as supplied by publisher]PMCID: PMC2337775Free PMC


Ann Intern Med. 1946 Jul;25:146-50.

Myxedema, controlled by thyroid extract for 52 years; report of a case.



Hart, FD. Oral thyroxine in treatment of myxoedema. BMJ march 4 1950

Page 512


Ann Intern Med. 1986 Jul;105(1):11-5.

L-thyroxine dosage: a reevaluation of therapy with contemporary preparations.

Hennessey JV, Evaul JE, Tseng YC, Burman KD, Wartofsky L.



September 1997 -- If you are taking one of the thyroid hormone replacement drugs that -- like Synthroid, Levoxyl, and others -- contain levothyroxine sodium, then the following news is of major importance to your health.

According to the Federal Register, no currently marketed orally administered levothyroxine sodium product has been shown to demonstrate consistent potency and stability and, thus, no currently marketed orally administered levothyroxine sodium product is generally recognized as safe and effective.

The government found that often levothyroxine sodium drugs do not remain potent through their expiration dates, and tablets of the same dosage strength from the same manufacturer have been found to vary in potency from lot to lot in terms of the amount of active ingredient present. This lack of stability and consistent potency has the potential to cause serious health consequences to those of us taking these drugs.

Levothyroxine sodium was first introduced into the market before 1962, without an approved "New Drug Application" (NDA), apparently in the belief that it was not a new drug.

Since that time, almost every manufacturer of orally administered levothyroxine sodium products, including Synthroid, has regularly reported recalls that were the result of potency or stability problems.

In some cases, problems result from the fact that levothyroxine sodium is unstable in the presence of light, temperature, air, and humidity. Just since 1991, there have been no less than 10 recalls of levothyroxine sodium tablets involving 150 lots and more than 100 million tablets. In all but one case, the recalls were initiated because tablets were found to be subpotent or because their levothyroxine tablets lose potency before their expiration dates. The remaining recall was initiated for a product that was found to be too potent. During this period, FDA also issued warnings to a manufacturer regarding a levothyroxine sodium product that lost potency when stored at the higher end of the recommended temperature range, and one whose potency ranged from 74.7 percent to 90.4, instead of the required 90 percent to 110 percent.

Problems also stem from formulation changes. Because these products are marketed without NDA's, manufacturers have not had to file for FDA approval each time they reformulate their levothyroxine sodium products. Manufacturers have changed inactive ingredients, physical form of coloring agents and other product aspects, resulting in significant changes in potency, in some cases increasing or decreasing potency by as much as 30 percent. As a result, in some cases, people on the same dosage for years became toxic on the same dose. There is evidence that manufacturers continue to make these sorts of formulation changes which affect potency.

Now, 35 years after their introduction, the U.S. Food and Drug Administration (FDA) issued notice (Federal Register, August 14, 1997) that orally administered drug products containing levothyroxine sodium are officially classified as "new drugs" and will need to go through the NDA process because of the stability and potency problems that have recently come to light.

In order to continue marketing these drugs, manufacturers will need to submit an NDA with documented evidence that each company's product is safe, effective, and manufactured in a way to ensure consistent potency. Because the drug is necessary to millions of Americans, the FDA is allowing manufacturers to continue to market these products without approved NDA's until August 14, 2000, in order to give the companies enough time to conduct the various research studies and to submit their NDAs.



J Clin Invest. 1995 Dec;96(6):2828-38.

Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats.

Escobar-Morreale HF, Obregón MJ, Escobar del Rey F, Morreale de Escobar G.

Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas y Universidad Autónoma, Madrid, Spain.


We have studied whether, or not, tissue-specific regulatory mechanisms provide normal 3,5,3'-triiodothyronine (T3) concentrations simultaneously in all tissues of a hypothyroid animal receiving thyroxine (T4), an assumption implicit in the replacement therapy of hypothyroid patients with T4 alone. Thyroidectomized rats were infused with placebo or 1 of 10 T4 doses (0.2-8.0 micrograms per 100 grams of body weight per day). Placebo-infused intact rats served as controls. Plasma and 10 tissues were obtained after 12-13 d of infusion. Plasma thyrotropin and plasma and tissue T4 and T3 were determined by RIA. Iodothyronine-deiodinase activities were assayed using cerebral cortex, liver, and lung. No single dose of T4 was able to restore normal plasma thyrotropin, T4 and T3, as well as T4 and T3 in all tissues, or at least to restore T3 simultaneously in plasma and all tissues. Moreover, in most tissues, the dose of T4 needed to ensure normal T3 levels resulted in supraphysiological T4 concentrations. Notable exceptions were the cortex, brown adipose tissue, and cerebellum, which maintained T3 homeostasis over a wide range of plasma T4 and T3 levels. Deiodinase activities explained some, but not all, of the tissue-specific and dose related changes in tissue T3 concentrations. In conclusion, euthyroidism is not restored in plasma and all tissues of thyroidectomized rats on T4 alone. These results may well be pertinent to patients on T4 replacement therapy.

PMID: 8675653 [PubMed - indexed for MEDLINE]PMCID: PMC185993 Free PMC Article


Endocrinology. 1996 Jun;137(6):2490-502.

Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat.

Escobar-Morreale HF, del Rey FE, Obregón MJ, de Escobar GM.


PMID: 8641203 [PubMed - indexed for MEDLINE]


BMJ. 2001 Oct 20;323(7318):891-5.

Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the reference range: randomised double blind placebo controlled crossover trial.

Pollock MA, Sturrock A, Marshall K, Davidson KM, Kelly CJ, McMahon AD, McLaren EH.


PMID: 11668132 [PubMed - indexed for MEDLINE]PMCID: PMC58535Free PMC Article



Med J Aust. 2001 Feb 5;174(3):141-3.

What is the optimal treatment for hypothyroidism?


Walsh JP, Stuckey BG.


Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, WA.



Standard treatment of primary hypothyroidism is with thyroxine, with the aim of relieving symptoms and bringing the serum TSH (thyroid-stimulating hormone) concentration to within the reference range. Recent research suggests that in some patients symptoms of hypothyroidism persist despite standard thyroxine replacement therapy. The optimal treatment of these patients is not known. Adjusting the thyroxine dose until the serum TSH concentration is in the lower part of the reference range (eg, 0.3-2.0 mU/L) may be beneficial. Animal studies and a single small clinical trial suggest that a combination of thyroxine and T3 (triiodothyronine), rather than thyroxine alone, may be required for optimal thyroid replacement therapy. Further research is needed to determine why some patients appear to have a suboptimal response to thyroxine, and whether combined thyroxine/T3 treatment is preferable to thyroxine alone in these patients.


PMID: 11247618 [PubMed - indexed for MEDLINE]


N Engl J Med. 1999 Feb 11;340(6):424-9.

Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism.

Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ Jr.


