APPROACH TO THE PATIENT Fetal and neonatal thyroid dysfunction

Fetal and neonatal dysfunctions include rare serious disorders involving abnormal thyroid function during the second half of gestation, which may persist throughout life, as for most congenital thyroid disorders, or be transient, resolving in the first few weeks of life, as in autoimmune hyperthyroidism or hypothyroidism and some cases of congenital hypothyroidism (CH) with the thyroid gland in situ. Primary CH is diagnosed by neonatal screening, which has been implemented for 40 years in developed countries and should be introduced worldwide, as early treatment prevents irreversible neurodevelopmental delay.Central CH is a rarer entity occurring mostly in association with multiple pituitary hormone deficiencies. Other rare disorders impair the action of thyroid hormones. Neonatal Grave’s disease (GD) results from the passage of thyrotropin receptor antibodies (TRAb) across the placenta, from mother to fetus. It may affect the fetuses and neonates of mothers with a history of current or past GD, but hyperthyroidism develops only in those with high levels of stimulatory TRAb activity. The presence of antibodies predominantly blocking TSH receptors may result in transient hypothyroidism, possibly followed by neonatal hyperthyroidism, depending on the balance between the antibodies present. Antithyroid drugs taken by the mother cross the placenta, treating potential fetal hyperthyroidism,but they may also cause transient fetal and neonatal hypothyroidism. Early diagnosis and treatment are key to optimizing the child’s prognosis. This review focuses on the diagnosis and management of these patients during the fetal and neonatal periods. It includes the description of a case of fetal and neonatal autoimmune hyperthyroidism.

Hyperthyroidism in Pregnancy: The Delicate Balance between too Much or too Little Antithyroid Drug

Overt hyperthyroidism (HT) during pregnancy is associated with a risk of maternal–fetal complications. Antithyroid drugs (ATD) have a potential risk for teratogenic effects and fetal–neonatal hypothyroidism. This study evaluated ATD treatment and thyroid function control during pregnancy, and pregnancy outcome in women with HT. Patients and methods: A retrospective analysis of 36 single fetus pregnancies in 29 consecutive women (median age 30.3 ± 4.7 years) with HT diagnosed before or during pregnancy; a control group of 39 healthy euthyroid pregnant women was used. Results: Twenty-six women had Graves’ disease (GD, 33 pregnancies), 1 had a hyperfunctioning autonomous nodule, and 2 had gestational transient thyrotoxicosis (GTT). Methimazole (MMI) was administered in 22 pregnancies (78.5%), Propylthiouracil (PTU) in 2 (7.1%), switch from MMI to PTU in 4 (14.2%), no treatment in 8 pregnancies (3 with subclinical HT, 5 euthyroid with previous GD remission before conception). In the 8 pregnancies of GD patients diagnosed during gestation or shortly before (<6 weeks), i.e., with fetal exposure to uncontrolled HT, there was 1 spontaneous abortion at 5 weeks (3.4% of all ATD-treated pregnancies), and 1 premature delivery at 32 weeks with neonatal death in 24 h (3.4%); 1 child had neonatal hyperthyroidism (3.3% of live children in GD women) and a small atrial sept defect (4% of live children in ATD treated women). In women treated more than 6 months until conception (20 pregnancies): (a) median ATD doses were lower than those in women diagnosed shortly before or during pregnancy; (b) ATD was withdrawn in 40% of pregnancies in trimester (T)1, all on MMI < 10 mg/day (relapse in 14.2%), and in up to 55% in T3; (c) TSH level was below normal in 37%, 35% and 22% of pregnancies in T1, T2 and T3 respectively; FT4 was increased in 5.8% (T1) and subnormal in 11.75% in T2 and T3; (d) no fetal birth defects were recorded; one fetal death due to a true umbilical cord knot was registered. Mean birth weight was similar in both ATD-treated and control groups. Hyperthyroidism relapsed postpartum in 83% of GD patients (at median 3 ± 2.6 months). Conclusion: In hyperthyroid women with long-term ATD treatment before conception, drugs could be withdrawn in T1 in 40% of them, the thyroid function control was better, and pregnancy and fetal complications were rarer, compared to women diagnosed during pregnancy. Frequent serum TSH and FT4 monitoring is needed to maintain optimal thyroid function during pregnancy.

