Schildklieraandoeningen, type 1 diabetes en vitB12 gebrek komen vaak samen voor.

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1. Indian J Clin Biochem. 2015 Apr;30(2):217-20. doi: 10.1007/s12291-014-0418-4.
Epub 2014 Feb 6.

Evaluation of serum vitamin B12 levels and its correlation with
anti-thyroperoxidase antibody in patients with autoimmune thyroid disorders.

Jaya Kumari S(1), Bantwal G(2), Devanath A(1), Aiyyar V(2), Patil M(2).

Author information:
(1)Department of Biochemistry, St John’s Medical College and Hospital, Bangalore,
(2)Department of Endocrinology, St John’s Medical College and Hospital,
Bangalore, India.

Vitamin B12 deficiency has been reported in patients with Autoimmune thyroid
disorders. However there is limited data on exact prevalence of low B12 and its
correlation with anti-thyroperoxidase antibody (anti-TPO) levels in these
patients. The aim of our study was to estimate serum vitamin B12 levels in
autoimmune thyroid disorders and to correlate B12 levels with anti-TPO. 350
patients were selected by convenient sampling. Vitamin B12 levels and thyroid
parameters were estimated using fully automated chemiluminescence method on
Access 2. Results of our study shows that using the manufacturer’s cut-off of
145 pg/mL, the prevalence of low serum vitamin B12 was found to be 45.50 %.
Higher prevalence (55 %) was seen based on the published cut-off of 200 pg/mL The
study however did not demonstrate any significant correlation between vitamin B12
levels and anti-TPO (r = -0.11 and p value of 0.30).

DOI: 10.1007/s12291-014-0418-4
PMCID: PMC4393379
PMID: 25883432


2. Rev Esp Geriatr Gerontol. 2015 May-Jun;50(3):126-8. doi:
10.1016/j.regg.2014.10.004. Epub 2015 Jan 8.

[Pernicious anemia and autoimmune thyroid diseases in elderly people].

[Article in Spanish]

Velarde-Mayol C(1), de la Hoz-García B(2), del Cañizo-Fernández-Roldán C(2),
Hernández-López AM(2), Loza-Candia I(2), Cardona-Hernández A(2).

Author information:
(1)Equipo de Atención Primaria de Segovia I, Unidad Docente Multiprofesional de
Atención Familiar y Comunitaria de Segovia, Segovia, España. Electronic address:
(2)Equipo de Atención Primaria de Segovia I, Unidad Docente Multiprofesional de
Atención Familiar y Comunitaria de Segovia, Segovia, España.

OBJECTIVE: Autoimmune thyroid diseases (ATD), and pernicious anemia (PA) in
particular, are common in elderly people. The relationship between both of these
is currently being discussed. The objective of this study is to determine the
correlation between ATD and PA in elderly people, and if there are other
associated factors affecting this relationship.
MATERIAL AND METHODS: The factors studied to analyse this association were
social-health variables, autoimmune comorbidity (type 1 diabetes and other
autoimmune diseases), the taking of drugs that alter vitamin B12 levels
(Metformin and protein bomb inhibitors), and the chronological order in which
both diseases appear in this population. A logistic regression analysis was
performed to determine which of the described variables could have an on both
RESULTS: The prevalence was 8.2% for ATD and 3.3% for PA, with a progressive
increase in the annual incidence in the past 10 years from 7.1 to 12.7 cases per
1,000 persons>65 years for ATI, and from 1.6 to 7.4 cases for PA. PA was found in
18.6% of the patients with ATD, and the 45% of PA presented with ATD, mainly in
women (RR=6.0). The average time in diagnosing the second disease was about 8
years. When there was a third autoimmune disease the likelihood of ATD and PA
increased fourfold. Patients with ATD and consuming drugs which were affecting
the absorption of vitamin B12 had double the probability of developing a PA
compared with those who were not taking medications.
CONCLUSIONS: The results of this study confirm the association between ATI and AP
among people 65 or older, also a progressive increase in the incidence of these

Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

DOI: 10.1016/j.regg.2014.10.004
PMID: 25579235 [Indexed for MEDLINE]


3. J Formos Med Assoc. 2014 Mar;113(3):155-60. doi: 10.1016/j.jfma.2012.04.003. Epub
2012 Jun 29.

Hemoglobin, iron, and vitamin B12 deficiencies and high blood homocysteine levels
in patients with anti-thyroid autoantibodies.

Wang YP(1), Lin HP(1), Chen HM(2), Kuo YS(3), Lang MJ(3), Sun A(4).

