Maternal thyroid disease in pregnancy and timing of pubertal development in sons and daughters.

OBJECTIVE: To study whether maternal thyroid disease in pregnancy is associated with pubertal timing in sons and daughters. DESIGN: Cohort study. SETTING: National birth cohort and health registers. PATIENT(S): A total of 15,763 mothers and children from the Danish National Birth Cohort and its Puberty Cohort. INTERVENTION(S): Register-based and self-reported information on maternal thyroid diseases during pregnancy (hyperthyroidism, hypothyroidism, benign goiter, or no thyroid disease [reference group]). MAIN OUTCOME MEASURE(S): The adjusted mean age difference (months) at attaining several self-reported pubertal milestones collected every 6 months using an interval-censored regression and the average difference in age at attaining all pubertal milestones using the Huber-White robust variance estimation (primary outcome). RESULT(S): Sons of mothers with hyperthyroidism had earlier pubertal development (average difference, -2.9 [95% confidence interval (CI), -5.0 to -0.7] months) than unexposed sons. Maternal hypothyroidism was not associated with pubertal development in sons (average difference, -1.2 [95% CI, -5.1 to 2.7] months). We observed nonstatistically significant indications of earlier pubertal development in sons of mothers with benign goiter (average difference, -1.9 [95% CI, -4.6 to 0.9] months). Maternal thyroid disease was not associated with pubertal development in daughters (average difference (months), hyperthyroidism, -0.8 [95% CI, -2.8 to 1.2]; hypothyroidism, 0.3 [95% CI, -3.1 to 3.8]; and benign goiter, 0.7 [95% CI, -2.0 to 3.4]). CONCLUSION(S): We found indications of earlier pubertal development in sons of mothers with hyperthyroidism. More research is needed to further investigate the observed sex-specific association.

Raised mortality in old adults with a history of hyperthyroidism following iodine fortification.

OBJECTIVE: A transient rise in the occurrence of hyperthyroidism ensued the introduction of iodine fortification (IF) of salt in Denmark. Older adults are at risk of complications to hyperthyroidism that could prove fatal to vulnerable individuals. We evaluated the association between thyroid function and mortality in older adults before and after nationwide implementation of IF. DESIGN: Retrospective cohort study. PATIENTS: All 68-year-olds from the general population in the city of Randers were invited to participate in a clinical study in 1988 and followed until death, emigration or end of study (31 December 2017) using Danish registries. MEASUREMENTS: Baseline measures comprised of a questionnaire, physical examination and blood and urine samples. Kaplan-Meier survival curves and Cox regression were used to determine the association between thyroid function and death before and after IF. Time-stratification of results before and after IF was employed due to violation of proportional hazards assumptions in Cox regression. RESULTS: Median urinary iodine concentration was 42 µg/L at baseline consistent with moderate iodine deficiency. Hyperthyroidism (thyrotropin < 0.4 mIU/L) occurred in 37 (9.1%) participants. Kaplan-Meier survival curves showed an increase in mortality among participants with hyperthyroidism after IF. There was no significant association between hyperthyroidism and mortality before IF compared to euthyroid participants, but after IF hyperthyroid subjects had an increased mortality (adjusted hazard ratio: 2.22, 95% confidence interval: 1.44-3.44). CONCLUSIONS: IF was associated with raised mortality among older adults with a history of hyperthyroidism and moderate iodine deficiency. Our results highlight the need for cautious iodine supplementation and for monitoring of IF.

Long-term iodine nutrition is associated with longevity in older adults: a 20 years' follow-up of the Randers-Skagen study.

Iodine intake affects the occurrence of thyroid disorders. However, the association of iodine intake with longevity remains to be described. This led us to perform a 20 years' follow-up on participants from the Randers-Skagen (RaSk) study. Residents in Randers born in 1920 (n 210) and Skagen born in 1918-1923 (n 218) were included in a clinical study in 1997-1998. Mean iodine content in drinking water was 2 µg/l in Randers and 139 µg/l in Skagen. We collected baseline data through questionnaires, performed physical examinations and measured iodine concentrations in spot urine samples. Income data were retrieved from Danish registries. We performed follow-up on mortality until 31 December 2017 using Danish registries. Complete follow-up data were available on 428 out of 430 of participants (99·5 %). At baseline, the median urinary iodine concentration was 55 µg/l in Randers and 160 µg/l in Skagen residents. Participants were long-term residents with 72·8 and 92·7 % residing for more than 25 years in Randers and Skagen, respectively. Cox regression showed that living in Skagen compared with Randers was associated with a lower hazard ratio (HR) of death in both age- and sex-adjusted analyses (HR 0·60, 95 % CI 0·41, 0·87, P = 0·006), but also after adjustment for age, sex, number of drugs, Charlson co-morbidity index, smoking, alcohol and income (HR 0·60, 95 % CI 0·41, 0·87, P = 0·008). Residing in iodine-replete Skagen was associated with increased longevity. This indicates that long-term residency in an iodine-replete environment may be associated with increased longevity compared with residency in an iodine-deficient environment.

Risk of embryopathies with use of antithyroidal medications.

