FREE ALPHA-SUBUNIT AND INTACT TSH SECRETION IN-VITRO ARE CLOSELY ASSOCIATED IN HUMAN SOMATOTROPH ADENOMAS

Objective: GH-secreting pituitary adenomas frequently co-secrete prola ctin and glycoprotein hormone alpha-subunit (alpha SU), but expression of additional hormones is considered unusual. The aim of this study w as to establish the frequency with which acromegalic tumours secrete i ntact glycoprotein hormones LH, FSH and TSH, in comparison with other types of pituitary adenoma. Design and methods: Pituitary tumours were studied by cell culture, measuring the basal secretion of anterior pi tuitary hormones in vitro. Light microscopy was used to exclude tumour s where normal pituitary tissue was present, and immunocytochemistry w as employed to confirm the clinical diagnosis and for comparison with tissue culture data. Results: TSH secret-ion was observed in vitro in 15/23 somatotroph adenomas, but from only 1/8 lactotroph, 4/29 null ce ll, 2/12 gonadotroph and 1/10 corticotroph adenomas: moreover, somatot roph adenomas secreted the largest amounts of TSH (P < 0.001). Somatot roph adenomas also secreted LH (7/23) and FSH (2/23) but less frequent ly than gonadotroph adenomas. Immunocytochemistry demonstrated glycopr otein expression in somatotroph adenomas (LH beta: 13%, FSH beta: 26%. TSH beta: 30%, alpha SU: 46%) more frequently than in lactotroph, cor ticotroph and null cell adenomas. A strong correlation was found betwe en alpha SU secretion and TSH secretion in somatotroph adenomas (rho = 0.683, pc:0.001). Conclusions: TSH beta is frequently expressed by so matotroph adenomas, often associated with alpha SU expression. Both GH and TSH beta are dependent on the transcription factor, Pit-1, which is frequently expressed in somatotroph adenomas, although the expressi on of alpha SU requires an alternative explanation. Increased expressi on of alpha SU compared with TSH beta may account for the secretion of free alpha SU by somatotroph adenomas.