Octreotide: a therapeutic option for idiopathic intracranial hypertension.

PURPOSE: To study the effects of octreotide, a somatostatin analogue, in patients with Idiopathic Intracranial Hypertension (IIH). METHODS: We performed a prospective, open-label study of the effect of Octreotide on 26 patients with symptoms and signs of IIH, investigated by brain MRI and lumbar puncture. Octreotide was administered subcutaneously, at an initial dose of 0.3 mg/day; and was gradually increased until headache was relieved (upper-dose limit: 1 mg/day). Treatment with octreotide at 1 mg/day was administered for a maximum of six to eight months and afterwards the dose was gradually tapered. Patients were followed prospectively every month for three years. CSF opening pressure was measured before the treatment was started and again in the first follow-up examination, on month one. In all follow-up visits the presence of papilledema was evaluated by fundoscopy; visual fields and visual acuity were also examined. RESULTS: Overall 24/26 patients improved significantly (92%). Headache was relieved within days (1-10, median 7 days). Papilledema subsided in all 24 patients, in up to two months (35 to 68, median 45 days). Visual disturbances, initially presenting in 20 of our patients, improved in 18 (90%). The mean reduction in CSF pressure after treatment was 20.72A+/-10.7 cmH2O (range 2 to 48). Patients were followed for three years after cessation of treatment. No recurrence of papilledema, or any other symptoms, has been observed. CONCLUSIONS: Octreotide resulted in a significant and sustained improvement of IIH in our patients. These results suggest that it may be an effective alternative to existing treatments for IIH.

Ectopic bioactive luteinizing hormone secretion by a pancreatic endocrine tumor, manifested as luteinized granulosa-thecal cell tumor of the ovaries.

Endocrine pancreatic tumors are rare neoplasms consisting of multipotent cells capable of secreting various bioactive substances causing characteristic clinical syndromes. Ovarian stromal hyperthecosis is characterized by varying degrees of luteinized stromal cell proliferation after sustained LH and/or human chorionic gonadotropin stimulation, clinically manifested by symptoms/signs of virilization resembling the polycystic ovary syndrome (PCOS). We report a case of ectopic bioactive LH production from a pancreatic endocrine tumor in a 33-yr-old woman with rapidly developing symptoms/signs of hyperandrogenism and markedly elevated serum androgen and LH levels leading to hyperthecosis and bilateral luteinized granulosa-thecal cell tumors of the ovaries. Although the patient was initially thought to have either severe PCOS or an LH-secreting pituitary tumor, an LH-producing pancreatic endocrine tumor bearing somatostatin receptors was demonstrated on scintigraphy with [111In]octreotide and abdominal imaging. Symptoms and signs of hyperandrogenism resolved after the resection of the tumor. Immunohistochemistry, in situ hybridization, and electron microscopy studies confirmed LH synthesis by the tumor cell. Although extremely rare, ectopic LH production from nonpituitary endocrine tumors should be considered in the differential diagnosis of hyperandrogenism, particularly when associated with highly elevated serum LH levels.

The effect of sequential administration of octreotide alone and octreotide/growth hormone simultaneously on buserelin stimulated ovarian steroid secretion in women with polycystic ovary syndrome.

