Autoimmune thyroid disease, Vitamin B-12, atrophic gastritis, H. pylori, anemia and the Israeli Air Force

 

Jacob Schor, ND

August 20, 2007

 

The city of Kfar Saba lies to the northeast of Tel Aviv on the way to Nabulus . Translated from Hebrew, Kfar Saba means ‘grandfather's village.' Googling and reading about Kfar Saba is easier than figuring out how to write this article. It starts out simple enough though.

 

The American Journal of Medical Science published a paper last year written by several researchers from Kfar Saba. Their paper reported a high prevalence of vitamin B-12 deficiency in people suffering from autoimmune thyroid disease. Of the 115 people in the study, all of who had autoimmune thyroid disease (AITD), 32 of them had low vitamin B-12 levels. That's 28%, slightly more than 1 in 4. Of those patients who were B-12 deficient, 31% had pernicious anemia. [i] So there is a clear relationship between vitamin B-12 absorption and autoimmune thyroid disease, that is what most people who are hypothyroid have.

 

The land of Kfar Saba was bought up in 1892 by Zionist settlers who apparently never settled there. They sold it in 1896 to the Baron Rothschild who resold it in 1903 to settlers from Petah Tikva who sold it yet again. Back then, the area was so remote and desolate, no one was willing to settle there. When settlements were finally established, the Ottoman government refused to grant building permits. It wasn't until 1912 that permanent houses were built on the land. Today 81,000 people live in Kfar Saba.

 

Vitamin B-12 acts as a coenzyme in the transformation of homocysteine to methionine. This is reaction is essential to make S-adenosylmethionine (SAMe) which is needed to make myelin. Without myelin, nerves do not work properly. This is why B12 deficiency causes neuropathies. SAMe is also involved in making certain neurotransmitters. These neurotransmitters are important for maintaining mood, explaining why depression is associated with B12 deficiency. This is why people take SAMe as an antidepressant.

 

 

Vitamin B-12 is the biggest vitamin in size and finding it in food is complicated. Neither plants nor animals make vitamin B-12. Only bacteria and archaea can make it. If you haven't heard of archea, don't be alarmed, I didn't recognize the term either. Archaea are single celled organisms genetically about halfway between prokaryotic and eukaryotic organisms. They adapt to live in extreme environments, like the geysers in Yellowstone , and aren't relevant to this discussion unless you want to consider Kfar Saba of the 1890s an extreme environment. Meat and dairy are the only reliable food source of vitamin B-12 in our diets. They contain B-12 only because feed is either fermented or enriched. Tempeh, a mold and soy bean product, may contain vitamin B-12, but only if allowed to ferment to a degree past where most Americans will eat it.

 

 

 

To move vitamin B-12 out of food into the blood system is complicated. Many things can go wrong in this process preventing absorption. As vitamin B-12 is pulled out of food in the stomach, proteins secreted in the digestive tract, called salivary R-binders, attach to it. Acid from the stomach and pancreatic proteolytic enzymes are both needed to releases the B-12 from these ‘binders.' Without both, the B-12 will not be absorbed. [ii]

 

Once free of the R-binders, B-12 is grabbed up by chemical called B-12 intrinsic factor. B-12 needs to attach to intrinsic factor to be absorbed through the intestine into the blood. Specialized cells called parietal cells that line the stomach secrete intrinsic factor. The vitamin B12 and intrinsic factor complex can only be absorbed through a short section of the small intestine, called the terminal ileum. This is way down near the appendix. Even with adequate dietary B-12, moving it into the blood stream still requires that the stomach generates both acid and intrinsic factor, a pancreas that generates the enzymes to release B-12 from the binding proteins, and small bowel capable of absorbing the B-12. Any of these can be a weak link leading to B-12 deficiency.

 

When I mentioned that I was reading about Kfar Saba, Dr. Bloom, she informed me that she once lived there. Well actually her mother, my mother-in-law, had an apartment in Kfar Saba in the 1970s. I never knew.

