RESUMO
Differentiating Cushing's disease (CD) from pseudo-Cushing (PC) states may still be difficult in current practice. Because desmopressin (1-deamino-8D-arginine vasopressin, DDAVP), a vasopressin analogue, stimulates ACTH release in patients with CD but not in the majority of normal, obese, and depressed subjects, we investigated its ability to discriminate CD from PC states. One hundred seventy-three subjects (76 with active CD, 30 with PC, 36 with simple obesity, and 31 healthy volunteers) were tested with an iv bolus of 10 microg DDAVP. Sixty-one of these subjects also underwent a control study with saline. DDAVP induced marked ACTH and cortisol rises in CD (P < 0.005 vs. saline, for both ACTH and cortisol) but not in PC. A significant ACTH elevation occurred upon DDAVP administration also in normal and obese subjects, but it was much smaller than that observed in patients with CD (P < 0.0001). A peak absolute ACTH increase (> or =6 pmol/L), after DDAVP, allowed us to recognize 66 of 76 patients with CD and 88 of 97 subjects of the other groups. The same criterion correctly identified 18 of 20 patients with mild CD (24-h urinary free cortisol < or = 690 nmol/day) and 29 of 30 PC, resulting in a diagnostic accuracy of 94%, which was definitely higher than that displayed by urinary free cortisol, overnight 1-mg dexamethasone suppression test, and midnight plasma cortisol. In conclusion, the DDAVP test seems to be a useful adjunctive tool for the evaluation of hypercortisolemic patients chiefly because of its ability to differentiate mild CD from PC states.
Assuntos
Síndrome de Cushing/diagnóstico , Desamino Arginina Vasopressina , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Criança , Síndrome de Cushing/sangue , Diagnóstico Diferencial , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicaçõesRESUMO
Dopamine infused at a rate of 4 micrograms/kg . min for 120 min induced at the end of the infusion period a clear-cut and similar suppression of circulating PRL levels in normal and puerperal women as well as in patients with hyperprolactinemia either due to a tumor or of unknown etiology. At the discontinuation of the infusion there was a marked PRL rebound above baseline levels in normal subjects and a rapid return to basal levels in subjects with pathological hyperprolactinemia. In contrast, there was no increase in plasma PRL in puerperal women, in whom PRL levels remained suppressed during the whole postinfusion period. The reason(s) for this pattern in puerperal women is presently unknown, although previous estrogen loading of the lactotropes during pregnancy may be involved.
Assuntos
Dopamina , Período Pós-Parto , Prolactina/sangue , Transtornos Puerperais/sangue , Adolescente , Adulto , Feminino , Humanos , Cinética , Neoplasias Hipofisárias/metabolismo , Gravidez , Prolactina/metabolismoRESUMO
This study was designed to further investigate the purported dopaminergic activity of phospholipid liposomes (PL) prepared from bovine cerebral extracts, and to obtain further indications about their pituitary or suprapituitary site of action. In eight normal subjects, we have studied the effects of PL administration (250 mg as IV bolus plus additional 250 mg infused IV over a 60-min period), compared to placebo, on the prolactin (PRL), cortisol and growth hormone (GH) response to an insulin tolerance test (ITT). In eight additional subjects, the effects of PL on the PRL and TSH response to TRH were evaluated. PL medication blunted the PRL and cortisol response in the ITT: significant differences, with respect to placebo administration, were observed between mean peak PRL values (51.9 +/- 13.63 SEM vs 83.4 +/- 26.35 ng/ml, P less than 0.05) and mean cortisol values at 120 min time (20.9 +/- 0.67 vs 26.7 +/- 2.46 micrograms/dl, P less than 0.05). In contrast, PL administration did not modify the ITT-related GH rise or the PRL and TSH release in response to TRH. These findings favour the view that PL are endowed with intrinsic biological activity which is dopamine-mediated, and point to the hypothalamus as their primary site of action.
