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

CONTEXT

Resistance to thyroid hormone (RTH) β is due to mutations in the β-isoform of the thyroid hormone receptor (TR). TSH-secreting adenomas (TSHomas) are presumed to represent clonal expansion and have been reported to contain TRβ gene mutations. Mice with a knock-in mutation in the TRβ gene spontaneously develop TSHomas, although as yet no patient has been reported to have both a TSHoma and RTHβ.

OBJECTIVE

We investigated a 12-year-old girl with elevated serum T4 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 T3, 14.25 pmol/L (2.63-5.7 pmol/L); free T4, 28.79 pmol/L (9.01-19.05 pmol/L); serum glycoprotein hormone alpha-subunit (α-GSU), 0.32 ng/ml (0.22-0.39 ng/ml); and α-GSU/TSH, 0.15. Thyroid radioiodine uptake was increased by 94.4% at 24 hours. A T3 suppression test showed incomplete suppression of the serum TSH concentration and blunted response of the peripheral thyroid hormone markers. The sequence of TRβ exons confirmed a P453T mutation in the TRβ 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-β, human Chorionic Gonadotropin alpha (HCG-α), 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 RTHβ had a TSHoma consistent with previous findings linking somatic TRβ mutations to TSHomas.