 

B-12 deficiency leads to a form of anemia called megaloblastic anemia in which red blood cells become swollen and bloated. On a complete blood count, the Mean Corpuscular Volume (MCV) increases and the Red Blood Cell (RBC) count decreases. The most common cause of B-12 deficiency is atrophic gastritis, a condition that damages the parietal cells preventing them from making intrinsic factor. We call this condition pernicious anemia. Sometimes the term pernicious anemia is used incorrectly to refer to any B-12 deficiency anemia, but technically, pernicious anemia is caused by atrophic gastritis.

 

Atrophic Gastritis is usually the result of an autoimmune process in which the immune system inappropriately makes antibodies that attack the parietal cells or intrinsic factor itself. Approximately 90% of individuals with pernicious anemia have antibodies for parietal cells, however only 50% of individuals with these antibodies have pernicious anemia.

 

This Kfar Saba study is not the first to report an association between autoimmune thyroid disease and B-12 deficiency. An Italian study, published in the Archives of Internal medicine back in 1999 reported that 22 out of 62 autoimmune thyroid disease (AITD) patients had confirmed atrophic gastritis. Antiparietal cell antibodies were found in 68% (15/22) of patients with atrophic gastritis. Anemia was observed in 82% (18/ 22) of patients with AITD and atrophic gastritis. It was not just macrocytic, B-12 deficiency anemia, AITD patients also have a higher incidence of iron deficiency anemia. [iii]

 

 

 

Autoimmune gastritis also causes iron deficiency anemia. Atrophic gastritis causes about one quarter of all cases of chronic iron deficiency anemia. Destruction of the parietal cells stops acid production in the stomach. An acidic stomach is necessary to absorb iron. Thus, atrophic gastritis can trigger both iron deficiency and B-12 deficiency. [iv] This complicates things. Iron deficiency causes microcytic anemia, a form of anemia where the red blood cells shrivel up in size. The Mean Corpuscular Volume (MCV) decreases. If B-12 and iron deficiencies coexist, the combined average volume of big and small red blood cells expressed as MCV may appear normal. The only hint on the lab numbers may be an elevated RDW, but that is more detail than you will want.

 

Other conditions besides autoimmune attack can cause atrophic gastritis. The first that comes to mind is Helicobacter pylori. In fact, these infections may be a more common cause of atrophic gastritis than we initially thought.

 

Helicobacter pylori infections cause about one quarter of all cases of atrophic gastritis. [v] Treating and curing the H. pylori infection will usually improve the damaged tissue but not all the time. One study showed reduction in tissue damage in only about half of the patients cured of H. pylori infection. [vi]

 

Here is where it starts to get complicated. There appear to be several diseases that seem closely related. Autoimmune thyroid disease no longer appears to be lone entity. One in four people with AITD, that is who make antibodies that attack their thyroid, also make antibodies that attack the parietal glands in the causing B-12 deficiency.

 

Rena tells me that she used to stay at her mom's apartment in Kfar Saba when on weekend leave. This is back when she served in the Israeli Air Force in the 1970s. This side story is suddenly more than a distraction, it is getting complicated as well.

 

There is also celiac disease. People with celiac disease have a higher than normal incidence of autoimmune thyroid disease, about twice the expected. It works both ways; people with thyroid disease are also more likely to have celiac disease. [vii] Celiac disease also increases risk of B-12 deficiency. According to one study, 12% of celiac patients will be B-12 deficient. [viii] There are two possible explanations for this increase. First, celiac disease inflames the terminal ileum where B-12 is absorbed. Second, celiac disease patients may make antibodies against parietal cells and so cause atrophic gastritis. It turns out that only about 10% of the B-12 deficient celiac patients have atrophic damage in the stomach, so the first scenario, damage to the colon prevents absorption, is probably more often the reason.