PMID: 9971866 [PubMed - indexed for MEDLINE]Free Article


Does a combination regimen of thyroxine (T4) and 3,5,3'-triiodothyronine improve depressive symptoms better than T4 alone in patients with hypothyroidism? Results of a double-blind, randomized, controlled trial.

Sawka AM, Gerstein HC, Marriott MJ, MacQueen GM, Joffe RT.

J Clin Endocrinol Metab. 2003 Oct;88(10):4551-5.PMID: 14557420 [PubMed - indexed for MEDLINE]Free Article


Combined thyroxine/liothyronine treatment does not improve well-being, quality of life, or cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism.

Walsh JP, Shiels L, Lim EM, Bhagat CI, Ward LC, Stuckey BG, Dhaliwal SS, Chew GT, Bhagat MC, Cussons AJ.

J Clin Endocrinol Metab. 2003 Oct;88(10):4543-50.PMID: 14557419 [PubMed - indexed for MEDLINE]Free ArticleRelated citations


Endocrinol Nutr. 2010 Dec 30. [Epub ahead of print]

Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism.

[Article in English, Spanish]

Sesmilo G, Simó O, Choque L, Casamitjana R, Puig-Domingo M, Halperin I.


J Clin Endocrinol Metab. 2005 Feb;90(2):805-12. Epub 2004 Dec 7.

Partial substitution of thyroxine (T4) with tri-iodothyronine in patients on T4 replacement therapy: results of a large community-based randomized controlled trial.


Saravanan P, Simmons DJ, Greenwood R, Peters TJ, Dayan CM.


PMID: 15585551 [PubMed - indexed for MEDLINE]Free Article


Altern Med Rev. 2004 Jun;9(2):157-79.

Sub-laboratory hypothyroidism and the empirical use of Armour thyroid.

Gaby AR.


PMID: 15253676 [PubMed - indexed for MEDLINE]Free Article


Thyroid. 1998 Mar;8(3):229-34.

Induction of oral tolerance in human autoimmune thyroid disease.


Lee S, Scherberg N, DeGroot LJ.


Thyroid. 2008 Mar;18(3):293-301.Click here to read Links

    Altered intestinal absorption of L-thyroxine caused by coffee.

    Benvenga S, Bartolone L, Pappalardo MA, Russo A, Lapa D, Giorgianni G, Saraceno G, Trimarchi F.



Sperber AD, Liel Y. Evidence for interference with the intestinal absorption of levothyroxine sodium by aluminum hydroxide. Intern Med. 1992 Jan;152(1):183-4.



Ann Intern Med. 1992 Dec 15;117(12):1010-3.Links

    Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism.

    Campbell NR, Hasinoff BB, Stalts H, Rao B, Wong NC.



JAMA. 2000 Jun 7;283(21):2822-5.

    Effect of calcium carbonate on the absorption of levothyroxine.

    Singh N, Singh PN, Hershman JM.


Endocr Pract. 2001 May-Jun;7(3):193-4.Click here to read Links

    Use of soy protein supplement and resultant need for increased dose of levothyroxine.

    Bell DS, Ovalle F.


Br J Clin Pharmacol. 2005 Sep;60(3):337-41.

Effects of grapefruit juice on the absorption of levothyroxine.

Lilja JJ, Laitinen K, Neuvonen PJ.


PMID: 16120075 [PubMed - indexed for MEDLINE]PMCID: PMC1884777Free PMC Article


Arch Intern Med. 2010 Dec 13;170(22):1996-2003.

Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial.


Bolk N, Visser TJ, Nijman J, Jongste IJ, Tijssen JG, Berghout A.


PMID: 21149757 [PubMed - in process]


Environ Health Perspect. 2005 Nov;113(11):1479-84.

Genetic factors that might lead to different responses in individuals exposed to perchlorate.


Scinicariello F, Murray HE, Smith L, Wilbur S, Fowler BA.




J Occup Environ Med. 2010 Jun;52(6):653-60.

The epidemiology of environmental perchlorate exposure and thyroid function: a comprehensive review.

Tarone RE, Lipworth L, McLaughlin JK.


PMID: 20523234 [PubMed - indexed for MEDLINE]


J Clin Endocrinol Metab. 2010 Jul;95(7):3207-15. Epub 2010 Apr 28.

Perchlorate and thiocyanate exposure and thyroid function in first-trimester pregnant women.


Pearce EN, Lazarus JH, Smyth PP, He X, Dall'amico D, Parkes AB, Burns R, Smith DF, Maina A, Bestwick JP, Jooman M, Leung AM, Braverman LE.

PMID: 20427488 [PubMed - indexed for MEDLINE]


Best Pract Res Clin Endocrinol Metab. 2010 Feb;24(1):133-41.

Perchlorate, iodine and the thyroid.


Leung AM, Pearce EN, Braverman LE.




Clin Endocrinol (Oxf). 2010 Sep;73(3):396-403. Epub 2010 Apr 23.

The association between serum thyrotropin (TSH) levels and bone mineral density in healthy euthyroid men.


Kim BJ, Lee SH, Bae SJ, Kim HK, Choe JW, Kim HY, Koh JM, Kim GS.


Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.



OBJECTIVE: Although osteoporosis is increasingly shown to occur in a considerable proportion of men, data on risk factors for male osteoporosis are limited. In this study, we investigated the association between serum thyrotropin (TSH) concentration and bone mineral density (BMD) in healthy euthyroid men. Design A cross-sectional community (health promotion centre)-based survey.


SUBJECTS AND MEASUREMENTS: For 1478 apparently healthy euthyroid men who participated in a routine health screening examination, we measured BMD at the lumbar spine and femoral neck using dual energy X-ray absorptiometry and serum TSH concentrations using immunoluminometry.


RESULTS: Lumbar spine BMD linearly increased with TSH level after adjustment for age, weight and height (P for trend = 0.002), and statistical significance persisted after additional adjustment for smoking and drinking habits (P for trend = 0.010). When serum alkaline phosphatase was added as a confounding variable, the relationship was still significant (P for trend = 0.016). Femoral neck BMD also tended to increase in higher TSH concentration after adjustment for age, weight and height (P for trend = 0.042), but this association disappeared after additional adjustment for smoking and drinking habits. The odds of lower BMD (i.e. osteopaenia and osteoporosis combined) were significantly increased in subjects with low-normal TSH (i.e. 0.4-1.2 mU/l), when compared to high-normal TSH (i.e. 3.1-5.0 mU/l), after adjustment for confounding factors (odds ratio = 1.45, 95% CI = 1.02-2.10).


CONCLUSION: These results suggest that a serum TSH concentration at the lower end of the reference range may be associated with low BMD in men.


PMID: 20455884 [PubMed - in process]



J Clin Endocrinol Metab. 2010 Jul;95(7):3173-81. Epub 2010 Apr 21.

