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• Importance of long term thyroid function monitoring in central congenital hypothyroidism secondary to maternal thyrotoxicosis
  Lit Kim Chin, Mary White and Peter Simm
  Published on: 21 August 2019

• Published on: 21 August 2019

  Importance of long term thyroid function monitoring in central congenital hypothyroidism secondary to maternal thyrotoxicosis

  • Lit Kim Chin, Paediatrician The Royal Children's Hospital
  • Other Contributors:
    • Mary White, Paediatric Endocrinologist
    • Peter Simm, Paediatric Endocrinologist

  We wish to share our clinical experience and support the importance of long term monitoring of thyroid function in patients with central congenital hypothyroidism caused by maternal thyrotoxicosis. This is a case series of three infants with prolonged hypothyroxinaemia unrelated to the initial management of neonatal Graves’ disease (NGD). In contrast to the minimal antenatal care reported in the case report. mothers of all infants in our case series had antenatal diagnosis of Graves’ disease with appropriate management and close follow up for signs of fetal hyperthyroidism. All infants were diagnosed with NGD within two weeks of birth with two infants being commenced on antithyroid medication for 2-4 weeks as they were symptomatic with NGD.

  With resolution of NGD, thyroid function tests were monitored with subsequent hypothyroxinaemia noted between 4-8 weeks of age. Having confirmed persistent hypothyroxinaemia, all infants were commenced on thyroxine (4-10mcg/kg/day) with regular follow up of their thyroid function tests.

  The development of hypothyroxinaemia after initial treatment of NGD is uncommon however has been described previously (1). In most cases, NGD remits by 3-12 weeks once maternal antibodies are cleared (2, 3). Early transient hypothyroxinaemia in infants of poorly controlled maternal Graves’ is well reported due to high circulating antibodies particularly in the third trimester (1, 4). Postulated mechanisms include suppression of the pituita...

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  We wish to share our clinical experience and support the importance of long term monitoring of thyroid function in patients with central congenital hypothyroidism caused by maternal thyrotoxicosis. This is a case series of three infants with prolonged hypothyroxinaemia unrelated to the initial management of neonatal Graves’ disease (NGD). In contrast to the minimal antenatal care reported in the case report. mothers of all infants in our case series had antenatal diagnosis of Graves’ disease with appropriate management and close follow up for signs of fetal hyperthyroidism. All infants were diagnosed with NGD within two weeks of birth with two infants being commenced on antithyroid medication for 2-4 weeks as they were symptomatic with NGD.

  With resolution of NGD, thyroid function tests were monitored with subsequent hypothyroxinaemia noted between 4-8 weeks of age. Having confirmed persistent hypothyroxinaemia, all infants were commenced on thyroxine (4-10mcg/kg/day) with regular follow up of their thyroid function tests.

  The development of hypothyroxinaemia after initial treatment of NGD is uncommon however has been described previously (1). In most cases, NGD remits by 3-12 weeks once maternal antibodies are cleared (2, 3). Early transient hypothyroxinaemia in infants of poorly controlled maternal Graves’ is well reported due to high circulating antibodies particularly in the third trimester (1, 4). Postulated mechanisms include suppression of the pituitary-thyroid axis due to fetal hyperthyroxinaemia caused by transplacental transfer of thyroxine in untreated hyperthyroid mothers or of thyroid-stimulating immunoglobulin from the mother (4, 5). It is not surprising the longstanding effects of poorly controlled maternal Graves’ disease given the early effects on thyroid function, with TSH receptors becoming responsive to TSH and to TSH-receptor antibodies around 20 weeks (6) and the hypothalamic-pituitary-thyroid axis continues to mature from the second half of gestation until one to two months postnatal.

  The role of thyrotropin receptor antibodies has also been reported in the ‘switching’ between hypothyroidism to hyperthyroidism or vice versa. McLachlan et al described that varying concentration and affinities of thyroid stimulating versus blocking antibodies and immunological effect associated with the primary disease itself could contribute to ‘switching’ (7). Recovery of TSH levels tend to be delayed and has been reported to take up to 3-19 months in childhood Graves and up to 3¼ years in treated NGD (4).

  Hypothyroxinaemia post initial management of NGD is an uncommon entity in addition to the rare background occurrence of NGD, but requires early recognition so that appropriate treatment may be instigated. There are known risk factors that predict the development of NGD but from this case series, there were no obvious factors that suggested the subsequent development of hypothyroxinaemia. It raises the importance of frequent clinical monitoring of growth and development supported by ongoing screening of TFTs in NGD.

  References
  1. Papendieck P, Chiesa A, Prieto L, Gruneiro-Papendieck L. Thyroid disorders of neonates born to mothers with Graves' disease. J Pediatr Endocrinol Metab. 2009;22(6):547-53.
  2. Levy-Shraga Y, Tamir-Hostovsky L, Boyko V, Lerner-Geva L, Pinhas-Hamiel O. Follow-up of newborns of mothers with Graves' disease. Thyroid : official journal of the American Thyroid Association. 2014;24(6):1032-9.
  3. Kamishlian A, Matthews N, Gupta A, Filipov P, Maclaren N, Anhalt H, et al. Different outcomes of neonatal thyroid function after Graves' disease in pregnancy: patient reports and literature review. J Pediatr Endocrinol Metab. 2005;18(12):1357-63.
  4. Matsuura N, Harada S, Ohyama Y, Shibayama K, Fukushi M, Ishikawa N, et al. The mechanisms of transient hypothyroxinemia in infants born to mothers with Graves' disease. Pediatric research. 1997;42(2):214-8.
  5. Higuchi R, Kumagai T, Kobayashi M, Minami T, Koyama H, Ishii Y. Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease. Pediatrics. 2001;107(4):E57.
  6. Polak M, Le Gac I, Vuillard E, Guibourdenche J, Leger J, Toubert ME, et al. Fetal and neonatal thyroid function in relation to maternal Graves' disease. Best practice & research Clinical endocrinology & metabolism. 2004;18(2):289-302.
  7. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid : official journal of the American Thyroid Association. 2013;23(1):14-24.

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  Conflict of Interest:
  None declared.

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