 

A 2005 study looked at 190 patients with chronic unexplained iron deficiency anemia. Eight (5%) of the patients had celiac disease. Forty (27%) had autoimmune atrophic gastritis of whom 22 also had low serum vitamin B12 levels. Of the entire 190 patients, 29 (19%) only had H. pylori infection. But, H. pylori infection co-existed along with one of these other causes in 77 people (51%). None of the patients with celiac disease responded or improved with iron supplements. Most (71%) of the patients with autoimmune atrophic gastritis also failed to respond. About the same lack of response (68%) was seen with H. pylori infection. But of the patients who tested negative for these three conditions (AITD, H. Pylori and celiac ), almost all (89%) responded to iron supplements. Killing off the H. pylori improved the response to iron supplements. [ix]

 

Though it sounds possible, studies tell us that there is no relationship between autoimmune thyroid disease and H. Pylori infection. [x]

 

The primary symptom of both iron deficiency and B-12 deficiency anemis and of autoimmune thyroid disease is the same. All three cause fatigue. Vitamin B-12 deficiency will also often present with neurologic symptoms, typically peripheral numbness or neuropathy. Helicobacter pylori infection presents with upper gastrointestinal symptoms. Celiac disease traditionally has been associated with digestive complaints, most commonly, chronic diarrhea. This opinion has shifted and it is now believed that digestive complaints are not that common in celiac disease, occurring in less than 20% of patients. Osteopenia and osteoporosis are common in celiac patients. The explanation typically given is that this results from chronic malabsorption of calcium. It may also be a result of low vitamin B-12 levels which lead to increased homocysteine levels which are linked to osteoporosis.

 

 

This adds a level of complexity to analyzing anemia in patients. First, there is need for vigilance in all cases of autoimmune thyroid disease watching for symptoms of anemia. It would be reasonable to test either B-12 or homocysteine routinely in this patient population. Also, iron and ferritin levels. Atrophic gastritis, of either autoimmune or infectious origin, can cause both iron and B-12 deficiency and there is no reason that both deficiencies can't occur at the same time.

 

Over the last few weeks, we have hosted participants from the Building Bridges for Peace program in our home. Past newsletters have described our involvement with this program. Participants come from the Israeli and Palestinian communities in Israel to Colorado each summer. Looking at old photos of Rena during her Air Force days when she spent her free time in Kfar Saba, I contemplate how our knowledge and understanding can grow and change during a lifetime. It is not just about vitamin B-12 chemistry that I am thinking.

 

No one ever promised that biology, medicine or life would be simple. Yet if one pays attention, it certainly can be interesting. As time goes on, we can work to learn more and understand the complexity of life more completely. Doing so allows us to practice better medicine, among other things.

 

 

Prior newsletter on Building Bridges for Peace:

http://www.denvernaturopathic.com/news/BBfP.html

 

Building Bridges for Peace:

http://s-c-g.org/

 

Photos of Rena during her Air Force days: http://www.denvernaturopathic.com/RenaAirForcephotos.htm

 

References:

[i] Am J Med Sci. 2006 Sep;332(3):119-22.

Prevalence and evaluation of B12 deficiency in patients with autoimmune thyroid disease.

Ness-Abramof R , Nabriski DA , Braverman LE , Shilo L , Weiss E , Reshef T , Shapiro MS , Shenkman L .

Endocrine Unit, Sapir Medical Center , Tchernikovsky 53, Kfar Saba , Israel 44261. Rosane-Abramof.Ness@clalit.org.il

