Endocrine Abstracts

Graves’ disease is the most common cause of autoimmune hyperthyroidism in pregnancy accounting for 0.1 to 1% (0.4% clinical and 0.6% subclinical) of all pregnancies. It may be diagnosed for the first time in pregnancy, may present as a recurrent episode in a woman with past history of hyperthyroidism, or in a women on antithyroid drugs (ATD). Less common non autoimmune causes include multinodular goiter, toxic adenoma, and factitious hyperthyroidism. More frequent than Graves’ disease as the cause of hyperthyroidism is the syndrome of gestational hyperthyroidism defined as ‘transient hyperthyroidism, limited to the first half of pregnancy characterized by elevated FT₄ or adjusted TT₄ and suppressed or undetectable serum TSH, in the absence of serum markers of thyroid autoimmunity’.

Poor control of thyrotoxicosis is associated with miscarriages, PIH, prematurity, low birth weight, intrauterine growth restriction, stillbirth, thyroid storm and maternal congestive heart failure. Antithyroid drugs are the mainstay of treatment for hyperthyroidism during pregnancy. Side effects occur in a 3–5%, of patients taking thionamide drugs, mostly allergic reactions such as skin rash. The greatest concern in the use of ATD in pregnancy is related to teratogenic effects. Exposure to MMI may produce several congenital malformations, mainly aplasia cutis and the syndrome of ‘methimazole embryopathy’ that includes choanal or esophageal atresia, and dysmorphic faces. Although very rare complications, they have not been reported with the use of PTU. Report from the Adverse Event Reporting System of the Food and Drug Administration (FDA) has called attention to the risk of hepatotoxicity in patients exposed to PTU and an advisory committee recommended to limit the use of PTU to the first trimester of pregnancy. Hepatotoxicity may occur at any time during PTU treatment, without warning; however it may be appropriate to monitor liver function tests regularly while PTU is administered. In women with hyperthyroidism due to Graves’ disease or a toxic nodule goiter, ATDs are initiated, or adjusted in those women on treatment, at conception. PTU is preferred in the first trimester. Following the first trimester, PTU should be switched to methimazole.

The combination of ATD plus levothyroxine is not recommended in the management of hyperthyroidism in pregnancy. Adrenergic β blocking agents, such as propranolol 20–40 mg every 6–8 h may be used for controlling hyper-metabolic symptoms. In the vast majority of cases the drug could be discontinued in 2 to 6 weeks. Long term treatment with propranolol has been associated with intrauterine growth restriction, fetal bradycardia and neonatal hypoglycemia. Thyroidectomy should be considered in cases of allergies to both ATDs, women requiring large doses of ATDs and the occasional patient who is not adherent to drug therapy. If surgery is indicated, second trimester is the optimal time. A determination of serum TRAb titers is mandatory at the time of surgery in order to assess the potential risk of fetal hyperthyroidism. Preparation with β-blocking agents and a short course of potassium iodine solution (50–100 mg a day) are recommended.