Thyroid function within the upper normal range is associated with reduced bone mineral density and an increased risk of nonvertebral fractures in healthy euthyroid postmenopausal women.


Murphy E, Glüer CC, Reid DM, Felsenberg D, Roux C, Eastell R, Williams GR.


Molecular Endocrinology Group, 7th Floor Commonwealth Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.



CONTEXT: The relationship between thyroid function and bone mineral density (BMD) is controversial. Existing studies are conflicting and confounded by differences in study design, small patient numbers, and sparse prospective data.


OBJECTIVE: We hypothesized that variation across the normal range of thyroid status in healthy postmenopausal women is associated with differences in BMD and fracture susceptibility.


DESIGN: The Osteoporosis and Ultrasound Study (OPUS) is a 6-yr prospective study of fracture-related factors.


SETTING: We studied a population-based cohort from five European cities.


PARTICIPANTS: A total of 2374 postmenopausal women participated. Subjects with thyroid disease and nonthyroidal illness and those receiving drugs affecting thyroid status or bone metabolism were excluded, leaving a study population of 1278 healthy euthyroid postmenopausal women.


INTERVENTIONS: There were no interventions.


MAIN OUTCOME MEASURES: We measured free T(4) (fT4) (picomoles/liter), free T(3) (fT3) (picomoles/liter), TSH (milliunits/liter), bone turnover markers, BMD, and vertebral, hip, and nonvertebral fractures.


RESULTS: Higher fT4 (beta = -0.091; P = 0.004) and fT3 (beta = -0.087; P = 0.005) were associated with lower BMD at the hip, and higher fT4 was associated with increasing bone loss at the hip (beta = -0.09; P = 0.015). After adjustment for age, body mass index, and BMD, the risk of nonvertebral fracture was increased by 20% (P = 0.002) and 33% (P = 0.006) in women with higher fT4 or fT3, respectively, whereas higher TSH was protective and the risk was reduced by 35% (P = 0.028). There were independent associations between fT3 and pulse rate (beta = 0.080; P = 0.006), increased grip strength (beta = 0.171; P<0.001), and better balance (beta = 0.099; P < 0.001), indicating that the relationship between thyroid status and fracture risk is complex.


CONCLUSIONS: Physiological variation in normal thyroid status is related to BMD and nonvertebral fracture.


PMID: 20410228



Endocr Regul. 2010 Jan;44(1):9-15.

The level of TSH appeared favourable in maintaining bone mineral density in postmenopausal women.


Baqi L, Payer J, Killinger Z, Susienkova K, Jackuliak P, Cierny D, Langer P.


5th Clinic of Internal Medicine, Faculty Hospital Ruzinov, and Department of Statistics, Economics University, Bratislava, Slovakia.



OBJECTIVE: Since the positive role of thyrotropin (TSH) in bone remodeling has been recently emphasized, this cross-section study is aimed to evaluate the association of bone status with the level of TSH and free thyroxine (FT4) in the cohort of postmenopausal women after long-term treatment of thyroid disorders and age matched controls.


METHODS: Urinary calcium (dUCa) and serum level of TSH, FT4 and of bone turnover markers (BTMs) such as alkaline phosphatase (ALP), osteocalcin (OC), cross linked N-telopeptide of type 1 collagen (NTx) as well as lumbar spine L 1-4 (BMD-L) and femoral hip (BMD-F) mineral density were determined in 113 postmenopausal women consisting of 42 patients with Graves disease treated by carbimazole, 32 patients with thyroid cancer treated with L-thyroxine and 39 age matched women without any thyroid and osteological disorders. For statistical evaluation t-test, Pearson's correlation coefficient and linear multiple regression were used.


RESULTS: To compare the association of TSH versus FT4 with BMD and BTMs the pooled cohort of all 113 women was divided in two groups in terms of TSH level: 1. 34 women with low TSH (>or=0.50 mU/l); 2. 79 women with normal TSH (0.51-4.3 mU/l). In spite of significantly higher FT4 level, the Group 2 with normal TSH level had significantly higher BMD-L and BMD-F (p<0.001) and, in contrast, significantly lower urinary dUCa, ALP, OC (all at p<0.001) and NTx (p<0.01) as compared to the Group 1 with low TSH level. Linear multiple regression showed highly significant influence of TSH on BMD-L and BMD-F0 (p<0.001) independent of age, FT4 and body mass index, while that of FT4 was not significant. The strength of linear interrelation between all variables used was finally tested by Pearson's correlation coefficient (Table 3) which was highly positive for TSH with BMD-F and BMD-L, but highly negative for TSH with serum NTx, OC, ALP) and urinary calcium (dUCa). In contrast, no significant correlation was found between the level of FT4 and BMD.


CONCLUSIONS: Irrespectively of FT4 level, postmenopausal women with normal TSH level showed a favorable bone status as compared to these with low level of TSH which is consistent with the view that TSH itself possibly participates in playing a favorable role in influencing the bone mineral density in adult women.


PMID: 20151763 [PubMed - indexed for MEDLINE]



Thyroid. 2008 Jul;18(7):747-54.

Thyroid autoimmunity in schoolchildren in an area with long-standing iodine sufficiency: correlation with gender, pubertal stage, and maternal thyroid autoimmunity.

Kaloumenou I, Mastorakos G, Alevizaki M, Duntas LH, Mantzou E, Ladopoulos C, Antoniou A, Chiotis D, Papassotiriou I, Chrousos GP, Dacou-Voutetakis C.

Endocrine Unit, First Department of Pediatrics, Athens University School of Medicine, Athens, Greece.


BACKGROUND: A strong genetic background and gender are believed to be involved in thyroid autoimmunity (TA). The age these factors become manifest is less clear, however. The objective of the present study was to determine the prevalence of TA in children and adolescents and to determine if there are relationships between the period of onset of TA and gender and between TA and maternal autoimmunity.

METHODS: Antithyroperoxidase antibodies (anti-TPO Ab), antithyroglobulin antibodies (anti-Tg Ab), thyrotropin, thyroxine, triiodothyronine, and urinary iodine were determined in 440 healthy schoolchildren (200 boys and 240 girls), aged 5-18 years, and in 123 mothers living in an iodine-replete region.

RESULTS: The prevalence of positive anti-TPO and anti-Tg Ab was 4.6% and 4.3%, respectively. In girls, the prevalence of positive anti-TPO Ab was higher in Tanner stage II-V compared to Tanner stage I (8.2% vs. 2.2%; p < 0.05). No difference was detected with regard to anti-Tg Ab. In girls, positive anti-TPO and anti-Tg Ab levels were associated with significantly greater thyroid volume. Hypoechogenicity was detected in 52.6% and 36.8% of the children with positive anti-TPO or anti-Tg Ab, respectively (p = 0.0005). The prevalence of autoimmune thyroiditis, as defined by positive serum anti-TPO and/or anti-Tg and an echographic pattern of the thyroid gland having diffuse or irregular hypoechogenicity, was 2.5%. Mothers of anti-TPO Ab positive children had positive anti-TPO Ab more frequently compared to mothers of anti-TPO Ab negative children (82% vs. 18%; p = 0.0005). Mothers of anti-Tg Ab positive children had positive anti-Tg Ab more frequently compared to mothers of anti-Tg Ab negative children (75% vs. 25%; p = 0.0005).