BACKGROUND: Patients with autoimmune thyroid disease (AITD) have a higher prevalence of pernicious anemia compared with the general population. Clinical signs of B12 deficiency may be subtle and missed, particularly in patients with known autoimmune disease. We assessed the prevalence of vitamin B12 deficiency in patients with AITD and whether their evaluation may be simplified by measuring fasting gastrin levels. METHODS: Serum B12 levels was measured in 115 patients with AITD (7 men and 108 women), with a mean age of 47 +/- 15 years. In patients with low serum B12 levels (< or =133 pmol/L), fasting serum gastrin and parietal cell antibodies (PCA) were measured. RESULTS: Thirty-two patients (28%) with AITD had low B12 levels. Fasting serum gastrin was measured in 26 and was higher than normal in 8 patients. PCA were also measured in 27 patients with B12 deficiency and were positive in 8 patients. Five patients with high gastrin levels underwent gastroscopy with biopsy, and atrophic gastritis was diagnosed in all. The prevalence of pernicious anemia as assessed by high serum gastrin levels in patients with low B12 was 31%. CONCLUSIONS: Patients with AITD have a high prevalence of B12 deficiency and particularly of pernicious anemia. The evaluation of B12 deficiency can be simplified by measuring fasting serum gastrin and, if elevated, referring the patient for gastroscopy.

PMID: 16969140 [PubMed - indexed for MEDLINE]

 

[ii] J Clin Invest. 1980 Sep;66(3):430-40. Click here to read Links

Cobalamin malabsorption due to nondegradation of R proteins in the human intestine. Inhibited cobalamin absorption in exocrine pancreatic dysfunction.

Marcoullis G , Parmentier Y , Nicolas JP , Jimenez M , Gerard P .

In vivo studies demonstrate that the pancreatic enzymes and the ionic environment in the upper gastrointestinal tract are essential determining factors for transport and absorption of cobalamin in man. Jejunal fluid was aspirated from healthy human volunteers after administration of cyano[57Co]cobalamin preparations. Immunochemical analysis of the aspirates demonstrated that all isotopic vitamin was transferred to a protein that is identical to the gastric intrinsic factor in terms of molecular mass (57,500), ionic nature (mean pI, 5.09), and reactivity with anti-intrinsic factor sera. However, in the aspirates from patients with exocrine pancreatic dysfunction the vitamin was found to be coupled > 60% to a protein identical to R proteins in terms of molecular mass (125,000), ionic nature (mean pI, 3.51), and reactivity with anti-R protein and anti-intrinsic factor sera. The preferential transfer of cobalamin to R proteins in the patients and to intrinsic factor in healthy subjects was associated, respectively, with low and normal levels of pancreatic enzymes in the intestine and these in turn were paralleled respectively by impaired and normal ileal absorption of cobalamin. These findings confirm the suggestion that the formation of unabsorbable cobalamin complexes may be the reason of impaired vitamin absorption in exocrine pancreatic insufficiency. Observations made with other selected patients demonstrate: (a) that decreased enzyme activity and nondegradation of R proteins may also be due to nonactivation of pancreatic zymogens in an acidic pH of the intestinal juice the vitamin transported to the jejunum couples to intrinsic factor when pancreatic function is normal, and to intrinsic factor and R protein in exocrine pancreatic insufficiency. The observations made with these selected patients may explain why not all patients with exocrine pancreatic insufficiency develop imparied cobalamin absorption, and also why the malabsorption is corrected by the administration of bicarbonate in certain patients.

PMID: 7400324 [PubMed - indexed for MEDLINE]

 

[iii] Arch Intern Med. 1999 Aug 9-23;159(15):1726-30. Click here to read

Atrophic body gastritis in patients with autoimmune thyroid disease: an underdiagnosed association.

Centanni M , Marignani M , Gargano L , Corleto VD , Casini A , Delle Fave G , Andreoli M , Annibale B .

Department of Experimental Medicine, University of Rome La Sapienza, Rome , Italy .