Assuntos
Hidrocortisona/metabolismo , Hipoglicemia/metabolismo , Lipossomos/farmacologia , Prolactina/metabolismo , Extratos de Tecidos/farmacologia , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Feminino , Hormônio do Crescimento/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Insulina/farmacologia , Masculino , Pessoa de Meia-Idade , Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/farmacologiaRESUMO
Based on the facts that prolactin and adrenocorticotropic hormone (ACTH) each seem to influence the secretion of the other, that dopamine is the established inhibitory factor for prolactin secretion and negatively modulates ACTH release, and finally that alterations of the central dopaminergic tone have been postulated in tumorous hyperprolactinemia, we studied the effects of pharmacological manipulations of the dopaminergic system on ACTH and cortisol secretion in patients bearing a prolactinoma and in normal subjects. Twenty-seven patients with a prolactin-secreting pituitary tumor and 12 healthy controls were submitted to three tests: (a) 4-h saline infusion; (b) 10 mg metoclopramide (MTC) as an intravenous bolus after a 2-h saline infusion; and (c) 4-h dopamine infusion at the dose of 0.01 microgram/kg/min with a 10-mg intravenous bolus of MTC given at the second hour of dopamine infusion. Administration of MTC, compared to saline, caused a moderate (not significant) plasma ACTH increase, and a significant cortisol increase (p < 0.05), both in hyperprolactinemic and normal subjects, without statistically significant differences between the two group. When MTC was administered during dopamine infusion, the ACTH and cortisol elevation was significantly potentiated in prolactinoma patients while it was similar in magnitude to that recorded after MTC alone in control subjects. These findings support the concept of an inhibitory role exerted by dopamine and are compatible with a stimulatory influence exerted by prolactin on corticotropin-releasing hormone and ACTH secretion, and also favor the view of a reduced central dopaminergic tone in patients with tumorous hyperprolactinemia.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Antagonistas de Dopamina/farmacologia , Dopamina/farmacologia , Hidrocortisona/sangue , Hiperprolactinemia/fisiopatologia , Metoclopramida/farmacologia , Prolactina/sangue , Hormônio Adrenocorticotrópico/efeitos dos fármacos , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Dopamina/administração & dosagem , Antagonistas de Dopamina/administração & dosagem , Feminino , Humanos , Hidrocortisona/metabolismo , Bombas de Infusão , Injeções Intravenosas , Masculino , Metoclopramida/administração & dosagem , Pessoa de Meia-Idade , Prolactina/efeitos dos fármacos , Prolactina/metabolismo , Valores de ReferênciaRESUMO
Differences between micro- and macroprolactinomas, as regards the prolactin secretory pattern in response to pharmacological challenges, have been reported in in vivo and in vitro models, and interpreted as being due to different dopaminergic regulation of prolactin release. In 32 patients with prolactin-secreting tumors, 19 with microprolactinomas and 13 with macroprolactinomas, and ten healthy volunteers, we evaluated the prolactin secretion in response to pharmacological manipulations of central dopaminergic tone. To this end, three tests were performed, in random order: (1) 4-h saline infusion; (2) 10 mg metoclopramide as i.v. bolus; (3) 4-h dopamine infusion (0.01 microgram/kg/min) with a 10-mg metoclopramide bolus given after the second hour of infusion. Dopamine infusion, compared to saline, caused a significant prolactin decrease in all the three groups of subjects, without significant difference between micro- and macroprolactinoma patients. In prolactinoma patients, administration of metoclopramide induced a significant rise in plasma prolactin which, however, was significantly lower than the one displayed by controls. Again, no difference was observed between the two groups of hyperprolactinemic patients. Dopamine infusion induced a significant and comparable increase in the prolactin response to metoclopramide in micro- and macroprolactinoma patients, while it was ineffective in control subjects. In conclusion, no differences appear to exist between micro- and macroprolactinoma patients as regards the prolactin secretory pattern during pharmacological modifications of the dopaminergic tone. A central dopaminergic defect and an increased prolactin turnover with attendant reduction of the intracellular hormone pool may both be involved in the reduced prolactin release following provocative stimuli in patients with prolactinoma.
