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Inge Bülow Pedersen Department of Endocrinology and Medicine, Aalborg University Hospital, Aalborg, Denmark

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Peter Laurberg Department of Endocrinology and Medicine, Aalborg University Hospital, Aalborg, Denmark

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We describe a case of biochemical neonatal thyrotoxicosis caused by biotin supplementation. Biotin may interact with thyroid function testing to imitate thyrotoxicosis with low thyroid-stimulating hormone and elevated triiodothyronine and thyroxine levels.

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Peter Laurberg Department of Endocrinology, Aalborg Hospital, Aalborg

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Nils Knudsen Medical Clinic I, Bispebjerg Hospital, Copenhagen, Denmark

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Stig Andersen Department of Endocrinology, Aalborg Hospital, Aalborg

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Allan Carlé Department of Endocrinology, Aalborg Hospital, Aalborg

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Inge Bülow Pedersen Department of Endocrinology, Aalborg Hospital, Aalborg

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Jesper Karmisholt Department of Endocrinology, Aalborg Hospital, Aalborg

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Important interaction exists between thyroid function, weight control, and obesity. Several mechanisms seem to be involved, and in studies of groups of people the pattern of thyroid function tests depends on the balance of obesity and underlying thyroid disease in the cohort studied. Obese people with a normal thyroid gland tend to have activation of the hypothalamic-pituitary-thyroid axis with higher serum TSH and thyroid hormones in serum. On the other hand, small differences in thyroid function are associated with up to 5 kg difference in body weight. The weight loss after therapy of overt hypothyroidism is caused by excretion of water bound in tissues (myxoedema). Many patients treated for hyperthyroidism experience a gain of more weight than they lost during the active phase of the disease. The mechanism for this excessive weight gain has not been fully elucidated. New studies on the relation between L-T<sub>3</sub> therapy and weight control are discussed. The interaction between weight control and therapy of thyroid disease is important to many patients and it should be studied in more detail.

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Paneeraq Noahsen Arctic Health Research Centre, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Ilisimatusarfik, University of Greenland, Nuuk, Greenland
National Board of Health, Nuuk, Greenland

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Karsten F Rex Arctic Health Research Centre, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Ilisimatusarfik, University of Greenland, Nuuk, Greenland
Department of Internal Medicine, Queen Ingrid’s Hospital, Nuuk, Greenland

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Inge Bülow Pedersen Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark

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Gert Mulvad Ilisimatusarfik, University of Greenland, Nuuk, Greenland
Queen Ingrid’s Health Care Centre, Nuuk, Greenland

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Hans Christian Florian-Sørensen Tasiilaq Health Care Center, Tasiilaq, Greenland

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Michael Lynge Pedersen Steno Diabetes Center Nuuk, Nuuk, Greenland

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Stig Andersen Arctic Health Research Centre, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Ilisimatusarfik, University of Greenland, Nuuk, Greenland
Department of Internal Medicine, Queen Ingrid’s Hospital, Nuuk, Greenland
Department of Geriatric Medicine, Aalborg University Hospital, Aalborg, Denmark

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Objective

This study aimed to provide the first data on the occurrence of thyroid autoimmunity among Inuit in Greenland, a distinct ethnic group who is not iodine deficient.

Design

This study is a population-based cross-sectional study.

Methods

Data were collected in Nuuk in West Greenland and in Ammassalik district in East Greenland. Information on lifestyle, diet and diseases was obtained using questionnaires. Thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) and thyroid-stimulating hormone (TSH) were measured in serum. Iodine and creatinine were measured in spot urine samples.

Results

The participation rate was 95% with 434 Inuit participants; 75% were smokers. Iodine excretion was 169 µg/24 h in urban West Greenland, 224 µg/24 h in the main town and 228 µg/24 h in settlements in rural East Greenland. TPOAb, TgAb or either of these was measured in the serum from 3.7, 5.9 and 8.3% of participants, respectively. TPOAb or TgAb was found in 9.3% of Inuit women and 7.5% of men and more frequently, in East Greenland Inuit with the higher iodine excretion (P  = 0.02). There was some evidence suggesting that thyroid autoimmunity was more frequent among non-smokers (12.5%) compared to smokers (7.0%). Harbouring a thyroid autoantibody was most frequent in participants with TSH above 3.6 mIU/L (P  < 0.001).

Conclusion

Thyroid autoantibodies were rare among Greenland Inuit. While iodine nutrition was associated with autoimmunity similarly to other ethnic groups, the influence of sex and smoking was limited. This could suggest genetic component in Inuit, but the impact of cold, selenium and persistent organic pollutants needs to be elucidated.