Author information:
(1)Graduate Institute of Clinical Dentistry, National Taiwan University, Taipei,
Taiwan; School of Dentistry, National Taiwan University, Taipei, Taiwan.
(2)School of Dentistry, National Taiwan University, Taipei, Taiwan; Graduate
Institute of Oral Biology, National Taiwan University, Taipei, Taiwan; Department
of Dentistry, National Taiwan University Hospital, College of Medicine, National
Taiwan University, Taipei, Taiwan.
(3)Department of Dentistry, Far Eastern Memorial Hospital, Taipei, Taiwan.
(4)School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of
Dentistry, National Taiwan University Hospital, College of Medicine, National
Taiwan University, Taipei, Taiwan. Electronic address:

BACKGROUND/PURPOSE: Autoimmune thyroiditis can be diagnosed by measuring
patients’ serum levels of thyroid stimulating hormone (TSH), anti-thyroglobulin
antibody (TGA), and anti-thyroid microsomal antibody (TMA). This study evaluated
whether there were hematinic deficiencies, high blood homocysteine levels, and
serum gastric parietal cell antibody (GPCA) positivity in patients with TGA or
METHODS: The blood hemoglobin (Hb), iron, vitamin B12, folic acid, homocysteine
and TSH concentrations and the serum GPCA level in 190 TGA- or TMA-positive
patients were measured and compared with the corresponding levels in 190 age- and
sex-matched healthy control subjects.
RESULTS: We found that 31 (16.3%), 27 (14.2%), 12 (6.3%), and 2 (1.1%) TGA- or
TMA-positive patients had deficiencies of Hb (Men<13g/dL, Women<12g/dL), iron (<
60μg/dL), vitamin B12 (< 200pg/mL), and folic acid (< 4ng/mL), respectively.
Moreover, 25 (13.2%) and 48 (25.3%) TGA- or TMA-positive patients had abnormally
high blood homocysteine level and serum GPCA positivity, respectively. TGA- or
TMA-positive patients had a significantly higher frequency of Hb (p<0.001), iron
(p<0.001), or vitamin B12 deficiency (p=0.001), of abnormally elevated blood
homocysteine level (p=0.001), or of serum GPCA positivity (p<0.001) than healthy
control subjects. Of 190 TGA- or TMA-positive patients, 8 (4.2%) had lower serum
TSH level (< 0.1μIU/mL, suggestive of hyperthyroidism), 163 (85.8%) had serum TSH
level within normal range (0.1-4.5μIU/mL), and 19 (10%) had higher serum TSH
level (>4.5μIU/mL, suggestive of hypothyroidis).
CONCLUSION: There are significant deficiencies of hemoglobin, iron, and vitamin
B12, abnormally high blood homocysteine levels, and serum GPCA positivity in TGA-
or TMA-positive patients. In addition, the majority (85.8%) of TGA- or
TMA-positive patients had euthyroid and only a small portion (14.2%) of TGA- or
TMA-positive patients had either hypothyroidism or hyperthyroidism.

Copyright © 2012. Published by Elsevier B.V.

DOI: 10.1016/j.jfma.2012.04.003
PMID: 24630032 [Indexed for MEDLINE]


4. Neth J Med. 2009 Dec;67(11):376-87.

Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review.

Van den Driessche A(1), Eenkhoorn V, Van Gaal L, De Block C.

Author information:
(1)Department of Diabetology and Endocrinology, Antwerp University Hospital,
Edegem, Belgium.

Type 1 diabetes mellitus (T1DM) results from autoimmune destruction of
insulin-producing beta cells and is characterised by the presence of insulitis
and &and beta-cell autoantibodies. Up to one third of patients develop an
autoimmune polyglandular syndrome. Fifteen to 30% of T1DM subjects have
autoimmune thyroid disease (Hashimoto’s or Graves’ disease), 5 to 10% are
diagnosed with autoimmune gastritis and/or pernicious anaemia (AIG /PA), 4 to 9%
present with coeliac disease (CD), 0.5% have Addison’s disease (AD), and 2 to 10%
show vitiligo. These diseases are characterised by the presence of autoantibodies
against thyroid peroxidase (for Hashimoto’s thyroiditis), TSH receptor (for
Graves’ disease), parietal cell or intrinsic factor (for AIG /PA), tissue
transglutaminase (for CD), and 21-hydroxylase (for AD). Early detection of
antibodies and latent organ-specific dysfunction is advocated to alert physicians
to take appropriate action in order to prevent full-blown disease. Hashimoto’s
hypothyroidism may cause weight gain, hyperlipidaemia, goitre, and may affect
diabetes control, menses, and pregnancy outcome. In contrast, Graves’
hyperthyroidism may induce weight loss, atrial fibrillation, heat intolerance,
and ophthalmopathy. Autoimmune gastritis may manifest via iron deficiency or
vitamin B12 deficiency anaemia with fatigue and painful neuropathy. Clinical
features of coeliac disease include abdominal discomfort, growth abnormalities,
infertility, low bone mineralisation, and iron deficiency anaemia. Adrenal
insufficiency may cause vomiting, anorexia, hypoglycaemia, malaise, fatigue,
muscular weakness, hyperkalaemia, hypotension, and generalised hyperpigmentation.
Here we will review prevalence, pathogenetic factors, clinical features, and
suggestions for screening, follow-up and treatment of patients with T1DM and/or
autoimmune polyglandular syndrome.