Clinico-epidemiological spectrum of thyroid illness after salt iodination program in Nepal

Background Thyroid disorder is an important endocrine disorder in Nepal which is mostly due to environmental deficiency of iodine. The earliest and potentially most damaging result of iodine deficiency is neonatal hypothyroidism and cretinism characterised by learning disabilities and poor motivation to achieve. Methods We selected one thousand known cases of thyroid disorders who visited biochemistry department of shree Birendra Hospital, chaunni for routine tests. A detailed history was obtained and free triiodothyronine (fT3), thyroxine (fT4) and thyroid stimulating hormone (TSH) estimation was done in Seimens CP Chemiluminiscence Immunoassay analyser. Result Puffiness of face, hoarseness of voice and weight gain were the presenting features in hypothyroid patients, whereas weight loss and restlessnes were predominant features in hyperthyroid patients. In our study the prevalence of hypothyroidism and hyperthyroidism was 27% and 12.5% respectively. Conclusion None of our patients had visible neck swellings or goiter which had subsided after salt iodination program in Nepal as environmental deficiency of iodine was the primary factor for development of goiter in Nepal.

Pathological changes and oxidative stress of the HPG axis in hypothyroid rat

Hypothyroidism is a common endocrine disease caused by a deficiency of thyroid hormones, which could affect the hypothalamus–pituitary–gonadal (HPG) axis and cause additional severe fertility problems. However, the pathogenesis of abnormal reproductive capacity caused by hypothyroidism and whether there are differences between females and males need more study. Here, we constructed a prolonged neonatal hypothyroid rat model using 6-propyl-2-thiouracil (PTU). H&E staining and RNA-sequencing were performed to detect histopathological and transcriptome changes. Our results indicated the numbers of ventromedial hypothalamus nuclei were increased, and the number of pituitary chromophobes was sharply increased, whereas the proportion of pituitary acidophils and pituitary basophils were obviously reduced. The differentially expressed genes of the HPG axis organs were identified, and different tissues shared similar steroid hormone and oxidative stress-related terms in gene ontology analysis. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis indicated oxidative stress and apoptosis-related genes were more enriched in male hypothyroid pituitaries, whereas the serum levels of growth hormone, follicle stimulating hormone, and luteinizing hormone that were detected by ELISA were also reduced more in male hypothyroid rats, suggesting that prolonged neonatal hypothyroidism may have a more significant impact on male pituitaries. Moreover, the multi-organ oxidative stress in hypothyroid rats was confirmed by the higher expression of oxidative stress-related genes such as the Txnip. The increased level of oxidative stress may have contributed to the histopathological and transcriptome changes of HPG axis organs in the prolonged neonatal hypothyroidism rats, especially in male pituitaries.

Pregnancy and Graves’ Disease

Graves’ disease (GD) is one of the most common autoimmune conditions in women of reproductive age. The disorder is characterized by the presence of pathogenic immunoglobulins that bind the TSH receptors (TRAbs) and stimulate the production of thyroid hormones leading to hyperthyroidism (the occurrence of inhibiting or neutral antibodies being rare). Affected individuals can be treated by radioiodine therapy, surgical removal of the gland or by antithyroid drugs (ATDs). Thyroid stimulating immunoglobulins may persist for years after medical treatment, radioiodine therapy or surgical removal of the gland in those affected by GD and during pregnancy can cross the placenta and can act on the fetal thyroid gland resulting in the development of fetal and neonatal hyperthyroidism and sometimes to goiter. Antithyroid drugs used during pregnancy can also cross the placenta and may be teratogenic and act on the fetal thyroid gland, leading to fetal and neonatal hypothyroidism and goiter. This chapter will discuss specific aspects of GD during pregnancy and postpartum focusing on fetal and neonatal consequences related to this disorder.