Assuntos
Dopamina , Metoclopramida , Neoplasias Hipofisárias/metabolismo , Prolactina/metabolismo , Prolactinoma/metabolismo , Adolescente , Adulto , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-IdadeRESUMO
To investigate a possible hypothalamic alteration in obesity, we have studied the pattern of PRL secretion in response to insulin hypoglycemia, arginine infusion and TRH injection in 12 grossly obese patients and in 12 normal-weight controls. In the obese patients, PRL secretion was significantly lower than in normal subjects in response to insulin hypoglycemia and arginine infusion, while it was not significantly different from that in controls in response to TRH. The mean +/- SE values of the areas subtended by the PRL curves in the 3 above tests were 54.7 +/- 155.81 vs 3677.3 +/- 520.30 ng/2h, p less than 0,01, 210.3 +/- 148.93 vs 1034.8 +/- 203.15 ng/2h, p less than 0.05 and 1476.8 +/- 275.13 vs 2148.6 +/- 682.06 ng/2h, NS, respectively, in the obese and in controls. These results are compatible with the concept of impaired hypothalamic control of PRL secretion in obesity, although it is still unclear what role this may play in the pathogenesis of this disorder.
Assuntos
Hipotálamo/fisiopatologia , Obesidade/fisiopatologia , Prolactina/metabolismo , Adulto , Arginina , Jejum , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Insulina , Masculino , Pessoa de Meia-Idade , Prolactina/sangue , Hormônio Liberador de TireotropinaRESUMO
The aim of this study was to investigate the possible role of prostaglandins (PG) in the control of the hypohtalamic-pituitary-adrenocortical axis in normal volunteers. Acute oral administration of 100 mg indomethacin (ID) or 1.5 g acetylsalicylic acid (ASA) did not alter ACTH and cortisol plasma levels. Administration of 300 mg daily ID for 4 days delayed the onset, but increased the magnitude, of the response of ACTH to insulin hypoglycaemia, while it blunted the cortisol response. Administration of 3.2 g ASA daily depressed ACTH response to hypoglycaemia leaving the cortisol response unchanged, except for a 15 min delay in onset. These results are interpreted assuming that ID and ASA chiefly acted at the pituitary and hypothalamic level, respectively, and that ID, but not ASA, interfered with adrenocortical cortisol production. Our findings support the concept, based on animal studies, that PG enhance hypothalamic CRF release and adrenocortical steroidogenesis and may restrain ACTH secretion in the pituitary.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Aspirina/farmacologia , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/fisiologia , Indometacina/farmacologia , Sistema Hipófise-Suprarrenal/fisiologia , Prostaglandinas/fisiologia , Administração Oral , Adulto , Aspirina/administração & dosagem , Glicemia/análise , Feminino , Humanos , Indometacina/administração & dosagem , Insulina , Pessoa de Meia-IdadeRESUMO
A single oral dose of 5 g gamma aminobutyric acid (GABA) was given to 19 subjects and serial venous blood samples were obtained before and 3 h after drug administration. A placebo was administered to 18 subjects who served as controls. GABA caused a significant elevation of plasma growth hormone levels (P less than 0.001), but did not consistently alter plasma prolactin concentration since only 5 out of 15 subjects showed an increase of the hormone. Eight additional subjects were submitted to an insulin tolerance test before and after per os administration of 18 g GABA daily for 4 days. Protracted GABA treatment significantly blunted the response of growth hormone and enhanced that of prolactin to insulin hypoglycaemia (P less than 0.01). These results indicate that pharmacological doses of GABA affect growth hormone and prolactin secretion in man. The precise nature of GABA's effects as well as its mechanism of action remains to be clarified.