PMID: 20009114 [Indexed for MEDLINE]


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

Vitamin B12 deficiency common in primary hypothyroidism.

Jabbar A(1), Yawar A, Waseem S, Islam N, Ul Haque N, Zuberi L, Khan A, Akhter J.

Author information:
(1)Department of Medicine, Aga Khan University, Karachi, Pakistan.

Erratum in
J Pak Med Assoc. 2009 Feb;59(2):126. Wasim, Sabeha [corrected to Waseem, Sabiha].

OBJECTIVE: To assess the prevalence and clinical features of B12 deficiency in
hypothyroid patients and to evaluate clinical response in symptoms to B12
replacement therapy.
METHODS: One hundred and sixteen hypothyroid patients from our endocrine clinic
were evaluated for signs and symptoms of vitamin B12 deficiency. Laboratory
parameters including Haemoglobin (Hb), MCV, Vitamin B12 levels and presence of
anti thyroid antibodies were analyzed. Patients with low B12 levels were treated
with parenteral intramuscular vitamin B12 monthly, and monitored for improvement
of symptoms.
RESULTS: A total of 116 patients (95 females and 21 males) were evaluated. Forty
six (39.6%) hypothyroid patients had low vitamin B12 levels. Males and females
had the same prevalence of B12 deficiency. Generalized weakness, impaired memory,
depression, numbness and decreased reflexes were more frequently noted in B12
deficient patients, but failed to achieve statistical significance when compared
with B12 sufficient patients. The mean Hb in B12 deficient group was 11.9 +/- 1.6
mg/dl and 12.4 +/- 1.7 mg/dl in the B12 sufficient group, however the mean MCV
did not differ in the two groups. Patients with B12 deficiency did not have a
higher prevalence of anaemia. Thyroid antibodies were checked in half the
patients and 67% had positive titers for anti thyroid antibodies. Prevalence of
vitamin B12 deficiency did not differ in patients with positive antibodies
(43.2%) compared to those with negative antibodies (38.9%) (p= 0.759). Twenty
four hypothyroid patients with B12 deficiency received intramuscular vitamin B12
injections monthly and improvement in symptoms was noted in 58.3% of these
subjects. Additionally, 21 subjects complained of symptoms consistent with B12
deficiency but who had normal range B12, levels and were prescribed monthly B12
injections and 8 (40%) had good subjective clinical response at 6 months.
CONCLUSIONS: There is a high (approx 40%) prevalence of B12 deficiency in
hypothyroid patients. Traditional symptoms are not a good guide to determining
presence of B12 deficiency. Screening for vitamin B12 levels should be undertaken
in all hypothyroid patients, irrespective of their thyroid antibody status.
Replacement of B12 leads to improvement in symptoms, although a placebo effect
cannot be excluded, as a number of patients without B12 deficiency also appeared
to respond to B12, administration.


PMID: 18655403 [Indexed for MEDLINE]


6. Am J Med Sci. 2008 Jul;336(1):50-2. doi: 10.1097/MAJ.0b013e31815c3b5b.

Prevalence of folic Acid and vitamin B12 deficiencies in patients with thyroid

Lippi G(1), Montagnana M, Targher G, Salvagno GL, Guidi GC.

Author information:
(1)Sezione di Chimica Clinica, Dipartimento di Scienze Morfologico-Biomediche,
Università di Verona, Verona, Italy.

