SUN-407 - TSH-Producing Pituitary Adenoma Versus Thyroid Hormone Resistance: A Diagnostic Challenge

Elevated thyroid hormones levels, with a non-suppressed thyroid-stimulating hormone (TSH) in a patient with a macroadenoma, not on thyroid hormone replacement, can present a diagnostic challenge. In this clinical setting, the diagnosis of a TSH producing tumor is favored; however, diagnostic dilemmas arise when dynamic testing does not support the likely diagnosis. 

A 19-year-old female with history of headaches and anxiety, but no known family history of thyroid disease, was found to have a pituitary mass during evaluation of mild hyperprolactinemia in 2024. She reported symptoms of insomnia, fatigue, heat intolerance, and increased perspiration. Pituitary directed MRI demonstrated a 2.0 x 1.7 x 1.7 cm macroadenoma. Thyroid function tests revealed elevated free T4 (1.49 ng/dL; reference range 0.70-1.48) and elevated free T3 (6.4 pg/mL; reference range 1.7-3.7) with an inappropriately normal TSH (2.959 µIU/mL). Repeat MRI six months after the initial diagnosis showed a mild increase in the size of the tumor. Endocrinology initiated hormonal evaluation, which showed elevated sex hormone-binding globulin at 233 nmol/L; although she was taking combined oral contraceptives. HAMA testing was negative. A normal alpha-subunit level (0.6 ng/mL) and a normal alpha-subunit-to-TSH ratio (0.2); these findings were more consistent with thyroid hormone resistance. A trial of subcutaneous octreotide was initiated at 50 mcg TID to help differentiate between thyroid resistance syndrome and TSH producing adenoma. The dosage was escalated to 200 mcg TID; however, TSH levels remained persistently elevated after 2 weeks of treatment. TSH levels checked on Day 5 and Day 9 on Cytomel 25 mcg TID did not show TSH suppression.

This patient’s macroadenoma with interval increase in size and desire for pregnancy warrants elective transsphenoidal surgery. Staining for TSH on pathology and post procedure labs will give us the definite diagnosis. Cure rate of TSH adenoma is 40% following TSR (transsphenoidal resection) and therefore ruling out thyroid resistance syndrome with genetic testing will be very helpful (1).  Testing done thus far points to thyroid hormone resistance due to a mutation of thyroid hormone receptor beta (THR-ß). TRH stimulation test is not possible because of lack of availability of TRH. Data shows a TSH reduction in 91% of patients with 2-week treatment with octreotide in TSH adenoma patients.  Acute drop in TSH was observed after a single octreotide subcutaneous injection (2). Genetic testing for THR-ß is pending currently.

References:   
1. Smallridge RC. Thyrotropin-secreting pituitary tumors. Endocrinol Metab Clin North Am. 1987;16:765-92 
2. Philippe Chanson, Bruce D. Weintraub, Alan G. Harris. Octreotide Therapy for Thyroid-Stimulating Hormone-Secreting Pituitary Adenomas: A Follow-up of 52 Patients. Ann Intern Med.1993; 119:236-240. doi:10.7326/0003-4819-119-3-199308010-00010

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*