CONCLUSIONS: These findings demonstrate that thyroid antibody positivity in children was significantly associated with maternal autoimmunity and their development in girls emerges at puberty. Since heredity, female gender, and puberty are strongly associated with TA, girls in families with TA should be examined at the onset of puberty.

PMID: 18631003 [PubMed - indexed for MEDLINE]


J Pediatr. 2009 Jul;155(1):51-5, 55.e1. Epub 2009 Mar 25.

Prevalence of autoimmune thyroiditis in children with celiac disease and effect of gluten withdrawal.


Meloni A, Mandas C, Jores RD, Congia M.


Pediatric Clinic II, Microcitemico Hospital ASL 8, Department of Biological Sciences and Biotechnology, University of Cagliari, Sardinia, Italy.



OBJECTIVE: To study the prevalence of autoimmune thyroiditis (AT) in Sardinian children with celiac disease (CD) and the effects of a gluten-free diet (GFD) on thyroid function.


STUDY DESIGN: Children with biopsy-proven CD (n = 324; female:male 2:1; mean age, 6.6 years) followed from 1 to 15 years, were retrospectively evaluated for AT at onset of CD and during GFD. Serum thyroid peroxidase and thyroglobulin antibodies (AbTPO, AbTG), thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid ultrasonography were considered. Age-matched Sardinian schoolchildren (n = 8040), previously evaluated for antithyroid antibodies and thyroid function, were used as controls.


RESULTS: Thirty-four patients with CD (10.5%) developed AT (female:male 4,5:1; mean age, 10.5 years), 11 at onset of CD and 23 during GFD, with a higher prevalence than controls (P = 2.9(-13)). Twenty-eight patients were euthyroid and 6 hypothyroid. AbTPO and/or AbTG persisted elevated for 2 to 9 years despite the GFD in 9 of 11 patients with AT at onset of CD.


CONCLUSIONS: AT is strongly associated with CD in Sardinian children, has an age of onset of 10.5 years, and appears to be gluten-independent. In children with CD with AT, the female:male bias reported in adult AT is present before puberty


    Biochimie. 1999 May;81(5):527-33.

The trace element selenium and the thyroid gland.

Köhrle J.



Thyroid. 2002 Oct;12(10):867-78.

The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health.

Zimmermann MB, Köhrle J.


Biochimie. 1999 May;81(5):527-33.

The trace element selenium and the thyroid gland.

Köhrle J.



Ann Ist Super Sanita. 2010;46(4):389-399.

Selenium status and over-expression of interleukin-15 in celiac disease and autoimmune thyroid diseases.

Stazi AV, Trinti B.


PMID: 21169670 [PubMed - as supplied by publisher]Free Article


Antioxid Redox Signal. 2010 Sep 2. [Epub ahead of print]

Selenium in Human Health and Disease.

Fairweather-Tait S, Bao Y, Broadley M, Collings R, Ford D, Hesketh J, Hurst R.


PMID: 20812787 [PubMed - as supplied by publisher]


Rayman MP. The importance of selenium to human health. Lancet. 2000;356(9225):233-241.


Gärtner R. Selenium and thyroid hormone axis in critical ill states: an overview of conflicting view points. J Trace Elem Med Biol. 2009;23(2):71-4. Epub 2009 Feb 25.


PMID: 19398053 [PubMed - indexed for MEDLINE]


  Foster LH, Sumar S. Selenium in health and disease: a review. Crit Rev Food Sci Nutr. 1997 Apr;37(3):211-28.


Brzozowska M, Kretowski A, Podkowicz K, Szmitkowski M, Borawska M, Kinalska I. [Evaluation of influence of selenium, copper, zinc and iron concentrations on thyroid gland size in school children with normal ioduria]. Pol Merkur Lekarski. 2006 Jun;20(120):672-7.


PMID: 17007265 [PubMed - indexed for MEDLINE]


Biol Trace Elem Res. 2002 Jul;88(1):25-30.

Concentration of selenium in the whole blood and the thyroid tissue of patients with various thyroid diseases.


Kucharzewski M, Braziewicz J, Majewska U, Gó?d? S.


PMID: 12117262 [PubMed - indexed for MEDLINE]


Jackson ML. Selenium: geochemical distribution and associations with human heart and cancer death rates and longevity in China and the United States. Biol Trace Elem Res. 1988 Jan-Apr;15:13-21.


PMID: 2484511 [PubMed - indexed for MEDLINE]


Public Health Nutr. 2001 Apr;4(2B):593-9.

Selenium, selenoproteins and human health: a review.

Brown KM, Arthur JR.


PMID: 11683552 [PubMed


Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations.


Gärtner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW.


J Clin Endocrinol Metab. 2002 Apr;87(4):1687-91.PMID: 11932302 [PubMed - indexed for MEDLINE]Free Article


Biofactors. 2003;19(3-4):165-70.

Selenium in the treatment of autoimmune thyroiditis.


Gärtner R, Gasnier BC.


Department of Endocrinology, Medizinische Klinik Innenstadt, University of Munich, D-80336 Munich, Germany.



We recently conducted a prospective, placebo-controlled clinical study, where we could demonstrate, that a substitution of 200 microg sodium selenite for three months in patients with autoimmune thyroiditis reduced thyroid peroxidase antibody (TPO-Ab) concentrations significantly. Forty-seven patients from the initially 70 patients agreed to participate in a follow-up cross-over study for further six months. One group (n = 13), which initially received selenium continued to take 200 microg sodium selenite (Se-Se), one group stopped taking selenium (Se-0) ( n = 9), another group which received placebo started to take 200 microg selenium (n = 14) (Plac-Se) and the last group was without selenium substitution (Plac-0) (n = 11). TPO-Ab concentrations were measured at beginning and the end of the study. In the Se-Se group, the TPO-Ab concentrations further significantly p = 0.004) decreased from 625 +/- 470 U/ml to 354 +/- 321 U/ml, in the Se-0 group the TPO-Ab concentrations increased significantly p = 0.017) from 450 +/- 335 to 708 +/- 313 U/ml. In the placebo group, the TPO-Ab concentrations in those patients who were followed without selenium substitution were unchanged (1351 +/- 940 vs. 1724 +/- 1112 U/ml, p = 0.555). In contrast, the patients who received 200 microg sodium selenite after placebo, the TPO-Ab concentrations decreased significantly (p = 0.029) from 1182 +/- 723 to 643 +/- 477 U/ml.


