naloxone and Acromegaly

Two acromegalic patients with severe headache were treated with the somatostatin analogue, octreotide (Sandostatin). A double-blind study of octreotide versus placebo in which pain intensity was measured using a visual analogue scale (VAS) was performed initially with these patients. A rapid (within 4-15 min) pain relief occurred lasting 2-8.5 h after injection of 100 micrograms of octreotide, an effect that was not reversed by intravenous (i.v.) naloxone. These 2 acromegalic patients then received treatment for 71 and 82 months, respectively, with doses starting at 500 micrograms/day and 1500 micrograms/day, respectively, without evidence of either tolerance or dependence, although the effect of octreotide on headache appears to be selective. No unwanted sedative effect has been observed. A screening procedure with injection of 50 micrograms of subcutaneous (s.c.) octreotide was performed in 11 other patients with chronic severe pain associated with various conditions. Only 3 patients (2 with diabetic polyneuropathy and 1 with bone pain associated with myelodysplastic syndrome) reported more than 50% pain relief. In the insulin-dependent diabetic patients the double-blind check was not performed due to the risk of octreotide-induced hypoglycemia. In the patient with bone pain the same double-blind check as in the acromegalic patients could not confirm the analgesic effect. It may thus be concluded that octreotide appears to be useful for the treatment of both chronic and acute severe painful conditions in acromegalic patients. However, since its analgesic effect in our patients was confined to headaches only, further controlled studies must be carried out in order to determine appropriate target groups.

Topics: Acromegaly; Adult; Analgesics; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Headache; Humans; Injections, Subcutaneous; Male; Naloxone; Octreotide; Radiography

We examined the effects of high-dose intravenous naloxone administration in four acromegalic patients (mean serum growth hormone level 72 ng/ml) and in seven hyperprolactinaemic women (mean serum prolactin level 59 ng/ml), in order to assess whether this opiate antagonist would be effective in lowering growth hormone and prolactin levels. No effect was observed. This lack of effect suggests that an opioid pathway is not involved in the maintenance of elevated growth hormone or prolactin secretion in these patients. However, conclusions regarding the possible role of endogenous opioids in regulation of pituitary function in normal individuals cannot be drawn from this study.

Topics: Acromegaly; Adult; Clinical Trials as Topic; Female; Growth Hormone; Humans; Middle Aged; Naloxone; Pituitary Diseases; Prolactin

In order to gain insight into the neuroendocrine mechanism underlying the paradoxical GH response to TRH in acromegalic patients, we have investigated the effect of an infusion of Naloxone (Nal, 1.6 mg/hr for two hours), on a TRH test performed both in responder (n = 9) and non-responder (n = 5) acromegalic patients. The response of GH, PRL and TSH to TRH injection were evaluated. NAL did not exert significant variations in the GH response, even if different patterns of GH response during NAL were observed in the group of TRH-responder patients. Similarly, TRH-induced PRL response was not significantly affected by the infusion of an opiate antagonist. On the contrary, a significant inhibition of the TSH response was observed in the group of TRH-responder patients (delta TSH after TRH 4.76 +/- 1.11 microU/ml, after NAL + TRH 2.81 +/- 0.99 microU/ml, p < 0.05). No significant effects were observed in the TRH non-responder patients (delta TSH after TRH 4.58 +/- 1.44 microU/ml, after NAL + TRH 6.26 +/- 3.27 microU/ml). The differences observed in the two groups of patients could be ascribed to a different endogenous somatostatinergic tone and could furnish a prognostic indication in acromegalic patients.

Topics: Acromegaly; Adult; Female; Growth Hormone; Humans; Infusions, Intravenous; Male; Middle Aged; Naloxone; Prolactin; Random Allocation; Thyrotropin; Thyrotropin-Releasing Hormone

We report a patient with acromegaly who had severe, intractable headache unrelated to tumor size which dramatically resolved with the somatostatin analog octreotide. The analgesic effects of octreotide were neither related to significant inhibition of growth hormone nor influenced by naloxone. Our data suggest that octreotide should be considered in patients with intractable headache associated with pituitary adenomas. Mechanisms other than tumor size or interaction with the opioid system, such as non-opioid algesic peptide secretion, may be the explanation for severe head pain in some pituitary adenomas.

Topics: Acromegaly; Adenoma; Adult; Growth Hormone; Headache; Humans; Male; Naloxone; Octreotide; Pain, Intractable; Pituitary Neoplasms; Receptors, Opioid

Topics: Acromegaly; Addison Disease; Adolescent; Adrenocorticotropic Hormone; Adult; beta-Lipotropin; Diethylstilbestrol; Female; Growth Hormone; Humans; Hydrocortisone; Male; Middle Aged; Naloxone; Nelson Syndrome; Pituitary Hormones, Anterior; Pituitary Neoplasms; Prolactin

The effect of a long-acting analogue of Met-enkephalin (Damme) and naloxone on anterior pituitary hormone secretion has been investigated in 14 acromegalic patients. Damme produced a progressive fall in circulating LH and cortisol and stimulated prolactin release in normoprolactinaemic patients. Naloxone infusion significantly stimulated gonadotrophin and cortisol secretion without modifying basal prolactin release both in normo-and hyperprolactinamic patients. GH levels remained unchanged during naloxone and Damme infusion. The data suggest that endogenous opiate receptors do not play a major role in modulating GH hypersecretion in acromegaly.

Topics: Acromegaly; Adult; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Enkephalins; Female; Follicle Stimulating Hormone; Growth Hormone; Hormones; Humans; Hydrocortisone; Luteinizing Hormone; Male; Middle Aged; Naloxone; Pituitary Hormones, Anterior; Prolactin; Receptors, Opioid; Thyrotropin

The present study was undertaken with the aim of exploring the role that opiate systems may have in neuroendocrine control in acromegaly. The effects of naloxone (0.4 mg, i.m.), of 2-Br-alpha-ergocryptine (CB154, 2.5 mg, p.o.) and of the interaction between CB154 and naloxone on growth hormone (GH) and prolactin (PRL) secretion were studied in 11 acromegalic patients. CB154 reduced both GH and PRL serum levels, naloxone only GH serum levels. The latter effect deserves further study aimed at a possible new therapeutic approach to GH hypersecretion observed in acromegaly. Naloxone also interfered with the lowering effects of CB154 and GH and PRL serum levels, pointing to the existence of an interaction between dopaminergic and opiate control of GH and PRL secretion in acromegaly.

Topics: Acromegaly; Adult; Bromocriptine; Drug Interactions; Female; Growth Hormone; Humans; Male; Middle Aged; Naloxone; Prolactin; Secretory Rate