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Allan Carlé Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Institute, Aalborg University, Aalborg, Denmark

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Nils Knudsen Department of Endocrinology I, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark

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Torben Jørgensen Centre for Clinical Research and Prevention, Capital Region of Denmark, Copenhagen, Denmark
Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Bettina Thuesen Centre for Clinical Research and Prevention, Capital Region of Denmark, Copenhagen, Denmark

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Jesper Karmisholt Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Institute, Aalborg University, Aalborg, Denmark

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Stine Linding Andersen Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Inge Bülow Pedersen Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Institute, Aalborg University, Aalborg, Denmark

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Objective: To investigate the association between reproductive history and later development of various nosological subtypes of overt hyperthyroidism. Study Design: From the Danish population, we included incident hyperthyroid women, and for each case we recruited 4 euthyroid age-sex-region-matched controls from the same sub-population. Hyperthyroid cases/controls were: Graves’ disease (GD, n = 232/928), multinodular toxic goitre (MNTG, n = 91/364), solitary toxic adenoma (STA, n = 21/84). Patients diagnosed with hyperthyroidism within 1 year after delivery including post-partum GD were excluded. In multivariate conditional regression models (reference: no reproductive events), we analysed the association between development of GD/MNTG/STA and reproductive factors such as age at menarche/menopause, reproductive span, number of pregnancies/childbirths/abortions, investigations for infertility, and years on oral contraceptives. We adjusted for possible confounders such as alcohol intake, smoking, co-morbidity, and education. Age was studied as a potential effect measure modifier. Results: GD patients diagnosed before the age of 40 years had given births more often than control subjects (OR [95% CI] for 1/2/3+ births [ref.: nulliparous] were 1.57 [0.80–3.11]/2.06 [1.001–4.22]/3.07 [1.50–6.26]), and they had induced abortions performed more often (OR for 1/2+ induced abortions [ref.: no: events] were 0.99 [0.54–1.84]/2.24 [1.12–4.45]). No associations were observed between any reproductive factor and the development of MNTG or STA. Conclusions: Childbirths and induced abortions may be followed by development of Graves’ hyperthyroidism after the post-partum period. This was not the case for the non-autoimmune subtypes of hyperthyroidism.

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Stine Linding Andersen Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

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Niels Henrik Bruun Unit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark

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Peter Astrup Christensen Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

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Simon Lykkeboe Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Aase Handberg Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

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Annebirthe Bo Hansen Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Maja Hjelm Lundgaard Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Louise Knøsgaard Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

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Nanna Maria Uldall Torp Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

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Allan Carlé Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark

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Jesper Karmisholt Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark

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Inge Bülow Pedersen Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark

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Peter Vestergaard Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark

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Stig Andersen Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Geriatrics, Aalborg University Hospital, Aalborg, Denmark

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Objective

Thyroid disease in women of reproductive age is mainly of autoimmune origin, and thyroid peroxidase antibodies (TPO-Ab) as well as thyroglobulin antibodies (Tg-Ab) are key markers. Adding to this, much focus in pregnancy is on euthyroid women who are thyroid antibody positive. Evidence to substantiate the cut-offs for the definition of thyroid autoantibody positivity in early pregnant women is warranted.

Methods

Stored serum samples from 14,030 Danish pregnant women were used for the measurement of TPO-Ab, Tg-Ab, TSH, and free thyroxine (ADVIA Centaur XPT, Siemens Healthineers). Among all women, a reference cohort of 10,905 individuals was identified for the establishment of antibody cut-offs. Percentile cut-offs for TPO-Ab and Tg-Ab were determined using regression on order statistics (the reference cohort). The established cut-offs were then applied (the full cohort), and frequencies of early pregnancy as well as later diagnosis of hypothyroidism were evaluated.

Results

The highest established cut-offs (95th, 97.5th, and 99th percentiles) were 59, 68, and 81 U/mL for TPO-Ab and 33, 41, and 52 U/mL for Tg-Ab. When the cut-offs were applied in the full cohort, 11.0, 10.2, and 9.7% were TPO-Ab positive, whereas 13.3, 12.3, and 11.2% were Tg-Ab positive. Antibody-positive women (TPO-Ab and/or Tg-Ab) had higher median TSH and were more likely to have hypothyroidism in early pregnancy and to be diagnosed with hypothyroidism during follow-up.

Conclusions

This large study established and evaluated pregnancy-specific cut-offs for TPO-Ab and Tg-Ab. The findings are important regarding the classification of exposure in pregnancy and assessment of thyroid autoimmunity per se.

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Line Tang Møllehave Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Nils Knudsen Department of Endocrinology, Bispebjerg University Hospital, University of Copenhagen, Denmark

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Allan Linneberg Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Inge Bülow Pedersen Department of Endocrinology and Medicine, Aalborg University Hospital, Aalborg, Denmark

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Gitte Ravn-Haren Research Group for Risk Benefit, National Food Institute, Technical University of Denmark, Lyngby, Denmark

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Anja Lykke Madsen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Allan Carlé Department of Endocrinology and Medicine, Aalborg University Hospital, Aalborg, Denmark

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Charlotte Cerqueira The Danish Clinical Quality Program – National Clinical Registries (RKKP), Denmark

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Anne Krejbjerg Department of Oncology, Aalborg University Hospital, Aalborg, Denmark

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Lone Banke Rasmussen Independent researcher, Klemensker, Denmark

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Lars Ovesen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Hans Perrild Department of Endocrinology, Bispebjerg University Hospital, University of Copenhagen, Denmark

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Lena Bjergved Sigurd Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Internal Medicine, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark

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Betina Heinsbæk Thuesen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Pernille Vejbjerg Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

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Torben Jørgensen Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild–moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program – as IF – is initiated.

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