Endocrine Abstracts

Introduction: Inappropriate secretion of TSH, despite elevated levels of T4, is due to either a TSH-secreting adenoma (TSHoma) or thyroid hormone resistance (RTH). RTH is a rare disorder, usually caused by mutations in the thyroid hormone receptor beta, characterized by a variable tissue hyporesponsiveness to thyroid hormone. The increased level of TSH may predispose to thyrotroph hyperplasia and possible adenoma formation.

Case report: A 21 years old female patient adresses for the first time in 2011 for primary amenorrhea. The clinical features like short stature (−2.3DS), obesity, round face and short fourth metacarpal, along with the primary amenorrhea raised the suspicion of Turner syndrome or pseudohypoparathyroidism, excluded by genetic tests (karyotype 45, XX), normal phospho-calcic profile but without the posibility for GNAS1 testing. Subsequent investigations revealed an elevated TSH (7.1 μUI/ml, N: 0.4-4) with normal fT4 (1.44 ng/dl,N:0.89–1.76), FSH and LH at the upper limit (16 mIU/ml, respectively 26 mIU/ml) and the pelvic ultrasonography revealed 3–5 bilateral follicular cysts. Treatment with progesterone and 50 μg of levothyroxine was initiated, but despite treatment TSH remained unsupressed with high fT4. Five years later, after therapy had been discontinued for 3 months, she was admitted for reevaluation: tahycardia (100/min), persistent high TSH (7.88 μUI/ml) and fT4 (2.13 ng/dl) and low IGF1 (101 ng/ml, N:116-358). The rest of the hormonal profile including FSH, LH, estradiol, ACTH, cortisol, PRL were normal. The magnetic resonance imaging revealed a 11/10 mm adenoma witch raised the suspicion of a TSHoma or an incidental macroadenoma. Sex-hormone binding globulin, feritin and thyroglobulin were normal and the ultrasonography showed no goiter. On the TRH stimulation test, the brisk response of TSH (from 6.59 μUI/ml to 37.1 μUI/ml at 20 min) was suggestive for RTH. In January 2018, the patient underwent transsphenoidal pituitary adenomectomy and after removal of the tumor TSH value suddenly decreased to 0.2 μUI/ml.

Conclusions: This case highlights the difficulties in distinguishing the cause of inappropriate TSH secretion when a pituitary adenoma coexists. None of the investigations are entirely pathognomonic but a combination of tests can be suggestive of either RTH or TSHoma. In our case, although biological examination strongly suggested that this patient was suffering from RTH (normal SHBG and feritin, brisk response to TRH), the decrease in TSH value after surgery was suggestive for TSHoma. This case, along with previous reports and animals models, suggest that RTH may lead to the development of TSH-omas.