Background: TSH-secreting pituitary adenomas (TSHomas) are rare causes of central hyperthyroidism and are frequently misdiagnosed due to overlap with thyroid hormone resistance and assay interference. Delayed recognition often leads to inappropriate thyroid-directed therapies.
Case Presentation: A 62-year-old man with presumed primary hypothyroidism on levothyroxine was referred for persistent biochemical abnormalities. Despite dose reductions and eventual discontinuation of levothyroxine, thyroid function tests repeatedly demonstrated elevated free thyroxine (FT4) with an inappropriately normal to mildly elevated TSH. He reported intermittent palpitations and heat intolerance but was clinically euthyroid on examination. There was no family history of thyroid or pituitary disease.
Diagnostic Evaluation: Repeat testing on alternate assay platforms confirmed elevated FT4 with non-suppressed TSH, reducing the likelihood of assay interference. Peripheral markers of thyroid hormone action showed elevated sex hormone–binding globulin, supporting true tissue thyrotoxicosis rather than thyroid hormone resistance. Serum α-subunit was elevated with an increased α-subunit/TSH molar ratio. Pituitary MRI revealed a 5-mm pituitary microadenoma without optic chiasm involvement.
Management and Outcome: The patient was treated preoperatively with a somatostatin analog, resulting in biochemical improvement. He subsequently underwent transsphenoidal pituitary surgery. Pathology confirmed a TSH-producing pituitary adenoma. Postoperatively, thyroid function tests normalized, symptoms resolved, and follow-up imaging showed no residual tumor.
Conclusion: This case highlights the importance of considering central hyperthyroidism in patients with discordant thyroid function tests. A systematic diagnostic approach—including exclusion of assay interference, assessment of peripheral thyroid hormone action, α-subunit measurement, and pituitary imaging—is essential for timely diagnosis. Early recognition of TSHoma allows for definitive surgical management and favorable outcomes.
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