A Patient With a Thyrotropin-Secreting Microadenoma and Resistance to Thyroid Hormone (P453T)

Context: Resistance to thyroid hormone (RTH) beta is due to mutations in the beta-isoform of the thyroid hormone receptor (TR). TSH-secreting adenomas (TSHomas) are presumed to represent clonal expansion and have been reported to contain TR beta gene mutations. Mice with a knock-in mutation in the TR beta gene spontaneously develop TSHomas, although as yet no patient has been reported to have both a TSHoma and RTH beta. Objective: We investigated a 12-year-old girl with elevated serum T-4 concentration, inappropriately high TSH levels, and a pituitary adenoma. Design and Intervention: Clinical, biochemical, and radiological assessments were performed at baseline and after a transsphenoidal pituitary adenomectomy. Results: The patient's laboratory results included: TSH, 21.12 mIU/L (0.35-4.94 mIU/L); free T-3, 14.25 pmol/L (2.63-5.7 pmol/L); free T-4, 28.79 pmol/L (9.01-19.05 pmol/L); serum glycoprotein hormone alpha-subunit (alpha-GSU), 0.32 ng/ml (0.22-0.39 ng/ml); and alpha-GSU/TSH, 0.15. Thyroid radioiodine uptake was increased by 94.4% at 24 hours. A T-3 suppression test showed incomplete suppression of the serum TSH concentration and blunted response of the peripheral thyroid hormone markers. The sequence of TR beta exons confirmed a P453T mutation in the TR beta gene. Pituitary magnetic resonance imaging revealed a microadenoma in the left side of the pituitary. The patient underwent transsphenoidal pituitary adenomectomy. Histologically, the tumor stained positively for TSH-beta, human Chorionic Gonadotropin alpha (HCG-alpha), GH, prolactin, and ACTH. After removal of the tumor, the patient's thyroid function improved significantly, and she experienced the onset of menarche and an increase in linear growth as well. Conclusions: This patient with RTH beta had a TSHoma consistent with previous findings linking somatic TR beta mutations to TSHomas.