Hydrops Fetalis Secondary to Maternal Exposure to Propylthiouracil

Abstract

Turkish Abstract

Introduction

Thyroid hormones are essential for fetal neurological development ¹. Fetal hypothyroidism may result from maternal exposure to anti-thyroid drugs (ATD) ². Intra-amniotic treatment with levothyroxine normalizes fetal thyroid functions and reduces size of goiter. Fetal hypothyroidism is an uncommon condition in the etiology of hydropsfetalis. Maternal exposure to ATD may additionally lead to congenital anomalies of musculoskeletal system and urogenital system. Herein, we present a pregnant woman with hydropsfetalis secondary to maternal exposure to high-dose propylthiouracil.

Case Report

A 20-year-old primigravida consults her physician for routine control in the 12^thweek of first gestation. Meanwhile, she mentions about sweatcomplaint existing for the last one year. Results of laboratory analyses performed accordingly were as follows: free T3:3.76 (2.5-3.9) pg/ml, free T4:1.18 (0.61-1.12) ng/dl,and TSH:0.42 (0.34-5.6) ?IU/ml. The patient had been told that she had no pregnancy-related problem but had hypothyroidism. Propylthiouracyl (PTU) 100 mg/day had been commenced and she had been asked to come for control visit after one month. On the control visit after one month, she had been informed that there was no problem regarding pregnancy, but the dose of PTU had been increased to 150 mg/day since fT3 was 3.4 (2.3-4.2) pg/ml, fT4 was 1.29 (0.88-1.72) ng/dl, and TSH was 0.13 (0.57-5.6) ?IU/ml, and she had been invited for control again after one month. On that control visit, again she had has no pregnancy-related problem, but the dose of PTU had been increased to 300 mg/day since fT3 was 3.32 (2.3-4.2) pg/ml, fT4 was 1.02 (0.88-1.72) ng/dl, and TSH was 0.53 (0.57-5.6) ?IU/ml. On the control visit again after one month, results of thyroid function test were as follows: fT3:2.64 pg/ml (2.3-4.2), fT4:0.98 (0.88-1.72) ng/dl, and TSH: 1.77 (0.57-5.6) ?IU/ml. However, US revealed hydropsfetalis, and the patient has been referred to our policlinic (Figure 1).

Figure 1 Propilthiouracil after fetal hydrops ultrasonografi appearance

We discontinued PTU; Anti-TG, Anti-TPO, and Thyroid receptor antibodies were found negative and the patients called for control after 15 days. On her control visit, fT3 was 2.81 (2.3-4.2) pg/ml, fT4 was 0.82 (0.88-1.72) ng/dl, and TSH was 1.65 (0.57-5.6) ?IU/ml; control US revealed regression of fetal hydrops (Figure 2).

Figure 2 Revealed regression of fetal hydrops

A normal-birth-weight (3150 gr) female infant born  (a cesarean section was performed) at 37+2 weeks?gestational age. A euthyroid, non-edematous, non-goitrous neonate was delivered and newborn?s psychomotor development was normal.

Discussion

Pregnancy is a time of complex hormonal changes. In women with normal thyroid function, there is an increase in thyroxine (T₄) and triiodothyronine (T₃) production, which results in inhibition of thyroid-stimulating hormone (TSH) in the first trimester of pregnancy, due to a high human chorionic gonadotropin (hCG) level that stimulates the TSH receptor because of partial structural similarity³. Clinical or subclinical thyroid disorders are usually detected during pre-conceptional counseling or in women who have just conceived and have done tests for thyroid function. According to recent American Thyroid Association (ATA) guidelines, if laboratory-dependent, trimester-specific ranges for TSH are not available, the recommended reference ranges for TSH are 0.1 to 2.5 mIU/L in the first trimester, 0.2 to 3.0 mIU/L in the second trimester, and 0.3 to 3.0 mIU/L in the third trimester. Medical therapy of hyperthyroidism in Grave?s disease is limited to two antithyroid drugs (ATD)s, namely PTU and methimazole (MMI). PTU is believed to be somewhat safer for pregnant women than MMI⁴. In the literature, neonatal anomalies due to maternal exposure to ATD are quite common. Maternal side effects of ATDs include toxic reactions such as fever, nausea, pruritus, skin rash and arthralgia and metallic taste and serious complications such as granulocytopenia, agranulocytosis, vasculitis, lupus-like syndrome and hepatitis⁵. ATDs may affect the fetus also. In addition to fetal hypothyroidism and the development of fetal goiter, the use of PTU and MMI has been reported to be associated with congenital anomalies including muscular hypotonicity, cryptorchidism, aortic atresia, hypospadias, congenital dislocation of the hip, aplasia cutis congenita, choanal atresia and syndactyly. However, no effect on long-term cognitive or somatic development has been found in infants exposed in utero to ATDs⁶. The treatment of fetal hypothyroidism involves normalizing maternal thyroid functions, discontinuation of ATDs, as well as possible direct intra-amniotic treatment with thyroid hormone. It is unclear whether intra-amniotic fetal treatment for hypothyroidism is necessary in a euthyroid mother. In most instances, maternal T4 transfer through the placenta will provide for the needs of the fetus⁷. Herein we presented a case, in whichfetal hydrops has been developed secondary to maternal exposure to high-dose PTU. But, intra-amniotic fetal treatment for hypothyroidism is not necessary for our patient.  A euthyroid, non-edematous, non-goitrous neonate was delivered and newborn?s psychomotor development was normal. However, fetal hydrops secondary to hypothyroidism caused by maternal exposure to ATD is a quite rare condition. Non-immune hydrops has been described previously in a neonate with congenital hypothyroidism delivered to a healthy mother^8.

Gestational thyrotoxicosis is known to cause thyroid dysfunction. Such changes during pregnancy should be well-known and be intervened accurately. Therefore, these patients should certainly be consulted with endocrinologists. 

References

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Information Presentation

36. Türkiye Endokrinoloji ve Metabolizma Hastalıkları Kongresi