Effect of TRH on β-gonadotropin subunits in patients with pituitary microincidentalomas

Abstract

Objective: To explore the hypothesis that most of the pituitary abnormalities compatible with the diagnosis of microadenoma, and detected in about 10% of the normal adult population, represent asymptomatic gonadotropinomas. Design: Patients diagnosed with pituitary microincidentalomas at the Institute of Endocrinology of the Tel Aviv Medical Center were evaluated. Circulating β-subunits of gonadotropin hormones were measured before and 30, 45, 60 and 90 min after the intravenous injection of 400 μg TRH. Patients: Twenty-two patients with pituitary incidentaloma and 16 normal volunteers were tested. Results: In 16 of the 22 patients, an abnormal β-subunit response was detected after the TRH challenge. Three patients had an abnormal increase in both β-FSH and β-LH after TRH administration. Isolated pathological β-FSH or β-LH responses were demonstrated in five and eight patients respectively. Six patients had normal basal and stimulated gonadotropin subunit values, raising the possibility that their lesions were not pituitary microadenomas. There was a significant overall difference between the response to TRH of the patient and control groups. In the gonadotropin positive group, comprising 16 patients, serum β-FSH increased from 6.4±1.6 ng/ml to 9.2±1.3 ng/ml (P=0.042) 1 h after TRH stimulation, whereas no changes were detected in the control group after TRH injection (basal: 4.1±0.8 ng/ml, peak: 5.1±0.8 ng/ml; P=0.15). Serum β-LH increased from 10.5±3.2 ng/ml to 23.4±4.9 ng/ml (P=0.0037) at this time, in contrast to a lack of response in controls (basal: 6.4±1.5 ng/ml, peak: 8.2±2.3 ng/ml; P=0.24). Conclusion: In about 73% of patients with pituitary incidentalomas smaller than 10 mm, TRH elicits an increase in gonadotropin β-subunits. This observation raises the possibility that non-functioning pituitary micro- and macroadenomas, which share a similar response to TRH, originate in a common ancestor cell type, probably a pituitary gonadotrope.