MON-107 - Diagnosing an Invisible Thyrotropin-Secreting Pituitary Adenoma with the Octreotide Suppression Test

A 52 year old woman with a history of atrial fibrillation presented with elevated thyroid stimulating hormone (TSH) and concomitant elevation in free thyroxine (FT4) in November 2024.
The patient had palpitations attributed to known atrial fibrillation. She denied tremors, frequent bowel movements, anxiety, agitation, or weight loss. She denied amiodarone use, recent iodine load, or family history of thyroid disease.
Initial labs demonstrated FT4 of 2.9 µg/dL (normal range 0.7-1.7), free triiodothyronine (FT3) of 6.7 pg/mL (2.0-4.4), and a TSH of 2.72 uIU/mL (0.30 – 5.0). Assay interference was ruled out with elevated TSH, FT4, and FT3 by dialysis. Graves disease was ruled out by negative antibody test results. Ga-68 DOTOTATE-PET scan did not identify ectopic neuroendocrine tumor. Failure to suppress TSH with elevated FT4 was concerning for either a TSH-producing pituitary adenoma (TSHoma) or thyroid hormone resistance (THR).
Sex hormone binding globulin was elevated at 153 nmol/L (17.3-125.0) and I-123 thyroid uptake and scan demonstrated diffusely increased uptake of 44.6% (13-32%), which are both associated with TSHoma. Genetic testing did not identify a TSH-beta thyroid hormone receptor mutation.
This data all strongly suggested a TSHoma, and MRI sella was obtained for definitive diagnosis. However, MRI sella failed to demonstrate a pituitary adenoma. Without confirming TSHoma, it was unclear whether initiating treatment for hyperthyroidism was appropriate.
To confidently differentiate TSHoma from THR, an octreotide suppression test was performed based on the protocol designed by Han et al (Thyroid 2020). Octreotide 0.1mg was administered at baseline, hours 8 and 16, and TSH, FT4, and FT3 levels were obtained at hours 2, 4, 6, 8, and 24. Our patient’s results showed a 2 hour to 24 hour TSH ratio of 46.04%, consistent with TSHoma, and lacked a rebound pattern.
The patient started methimazole 10mg daily resulting in FT4 within normal range at 1.4 µg/dL and spontaneous conversion to normal sinus rhythm.
TSHomas express somatostatin receptors, and somatostatin receptor antagonist therapy is an effective treatment for TSHoma. Patients with THR are less sensitive to SSA therapy; therefore octreotide, a somatostatin receptor antagonist, can be used to differentiate these conditions. Octreotide administration should have a sustained suppression of TSH in TSHoma, with a rebound in TSH production in THR. A 2 hour to 24 hour TSH ratio greater than or equal to 44.46% has a 95% sensitivity and 93.7% specificity for a TSH-secreting pituitary adenoma, as seen in this patient. Her response to thyroid hormone suppression with methimazole further supports underlying thyroid hormone excess as expected in TSHoma versus THR.
This case highlights the difficulty in distinguishing thyroid hormone resistance from TSHoma in patients without structural evidence adenoma, and provides a framework for assessment.

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