MON-446 - Thinking Beyond the Thyroid: Refractory Thyrotropin Elevation after Thyroid Cancer Treatment

Background:
Papillary thyroid carcinoma (PTC), sclerosing variant, is an aggressive subtype of differentiated thyroid cancer with elevated recurrence rates. After surgical management, thyrotropin (TSH) suppressing hormone therapy is initiated to maintain a specific TSH goal range. TSH-secreting pituitary adenomas (TSHomas) are rare causes of central hyperthyroidism, presenting with elevated TSH and T4 levels, and can complicate management in thyroid cancer survivors. We present a unique case of a patient with a history of high-risk PTC, treated with surgery and radioactive iodine, who subsequently developed elevated TSH levels despite increasing levothyroxine doses. Further evaluation revealed a pituitary macroadenoma with biochemical and radiographic evidence of a TSHoma.

Case Presentation:
A 62-year-old male with a history of multifocal, sclerosing variant PTC (pT3N0Mx), status post total thyroidectomy and radioactive iodine ablation eleven years prior, was followed for several years with undetectable thyroglobulin and no evidence of structural recurrence. Over the past three years, he developed persistently elevated TSH levels as high as 15.89 uIU/mL (0.4-4.5 uIU/mL) with inappropriately normal to elevated free T4 levels despite escalation of levothyroxine. He reported taking levothyroxine as prescribed, on an empty stomach each morning and separate from other medications. Serial imaging showed no evidence of recurrent or metastatic thyroid cancer. Workup for central causes of hyperthyroidism revealed a 1.5 cm sellar mass with suprasellar extension on MRI, consistent with a pituitary macroadenoma. Biochemical evaluation ruled out resistance to thyroid hormone beta (RTHb) and supported the suspicion of TSHoma, with an elevated alpha subunit and an elevated alpha subunit to TSH molar ratio of 4.3 (>1.0). The patient underwent transsphenoidal resection of the pituitary tumor with improvement in post-operative day one TSH to 1.30 uIU/mL. Surgical pathology was consistent with a pituitary neuroendocrine tumor with positive staining for TSH in a subset of cells. In concordance with successful treatment of TSHoma, a 6-week post-operative lab evaluation showed a TSH level of 0.04 uIU/mL and a free T4 of 1.29 ng/dL (0.64-1.42 ng/dL) prompting a decrease in the levothyroxine dose.

Conclusion:
This case highlights the challenge of delineating the cause of discordant thyroid function tests in a thyroid cancer survivor on levothyroxine suppression therapy. New and progressive elevation of TSH and free T4 levels in a patient compliant with escalating doses of levothyroxine, and neither radiographic nor biochemical evidence of thyroid cancer recurrence, should prompt early evaluation for alternative causes of TSH elevation, including TSHoma. Timely recognition and multidisciplinary management are essential for optimal outcomes.

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