Neonatal thyroid screening a tertiary care experience at VSS Medical College and Hospital, Burla

Background: Congenital hypothyroidism is one of the most common preventable etiologies of mental retardation. The worldwide incidence of CH ranges from 1 in 3000 to 1 in 4000 live newborn. Objective of the study was to know the incidence of congenital hypothyroidism in this part of the country, which is necessary to understand the burden of congenital hypothyroidism to the society.Methods: Primary serum TSH measurement in screening neonates with backup thyroxine (T4) determination in infants with high TSH levels (>20 mIU/l). TSH and FT4 were estimated by chemi luminescence immunoassay (CLIA) method using reagent monobind, INC.Results: Serum TSH of screened neonates ranged between 0.16 mIU/l and 80.32 mIU/l, Mean±SD of sTSH being 5.80±3.96 mIU/l. Out of 2212 screened newborns, 9 newborns had sTSH value >20 mIU/l, who were recalled for confirmatory test, giving a recall rate of 0.4%. Out of 9 recalled newborns, 3 had persistently elevated sTSH >20 mIU/l making incidence of congenital hypothyroidism of 1:737 in our study.Conclusions: We found a higher incidence of 1:737 neonatal hypothyroidism in this region as compared to estimated national incidence. CH being preventable cause of mental retardation and other harmful effects on a growing newborn, neonatal screening programme for congenital hypothyroidism is highly recommended.

Armenia's experience in achieving an adequate iodine status of the population

Armenia was one of the first post-Soviet countries, that after a relatively short break has restored the production of iodized salt at the beginning of the 2000s, and in 2004 adopted a decree that made the production and import of iodized salt mandatory, as well as its use in the food industry. A 2016 national survey showed high sustainability of the iodine prophylaxis program in Armenia – median urinary iodine concentration (UIC) in schoolchildren and pregnant women (PW) was in the optimal range (242 and 226 μg/l, respectively), and coverage of households with quality iodized salt was 95%. In addition to iodized salt used in households, more than 50% of iodine was consumed with processed foods, primarily bakery products. An essential advantage of the iodine prophylaxis program in Armenia is that it provides adequate iodine status not only for the general population, but also for PW. At the same time about 37% of PW used iodine supplements, which were not necessary. The experience of Armenia shows that the analysis of screening datasets for neonatal hypothyroidism screening makes it possible to efficiently and at minimal cost annually evaluate the iodine status of the population. And if the frequency of TSH levels > 5 mIU/L exceeds 3%, the health authorities should consider this as an alarm and conduct a more detailed assessment to find out the cause of the iodine status insufficiency and take appropriate measures

Effect of Fetal and Neonatal Hypothyroidism on Glucose Tolerance in Middle-Aged Female Rats

Background and objective: The effects of hypothyroidism during pregnancy and lactation on carbohydrate metabolism have been mostly studied in male animals. The aim of this study is therefore to investigate effect of fetal and neonatal hypothyroidism (FH and NH) on the glucose tolerance in middle-aged female rat offspring. Methods: Pregnant female rats were divided into three groups: Rats in the control group consumed tap water, while those in the FH and NH groups consumed 250 mg/L of 6-propyl-2-thiouracil (PTU) in their drinking water during gestation or lactation periods, respectively. After weaning, the female offspring were separated and divided into 3 groups (n=8/group): Control, FH, and NH. Body weight was recorded monthly and intravenous glucose tolerance test (IVGTT) was performed at month 12. Results: Compared to controls, female rats in the FH group had significantly higher plasma glucose levels than controls throughout the IVGTT except at min 60. Values at min 5 of the FH and control group were 196.1±1.9 and 155.3±5.9 mg/dL, respectively (P<0.05). In the NH group, plasma glucose levels were significantly higher only at min 5 (185.7±14.1 vs. 155.3±5.9 mg/dL, P<0.05). Conclusion: Hypothyroidism during fetal or neonatal periods caused glucose intolerance in middle-aged female offspring rats.