Thyroid-Stimulating Hormone (TSH)-Secreting Pituitary Tumor Misdiagnosed for 20 Years: Possible Effect of Long-Term Treatment With Thyroid Hormone

Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas (TSHomas) are rare causes of central hyperthyroidism. Misdiagnosis may lead to prolonged inappropriate thyroid hormone therapy. I present a 65-year-old woman who was treated with high-dose levothyroxine for 20 years for presumed primary hypothyroidism despite persistently elevated TSH with normal to high free T4 and T3 levels. Central hyperthyroidism was not considered. A 9-11 mm pituitary lesion remained stable for two decades. Biochemical evaluation revealed an elevated alpha-subunit with negative heterophile antibodies, confirming a TSHoma. She underwent transsphenoidal resection; pathology confirmed a plurihormonal PIT-1-positive adenoma. This case challenges the traditional view that TSHomas are uniformly resistant to thyroid hormone feedback. The tumor's long-term radiographic stability during supraphysiologic levothyroxine therapy raises the possibility of partial feedback sensitivity. The absence of measurable growth over two decades could be supportive of this hypothesis. Discordant thyroid function tests should prompt evaluation for central hyperthyroidism. Biological heterogeneity among TSHomas may influence tumor behavior and therapeutic responsiveness.