PURPOSE OF REVIEW: Hyperthyroidism in pregnant women should be adequately treated to prevent maternal and fetal complications. The treatment of choice in pregnancy is antithyroidal medications (ATDs). The risk of embryopathies associated with the use of Methimazole (MMI) and Propylthiouracil (PTU) in early pregnancy is a matter of clinical attention and concern. This review describes current evidence and how scientific findings are reflected in current clinical guidelines. RECENT FINDINGS: Embryopathies after the use of ATDs were previously mainly described in case reports and considered rare. Recent large observational studies, including nonexposed control groups, have quantified an increased risk of embryopathies associated with use of ATDs during pregnancy. Findings suggest a risk of embryopathies with the use of both MMI and PTU, but the pattern of embryopathies differs, and embryopathies with the use of PTU appear less severe. SUMMARY: Current guidelines highlight the need for clinical attention on the use of ATDs in early pregnancy. Patients managed on ATDs for the treatment of hyperthyroidism should be counseled to report a pregnancy as early as possible. PTU is the recommended treatment in early pregnancy, but if the risk of relapse or worsening of hyperthyroidism is considered low, it is suggested that ATD treatment can be withdrawn followed by frequent monitoring of thyroid function.

Maternal thyroid function in pregnancy may program offspring blood pressure, but not adiposity at 20 y of age.

BACKGROUND: Experimental evidence exists indicating that maternal thyroid hormones during pregnancy may affect the metabolic set point and cardio-vascular function in the offspring. The objective of this study was to investigate the association between maternal thyroid function in week 30 of gestation and offspring adiposity and blood pressure at 20 y. METHODS: The study was based on the follow up of a Danish birth cohort from 1988 to 1989 (n = 965). A blood sample was drawn from the pregnant women in week 30 of gestation (N = 877). In 2008-2009, the offspring were followed up with self-reported anthropometrics (N = 645) and a clinically measured blood pressure (N = 425). Multiple linear regressions were used to estimate the association between maternal thyroid function and offspring BMI, waist circumference, and blood pressure. RESULTS: Offspring of subclinical hypothyroid women had higher systolic blood pressure (adjusted difference = 3.6, 95% confidence interval: 0.2, 7.0 mmHg) and a tendency toward higher diastolic blood pressure (adjusted difference = 2.3, 95% confidence interval: -0.2, 4.9 mmHg) compared to offspring of euthyroid women. No association was found with offspring BMI and waist circumference. CONCLUSION: Maternal thyroid function during third trimester of pregnancy may affect long-term blood pressure in the offspring.

Screening for overt thyroid disease in early pregnancy may be preferable to searching for small aberrations in thyroid function tests.

Thyroid hormones are important regulators of foetal development, and in recent years, there has been much focus on the screening and treatment of pregnant women for even small aberrations in thyroid function tests. We searched PubMed for publications on thyroid function and pregnancy outcomes including child cognition, and included references from the retrieved articles. Both small aberrations in thyroid function tests in early pregnancy and an increase in risk of pregnancy complications may be caused by a functional change in the uteroplacental unit. Thus, the association found in several studies between small thyroid test abnormalities and pregnancy complications may be due to confounding, and thyroid hormone therapy will have no effect. On the other hand, screening of thyroid function in early pregnancy may identify 200-300 women with undiagnosed overt hypothyroidism per 100,000 pregnancies, which is at least five times more than the number of hypothyroid newborns identified by screening. A number of studies indicate that untreated overt thyroid disease in pregnancy may lead to complications. The potential benefit of screening and early therapy is supported by evidence, indicating that even severe maternal hypothyroidism does not lead to neurocognitive deficiencies in the child, if the condition is detected and treated during the first half of pregnancy. Screening and therapy for overt thyroid dysfunction in early pregnancy may be indicated, rather than focusing on identifying and treating small aberrations in thyroid function tests.

Thyroglobulin in smoking mothers and their newborns at delivery suggests autoregulation of placental iodide transport overcoming thiocyanate inhibition.

BACKGROUND: Placental transport of iodide is required for fetal thyroid hormone production. The sodium iodide symporter (NIS) mediates active iodide transport into the thyroid and the lactating mammary gland and is also present in placenta. NIS is competitively inhibited by thiocyanate from maternal smoking, but compensatory autoregulation of iodide transport differs between organs. The extent of autoregulation of placental iodide transport remains to be clarified. OBJECTIVE: To compare the impact of maternal smoking on thyroglobulin (Tg) levels in maternal serum at delivery and in cord serum as markers of maternal and fetal iodine deficiency. METHODS: One hundred and forty healthy, pregnant women admitted for delivery and their newborns were studied before the iodine fortification of salt in Denmark. Cotinine in urine and serum classified mothers as smokers (n=50) or nonsmokers (n=90). The pregnant women reported on intake of iodine-containing supplements during pregnancy and Tg in maternal serum at delivery and in cord serum were analyzed. RESULTS: In a context of mild-to-moderate iodine deficiency, smoking mothers had significantly higher serum Tg than nonsmoking mothers (mean Tg smokers 40.2 vs nonsmokers 24.4 µg/l, P=0.004) and so had their respective newborns (cord Tg 80.2 vs 52.4 µg/l, P=0.006), but the ratio between Tg in cord serum and maternal serum was not significantly different in smokers compared with nonsmokers (smoking 2.06 vs nonsmoking 2.22, P=0.69). CONCLUSION: Maternal smoking increased the degree of iodine deficiency in parallel in the mother and the fetus, as reflected by increased Tg levels. However, placental iodide transport seemed unaffected despite high thiocyanate levels, suggesting that thiocyanate-insensitive iodide transporters alternative to NIS are active or that NIS in the placenta is autoregulated to keep iodide transport unaltered.