Clinically nonfunctioning pituitary adenoma and octreotide response to long term high dose treatment, and studies in vitro.

Abstract

We have studied seven patients with a clinically nonfunctioning or alpha-subunit-secreting pituitary macroadenoma, four of whom received long term, high dose octreotide treatment. We have attempted to correlate the presence of somatostatin receptors (SS-R) in the adenomas and the outcome of octreotide treatment, as measured by tumor size, improvements in visual field defects, and hormonal response. The presence of SS-R in the pituitary adenomas was demonstrated in vivo using [111indium]octreotide scintigraphy and in vitro by autoradiography of tissue fragments obtained after transsphenoidal surgery. Adenomas from six of the seven subjects were SS-R positive. High dose (1200 micrograms, sc, daily) octreotide treatment was given to four subjects, three of whom were SS-R positive. Improvement of the visual field defects was observed in three of four patients (including the SS-R-negative subject), although no computed tomographic scan-assessed tumor size reduction was found. Two of four patients showed small but significant reductions in serum FSH concentrations (to 83% and 93% of initial values) with treatment. These in vivo responses to high dose octreotide treatment could not be predicted by pretreatment responses to 200 micrograms TRH or 100 micrograms octreotide. Tissue fragments for cell culture were obtained from six patients, and in vitro release of gonadotropins and/or alpha-subunit could be demonstrated in five cultures. In vitro, octreotide (10 nmol/L) significantly decreased gonadotropiin or subunit release in three of five cultures, whereas bromocriptine (10 nmol/L) significantly reduced the release in four of five cultures and to a significantly greater extent than octreotide. In conclusion, in six of seven patients with a clinically nonfunctioning or alpha-subunit-secreting pituitary adenoma, SS-R were demonstrated in the tumor. In vitro incubation of adenoma cells with octreotide resulted in mild inhibition of gonadotropin or alpha-subunit release. Although in vivo long term treatment with high doses of octreotide did not result in substantial tumor size reduction, improvement of visual field defects was observed in three of four subjects.

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

“…In three previous series, 29 gonadotroph adenomas were studied in cell culture (4,16,17). Somatostatin produced, in vitro, a partial (28±34%) inhibition of FSH, LH or a-subunit in less than 28% of these tumours.…”

“…Indeed, such findings led to the study of the effect of long-term octreotide therapy in patients with pituitary tumours which released luteinizing (LH) and follicle-stimulating (FSH) hormones and/or free a-subunit. If octreotide was poorly effective upon tumour shrinkage, a significant reduction in serum FSH concentrations could be found in two out of four patients under long-term octreotide administration (4). More recently, it was shown by cell culture studies that somatostatin and its analogue, lanreotide, inhibited the proliferation of dispersed human non-functioning pituitary cells (5), which, in their majority, do synthesize LH, FSH or the a subunit (6±8).…”

Octreotide

“…45 Therapy with octreotide seldom results in a reduction in the size of the tumor, but 30 to 40 percent of patients have improvement in visual-field defects within days after the initiation of treatment. 46 This response may reflect a direct effect of octreotide on the retina or optic nerve.…”

Reduction of Plasma Gonadotropin Levels and Pituitary Tumor Size by Treatment with Bromocriptine in a Patient with Gonadotropinoma.

“…Katznelson et al (6) reported that octreotide reduced tumor size with or without an accompanyingdecrease in serum tumor marker levels in a small percentage of patients with clinically nonfunctioning pituitary tumors and oc-subunit hypersecretion. De Bruin et al (35) reported that high-dose, 1,200 jug/day, octreotide treatment induced improvement of visual field defects in three of four patients with clinically nonfunctioning pituitary adenomaand the effect of a single injection of octreotide on the gonadotropin levels had no correlation with the improvement of the clinical efficacy. Holland et al (36) reported that, from the results of the relation of the expression of five somatostatin receptor subtypes with the effect of somatostatin and its analogs on the secretion of gonadotropin from gonadotropinomacells in culture, novel somatostatin receptor subtype specific somatostatin analogs might be of benefit in the treatment of selected patients with somatostatin receptor positive secreting tumors not responding to octapeptide somatostatin-analog.…”