Although macrocytosis might occur with frequency in patients with thyroid
disorders, there is controversial information on the metabolic relationship
between thyroid stimulating hormone (TSH), folic acid and B12 in the general
population. We performed a retrospective analysis to retrieve results of serum
folic acid, B12, and TSH performed on consecutive outpatients referred by general
practitioners for routine blood testing over the last 2 years. A positive,
significant trend towards increased values of folic acid, but not of B12, could
be observed across the spectrum of TSH values suggestive for hypo- and
hyperthyroidism. However, the prevalence of subjects with folic acid or B12
deficiency did not differ significantly among the subgroups of subjects. In
multivariable linear regression analysis folic acid, but not B12, was associated
with TSH levels. These results do not support the routine screening for either
B12 or folic acid deficiency in subjects with subclinical disturbances of thyroid
function, though we can not rule out that it might still be useful in patients
with overt thyroid dysfunction.

DOI: 10.1097/MAJ.0b013e31815c3b5b
PMID: 18626236 [Indexed for MEDLINE]


7. Clin Chem Lab Med. 2007;45(2):143-7.

Association of thyroid dysfunction with vitamin B12, folate and plasma
homocysteine levels in the elderly: a population-based study in Sicily.

Stella G(1), Spada RS, Calabrese S, Bosco P, Anello G, Guéant-Rodriguez RM,
Romano A, Benamghar L, Proto C, Castellano A, Fajardo A, Lipari L, Sirna S,
Guéant JL.

Author information:
(1)Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS),
Troina (EN), Italy.

BACKGROUND: Association of thyroid dysfunction with plasma homocysteine levels
and vitamin B(12) has previously been reported. We evaluated these associations
in the elderly in San Teodoro, a mountainous village of Sicily.
METHODS: Subjects (n=279) aged 60-85 years (119 males and 160 females) were
examined using self-reported signs, clinical examination and laboratory tests.
RESULTS: Hypothyroidism and/or goiter were two characteristics that were not
associated with a significant change in homocysteine when compared with
euthyroidism and the absence of goiter. Vitamin B(12) was significantly higher in
subjects in the first quartile of the thyroid-stimulating hormone distribution,
compared with those in the fourth quartile (371+/-207 vs. 297+/-196 pmol/L,
p=0.0121). Homocysteine was significantly higher in the first quartile of the
free tri-iodothyronine distribution compared to the third quartile (18.0+/-5.7
vs. 16.0+/-6.2 micromol/L, p=0.0130) and was correlated with log
tri-iodothyronine in euthyroid subjects (p=0.0254). In multivariate analysis,
homocysteine was associated with vitamin B(12) (p=0.0014), folate (p<0.0001),
creatinine (p<0.0001) and age (p<0.0001), but not with either free
tri-iodothyronine (p=0.7680), tetra-iodothyronine (p=0.5706) or
thyroid-stimulating hormone (p=0.2294).
CONCLUSIONS: Our results suggest that the influence of thyroid hormones on
homocysteine is much weaker in elderly subjects than in selected patients with

DOI: 10.1515/CCLM.2007.066
PMID: 17311498 [Indexed for MEDLINE]


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

Prevalence and evaluation of B12 deficiency in patients with autoimmune thyroid

Ness-Abramof R(1), Nabriski DA, Braverman LE, Shilo L, Weiss E, Reshef T, Shapiro
MS, Shenkman L.

Author information:
(1)Endocrine Unit, Sapir Medical Center, Tchernikovsky 53, Kfar Saba, Israel

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
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 [Indexed for MEDLINE]


9. Diabet Med. 2000 Oct;17(10):749-51.

Prevalence of pernicious anaemia in patients with Type 1 diabetes mellitus and
autoimmune thyroid disease.

Perros P(1), Singh RK, Ludlam CA, Frier BM.

Author information:
(1)Department of Diabetes, Royal Infirmary, Edinburgh, Scotland, UK.

AIMS: To determine the prevalence of pernicious anaemia in patients with Type 1
diabetes mellitus and autoimmune thyroid disease.
METHODS: A randomly selected asymptomatic group of 63 patients with Type 1
diabetes who also had autoimmune thyroid disease was studied. Blood samples were
taken and assayed for serum B12. Those subjects with serum B12 concentrations
below the reference range had a further blood sample taken for determination of
intrinsic factor antibody.
RESULTS: One patient had been diagnosed previously to have pernicious anaemia.
Three patients had low serum B12 concentration and positive intrinsic factor
antibody, confirming the diagnosis of pernicious anaemia. The prevalence of
pernicious anaemia in this population with Type 1 diabetes and concomitant
autoimmune thyroid disease was 6.3%. In female patients the prevalence of
pernicious anaemia was 8.5%.
CONCLUSIONS: Patients who have both Type 1 diabetes mellitus and autoimmune
thyroid disease are at risk of developing pernicious anaemia.


PMID: 11110510 [Indexed for MEDLINE]