An update on thyroid disorders in the postpartum period.

PURPOSE: To review the pathophysiology, diagnosis and management of postpartum thyroid dysfunction, and related management of thyroid disorders during lactation. METHODS: We reviewed the literature on postpartum thyroid dysfunction and management of thyroid disorders during lactation. RESULTS: The postpartum period is characterized by a rebound from the immunotolerance induced by pregnancy. Routine thyroid function screening is not recommended for asymptomatic women in the postpartum period. Testing thyroid function should be considered at 6-12-week postpartum for high-risk populations, including women with a previous episode of postpartum thyroiditis, Graves' disease, or those with Hashimoto's thyroiditis on thyroid hormone replacement, known thyroid peroxidase antibody positivity, type 1 diabetes mellitus, other nonthyroidal autoimmune disease, or chronic hepatitis C. A serum TSH should also be checked in the setting of postpartum depression or difficulty lactating. If patients have thyrotoxicosis, new-onset or recurrent Graves' disease must be differentiated from postpartum thyroiditis, because the management differs. Periodic thyroid function testing is recommended following recovery from postpartum thyroiditis due to high lifetime risk of developing permanent hypothyroidism. Levothyroxine, and the lowest effective dose of antithyroid drugs, (propylthiouracil, methimazole, and carbimazole) can be safely used in lactating women. The use of radiopharmaceutical scanning is avoided during lactation and radioactive iodine treatment is contraindicated. CONCLUSIONS: Diagnosing postpartum thyroid dysfunction is challenging, because symptoms may be subtle. A team approach involving primary care providers, endocrinologists, and obstetricians is essential for transitioning thyroid care from the gestational to the postpartum setting.

TPO antibody in euthyroid pregnant women and cognitive ability in the offspring: a focused review.

PURPOSE: A link between maternal thyroid dysfunction during pregnancy and the risk of cognitive and behavioral problems in the offspring has previously been established; however, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism are less clear. The present review aims to highlight the gaps in knowledge in this regard and provide a thorough assessment of relevant literature. METHOD: Related keywords searched in MEDLINE, Web of Science, and Scopus till January 2021. RESULTS: There is some evidence that neuropsychological and intellectual developments of offspring are adversely affected by maternal thyroid autoimmunity, although the results of available studies are not concordant. The tools and measurements that have been applied in different studies to assess neurodevelopment or IQ vary widely and the children born to mothers with thyroid autoimmunity have been assessed at different chronological stages of life. Such variations may explain some of the differences across studies. In addition, the definition of thyroid autoimmunity has been based on TPOAb cut points provided by manufacturers in most cases, but it is preferable to define these values based on age, trimester, and method-specific reference ranges. CONCLUSION: Well-designed studies are needed to assess verbal and non-verbal neurocognition of offspring born to mothers with autoimmune thyroid disease before or during pregnancy.

Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Clinical case seminar in pediatric thyroid disease.

Pediatric thyroid diseases cover a large spectrum of congenital and acquired forms, ranging from congenital primary or central hypothyroidism, autoimmune thyroid disease, iodine deficiency, rare genetic defects of thyroid hormone action, metabolism and cell membrane transport to benign nodules and malignant tumors. The previous 15 papers of the textbook Paediatric Thyroidology gave a systematic overview of the current knowledge and guidelines on all these diseases. In this final paper, the authors collected a series of patient histories from their clinics illustrating frequently encountered clinical problems and providing key learning points and references to each case. Although not fully comprehensive, it aims at providing relevant clinical knowledge on thyroid diseases of the neonate, the child, and the adolescent.

Monitoring and effects of iodine deficiency in pregnancy: still an unsolved problem?

Iodine is required for the production of thyroid hormone. Thyroid hormone affects many metabolic processes in the body, including maturation of the central nervous system. In early pregnancy, the fetus is dependent on maternal thyroid hormone for normal brain development. If iodine deficiency leads to inadequate production of thyroid hormone during pregnancy, irreversible brain damage can result in the fetus. Therefore, achieving adequate iodine nutrition during pregnancy is an important public health objective. Although there have been tremendous gains over the last several decades in our understanding of the effects of iodine deficiency in pregnancy and how to combat them, a number of questions remain about how best to monitor the iodine status of pregnant populations, the effects of mild to moderate iodine deficiency on maternal and child outcomes, the safe upper limit of daily iodine intake in pregnant women and the risks and benefits of iodine supplementation for mildly iodine-deficient pregnant women.

