Prevalence and course of thyroid dysfunction in neonates at high risk of Graves' disease or with non-autoimmune hyperthyroidism

Eur J Endocrinol. 2021 Mar;184(3):427-436. doi: 10.1530/EJE-20-1320.

Abstract

Objective: Neonatal hyperthyroidism may be caused by a permanent non-autoimmune genetic disorder or, more frequently, by maternally transmitted high serum TRAb levels. Variable thyroid dysfunction may be observed in this second context. We aimed to evaluate the prevalence of neonatal non-autoimmune hyperthyroidism and of the different types of thyroid function in neonates with a high risk of hyperthyroidism due to maternal Graves' disease (GD).

Design and methods: This observational cohort study included all neonates identified in the database of a single academic pediatric care center, over a period of 13 years, as having non-autoimmune hyperthyroidism or an autoimmune disorder with high TRAb levels (above 6 IU/L) transmitted by their mothers. Patients were classified as having neonatal hyperthyroidism, hypothyroidism, or euthyroidism with a permanent or transient disorder.

Results: Two of the 34 consecutive neonates selected (6%) had permanent non-autoimmune hyperthyroidism due to germline (n = 1) or somatic (n = 1) mutations of the TSH receptor gene. The patients with high serum TRAb levels at birth had transient hyperthyroidism (n = 23), hypothyroidism (primary n = 2, central n = 3) or persistent euthyroidism (n = 4).

Conclusion: These original findings highlight the need for careful and appropriate monitoring of thyroid function in the long term, not only for the rare patients with non-autoimmune neonatal hyperthyroidism, but also for repeat monitoring during the first month of life in neonates with maternally transmitted high TRAb levels, to ensure the early identification of thyrotoxicosis in more than two thirds of cases and to detect primary or central hypothyroidism, thereby potentially decreasing associated morbidity.

Publication types

  • Observational Study

MeSH terms

  • Cohort Studies
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Graves Disease / diagnosis
  • Graves Disease / epidemiology
  • Graves Disease / etiology*
  • Graves Disease / genetics
  • Humans
  • Hyperthyroidism / congenital*
  • Hyperthyroidism / diagnosis
  • Hyperthyroidism / epidemiology*
  • Hyperthyroidism / genetics
  • Infant
  • Infant, Newborn
  • Infant, Newborn, Diseases / diagnosis
  • Infant, Newborn, Diseases / epidemiology
  • Infant, Newborn, Diseases / genetics
  • Infant, Newborn, Diseases / pathology
  • Male
  • Maternal Inheritance
  • Neonatal Screening
  • Pregnancy
  • Pregnancy Complications / diagnosis
  • Pregnancy Complications / epidemiology
  • Pregnancy Complications / genetics
  • Pregnancy Complications / pathology
  • Prevalence
  • Prognosis
  • Risk Factors
  • Thyroid Diseases / congenital*
  • Thyroid Diseases / diagnosis
  • Thyroid Diseases / epidemiology*
  • Thyroid Diseases / genetics
  • Thyroid Function Tests