In vivo secretory potential and the effect of combination therapy with octreotide and cabergoline in patients with clinically non-functioning pituitary adenomas.

Abstract

The secretory capacity, in vivo, of clinically non-functioning pituitary adenomas may possibly predict tumour volume reduction during intensive medical therapy. Ten patients (mean (range) 53 years (26-73)) with clinically non-functioning macroadenomas, > or = 10 mm were studied. The secretory capacity of the adenomas was examined using basal, NaCl and TRH-stimulated LH, FSH and alpha-subunit levels. The effect on tumour volume of 6 months' therapy with the combination of a somatostatin analogue, octreotide 200 microg x 3/day and a dopamine-D2-agonist, cabergoline 0.5 mg x 1/day was studied. The basal LH, FSH and alpha-subunit levels were determined before and during 6 months' therapy with octreotide and cabergoline, and MR scans were used to evaluate tumour volume before and during this period of therapy. Octopus-perimetry was used to examine the visual fields. A reduction in tumour volume (mean +/- SEM (range); 30% +/- 4% (18-46%)) during 6 months of combination therapy with octreotide and cabergoline was recorded only in patients with in vivo secretory potential. Tumour volume was not reduced in four patients: in three of these patients it remained unchanged while in one patient it was observed to have increased (by 14%). Of the six patients with pretherapy secretory capacity, one displayed a very high basal level of alpha-subunit (74 microg/l) despite unmeasurable levels of LH and TSH, and an FSH-level of 1 IU/l. The other five patients presented paradoxical LH, FSH and/or alpha-subunit responses to TRH. A reduction in basal levels of LH, FSH and/or alpha-subunit was observed in all six patients, and the maximum reduction of at least one of the hormonal levels was 66% +/- 7% (50-98%). The basal levels of LH, FSH and alpha-subunit in the 10 patients were (mean +/- SEM (range)), 3.0 IU/l +/- 1.0 (0.0-7.4), 12.7 IU/l +/- 5.0 (0.0-39.0) and 9.0 IU/l +/- 7.0 (0.2-74.0). During six months of therapy with octreotide and cabergoline, the basal levels of LH, FSH and alpha-subunit were reduced by > or = 50% in seven patients - including the six patients with in vivo secretion prior to therapy. No new visual field defects were detected during therapy and no deterioration of existing visual field defects was recorded. The medical therapy was well tolerated. The in vivo basal and TRH-stimulated secretory capacity of LH, FSH and alpha-subunit predicted tumour reduction following intensive medical therapy in all of our patients with non-functioning pituitary adenomas.