BACKGROUND: Atrophic body gastritis (ABG) has never been histologically characterized in patients with autoimmune thyroid disease (AITD), and its prevalence may be substantially different from that previously assessed based on only indirect evidence. OBJECTIVE: To detect and characterize the presence of ABG in patients with AITD. METHODS: Sixty-two patients with AITD (5 men and 57 women), aged between 21 and 74 years, have been screened for the presence of ABG by assaying serum gastrin levels . Patients with hypergastrinemia underwent gastroscopy followed by the histological examination of multiple biopsy specimens. The diagnosis of ABG was based on hypergastrinemia and pentagastrin-resistent achlorhydria, confirmed by histological examination. RESULTS: Twenty-two (35%) of 62 patients had hypergastrinemia (mean +/- SEM gastrin level, 1070+/-288 pmol/L). The diagnosis of ABG has been histologically confirmed in all 22 patients, and the score of atrophy was moderate to severe. In group A (patients aged 20-40 years; n = 21), 6 patients (29%) had ABG, compared with 11 patients (37%) in group B (patients aged 41-60 years; n = 30) and 5 patients (45%) in group C (patients aged 61-80 years; n = 11). Antiparietal cell antibodies were detected in only 68% (15/22) of patients with ABG. Anemia was observed in 82% (18/ 22) of patients with AITD and ABG but only in 22% (9/40) of patients without ABG (P<.0001). CONCLUSIONS: In the patients with AITD studied, about one third had ABG, which was diagnosed also in young patients; the measurement of gastrin levels represented the most reliable tool in the diagnosis of ABG; and the presence of anemia, even microcytic, was suggestive of undiagnosed ABG.

PMID: 10448775 [PubMed - indexed for MEDLINE]

 

[iv] Blood Cells Mol Dis. 2007 Sep-Oct;39(2):178-83. Epub 2007 May 9. Links

The anemia of achylia gastrica revisited.

Hershko C , Patz J , Ronson A .

Department of Hematology, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Israel; Hematology Clinic and Central Clinical Laboratories, Clalit Health Services, Hebrew University of Jerusalem, Israel.

Autoimmune atrophic gastritis is encountered in 20-27% of patients with obscure, or refractory iron deficiency anemia and is 4 to 6 times more common than celiac disease causing unexplained iron deficiency. The unique clinical features of iron deficiency anemia associated with achlorhydria and mucosal atrophy sparing the gastric antrum have all been accurately described by Faber and others over 100 years ago, including its refractoriness to oral iron treatment, female predominance, relatively young age, increased prevalence of thyroid disease and tendency to progress to pernicious anemia. A significant new development is the relation between autoimmune gastritis and Helicobacter pylori infection. H. pylori per se impairs gastric acid secretion and it is quite likely that a proportion of patients described originally as achylia gastrica represented H. pylori and not autoimmune gastritis. The demonstration of H. pylori antibodies in atrophic gastritis directed against epitopes on gastric mucosal cells implies an autoimmune mechanism triggered by H. pylori and directed against gastric parietal cells by antigenic mimicry of H(+)K(+)-ATPase, the most common autoantigen in pernicious anemia. These findings introduce a new element into the 100-year-old saga of achylia gastrica and open new options for its prevention and management.

PMID: 17493846 [PubMed - in process]

 

[v] Helicobacter. 1997 Jun;2(2):57-64. Links

Atrophic body gastritis: distinct features associated with Helicobacter pylori infection.

Annibale B , Marignani M , Azzoni C , D'Ambra G , Caruana P , D'Adda T , Delle Fave G , Bordi C .

Gastroenterology Unit, University La Sapienza Rome , Italy .