Assuntos
Hormônio do Crescimento/metabolismo , Prolactina/metabolismo , Ácido gama-Aminobutírico/farmacologia , Administração Oral , Adolescente , Adulto , Idoso , Feminino , Hormônio do Crescimento/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Prolactina/sangue , Ácido gama-Aminobutírico/administração & dosagemRESUMO
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)
Assuntos
Acromegalia/metabolismo , Hormônio do Crescimento/metabolismo , Doenças Hipotalâmicas/metabolismo , Neoplasias Hipofisárias/metabolismo , Prolactina/metabolismo , Adolescente , Adulto , Idoso , Encéfalo/efeitos dos fármacos , D-Ala(2),MePhe(4),Met(0)-ol-encefalina/farmacologia , Domperidona/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomifensina/farmacologia , Adeno-Hipófise/efeitos dos fármacos , Hormônio Liberador de Tireotropina/farmacologiaRESUMO
UNLABELLED: Forty-one patients with prolactinoma (25 micro-, 16 macroprolactinomas) were treated with a long-acting injectable preparation of bromocriptine (Parlodel LAR, Sandoz), 25-100 mg (mostly 50 mg) in every 4-8 weeks for as long as 43 months (median 19 months). The first injection caused a prompt fall of plasma PRL which reached its nadir value after 3 days. Thereafter, hormone levels remained well below initial values for 4 weeks or longer, though with the tendency, more pronounced in microprolactinoma patients, to rise again toward baseline. The prevalence of PRL normalization was greater in the macro- than in the microprolactinoma group. By repeated injections plasma PRL could be kept close to or within the normal limits in most of the patients. However, the extent of PRL inhibition was significantly greater in macro- than in microprolactinoma patients (p less than 0.01). Clinical improvement occurred in the majority of the patients, shrinkage of the tumour in 50% of them. Adverse reactions were generally mild or of moderate severity and subsided spontaneously in 24 h. They were less frequent (NS) and less severe (p less than 0.05) in macro- than in microprolactinoma patients. IN CONCLUSION: a. injectable bromocriptine (Parlodel LAR) is a highly effective preparation particularly suitable for the long-term treatment of tumourous hyperprolactinemia; b. patients with macroprolactinoma exhibit, compared with microprolactinoma patients, better responsiveness and better tolerability to injectable bromocriptine.
Assuntos
Bromocriptina/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactina/metabolismo , Prolactinoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Bromocriptina/administração & dosagem , Bromocriptina/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/metabolismo , Prolactina/sangue , Prolactinoma/metabolismoRESUMO
The efficacy and tolerability of a slow-release preparation of bromocriptine (Parlodel SRO) were compared to those of conventional bromocriptine (Parlodel R) in a double blind, double dummy study of 12 hyperprolactinemic women (plasma PRL 81.3 +/- 4.73, ng/ml mean +/- SEM). For 2 weeks, the patients received 2.5 mg b.i.d. Parlodel R or 5 mg once daily Parlodel SRO; for the following 2 weeks, the dose of the drugs was doubled. The patients were then treated, in an open study, with 2.5-10 mg daily Parlodel SRO for 6 months. Both preparations caused a prompt and sharp PRL fall. Hormone levels remained inhibited over the whole month of observation with both preparations. Daily PRL profiles were very close with either drug although morning PRl levels were slightly higher during Parlodel SRO than during Parlodel R administration. Doubling the doses of the two drugs did not result in further significant lowering of PRL values. During the 6-month study with Parlodel SRO, plasma PRL further decreased and normalized in 11 of 12 patients. Clinical improvement occurred in the majority of cases. Tolerability of Parlodel SRO appeared to be better, though without statistically significant differences, than that of Parlodel R. Side effects were less important with the former compound in their number, severity and duration. In conclusion, thanks to its favourable pharmacological profile, Parlodel SRO appears to be a valuable alternative to regular bromocriptine in the management of hyperprolactinemia.