Thyroid. 2008 Jan;18(1):7-12.

No immunological benefit of selenium in consecutive patients with autoimmune thyroiditis.

Karanikas G, Schuetz M, Kontur S, Duan H, Kommata S, Schoen R, Antoni A, Kletter K, Dudczak R, Willheim M.

Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Austria.

Comment in:


BACKGROUND: Recently it has been demonstrated that after selenium (Se) supplementation in autoimmune thyroiditis (AIT) patients, there was a significant decrease of thyroid peroxidase (TPO) autoantibody (TPOAb) levels. The aim of our study was to evaluate the immunological benefit of Se administration in unselected AIT patients and thus address the question whether Se administration should generally be recommended for AIT patients.

METHODS: Thirty-six consecutive AIT patients (aged 19-85 years) were included in the present study. In addition to their levothyroxine (LT(4)) treatment, 18 patients received 200 microg (2.53 micromol) sodium selenite per day orally for the time span of 3 months, whereas 18 patients received placebo. All patients had measurement of thyroid hormones, thyrotropin (TSH), autoantibodies (thyroglobulin antibodies [TgAb] and TPOAb), Se levels, and intracellular cytokine detection in CD4(+) and CD8(+) T cells of peripheral blood mononuclear cells (PBMC) by flow cytometry before and after Se or placebo administration.

RESULTS: No significant difference in the TPOAb levels was found after Se administration (524 +/- 452 vs. 505 +/- 464 IU/mL; p > 0.05). Furthermore, we found no significant differences in the CD4(+) or CD8(+) cytokine pattern (IFN-gamma, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-alpha, TNF-beta) in patients before and after Se administration, in patients before and after placebo administration and between Se group and placebo group before and after Se vs. placebo administration.

CONCLUSION: We demonstrate that Se administration in our AIT patient's cohort does not induce significant immunological changes, either in terms of cytokine production patterns of peripheral T lymphocytes or of TPOAb levels. Our data suggest that AIT patients with moderate disease activity (in terms of TPOAb and cytokine production patterns) may not (equally) benefit as patients with high disease activity.


Thyroid. 2002 Oct;12(10):867-78.

The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health.

Zimmermann MB, Köhrle J.


PMID: 12487769 [PubMed - indexed for MEDLINE]


J Clin Endocrinol Metab. 2009 Jan;94(1):151-6. Epub 2008 Nov 4.

Hematologic effects of levothyroxine in iron-deficient subclinical hypothyroid patients: a randomized, double-blind, controlled study.

Cinemre H, Bilir C, Gokosmanoglu F, Bahcebasi T.



PMID: 18984662


Bellisola G, Brätter P, Cinque G, Francia G, Galassini S, Gawlik D, Negretti de Brätter VE, Azzolina L. The TSH-dependent variation of the essential elements iodine, selenium and zinc within human thyroid tissues. J Trace Elem Med Biol. 1998 Nov;12(3):177-82.

Exp Clin Endocrinol Diabetes. 1999;107(6):356-60.

Incidence of sideropenia and effects of iron repletion treatment in women with subclinical hypothyroidism.

Duntas LH, Papanastasiou L, Mantzou E, Koutras DA.


PMID: 10543412 [PubMed - indexed for MEDLINE]


J Nutr. 1999 Jan;129(1):174-80.

Single and multiple selenium-zinc-iodine deficiencies affect rat thyroid metabolism and ultrastructure.

Ruz M, Codoceo J, Galgani J, Muñoz L, Gras N, Muzzo S, Leiva L, Bosco C.


Center for Human Nutrition, Faculty of Medicine, University of Chile, Santiago, Chile.


This study was conducted to evaluate the effects of single and combined deficiencies of Se, Zn and I on thyroid function in rats. Rats were fed amino acid-based diets for 6 wk starting from weaning. The diets contained either low or adequate amounts of these minerals. In addition to the control and control pair-fed groups, seven experimental groups were formed: Se deficient (Se-); I deficient (I-); Zn deficient (Zn-); Se and I deficient (Se-I-); Zn and I deficient (Zn-I-); Se and Zn deficient (Se-Zn); and Se, I and Zn deficient (Se-I-Zn-). Serum triiodothyronine (T3) was significantly lower than in controls in Zn-, Se-Zn- and Se-I- groups. Serum total thyroxine (T4) and free T4 were significantly lower and thyroid-stimulating hormone (TSH) greater in all iodine-deficient groups, regardless of Se or Zn status. Thyroid glutathione peroxidase activity was significantly reduced in Se- and Se-Zn- groups. Nevertheless, in the groups with a concurrent I deficiency, the activity of this enzyme was significantly greater than in controls. Severe alterations of the follicle cellular architecture, including signs compatible with apoptosis, were observed in the Zn- and Se-Zn- groups. These alterations appeared to be less severe when iodine deficiency was simultaneously present. Single and multiple deficiencies of Se, Zn and I have distinct effects on thyroid metabolism and structure.

PMID: 9915896 [PubMed - indexed for MEDLINE]Free Article


Horm Metab Res. 1996 May;28(5):223-6.

Influence of zinc and selenium deficiency on parameters relating to thyroid hormone metabolism.


Kralik A, Eder K, Kirchgessner M.


Institute of Nutrition Physiology, Technical University Munich, Freising-Weihenstephan, Germany.



48 weaned male Sprague-Dawley rats with an initial average body weight of 41 g were divided into 4 groups of 12 animals (zinc-deficient; zinc-adequate, pair-fed with zinc-deficient group; selenium-deficient; selenium-adequate) for 40 days. All groups were fed a semisynthetic diet with casein being the source of protein. In the selenium-deficient diet, there was a selenium concentration of 0.038 mg/kg. The other diets were supplemented with Na-selenite in order to adjust the selenium concentration to 0.3 mg/kg. In the zinc-deficient diet, there was a zinc concentration of 4.1 mg/kg. The zinc concentrations in the other diets were adjusted to 45 mg/kg by the addition of zinc-sulfate heptahydrate. Zinc-deficient rats were characterized by a markedly reduced alkaline phosphatase activity in their serum, whilst selenium-deficient rats showed a markedly reduced glutathione peroxidase in serum proving their respective zinc-deficient and selenium-deficient states. Zinc deficiency decreased concentrations of triiodothyronine (T3) and free thyroxine (fT4) in serum by approximately 30% when compared with zinc-adequate controls. The concentration of thyroxine (T4) in serum was not affected by zinc deficiency. Selenium-deficient animals had lower concentrations of T3 and T4 than selenium-adequate animals. The concentration of fT4 in serum was not affected by selenium deficiency. The activity of hepatic type I 5'deiodinase was decreased by 67% by zinc deficiency and by 47% by selenium deficiency compared to adequate controls. The study data show that both zinc and selenium deficiency affect the metabolism of thyroid hormones.