Transient congenital hypothyroidism in an iodine-replete area is not related to parental consanguinity, mode of delivery, goitrogens, iodine exposure, or thyrotropin receptor autoantibodies.

OBJECTIVE: To assess transient congenital hypothyroidism (TCH) etiologies in two Iranian cities. MATERIALS AND METHODS: Cord dried blood spot samples were collected from neonates in Tehran and Damavand. Serum TSH and T4 were measured in those with cord TSH > or =20 mIU/l. Normal serum values at 2-3 weeks of age confirmed transient hyperthyrotropinemia (THT), while persistently abnormal levels revealed congenital hypothyroidism (CH). Normal serum TSH and T4 4-6 weeks after levothyroxine replacement therapy discontinuation at 2-3 yr of age differentiated TCH from persistent CH. RESULTS: Among 50,409 screened newborns, 9 (1:5601 births) were diagnosed as TCH and compared to 88 full-term neonates (>/=37 weeks' gestation) with THT and 45 normal (cord TSH<20 mIU/l) neonates. At a median age of 11 days, median (range) serum TSH values in TCH, THT, and normal neonates were 36.8 (13-130), 3.6 (0.1-13.3), and 2.9 (0.7-8.0) mIU/l (p<0.0001) and serum T4 values were 97 (36-168), 142 (74-232), and 160 (79-228 nmol/l), respectively (p=0.002). Urinary iodine concentration (UIC) >220 microg/l was observed in 5 (55.6%) of TCH neonates. The occurrence of TCH was not associated with gender, parental consanguinity, mode of delivery, pre- or post-natal consumption of goitrogens and/or thyroid affecting medications, TSH receptor autoantibodies, or neonatal UIC. CONCLUSIONS: Elevated UIC was the most frequent finding in newborns with TCH but the distribution of excessive UIC was not significantly different among TCH, THT, and normal neonates. Since no other etiologies were found in TCH neonates without elevated UIC values, evaluation of other environmental and/or genetic factors is warranted.

Prevalence of goiter among schoolchildren from Gorgan, Iran, a decade after national iodine supplementation: association with age, gender, and thyroperoxidase antibodies.

BACKGROUND: One decade after universal salt iodization in Iran, goiter prevalence, urinary iodine concentration (UIC) and thyroperoxidase antibody (TPOAb) values were assessed among schoolchildren in Gorgan, Iran. METHODS: From 2003-2004, 500 girls and 900 boys aged 7-11 yr were evaluated for goiter by palpation. UIC was measured in 183 randomly-selected goitrous children. Serum TSH, T4, and TPOAb were measured in 53 goitrous and 30 non-goitrous children with adequate UIC. RESULTS: Goiter was detected in 370 (26.4%) children. Goiter was present in 31% of girls and 17% of boys age 9 (p<0.012); 37% of girls and 20% of boys age 10 (p<0.003); and 52% of girls and 19% of boys age 11 (p<0.0001). Median (range) UIC for all goitrous children sampled was 190 (20-600) microg/l; 220 (30590) in boys and 170 (20-600) in girls (p=0.001). Eight point seven percent of goitrous children and 22% of goitrous girls aged 10-11 had UIC<100 microg/l, while 47% of the goitrous children had UIC> or =200 microg/ l. TPOAb was present in 52.8% of goitrous children and 10% of non-goitrous children (p=0.0001). TPOAb was present in 53.9% of 10-11 and 22.7% of 7-9 yr old goitrous and non-goitrous children (p=0.003) with adequate UIC. Median (range) TSH was 2.9 (0.3-10.9) mlU/I in TPO-positive and 1.8 (0.5-4.1) in TPO-negative children (p=0.001). CONCLUSIONS: Gorgan, Iran, is an iodine-sufficient area and almost half of schoolchildren have more than adequate UIC. TPOAb is associated with endemic goiter. Despite sufficient UIC overall, some school-aged girls remain at risk of iodine deficiency.