BACKGROUND: Usually, atrophic body gastritis has been considered an autoimmune disease characterized by the presence of parietal cell antibodies. Previous investigations into the role of Helicobacter pylori infection have obtained conflicting results. The aim of this study was to investigate the prevalence and role of H. pylori in a prospectively investigated population of patients with corpus-predominant atrophic gastritis. PATIENTS AND METHODS: A consecutive series of 67 newly diagnosed cases of atrophic body gastritis was derived from a screening of 326 patients with unexplained anemia or dyspepsia. Criteria for diagnosis were fasting hypergastrinemia, pentagastrin-resistant achlorhydria, and histological confirmation of body atrophy. In all 67 patients, H. pylori infection was evaluated independently by histological assay and urease test. The gastritis status of both the fundic and antral mucosa were graded according to the Sydney system. Parietal cell and intrinsic factor antibodies also were determined. RESULTS: Active H. pylori infection was present in 26.8% of our patients and allowed us to identify a patient's subpopulation with a significantly smaller degree of body mucosa damage as shown by functional parameters (gastrin, gastric acid secretion, pepsinogen I) and histological assessment. In this subpopulation, a higher prevalence of gastric cancer familial history was found. Presence of parietal cell antibodies showed a similar prevalence in H. pylori-positive and H. pylori-negative patients (61.1% vs. 69.4%) and was not associated with significant functional and histological differences. Cure of infection determined an evident improvement of corporal atrophy as well as a reduction of hypergastrinemia. CONCLUSION: Active H. pylori infection, a potential cause of oxyntic gland atrophy, is found in one-fourth of patients with newly diagnosed atrophic body gastritis.

PMID: 9432330 [PubMed - indexed for MEDLINE]

[vi] Cure of Helicobacter pylori infection in atrophic body gastritis patients does not improve mucosal atrophy but reduces hypergastrinemia and its related effects on body ECL-cell hyperplasia.

Alimentary Pharmacology & Therapeutics. 14(5):625-634, May 2000.
ANNIBALE, B; APRILE, M ROSARIA; D'AMBRA, G; CARUANA, P; BORDI, C; FAVE, G DELLE

Abstract:
Background: The effects of H. pylori eradication on atrophic body gastritis are controversial.

Aim: To investigate the effect of triple therapy on atrophic body gastritis in H. pylori-positive patients and its effect on morpho-functional gastric parameters.

Methods: Thirty-five consecutive atrophic body gastritis patients with histological/serological evidence of H. pylori infection were treated. Before and 6 and 12 months after H. pylori eradication the patients were evaluated for fasting gastrinemia and pepsinogen I, basal and peak acid output, and detailed histological assessment including the ECL cell proliferative patterns.

Results: Six months after treatment, 25 out of 32 patients were cured (78%). Cure of infection was associated with improvement in both basal (basal acid output mean 0.23 +/- 0.14 mmol/h vs. 1.75 +/- 0.7 mmol/h, P < 0.005) and stimulated acid secretion (peak acid output mean 3.0 +/- 1.06 mmol/h vs. 16.6 +/- 4.1 mmol/h, P = 0.0017) as well as with reduction in hypergastrinemia (mean gastrin levels 444.1 +/- 110.7 pg/mL vs. 85.3. +/- 28 pg/mL; P < 0.005). In contrast, the eradication had no effect on body corporal atrophy and intestinal metaplasia, or pepsinogen I levels (mean 16.6 +/- 2.9 ng/mL vs. 14.2 +/- 2.1 ng/mL, N.S.). These results were confirmed at 12 months after eradication. A statistical inverse correlation was obtained (r = -0.3635, P < 0.05) between the corporal chronic infiltrate score and peak acid output values. A total of 53% of atrophic body gastritis patients showed a regression in severity of body ECL cell hyperplastic change.

Conclusion: Cure of H. pylori infection in patients with atrophic gastritis reverses some adverse effects on gastric function and ECL cell hyperplasia. H. pylori infection may be cured in atrophic body gastritis patients with partial reversion of its negative consequences on acid secretion and body ECL cell hyperplasia.

 

[vii] World J Gastroenterol. 2007 Mar 21;13(11):1715-22.

Coeliac disease in Dutch patients with Hashimoto's thyroiditis and vice versa.

Hadithi M , de Boer H , Meijer JW , Willekens F , Kerckhaert JA , Heijmans R , Peña AS , Stehouwer CD , Mulder CJ .

