This publication reports a rare and counterintuitive case of neonatal hyperthyroidism: mother has underactive thyroid, while the unborn baby has an overactive one. Although the mother has hypothyroidism from hashimoto's thyroiditis, she produces TSI (thyroid stimulating immunoglobulin) triggering excessive thyroid hormone formation by the fetus.
Paradoxically the mother was treated with both medications; levothyroxine for her hypothyroidism and methimazole for her fetus’ hyperthyroidism.
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Context: Fetal/neonatal thyrotoxicosis is a rare but potentially life-threatening condition. It is most commonly observed in poorly controlled Graves disease during pregnancy.
Case Description: Here we describe a fetus/newborn patient with thyrotoxicosis who was born of a mother with Hashimoto thyroiditis and levothyroxine-treated hypothyroidism. Transplacental passage of thyroid stimulating immunoglobulin (TSI), which were measured by a cell-based bioassay, was the underlying mechanism of fetal/neonatal thyrotoxicosis, although the mother had no history of hyperthyroidism.
Conclusion: Diagnosis and management of fetal hyperthyroidism can be challenging. TSI testing should be considered in pregnant women with any history of autoimmune thyroid disease and symptoms of fetal hyperthyroidism.
More information from the article:
A 31-year-old woman in gestational week 24 with Hashimoto's autoimmune thyroiditis who had been treated for hypothyroidism since the age of 18 years was referred to the Thyroid Outpatient Clinic at the Medical University of Vienna. She presented with fetal tachycardia (>180 bpm) but otherwise exhibited normal fetal vital signs and regular fetal growth curves. During her previous pregnancy she had experienced an episode of fetal tachycardia in gestational week 35 that had not been followed up. Her current medication was levothyroxine 125 mcg/d. She had always been in good health and had no history of nicotine use, alcohol use, or other substance abuse. Thyroid hormone testing revealed slight levothyroxine overtreatment with a baseline TSH 0.09 mU/L (reference range, 0.10 - 2.50 mU/L for that pregnancy period) and with both fT4 and fT3 levels in the normal range.
TPO and Tg Abs were substantially elevated, >600 U/mL and 788 U/mL, respectively, consistent with autoimmune thyroiditis. TSH receptor antibodies (TSH-R-Abs) were markedly increased (>40 U/L), although the patient had never suffered from hyperthyroidism. These findings suggested the unique constellation of TSH-R-Ab–induced fetal hyperthyroidism in a mother with levothyroxine-substituted hypothyroidism.
Hence, treatment with methimazole in addition to levothyroxine was begun, which normalized the fetal heart rate within 1 week. Weekly follow-ups were scheduled at both the Thyroid Outpatient Clinic and the Maternity Outpatient Clinic for high-risk pregnancies. Frequent ultrasound examinations and 2 fetal magnetic resonance imaging (MRI) scans revealed fetal goiter but otherwise regular organ development and normal growth. The fetal thyroid gland volume was 2 mL in gestational week 23 and 2.5 mL in gestational week 33 as determined by planimetric analyses from T1-weighted MRI sequences. Hence, the fetal thyroid gland was substantially enlarged compared with age-matched controls.
The most likely reason that the mother had never developed hyperthyroidism is that TSAb failed to stimulate thyroid hormone production in her thyroid gland because of chronic autoimmune-induced damage. To our knowledge, this is the first reported case of TSAb-mediated thyrotoxicosis in a fetus/newborn from a mother with levothyroxine-treated Hashimoto thyroiditis and no history of hyperthyroidism.
This case emphasizes several important aspects in the management of pregnant women with a history of thyroid disease. In general, fetal hyperthyroidism is a rare but potentially life-threatening condition, as illustrated here. It most commonly occurs in pregnant women with poorly controlled Graves disease.
Randomized controlled studies are lacking, and clinical guidelines are therefore very limited. Current guidelines recommend TSH-R-Ab testing during pregnancy only in women with a history of Graves disease. Our case emphasizes that TSH-R-Ab testing should also be considered in pregnant women with any history of autoimmune thyroid disease and symptoms of fetal hyperthyroidism (such as fetal tachycardia and/or fetal goiter).
This case also highlights the complexity of the management of fetal hyperthyroidism, particularly in the absence of a direct readout of fetal thyroid function. This case also suggests that elective preterm Cesarean section should be considered in patients with fetal hyperthyroidism because of the significantly increased risk for complications in the final phase of pregnancy.