TY - JOUR
T1 - Persistent neonatal thyrotoxicosis in a neonate secondary to a rare thyroid-stimulating hormone receptor activating mutation
T2 - Case report and literature review
AU - Watkins, Mark G.
AU - Dejkhamron, Prapai
AU - Huo, Jeffrey
AU - Vazquez, Delia M.
AU - Menon, Ram K.
PY - 2008
Y1 - 2008
N2 - Objective: To report the case of a neonate presenting with nonautoimmune thyrotoxicosis and failure to thrive in whom an activating TSHR mutation was suspected. Methods: We describe the clinical and laboratory findings in a neonate who presented with nonautoimmune thyrotoxicosis and failure to thrive, including results of DNA analysis of TSHR, which encodes the thyroid-stimulating hormone receptor (TSHR). Relevant literature is also reviewed. Results: The proband was born spontaneously at 35 weeks' gestation, and his early neonatal period was remarkable for meconium aspiration, pneumothorax, hepatomegaly with associated elevated transaminases, and direct hyperbilirubinemia. On days 9 and 11 of life, thyroid function studies revealed hyperthyroidism, which remained persistent on day 26 of life. On day 44 of life, the infant was admitted to the hospital. The mother reported he had an increased activity level, disturbed sleep, jitteriness, and exaggerated startle response. Weight was at the third percentile. After additional workup, Lugol's iodine solution, propanolol, and propylthiouracil were prescribed, which led to improvement in thyroid function. No TSHR antibodies were detected in the mother's or patient's sera. Analysis of the patient's DNA revealed a heterozygous T-to-C substitution at amino acid 568 in exon 10 (Ile568Thr), which predicts an isoleucine to threonine conversion in the second extracellular loop of TSHR. The mutation was not identified in the parents' DNA. Conclusions: A mutation causing constitutive activation of TSHR was confirmed in this patient, a finding that has implications for genetic counseling and consideration of total thyroidectomy or long-term thionamide therapy followed by radioiodide ablation as treatment options. Although rare, TSHR mutations should be considered in an infant presenting with thyrotoxicosis in absence of demonstrable TSHR antibodies in serum.
AB - Objective: To report the case of a neonate presenting with nonautoimmune thyrotoxicosis and failure to thrive in whom an activating TSHR mutation was suspected. Methods: We describe the clinical and laboratory findings in a neonate who presented with nonautoimmune thyrotoxicosis and failure to thrive, including results of DNA analysis of TSHR, which encodes the thyroid-stimulating hormone receptor (TSHR). Relevant literature is also reviewed. Results: The proband was born spontaneously at 35 weeks' gestation, and his early neonatal period was remarkable for meconium aspiration, pneumothorax, hepatomegaly with associated elevated transaminases, and direct hyperbilirubinemia. On days 9 and 11 of life, thyroid function studies revealed hyperthyroidism, which remained persistent on day 26 of life. On day 44 of life, the infant was admitted to the hospital. The mother reported he had an increased activity level, disturbed sleep, jitteriness, and exaggerated startle response. Weight was at the third percentile. After additional workup, Lugol's iodine solution, propanolol, and propylthiouracil were prescribed, which led to improvement in thyroid function. No TSHR antibodies were detected in the mother's or patient's sera. Analysis of the patient's DNA revealed a heterozygous T-to-C substitution at amino acid 568 in exon 10 (Ile568Thr), which predicts an isoleucine to threonine conversion in the second extracellular loop of TSHR. The mutation was not identified in the parents' DNA. Conclusions: A mutation causing constitutive activation of TSHR was confirmed in this patient, a finding that has implications for genetic counseling and consideration of total thyroidectomy or long-term thionamide therapy followed by radioiodide ablation as treatment options. Although rare, TSHR mutations should be considered in an infant presenting with thyrotoxicosis in absence of demonstrable TSHR antibodies in serum.
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U2 - 10.4158/EP.14.4.479
DO - 10.4158/EP.14.4.479
M3 - Article
C2 - 18558604
AN - SCOPUS:58149375164
SN - 1530-891X
VL - 14
SP - 479
EP - 483
JO - Endocrine Practice
JF - Endocrine Practice
IS - 4
ER -