|Year : 2018 | Volume
| Issue : 2 | Page : 96-98
Fluctuating thyroid function in an infant born to mother with Graves' disease: To treat or not to treat
Subhodip Pramanik, Sujoy Ghosh, Rana Bhattacharjee
Department of Endocrinology, IPGMER, Kolkata, West Bengal, India
|Date of Web Publication||17-Jul-2018|
257, F. G Street, Telinipara, Bhadreswar, Hooghly - 712 125, West Bengal
Source of Support: None, Conflict of Interest: None
Graves' disease (GD) in pregnancy is common, and management is often challenging during pregnancy and postpartum. Antithyroid drugs (ATDs) cross the placenta and inhibit fetal thyroid hormone production, whereas anti-thyrotropin receptor antibody (TRAb) cross the placenta and stimulate thyroid hormone production and last longer than ATDs in neonate's circulation (3–12 weeks vs. 7–10 days). The resultant clinical presentation, therefore, depends on the age of the child and the balance between the opposing effect of ATD and TRAb. We present a case of an infant born to a mother with active GD, on ATD treatment who presented with diagnostic and therapeutic dilemma. We performed masterly inactivity as his thyrotropin levels sequentially changed from elevated at birth to suppressed at 1 month age to stable after 3 months onward. Knowledge of natural history and pathogenesis of alteration of thyroid function test in an infant born to mothers of GD on carbimazole are essential for appropriate management.
Keywords: Graves' in pregnancy, neonatal central hypothyroidism, thyroid receptor antibody
|How to cite this article:|
Pramanik S, Ghosh S, Bhattacharjee R. Fluctuating thyroid function in an infant born to mother with Graves' disease: To treat or not to treat. Thyroid Res Pract 2018;15:96-8
|How to cite this URL:|
Pramanik S, Ghosh S, Bhattacharjee R. Fluctuating thyroid function in an infant born to mother with Graves' disease: To treat or not to treat. Thyroid Res Pract [serial online] 2018 [cited 2019 Sep 18];15:96-8. Available from: http://www.thetrp.net/text.asp?2018/15/2/96/236708
| Introduction|| |
Graves' disease (GD) complicates about 0.2% of all pregnancies, and 1%–5% of infants born to women suffering from GD suffer from neonatal hyperthyroidism. It usually manifests as hyperthyroidism within 1 week of birth. However, infants of mothers taking antithyroid drug (ATD) may have variable thyroid function test (TFT) results. We present a case of an infant born to a mother with active GD, on ATD treatment who presented with diagnostic and therapeutic dilemma.
| Case Report|| |
A 25-year-old primigravida was referred to an endocrinologist at 34 weeks of gestation as she had a history of GD predating 2 years and was on medical therapy (carbimazole 30 mg/days). In the early part of pregnancy, she was treated by the obstetrician and frequently underwent TFT and appropriate dose adjustment. The patient was referred for management of gestational diabetes mellitus for which insulin was started and was adjusted according to self-monitoring of blood glucose. Clinically, she was euthyroid with pulse rate 88/min, no tremor, grade Ib goiter, and no active ophthalmopathy, and she gained 10 kg weight in current pregnancy.
Thyrotropin receptor antibody (anti-TSH-R antibody/TRAb) done at 34 weeks was 15.77 IU/L (normal <1.75). Ultrasonography did not reveal any fetal goiter. She went into labor within 2 days after this report (normal delivery female child at 36 weeks, birth weight 3.2 kg). The baby underwent serial TFTs, and the results with reference ranges are provided in [Table 1]. We closely followed up the child without any active intervention as the TSH reports were raised from 39.6 mIU/L in cord blood to 71.5 mIU/L at day 3 and decreased to <0.004 mIU/L at 1 month. However at 3 months, she became euthyroid. Her TFT at that time revealed TSH 2.26 mIU/L, free thyroxine (FT4) 1.01 ng/dl, and repeat values at month 4 and 6 were almost similar.
|Table 1: Sequential thyroid function tests performed in a child born to a mother with active Graves’ disease (child’s date of birth - December 7, 2015)|
Click here to view
| Discussion|| |
ATDs are known to cross the placenta and inhibit fetal thyroid hormone production. Carbimazole has a half-life of approximately 5 h and is completely excreted in 7–10 days. Therefore, at birth, the child may be hypothyroid due to the effect of ATD, which gradually wanes off in a week or two. Maternal TRAb (stimulatory) can also cross the placenta and may act on fetal thyroid, producing hyperthyroidism. TRAb is cleared from fetal circulation in 3–12 weeks. The resultant clinical presentation, therefore, depends on the age of the child and the balance between the opposing effect of ATD and TRAb. Gradually, by the end of the 1st month or so, euthyroidism is restored in the fetus.
