Coexistence of Resistance to Thyroid Hormone and a Thyroid Stimulating Hormone-Secreting Pituitary Adenoma

Central hyperthyroidism, characterized by elevated thyroid hormone levels with a nonsuppressed thyroid-stimulating hormone (TSH), presents a diagnostic challenge in distinguishing thyroid hormone resistance (RTH) from a TSH-secreting pituitary adenoma (TSHoma).

We report a 56-year-old man with a history of atrial fibrillation, obesity, and obstructive sleep apnea who was referred to our center with a prior diagnosis of RTH made elsewhere. Laboratory testing revealed elevated free T4 (2.2 ng/dL) and total T3 (234 ng/dL) with an inappropriately normal TSH (3.1 μIU/mL). Thyrotropin receptor antibody was negative, and radioactive iodine uptake was diffusely elevated. Pituitary magnetic resonance imaging demonstrated a 6 × 9 × 9 mm pituitary microadenoma, initially raising suspicion for TSHoma. However, a preserved TSH response to thyrotropin-releasing hormone stimulation, partial TSH suppression with high-dose T3, normal TSH α-subunit and sex hormone-binding globulin levels, and a pathogenic thyroid hormone receptor beta gene mutation all supported the diagnosis of RTH. Despite these findings, the patient underwent transsphenoidal pituitary surgery, and histopathology confirmed a plurihormonal PIT-1 lineage adenoma positive for TSH, growth hormone, and prolactin. Postoperatively, the patient recovered well and was discharged home.

With postoperative normalization of TSH and free T4, it is conceivable that the pituitary tumor contributed to the TSH elevation, suggesting the possibility of dual pathology-concomitant TSHoma and RTH.

This case highlights the diagnostic dilemmas and overlapping features of RTH and TSHoma, emphasizing the need for comprehensive hormonal testing and genetic confirmation to avoid unnecessary surgery.