d-ala(2)-mephe(4)-met(0)-ol-enkephalin and Acromegaly

We undertook this study, because conflicting data were reported about the dopaminergic regulation of prolactin (PRL) secretion in patients with acromegaly and hyperprolactinemia. In order to clarify the dopaminergic regulation of PRL secretion in patients with acromegaly and hyperprolactinemia, the effects of nomifensine, a central dopamine agonist, FK 33-824, a centrally antidopaminergically acting agent, and domperidone, a peripheral dopamine antagonist, on plasma PRL in these patients were studied. The results were compared with those observed in normal subjects and hyperprolactinemic patients, with or without a pituitary tumor. Nomifensine did not lower the PRL levels and FK 33-824 did not raise the PRL levels in acromegalic patients. In hyperprolactinemic patients, nomifensine did not lower the PRL levels and FK 33-824 failed to raise the PRL levels. Domperidone did not increase PRL in about a third of acromegalic patients, while TRH increased PRL in the all normoprolactinemic acromegalic patients. These results suggest that in acromegalic patients there may be a disturbance in dopamine related neurotransmission and that such disorders also seem to be present in patients with hyperprolactinemia, with or without a pituitary tumor.

Topics: Acromegaly; Adult; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Domperidone; Female; Humans; Male; Middle Aged; Nomifensine; Pituitary Neoplasms; Prolactin; Radioimmunoassay

Prolactin (Prl) and growth hormone (GH) responses to different pharmacologic probes acting at the central nervous system (CNS) or the anterior pituitary (AP) level were evaluated in patients with distinct neuro-endocrine disorders. Thirteen patients with Prl-secreting tumours (PST), 10 acromegalics (A) and 8 patients with hypothalamic lesions (HL), as assessed on clinical, radiological and surgical grounds, underwent on separate occasions acute testing with the opioid peptide FK 33-824 (0.5 mg iv), the indirect dopamine (DA) agonist nomifensine (NOM, 200 mg po), the DA receptor antagonist domperidone (DOM, 10 mg iv), TRH (200 microgram iv) and insulin (ITT, 0.10-0.15 IU/kg iv). All patients were evaluated pre-surgery and 4 of them also post-surgery. Prl and GH were evaluated by RIA at different time intervals following treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acromegaly; Adolescent; Adult; Aged; Brain; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Domperidone; Female; Growth Hormone; Humans; Hypothalamic Diseases; Male; Middle Aged; Nomifensine; Pituitary Gland, Anterior; Pituitary Neoplasms; Prolactin; Thyrotropin-Releasing Hormone

Synthetic human pancreatic growth hormone releasing factor (pGRF) was administrated intravenously to 14 acromegalic patients, and the response of plasma GH to pGRF was compared with that to TRH, GnRH or other GH-stimulating agents in these patients. Three patients hyperresponded (more than 8 times), 4 patients responded (2-4 times), 4 patients hyporesponded (1.5-2.0 times) and 3 patients did not respond at all. There was no correlation between the responses to TRH and pGRF, however, an intimate relationship was observed between responses to pGRF and GnRH in the patients who hyperresponded to pGRF. A patient not responding to pGRF showed a marked response to insulin or clonidine and another patient not responding to insulin or clonidine did respond to pGRF. Similarly, some patients not responding to FK 33-824, a met-enkephalin analog, or arginine did respond to pGRF.

Topics: Acromegaly; Adult; Aged; Arginine; Clonidine; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Female; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Insulin; Male; Middle Aged; Pancreatic Hormones; Pituitary Hormone-Releasing Hormones; Thyrotropin-Releasing Hormone

D-Ala, Mephe, Met, enkephalin (Sandoz FK 33-824), 1.0 or 0.5 mg, was administered by i.v. infusion to normal subjects, patients with acromegaly and hyperprolactinemia due to pituitary adenoma and patients with pituitary dwarfism. FK 33-824 induced no significant change in plasma level of LH, FSH or TSH in any of the subjects studied. These results suggest a lesser role of opioid regulation in the release of above pituitary hormones compared with that in GH, PRL and cortisol.

Topics: Acromegaly; Adenoma; Adolescent; Adult; Child; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Dwarfism, Pituitary; Endorphins; Enkephalins; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Pituitary Diseases; Pituitary Neoplasms; Prolactin; Thyrotropin

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

D-Ala, Mephe, Met, enkephalin (Sandoz FK 33-824) is a stable long acting analog of methionine-enkephalin. FK 33-824 (0.5 or 1.0 mg), elicited plasma GH and PRL responses in normal subjects. In 23 patients with pituitary dwarfism, the response of plasma GH was markedly impaired, while PRL responded to a variable degree. In patients with acromegaly, there was little or no increase in GH and PRL after FK 33-824. Plasma GH increased to a variable degree after FK 33-824 in patients with hyperprolactinemia, with little change in plasma PRL. FK 33-824 decreased plasma cortisol in normal subjects and patients with pituitary disease. These results show that patients with acromegaly and hyperprolactinemia due to pituitary adenomas and patients with pituitary dwarfism do not respond well to FK 33-824, presumably because of hypothalamic or pituitary derangement.

Topics: Acromegaly; Adenoma; Adolescent; Adult; Child; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Dwarfism, Pituitary; Endorphins; Enkephalins; Female; Growth Hormone; Humans; Hydrocortisone; Hypothalamus; Kinetics; Male; Middle Aged; Pituitary Diseases; Pituitary Gland; Pituitary Neoplasms; Prolactin