(CSEMP049) IT'S NOT MY THYROID! A CASE OF TSH-PRODUCING MICROADENOMA (TSH-OMA)

Abstract:

Background:
Rare TSH-secreting pituitary adenomas (TSH-oma) are predominantly macroadenomas that inappropriately secrete TSH, independent of feedback regulation by thyroid hormone or thyrotropin releasing hormone (TRH) [1,2]. 70% of TSH-omas have an elevated serum glycoprotein alpha-subunit (A-GSU)[3]. Often other pituitary hormones are co-secreted [4].

Case Presentation:
A 33-year-old woman presented with a 3-year history of progressive thyrotoxic symptoms including anxiety, heat intolerance, palpitations, fine tremors and excessive perspiration. Clinical assessment revealed regular tachycardia (112 bpm), fine bilateral hand tremors, brisk upper reflexes, and diffusely enlarged thyroid gland. She had an elevated fT3 8.1 pmol/L (3.1-6.2 pmol/L) and fT4 of 25 pmol/L (9-19 pmol/L) and an inappropriately normal TSH 1.39 mIU/L (0.32-4 mIU/L). Interestingly, her sella MRI demonstrated only a 2-3 mm hypoenhancing nodule in the right pituitary. The rest of her pituitary function was normal, including A-GSU 0.3 ng/mL (normal <= 1.2 ng/mL).
Because several features were atypical for a TSHoma, other causes were sought. Laboratory interference was ruled out. In consideration of potential central thyroid hormone resistance (CTHR), the thyroid function of first-degree relatives was screened and was normal. Subsequent investigations were also more suggestive of TSH-oma than CTHR: stimulation with TRH failed to evoke the expected TSH surge, with levels only rising from 1.81 mU/L (baseline) to 2 mU/L (peak) and 1.6 mU/L (60 minutes post-TRH). Furthermore, on cytomel challenge, her TSH remained unsuppressed at 0.98 mIU/L on day 5, 1.18 mIU/L on day 8 and 1.09 mIU/L on day 11, aligning with a TSH-oma pattern.
Upon neurosurgical resection, the pathology demonstrated a thyrotroph Pit-NET dominated by TSH-expressing cells. Post-operatively, she developed central hypothyroidism: TSH levels plummeted to < 0.01 mIU/L, coupled with low fT3 (2.5 pmol/L) and borderline-low fT4 (10 pmol/L), requiring levothyroxine therapy. Her pituitary recovered TSH production 1 year later.

Discussion:
After ruling out lab interference (supplements, heterophile antibodies) to establish true inappropriate secretion of TSH [1,5], this case illustrates methods to differentiate between key differentials, the TSH-oma and CTHR [1]. This case was unusual because the TSH-oma was a microadenoma and A-GSU was normal [1,2]. Despite its Pit-1 lineage, this case also did not have co-secretion of growth hormone and prolactin [4]. Extra testing was conducted to support TSH-oma diagnosis before proceeding to surgery. The case also demonstrated anticipated central hypothyroidism post-adenoma resection and subsequent thyroid-hypothalamic-axis recovery.