PMID: 8738110 [PubMed - indexed for MEDLINE]


J Am Coll Nutr. 1994 Feb;13(1):62-7.

Zinc supplementation alters thyroid hormone metabolism in disabled patients with zinc deficiency.


Nishiyama S, Futagoishi-Suginohara Y, Matsukura M, Nakamura T, Higashi A, Shinohara M, Matsuda I.


PMID: 8157857 [PubMed - indexed for MEDLINE]


Indian J Exp Biol. 2008 Mar;46(3):171-9.

Beneficial effect of modified egg on serum T3, T4 and dyslipidaemia following dietary Zn-supplementation in Wistar rat.

Taneja SK, Mandal R.

Department of Zoology, Panjab University, Chandigarh, India.


A fall in serum T3 and T4 along with increase in serum cholesterol, triglycerides, LDL-c and VLDL-c and decrease in HDL-c was observed in albino Wistar rats when fed on semi-synthetic diet containing either 40 or 80mg Zn/kg diet. Zn concentrations were observed to increase with decreased concentration of Cu and Mg in their tissues. On including modified egg (Indian Patent Application No. 2264\Del\2005) in the Zn supplement diet, the levels of T3 and T4, lipid profile in serum and mineral status approached closer to control group-I. The data suggest that hypothyroidism and dyslipidaemia caused by excessive Zn in diet can be ameliorated on consuming these modified eggs due to restoration of mineral status in the body.

PMID: 18432056 [PubMed - indexed for MEDLINE]


Indian J Exp Biol. 2006 Sep;44(9):705-18.

Long term excessive Zn-supplementation promotes metabolic syndrome-X in Wistar rats fed sucrose and fat rich semisynthetic diet.

Taneja SK, Mandal R, Girhotra S.


PMID: 16999025 [PubMed - indexed for MEDLINE]


Folia Biol (Praha). 2007;53(5):183-8.

Investigation of zinc and copper levels in methimazole-induced hypothyroidism: relation with the oxidant-antioxidant status.

Alturfan AA, Zengin E, Dariyerli N, Alturfan EE, Gumustas MK, Aytac E, Aslan M, Balkis N, Aksu A, Yigit G, Uslu E, Kokoglu E.


PMID: 17976309 [PubMed - indexed for MEDLINE]Free Article


J Trace Elem Med Biol. 2010 Apr;24(2):106-10. Epub 2009 Dec 22.

Trace elements status in multinodular goiter.

Giray B, Arnaud J, Sayek I, Favier A, Hincal F.


Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara 06100, Turkey.


Importance of iodine and selenium in thyroid metabolism is well known, but the roles of other essential trace elements including copper, zinc, manganese and iron on thyroid hormone homeostasis remain unclear. The aim of this study was to investigate the status of those trace elements in benign thyroid diseases and evaluate possible links between trace element concentrations and thyroid hormones. The study group was composed of 25 patients with multinodular goiter. Concentrations of thyroid hormones (plasma-free thyroxine, FT(4); free triiodothyronine, FT(3); and thyrotropin, TSH), selenium, copper, zinc, manganese and iron in plasma, and urinary iodine were determined. The results were compared with those of a healthy control group (n=20) with no thyroid disorder. A mild iodine deficiency was observed in the patients with multinodular goiter whereas urinary iodine levels were in the range of "normal" values in healthy controls. All patients were euthyroid, and their thyroid hormone concentrations were not significantly different from the control group. Plasma selenium, zinc and iron concentrations did not differ from controls, while copper and manganese levels were found to be significantly higher in the patients with multinodular goiter indicating links between these trace elements and thyroid function and possibly in development of goiter. Besides iodine, there was a significant correlation between plasma copper concentration and FT(3)/FT(4) ratio.

2009 Elsevier GmbH. All rights reserved.


J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jan 1;878(1):34-8.

Determination of cadmium, cobalt, copper, iron, manganese, and zinc in thyroid glands of patients with diagnosed nodular goitre using ion chromatography.

B?azewicz A, Dolliver W, Sivsammye S, Deol A, Randhawa R, Orlicz-Szczesna G, B?azewicz R.


Endocrinology. 2010 Aug;151(8):4055-65. Epub 2010 Jun 23.

Perinatal iron and copper deficiencies alter neonatal rat circulating and brain thyroid hormone concentrations.

Bastian TW, Prohaska JR, Georgieff MK, Anderson GW.


PMID: 20573724 [PubMed - indexed for MEDLINE]


Chem Biol Interact. 2009 Jul 15;180(2):262-70. Epub 2009 Feb 13.

Modification of dietary copper levels on the early stage of tumor-promotion with propylthiouracil in a rat two-stage thyroid carcinogenesis model.

Shima T, Nishimura J, Dewa Y, Saegusa Y, Matsumoto S, Kawai M, Harada T, Mitsumori K, Shibutani M.


PMID: 19497425 [PubMed - indexed for MEDLINE]


Biometals. 2008 Jun;21(3):343-52. Epub 2007 Nov 24.

Multiple mechanisms account for lower plasma iron in young copper deficient rats.

Pyatskowit JW, Prohaska JR.


PMID: 18038202 [PubMed - indexed for MEDLINE]PMCID: PMC2701467Free PMC Article


J Nutr. 2008 Oct;138(10):1880-6.

Iron injection restores brain iron and hemoglobin deficits in perinatal copper-deficient rats.

Pyatskowit JW, Prohaska JR.



Cell Biochem Funct. 2005 Jan-Feb;23(1):1-8.

Oxidative stress and serum paraoxonase activity in experimental hypothyroidism: effect of vitamin E supplementation.

Sarandöl E, Ta? S, Dirican M, Serdar Z.


PMID: 15386442 [PubMed - indexed for MEDLINE]


   Folia Histochem Cytobiol. 2003;41(4):213-7.

Effect of vitamin E on follicular cell proliferation and expression of apoptosis-associated factors in rats with 6-N-propyl-2-thiouracil-induced goitrogenesis.


Oner J, Kükner A, Oner H, Ozan E, Yekeler H.


PMID: 14677760


Indian J Exp Biol. 2002 Jun;40(6):735-8.

Effect of antioxidants (vitamin C, E and turmeric extract) on methimazole induced hypothyroidism in rats.


Deshpande UR, Joseph LJ, Patwardhan UN, Samuel AM.


Radiation Medicine Centre (BARC), C/o Tata Memorial Centre Annexe, Parel, Mumbai 400 012, India.



