Gonadotrophin secretion in vitro by cells of a pituitary tumour from a patient with multiple endocrine neoplasia type I.
OBJECTIVE: The aim was to investigate the hormone secretory products of a pituitary tumour from a patient with multiple endocrine neoplasia type I (MEN I) utilizing cell culture and immunoassay techniques. DESIGN: Adenoma tissue was enzymically dispersed and established in cell culture. Medium was collected for hormone measurement after 2 days, and also after 24-hour periods during long-term culture. In addition, tissue fixed at surgery was analysed by immunocytochemistry and electron microscopy. PATIENT: The subject was a 59-year-old male with a clinical history characteristic of familial MEN I syndrome. MEASUREMENTS: Pituitary hormones in serum and culture medium were measured by fully characterized radioimmunoassays. RESULTS: Preoperative serum LH and FSH levels were normal, or slightly elevated, and there was a progressively blunted gonadotrophin response to GnRH throughout the 8 years prior to adenomectomy. TRH induced a small, paradoxical increase in serum gonadotrophin levels 2 weeks preoperatively. Post-operative pituitary hormone responses to standard stimulation tests showed an active normal pituitary. In vitro, the pituitary tumour cells secreted only gonadotrophins and glycoprotein hormone alpha-subunit. The fixed tumour tissue immunostained for alpha-subunit alone, and electron microscopy confirmed the presence of secretory granules with diameters of 100-280 nm. Gonadotrophin secretion continued throughout 77 days in long-term culture, but whilst LH was released at a steady rate, that of FSH transiently increased between days 29 and 48 in vitro. CONCLUSIONS: These data demonstrate that a pituitary tumour associated with the MEN I syndrome secreted gonadotrophins in vitro.