Transient neonatal hyperthyroidism is not uncommon in the setting of active maternal GD. It can also occur in mothers of GD previously treated with radioactive iodine and/or surgery. It results from transplacental passage of stimulatory TRAb. Hence, high maternal TRAb (>five times upper normal limit) in the third trimester is a risk factor for development of this disease. This was illustrated in a study of 29 pregnant women with a history of GD that confirmed the relationship of high TSHR-Ab and neonatal thyrotoxicosis. In the 35 live births, there were six cases of neonatal GD, all of whom had a TSHR-Ab level above 500% of normal. Ultrasonographic monitoring of fetus is recommended for fetal goiter, heart rate, and appearance of femoral epiphysis. Fetal goiter, however, can be a manifestation of both fetal hyperthyroid and hypothyroid state, although the goiter due to thyrotoxicosis usually has increased central vascularization. Immediate treatment with carbimazole and propranolol should be done to prevent possible adverse effect on central nervous system  and future development of central hypothyroidism.
Carbimazole is widely used for the management of GD worldwide, and its use can alter the presentation of neonatal Graves' altogether. In our case, this child presented with high TSH, which can be confused with congenital hypothyroidism. Despite the fact that we clinched the diagnosis in this case, there was therapeutic dilemma as to whether to start levothyroxine. In a large study  of 96 neonates born to mothers with GD, most had a “subclinical” course with high serum-free T4 levels peaking at 5 days of age; after 14 days of age, free T4 levels normalized, although serum TSH remained suppressed for up to 3 months. Similarly, in our case after initial hypothyroid phase, there is a very rapid shift to hyperthyroid state to euthyroidism; thus treating with levothyroxine is not only unnecessary but also may be harmful. Treatment with carbimazole was not started at 1 month age, as hyperthyroid state wanes off in 1–3 months after birth, thus avoiding unnecessary treatment. Our report thus underscores the importance of masterly inactivity in such situation which is commonly faced by physicians and pediatricians in day-to-day practice.
| Conclusion|| |
Fluctuating TFT results are not uncommon in infants born to mothers with GD. The clinical presentation depends on the age of the child and the balance between the opposing effect of ATD and TRAb. Close follow-up with no active intervention is a sensible treatment option in such cases.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, et al.
Management of thyroid dysfunction during pregnancy and postpartum: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2012;97:2543-65.
Levy-Shraga Y, Tamir-Hostovsky L, Boyko V, Lerner-Geva L, Pinhas-Hamiel O. Follow-up of newborns of mothers with Graves' disease. Thyroid 2014;24:1032.
Zakarija M, McKenzie JM, Hoffman WH. Prediction and therapy of intrauterine and late-onset neonatal hyperthyroidism. J Clin Endocrinol Metab 1986;62:368-71.
Sunshine P, Kusumoto H, Kriss JP. Survival time of circulating long-acting thyroid stimulator in neonatal thyrotoxicosis: Implications for diagnosis and therapy of the disorder. Pediatrics 1965;36:869-76.
Volpé R, Ehrlich R, Steiner G, Row VV. Graves' disease in pregnancy years after hypothyroidism with recurrent passive-transfer neonatal Graves' disease in offspring. Therapeutic considerations. Am J Med 1984;77:572-8.
Zakarija M, McKenzie JM. Pregnancy-associated changes in the thyroid-stimulating antibody of Graves' disease and the relationship to neonatal hyperthyroidism. J Clin Endocrinol Metab 1983;57:1036-40.
Huel C, Guibourdenche J, Vuillard E, Ouahba J, Piketty M, Oury JF, et al.
Use of ultrasound to distinguish between fetal hyperthyroidism and hypothyroidism on discovery of a goiter. Ultrasound Obstet Gynecol 2009;33:412-20.
Daneman D, Howard NJ. Neonatal thyrotoxicosis: Intellectual impairment and craniosynostosis in later years. J Pediatr 1980;97:257-9.
Mandel SH, Hanna CE, LaFranchi SH. Diminished thyroid-stimulating hormone secretion associated with neonatal thyrotoxicosis. J Pediatr 1986;109:662-5.
Levy-Shraga Y, Tamir-Hostovsky L, Boyko V, Lerner-Geva L, Pinhas-Hamiel O. Follow-up of newborns of mothers with Graves' disease. Thyroid 2014;24:1032-9.