The study was to investigate the protective effect of antioxidants against methimazole (MMI) induced hypothyroidism in rats. Male Wistar rats were fed MMI, MMI plus vitamin C, MMI plus vitamin E and MMI plus turmeric extract (TE) supplemented diet. At the end of the experiments, thyroid weights, thyroxine (T4), triiodothyronine (T3) and cholesterol levels were determined. It was observed that MMI treated rats showed increase in thyroid weights, very low levels of circulating T4, T3 and increased levels of total cholesterol as compared to controls (P< 0.001). However, rats which received Vit. C, Vit. E or TE along with MMI showed reduced weights (38-55% less) in thyroid glands (P < 0.01), less suppressed T4 and T3 levels (2-6% and 7-35% respectively) and less increase in total cholesterol levels (19-52%) which are statistically significant. The data suggest the positive effect of antioxidants on thyroid gland which could be due to direct involvement of antioxidants on thyroid gland.


PMID: 12587721


Life Sci. 2009 Mar 13;84(11-12):372-9. Epub 2009 Jan 13.

Supplementation of curcumin and vitamin E enhances oxidative stress, but restores hepatic histoarchitecture in hypothyroid rats.


Subudhi U, Das K, Paital B, Bhanja S, Chainy GB.


PMID: 19174171 [PubMed - indexed for MEDLINE]


Am J Med Sci. 2009 Jun;337(6):432-7.

Pattern of thyroid autoimmunity in chinese patients with pernicious anemia.


Chan JC, Liu HS, Kho BC, Lau TK, Li VL, Chan FH, Leong IS, Pang HK, Lee CK, Liang YS.


Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China SAR.



BACKGROUND: Autoimmune thyroid disease (AITD) often coexists with pernicious anemia (PA) among whites. The study aimed to determine thyroid autoimmunity in Chinese patients with PA.


METHODS: From the data of a hospital-based longitudinal study of Chinese PA patients (1994-2007), those with complete information of antibodies to thyroid peroxidase (TPO), thyroglobulin (Tg), and gastric parietal cell; serum thyroid-stimulating hormone and free thyroxine; gastric mucosal histology; and family history of AITD were analyzed.


RESULTS: Among 126 Chinese PA patients, 44% had TPO/Tg antibodies and 13.5% AITD. TPO/Tg antibodies occurred in 33% (16 of 49) of male and 52% (40 of 77) of female patients (P = 0.034). Graves disease (8 patients) tended to antedate PA and was associated with no or low titers of TPO/Tg antibodies. Primary hypothyroidism (9 patients) developed during follow-up and was associated with high TPO/Tg antibody titers. The TPO/Tg antibodies did not affect the clinical course of PA but was associated with an enhanced risk of developing AITD and vitiligo. Overall, AITD (before and after PA) occurred in 23% (13 of 56) and 5.7% (4 of 70) of PA patients with and without antibodies (P = 004). During follow-up (mean duration of 75.24 +/- 46.39 months), 10 patients developed AITD-7 new onset of hypothyroidism and 3 progression/relapse of prior AITD. Logistic regression analysis of presenting features of PA revealed 2 independent factors for AITD development during follow-up-presence of thyroid antibodies (odds ratio 20.2, 95% confidence interval 1.8-223) and history of prior AITD (odds ratio 39.8, 95% confidence interval 2.3-679).


CONCLUSION: It is recommended to screen thyroid antibodies and monitor thyroid function during follow-up.


PMID: 19525662 [PubMed - indexed for MEDLINE]


Ann Endocrinol (Paris). 2009 Mar;70(1):55-8. Epub 2009 Jan 15.

Thyroid and gastric autoimmune diseases.

Morel S, Georges A, Bordenave L, Corcuff JB.

Department of Nuclear Medicine, University of Bordeaux, University Hospital of Bordeaux, France.


OBJECTIVES: Autoimmune thyroid disease (AITD) is frequently accompanied by other organ-specific diseases. We investigated the frequency of the association AITD-Biermer's disease (BD) in patients with AITD by investigating the prevalence of intrinsic factor antibodies (IF-Ab).

DESIGN AND METHODS: Sera from 113 patients with AITD (hypo- or hyperthyroidism) were screened for the presence of type I IF-Ab with a competitive automated immunoassay based. Matched sera from 113 patients with dysthyroidism (not AITD) were tested.

RESULTS: Four IF-Ab positive patients suffered from AITD. BD was known for two of them and strongly suspected in the two others. All patients with no AITD tested IF-Ab negative. B12 levels were often low whatever the etiology.

CONCLUSION: The prevalence of IF-AbI is higher (3.5%) in patients with AITD. Prospective studies should investigate whether correcting thyroid dysfunction improves vitamin B12 levels, and establish whether routine screening for gastric autoimmunity is clinically useful or purely academic.

PMID: 19150051 [PubMed - indexed for MEDLINE]


J Pak Med Assoc. 2008 May;58(5):258-61.

Vitamin B12 deficiency common in primary hypothyroidism.


Jabbar A, Yawar A, Waseem S, Islam N, Ul Haque N, Zuberi L, Khan A, Akhter J.


PMID: 18655403 [


Scand J Gastroenterol. 2008;43(9):1050-6.

Serum biomarkers for atrophic gastritis and antibodies against Helicobacter pylori in the elderly: Implications for vitamin B12, folic acid and iron status and response to oral vitamin therapy.


Lewerin C, Jacobsson S, Lindstedt G, Nilsson-Ehle H.


Presse Med. 2010 Dec 31. [Epub ahead of print]

[Role of Helicobacter pylori infection in iron deficiency anemia.]

Chaabane NB, Mansour IB, Hellara O, Loghmeri H, Bdioui F, Safer L, Saffar H.


J Clin Gastroenterol. 1998 Jun;26(4):259-63.

Helicobacter pylori infection is markedly increased in patients with autoimmune atrophic thyroiditis.


de Luis DA, Varela C, de La Calle H, Cantón R, de Argila CM, San Roman AL, Boixeda D.


PMID: 9649006 [PubMed - indexed for MEDLINE]


Br J Nutr. 2009 Aug;102(3):382-6. Epub 2009 Feb 10.

Prevalence of vitamin D deficiency and its relationship with thyroid autoimmunity in Asian Indians: a community-based survey.


Goswami R, Marwaha RK, Gupta N, Tandon N, Sreenivas V, Tomar N, Ray D, Kanwar R, Agarwal R.



PMID: 19203420 [PubMed


Clin Chem. 2000 Apr;46(4):523-8.

Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and pregnenolone sulfate concentrations in patients with hyperthyroidism and hypothyroidism.

Tagawa N, Tamanaka J, Fujinami A, Kobayashi Y, Takano T, Fukata S, Kuma K, Tada H, Amino N.

Clinical Chemistry Laboratory, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.t-noriko@kobe


BACKGROUND: Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to have protective effects against cardiovascular disease, cancer, immune-modulated diseases, and aging. We examined serum concentrations of DHEA, DHEA-S, and pregnenolone sulfate (PREG-S) in patients with thyroid dysfunction.

