A luteinizing hormone-, alpha-subunit- and prolactin-secreting pituitary adenoma responsive to somatostatin analogs: in vivo and in vitro studies

Objective: Evaluation of the efficiency of somatostatin analogues in the tr eatment of a mixed luteinizing hormone (LH)-, alpha -subunit-. prolactin (P RL)-secreting pituitary adenoma. Design: A 30-year-old woman, with amenorrhaea-galactorrhaea. presented with a pituitary macroadenoma. The endocrine evaluation showed high plasma Leve ls of PRL, LH, and alpha -subunit inhibited by 65%, 65% and 33% respectivel y under octreotide test (200 mug. s,c.). Long-term treatment with slow rele ase (SR) lanreotide (30 mg/10 days, i.m.) restored menstrual cycles and nor malized PRL values. Due to persisting supranormal levels of LH and alpha -s ubunit, and to the absence of tumoral shrinkage, the adenoma was resected b y the transsphenoidal route. Methods: In vitro characterization of the somatostatin receptor subtypes (S STR) expression and functionality. Real-time polymerase chain reaction was performed to quantify the expression of SSTR mRNAs and functionality of the SSTRs was assessed in cell culture studies with various concentrations of native somatostatin (SRIF-14) and of analogues preferential for SSTR2 or SS TR5. Results: This adenoma presented with high levels of SSTR2, SSTR3 and SSTR5 mRNAs, as compared with a series of gonadotroph adenomas. In cell culture s tudies, PRL, LH and alpha -subunit were inhibited by 60%, 47% and 33% respe ctively by SRIF-14 at a concentration of 10 nmol/l. The SSTR2 (BIM-23197, l anreotide) and SSTR5 (BIM-23268) preferential analogues both produced a par tial 21-38% inhibition of PRL, LH, and alpha -subunit release. Discussion: In this plurihormonal-secreting adenoma, the high efficacy of s omatostatin analogues to inhibit PRL, LH and alpha -subunit secretion in vi vo may be explained by the unusually high level of expression and by the fu nctionality of both SSTR2 and SSTR5 receptor subtypes.