Department of Gastroenterology, Rijnstate Hospital , The Netherlands . muhammed.hadithi@ghz.nl

AIM: To define the association between Hashimoto's thyroiditis and coeliac disease in Dutch patients. METHODS: A total of 104 consecutive patients with Hashimoto's thyroiditis underwent coeliac serological tests (antigliadins, transglutaminase and endomysium antibodies) and HLA-DQ typing. Small intestinal biopsy was performed when any of coeliac serological tests was positive. On the other hand, 184 patients with coeliac disease were subjected to thyroid biochemical (thyroid stimulating hormone and free thyroxine) and thyroid serological tests (thyroglobulin and thyroid peroxidase antibodies). RESULTS: Of 104 patients with Hashimoto's thyroiditis, sixteen (15%) were positive for coeliac serology and five patients with documented villous atrophy were diagnosed with coeliac disease (4.8%; 95% CI 0.7-8.9). HLA-DQ2 (and/or -DQ8) was present in all the five and 53 patients with Hashimoto's thyroiditis (50%; 95% CI 43-62). Of 184 patients with coeliac disease, 39 (21%) were positive for thyroid serology. Based on thyroid biochemistry, the 39 patients were subclassified into euthyroidism in ten (5%; 95% CI 2-9), subclinical hypothyroidism in seven (3.8%; 95% CI 1.8-7.6), and overt hypothyroidism (Hashimoto's thyroiditis) in 22 (12%; 95% CI 8-16). Moreover, four patients with coeliac disease had Graves' disease (2%; 95% CI 0.8-5) and one patient had post-partum thyroiditis. CONCLUSION: The data from a Dutch population confirm the association between Hashimoto's thyroiditis and coeliac disease. Screening patients with Hashimoto's thyroiditis for coeliac disease and vice versa is recommended.

 

[viii] Eur J Gastroenterol Hepatol. 2002 Apr;14(4):425-7. Links

Low serum vitamin B12 is common in coeliac disease and is not due to autoimmune gastritis.

Dickey W .

Department of Gastroenterology, Altnagelvin Hospital , Londonderry BT47 6SB , Northern Ireland . wildickey@aol.com

OBJECTIVE: Although coeliac disease is a disorder of the proximal small bowel, associated vitamin B12 deficiency has been reported. This study aimed to assess the prevalence of B12 deficiency in a large series of coeliac patients, and to exclude the possibility that it is due to associated autoimmune gastritis. DESIGN: Prospective routine measurement of serum B12 in coeliac patients, with investigations for pernicious anaemia/autoimmune gastritis in B12-deficient patients. SETTING: Gastroenterology department of a large district general hospital. INTERVENTIONS: If they were not taking vitamin B12 supplements already, patients had serum B12 measured before starting dietary gluten exclusion. Those with low levels also had gastric biopsies taken and plasma gastrin and serum gastric parietal cell and intrinsic factor antibodies measured. MAIN OUTCOME MEASURES: Prevalence of low serum B12, and presence or absence of indicators of pernicious anaemia/autoimmune gastritis in patients with low serum B12. RESULTS: Of 159 patients, 13 had low serum B12 at diagnosis. A further six had been receiving B12 replacement therapy for 3-37 years before diagnosis, giving an overall prevalence of 12% (19 patients). Only 2/19 patients had gastric corpus atrophy, one with intrinsic factor antibodies and the other with hypergastrinaemia. There was no relationship between low B12 and clinical characteristics. CONCLUSIONS: Low B12 is common in coeliac disease without concurrent pernicious anaemia, and may be a presenting manifestation. B12 status should be known before folic acid replacement is started.

PMID: 11943958 [PubMed - indexed for MEDLINE]

 

[ix] Haematologica. 2005 May;90(5):585-95. Links

Role of autoimmune gastritis, Helicobacter pylori and celiac disease in refractory or unexplained iron deficiency anemia.

Hershko C , Hoffbrand AV , Keret D , Souroujon M , Maschler I , Monselise Y , Lahad A .