METHODS: Steroids extracted with methanol from serum sample were separated into an unconjugated fraction (DHEA) and a monosulfate fraction (DHEA-S and PREG-S), using a solid-phase extraction and an ion-exchange column. After separation of unconjugated steroids by HPLC, the DHEA concentration was measured by enzyme immunoassay. The monosulfate fraction was treated with arylsulfatase, and the freed steroids were separated by HPLC. The DHEA and PREG fractions were determined by gas chromatography-mass spectrometry, and the concentrations were converted into those of DHEA-S and PREG-S.

RESULTS: Serum concentrations of DHEA, DHEA-S, and PREG-S were all significantly lower in patients with hypothyroidism (n = 24) than in age- and sex-matched healthy controls (n = 43). By contrast, in patients with hyperthyroidism (n = 22), serum DHEA-S and PREG-S concentrations were significantly higher, but the serum DHEA concentration was within the reference interval. Serum concentrations of these three steroids correlated with serum concentrations of thyroid hormones in these patients. Serum albumin and sex hormone-binding globulin concentrations were not related to these changes in the concentration of steroids.

CONCLUSIONS: Serum concentrations of DHEA, DHEA-S, and PREG-S were decreased in hypothyroidism, whereas serum DHEA-S and PREG-S concentrations were increased but DHEA was normal in hyperthyroidism. Thyroid hormone may stimulate the synthesis of these steroids, and DHEA sulfotransferase might be increased in hyperthyroidism.

PMID: 10759476 [PubMed - indexed for MEDLINE]Free Article


Endocr Pract. 2001 May-Jun;7(3):193-4.

Use of soy protein supplement and resultant need for increased dose of levothyroxine.


Bell DS, Ovalle F.


Division of Endocrinology and Metabolism, The University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama, USA.



OBJECTIVE: To report a case of difficulty in achieving suppressive serum levels of thyroid hormone because of malabsorption of exogenous levothyroxine attributable to daily ingestion in close temporal relationship to the intake of a soy protein-containing food supplement.


METHODS: We present the relevant history and laboratory data of the current case and provide supportive documentation from the literature.


RESULTS: A 45-year-old woman who had hypothyroidism after a near-total thyroidectomy and radioactive iodine ablative therapy for papillary carcinoma of the thyroid required unusually high oral doses of levothyroxine to achieve suppressive serum levels of free thyroxine (T(4)) and thyrotropin (thyroid-stimulating hormone or TSH). She had routinely been taking a "soy cocktail" protein supplement immediately after her levothyroxine. Temporal separation of the intake of the soy protein cocktail from the administration of the levothyroxine resulted in attainment of suppressive serum levels of free T(4) and TSH with use of lower doses of levothyroxine.


CONCLUSION: Administration of levothyroxine concurrently with a soy protein dietary supplement results in decreased absorption of levothyroxine and the need for higher oral doses of levothyroxine to attain therapeutic serum thyroid hormone levels.


PMID: 11421567 [PubMed - indexed for MEDLINE]


Endocr Regul. 2008 Jun;42(2-3):53-61.

Short-term effect of soy consumption on thyroid hormone levels and correlation with phytoestrogen level in healthy subjects.


Hampl R, Ostatnikova D, Celec P, Putz Z, Lapcík O, Matucha P.


Institute of Endocrinology, Prague, Czech Republic.



OBJECTIVE: Since soy isoflavones may influence the thyroid hormone feedback system by interference with their biosynthesis, secretion and metabolism, we tested whether their controlled shortterm consumption affects thyroid function.


METHODS: Eighty six volunteers--university students (32 males and 54 females) were eating unprocessed boiled natural soybeans (2 g/kg body weight/day) for 7 consecutive days. Thyrotropin, free thyroid hormones, antibodies to thyroid peroxidase and to thyroglobulin, and actual levels of unconjugated major soy phytoestrogens, daidzein and genistein, were measured in sera collected before, at the end and one week after finishing soy meal consumption.


RESULTS: Both phytoestrogens increased significantly (p<0.0001) at the end of soy-diet and fell down after its termination nearly back to the initial values. No significant changes were found in female group, while in males a significant transitory increase of thyrotropin (p<0.0001) was recorded. When actual levels of phytoestrogens were related to thyroid parameters, the only significant correlations were found between basal levels of daidzein and thyrotropin, daidzein and antithyroglobulin at the end of soy consumption in males, and between daidzein and free thyroxine at the end of the soy ingestion in females.


CONCLUSION: Though only modest and transitory effects on thyroid parameters occurred after controlled short-term soy consumption, some actual thyroid hormone parameters do correlate with actual isoflavone levels.


PMID: 18624607 [PubMed - indexed for MEDLINE]


Thyroid. 2007 Feb;17(2):131-7.

Soy protein isolates of varied isoflavone content do not influence serum thyroid hormones in healthy young men.


Dillingham BL, McVeigh BL, Lampe JW, Duncan AM.


Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.



OBJECTIVE: The ability of soy isoflavones to inhibit thyroid peroxidase and induce goiter in animals has generated concern regarding their potential antithyroid effects in humans. The purpose of this study was to determine the effects of soy protein isolates of varied isoflavone content on circulating thyroid hormones in healthy young men.


DESIGN: Thirty-five healthy men (27.9 +/- 5.7 years old) supplemented their habitual diets with milk protein isolate (MPI), low-isoflavone soy protein isolate (low-iso SPI; 1.64 +/- 0.19 mg iso/day), and high-isoflavone SPI (high-iso SPI; 61.7 +/- 7.4 mg iso/day) for 57 days each, separated by 4-week washouts in a randomized crossover design. Blood was collected on days 1, 29, and 57 of each treatment for analysis of total triiodothyronine (T3), free T3, total thyroxine (T4), free T4, thyroid stimulating hormone (TSH), and thyroid binding globulin (TBG). Twenty-four hour urines were collected at the end of each treatment for analysis of isoflavones.


MAIN OUTCOME: Results revealed no significant effects of the low-iso or high-iso SPIs on serum total T3, free T3, total T4, free T4, TSH, or TBG when compared with the MPI on either study days 29 or 57. Urinary data revealed that isoflavones were significantly increased by the high-iso SPI relative to the low-iso SPI and MPI.


CONCLUSIONS: Results of this study demonstrate that soy isoflavones in a protein matrix do not significantly influence circulating thyroid hormones in healthy young men.


PMID: 17316115 [PubMed - indexed for MEDLINE]

Personal communication

Hi Jacob,
Optimal iodine is 250 - 450 mcg per day. It suppresses thyroid output more by a
change in intake than in an absolute amount. Deficient populations manifest
thyroid antibodies when levels move from 150 to 250 mcg per day. Very high
doses such as 1000 - 50,000 mcg are in the literature as agents to suppress
thyroid storm but are not used since they can also worsen thyroid storm.

I'm a huge antagonist of the work of Drs Jorge Fleckas and David Brownstein's
which is just rehashed Guy Abraham's work.

I went though my experiences and findings in detail in this article from NDNR:

Alan Christianson, NMD
Scottsdale, AZ