OBJECTIVE: GH increases oestradiol secretion and promotes oocyte development in women with polycystic ovary syndrome (PCOS). However, there are no data on ovarian androgen production after GH treatment. We have therefore assessed the effect of sequential treatment with a long-acting somatostatin analogue (octreotide) alone and octreotide/GH simultaneously on ovarian steroid levels in PCOS and non-PCOS normal women. PATIENTS: Twenty-six PCOS and 12 non-PCOS women, aged 18-35 years, were studied. Ten of the PCOS and six of the non-PCOS women received sequential treatment with octreotide alone and followed by octreotide + GH together, while another eight PCOS and six non-PCOS women received saline instead of octreotide-octreotide + GH. The remaining eight PCOS women received GH alone. DESIGN: The octreotide-octreotide + GH and saline studies lasted 12 days, the GH alone 7 days. Octreotide (100 micrograms, s.c., t.d.s.) was given from the 2nd to the 10th and octreotide + GH (4 IU, s.c. at 2300h) from the 7th to the 10th day of the study. The GH alone treatment was given from the 2nd to the 5th day. On the 1st day, two tests were performed: (1) an oral glucose tolerance test (OGTT, 75 g, orally) at 0830h and (2) a buserelin (long-acting GnRH agonist) test (100 micrograms, s.c.) at the end of the OGTT. Both tests were repeated on the 6th and 11th days in the octreotide-octreotide + GH or on the 6th day only in the GH alone study. MEASUREMENTS: Blood glucose, insulin (IRI), C-peptide and IGF-I (at time 0 only) were measured before glucose administration and at 30-minute intervals for 3 hours and LH, FSH, delta 4-androstenedione (delta 4A), testosterone (TT), free testosterone (FT) and oestradiol (E2) before buserelin and at 1,2,6,10,14 and 18 hours. RESULTS: Octreotide alone significantly reduced the basal IGF-I stimulated LH and both basal and stimulated IRI, delta 4A, TT, FT and E2 levels in all PCOS women tested. Both octreotide + GH and GH alone increased significantly the basal IGF-I and both basal and stimulated IRI and E2 levels in all PCOS women, while the basal and stimulated LH, delta 4A, TT and FT levels were completely unaffected. In contrast, octreotide-octreotide + GH treatment did not modify either basal or stimulated gonadotrophin or ovarian steroid levels in non-PCOS women. No changes in either basal or stimulated hormone levels were observed in those PCOS women who received saline. Although both basal and stimulated levels of all ovarian androgens were significantly reduced by octreotide-octreotide + GH treatment in PCOS women, they still remained significantly higher than in the non-PCOS women. CONCLUSIONS: The data show that (1) octreotide is a potent inhibitor of ovarian steroid secretion, (2) GH increases oestradiol secretion, possibly by stimulating ovarian aromatase activity, and (3) the combined treatment with octreotide and GH significantly improves ovarlan function in women with PCOS and may thus have important clinical implications for the management of infertile women with this syndrome.

Dysfunction of the growth hormone/insulin-like growth factor-I axis in women with polycystic ovarian syndrome.

OBJECTIVE: Although a defect in GH regulation has been suggested in women with polycystic ovarian syndrome (PCOS), the data are limited and mechanism obscure. We have assessed the function of the GH/IGF-I axis in women with PCOS by measuring basal IGF-I levels and the ability of the pituitary to secrete GH following dopamine and GHRH. DESIGN: For each woman the complete study lasted 3 days. On the 1st and 2nd days, saline (0.9%, 5 ml/h for 3 h) and dopamine (4 micrograms/kg/min for 3 h) infusion tests were performed, respectively, in all PCOS and control women. Blood samples for GH measurement were obtained before and at 20-minute intervals for 3 hours. On the 3rd day a GHRH test (100 micrograms, i.v. bolus) was performed in 9 of the women with PCOS and in 9 controls. Blood samples for GH measurements were obtained before and at 20-minute intervals for 3 hours. Basal IGF-I levels were measured in the basal blood samples from the saline infusion test in all patients studied. SUBJECTS: Thirteen women with PCOS and 11 normally menstruating women (control group), aged 18-35 years, were studied. All women with PCOS had hirsutism and oligomenorrhoea since menarche, elevated serum values of at least one ovarian androgen and the typical ultrasound appearance of PCOS. RESULTS: Growth hormone releasing hormone (GHRH) induced a significant increase in GH secretion in both control and PCOS groups. However, the GH response to GHRH was found to be significantly lower in women with PCOS. The 3-hour infusion of dopamine induced a significant increase in GH levels only in the control group, while it failed to stimulate GH release in the women with PCOS. Although both dopamine and GHRH failed to induce a normal GH response in women with PCOS, their IGF-I levels did not differ significantly from those observed in control women. CONCLUSIONS: The diminished GH responses to both GHRH and dopamine in women with PCOS, in the presence of normal circulating IGF-I levels, suggests a dysregulation in GH secretion. Although the data are suggestive of a hypothalamic defect, further studies are required to clarify the underlying mechanism and the role, if any, of GH in the pathogenesis of polycyctic ovarian syndrome.