Department of Hematology, Shaare Zedek Med Center, Jerusalem , Israel . hershko@szmc.org.il

BACKGROUND AND OBJECTIVES: Conventional endoscopic and radiographic methods fail to identify a probable source of gastrointestinal blood loss in about one third of males and post-menopausal females and in most women of reproductive age with iron deficiency anemia (IDA). Such patients, as well as subjects refractory to oral iron treatment, are often referred for hematologic evaluation. DESIGN AND METHODS: Patient clinic, screened for non-bleeding gastrointestinal conditions including celiac disease (antiendomysial antibodies), autoimmune atrophic gastritis (hypergastrinemia with strongly positive antiparietal cell antibodies) and H. pylori infection (IgG antibodies confirmed by urease breath test). RESULTS: The mean age of all subjects was 39+/-18 years, and 119 of 150 were females. We identified 8 new cases of adult celiac disease (5%). Forty IDA patients (27%) had autoimmune atrophic gastritis of whom 22 had low serum vitamin B12 levels. H. pylori infection was the only finding in 29 patients (19%), but was a common co-existing finding in 77 (51%) of the entire group. Refractoriness to oral iron treatment was found in 100% of patients with celiac disease, 71% with autoimmune atrophic gastritis, 68% with H. pylori infection, but only 11% of subjects with no detected underlying abnormality. H. pylori eradication in previously refractory IDA patients in combination with continued oral iron therapy resulted in a significant increase in hemoglobin from 9.4+/-1.5 (mean +/- 1SD) before, to 13.5+/-1.2 g/ dL (p<0.001 by paired t test) within 3 to 6 months. INTERPRETATION AND CONCLUSIONS: The recognition that autoimmune atrophic gastritis and H. pylori infection may have a significant role in the development of unexplained or refractory IDA in a high proportion of patients should have a strong impact on our daily practice of diagnosing and managing IDA.

 

[x] Dig Dis Sci. 2005 Feb;50(2):385-8. Links

Is there anything to the reported association between Helicobacter pylori infection and autoimmune thyroiditis?

Tomasi PA , Dore MP , Fanciulli G , Sanciu F , Realdi G , Delitala G .

Clinica Medica, Università di Sassari, Viale S. Pietro 8, 07100 Sassari , Italy .

Higher serological prevalence rates of Helicobacter pylori (Hp) infection have been reported in patients with autoimmune thyroiditis (AT), and it has been suggested that monoclonal antibodies against Cag-A positive Hp strains can cross-react with follicular cells of the thyroid gland. We studied the prevalence of AT and thyroid functional status in patients who underwent gastroscopy for dyspeptic symptoms. Patients were tested for TSH, free thyroid hormones, and antithyroglobulin and antithyroperoxidase antibodies (ATPO). Hp positivity was determined using urea breath test (UBT). Serum samples from 302 patients (59.9% women) were evaluated. One hundred ninety-one subjects (63.2%) were Hp-negative, and 111 of 302 (36.8%) were Hp-positive. Forty-three of 191 Hp-negative patients (22.5%; 95% CI, 17.1-29.0%) had an increase of either antibody, compared to 30 of 111 (27.0%; 95% CI, 19.6-36.0%) Hp-positive patients (P = 0.40). Similar results were obtained using positivity for both antibodies (7.3 vs. 7.2%; P = 1) or for ATPO (18.8 vs. 21.6%; P = 0.54). The prevalences of hypothyroidism (4.7 vs. 5.5%) or hyperthyroidism (5.8 vs. 5.5%) were also similar (P = 0.95). Hormonal levels were not different in the two groups (P > 0.22 in all cases). The previously reported association between AT and Hp infection was not observed in our study. Infection by Hp does not appear to increase the risk of AT in individuals with dyspeptic symptoms, and screening for this condition in patients with a positive UBT is not indicated.

PMID: 15745105 [PubMed - indexed for MEDLINE]