Background: Weight gain during treatment of hyperthyroidism is a frequent and for many patients unwanted outcome. With this repeated measurement study, we explored the timing of weight changes during the first year of antithyroid drug (ATD) treatment and assessed the correlation between body weight changes and changes in thyroid hormones, resting energy expenditure (REE), physical activity level, and energy efficiency. Methods: Patients with new onset hyperthyroidism were investigated every second month during the first year of ATD treatment. At each investigation, the following were measured: body weight, thyroid hormone concentrations, physical activity level, and daily number of steps, REE, and exercise performance. Results: Two men and eleven women, all sedentary, mean age 49(SD: 9.3) years were included. Significant changes after 1 year occurred for body weight (68.9–74.1 kg), thyroid hormones (free T3 [fT3] 17.5 to 4.42 pmol/L), REE (1,630–1,484 kcal/24 h), and energy efficiency at lower (50 W) workloads (16.0–17.6%). In individual patients, only REE and fT3 correlated to changes in body weight. Physical activity level did not change during treatment. Conclusion: In this study, treatment of hyperthyroidism was associated with marked increase in body weight in the patients. This increase correlated to a decrease in REE and only to a negligible extent to changes in energy efficiency and not at all to changes in physical activity level of daily living.
Jesper Karmisholt, Allan Carlé, and Stig Andersen
Stine Linding Andersen and Stig Andersen
Thyroid disease in pregnant women needs attention from a clinical and scientific standpoint due to the potential severe adverse consequences. It is well-established that overt thyroid disease in pregnant women should be treated to prevent maternal and fetal complications, but routine testing for overt thyroid function test abnormalities has not been implemented. In contrast, the scientific focus has shifted towards smaller aberrations in maternal thyroid function including subclinical thyroid disease and isolated deviations in maternal thyroxine. In this focused review, we touch upon the assessment of maternal thyroid function in pregnancy and how the historical advancements in thyroid function tests parallel with the thyroid function test abnormalities described. Furthermore, we discuss how the scientific focus has evolved and how the field could turn in view of the existing discrepancies between results of observational studies and randomized controlled trials.
Jesper Karmisholt and Stig Andersen
Guidelines suggest that subclinical hypothyroid (SCH) patients with thyrotropin (TSH) between 4 and 10 mU/L and symptoms associated with hypothyroidism should receive L-T4 substitution treatment, be evaluated, and continue treatment if symptoms subside. The latter requires detecting a true change in symptoms, which can be calculated from within-person variation in symptom evaluation tools. This led us to assess within-person variation in hypothyroid symptoms, in mood-related symptoms, and quality of life in patients with untreated SCH in order to support the recommended evaluations. Method: The within-person coefficient of variation (CV) was estimated from 13 consecutive monthly evaluations in 15 patients with initial TSH between 5 and 12 mU/L and no trend in TSH. Results: The within-person CV was rather large for the Hospital Anxiety and Depression Scale (HADS) and Zulewski hypothyroid score at 41.6 and 60.9%, respectively. For quality of life the within-person CV was lower at 8.0% for the physical component summary and 8.7% for the mental component summary from the SF-36 questionnaire. The difference required between two measurements to detect a true change was 97% for mood-related symptoms (HADS) and 140% for hypothyroid symptoms. For quality of life (SF-36) the required difference was 20%. Conclusion: Score differences of almost 100% and higher were required to support a true change in mood (HADS) and hypothyroid symptom scores in untreated SCH patients. For quality of life a true change was detected at a 20% difference in SF-36 scores. The hypothyroid score and HADS questionnaire do not seem useful for the evaluation of individuals.
Louise Knøsgaard, Stig Andersen, Annebirthe Bo Hansen, Peter Vestergaard, and Stine Linding Andersen
The assessment of maternal thyroid function in early pregnancy is debated. It is well-established that pregnancy-specific reference ranges preferably should be used. We speculated if the use of repeated blood samples drawn in early pregnancy would influence the classification of maternal thyroid function.
Pregnant women with repeated early pregnancy blood samples were identified in the North Denmark Region Pregnancy Cohort. Each sample was used for the measurement of TSH, free T4 (fT4), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers). Method- and pregnancy week-specific reference ranges were used for the classification of maternal thyroid function.
Among 1466 pregnancies included, 89 women had TSH above the upper reference limit in the first sample (median pregnancy week 8) and 44 (49.4%) of these similarly had high TSH in the second sample (median week 10). A total of 47 women had TSH below the lower reference limit in the first sample and 19 (40.4%) of these similarly had low TSH in the second sample. Regarding women classified with isolated changes in fT4 in the first sample, less than 20% were similarly classified as such in the second sample. The percentage agreement between the samples was dependent on the level of TSH in the first sample and the presence of TPO- and Tg-Ab.
In a large cohort of pregnant women, the classification of maternal thyroid function varied considerably with the use of repeated blood samples. Results emphasize a focus on the severity of thyroid function abnormalities in pregnant women.
Peter Laurberg, Nils Knudsen, Stig Andersen, Allan Carlé, Inge Bülow Pedersen, and Jesper Karmisholt
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.
Paneeraq Noahsen, Karsten F Rex, Inge Bülow Pedersen, Gert Mulvad, Hans Christian Florian-Sørensen, Michael Lynge Pedersen, and Stig Andersen
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.
This study is a population-based cross-sectional study.
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.
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).
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.
Stine Linding Andersen, Niels Henrik Bruun, Peter Astrup Christensen, Simon Lykkeboe, Aase Handberg, Annebirthe Bo Hansen, Maja Hjelm Lundgaard, Louise Knøsgaard, Nanna Maria Uldall Torp, Allan Carlé, Jesper Karmisholt, Inge Bülow Pedersen, Peter Vestergaard, and Stig Andersen
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.
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.
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.
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.