beta-endorphin and Pituitary-Diseases

Nine normal volunteers received an intravenous bolus injection of 50, 100, and 200 micrograms ovine Corticotropin releasing factor. There was no dose response relationship between the injected oCRF dosage and stimulated ACTH, beta-endorphin, and cortisol secretion. When human synthetic CRF was injected (50 and 100 micrograms i.v.) no significant difference compared to the oCRF induced ACTH stimulation was observed. In contrast to the lacking relationship between the CRF dosage and the biological response there was a clearcut dose response relationship between the amount of oCRF injected and the CRF immunoreactivity measured 15 minutes after injection with a specific oCRF radioimmunoassay. No serious side effects were observed when the 100 micrograms CRF dosage was used as standard dose in the CRF test in patients with diseases of the hypothalamo-pituitary-adrenal axis. In patients with Cushing's syndrome the CRF test is helpful for the differential diagnosis (ACTH dependent Cushing's disease, autonomous cortisol secretion due to an adrenal adenoma or carcinoma, ectopic ACTH syndrome). In addition the CRF test is of prognostic value after surgical or neurosurgical therapy of Cushing's syndrome. Furthermore secondary adrenal failure after operative therapy can be documented by the CRF test. In patients on corticoid therapy the degree of suppression of CRF induced ACTH secretion correlated to the dosage and the duration of corticoid therapy. The main suppressive effect of corticoids on the hypothalamo-pituitary-adrenal axis seems to take place at the pituitary level. In patients with secondary adrenal failure the analysis of ACTH secretion after CRF administration allows the differential diagnosis between hypothalamic and pituitary ACTH hyposecretion. In conclusion the administration of oCRF has been shown to be a well tolerated and useful tool in the differential diagnosis of the causes of hyper- and hypofunction of the hypothalamo-pituitary-adrenal axis. Though there was only 10% cross reactivity with synthetic human CRF, CRF immunoreactivity could be detected in 53 out of 55 pregnant females. The results of measuring endogenous CRF levels in patients with diseases of the hypothalamo-pituitary-adrenal axis are preliminary but endogenous CRF levels measured by the heterologous oCRF radioimmunoassay, correlated well to the clinical situation and the ACTH-levels. These results have to be verified with a homologous hCRF radioimmunoassay.

Topics: Adrenal Gland Diseases; Adrenocorticotropic Hormone; beta-Endorphin; Corticotropin-Releasing Hormone; Cushing Syndrome; Endorphins; Humans; Hydrocortisone; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Pituitary Diseases; Pituitary-Adrenal System; Prognosis

Plasma ACTH, beta-endorphin and alpha-melanocyte-stimulating hormone levels were evaluated in the inferior petrosal sinuses and in the periphery of 22 patients affected by Cushing's disease, 11 patients with other pituitary diseases subjected to simultaneous and bilateral inferior petrosal sinus sampling and in the peripheral blood of 15 normal subjects. In patients with Cushing's disease ACTH, beta-endorphin and alpha-melanocyte-stimulating hormone levels in the inferior petrosal sinus ipsilateral to the adenoma were significantly higher than in the periphery and in the contralateral inferior petrosal sinus (p < 0.01, p < 0.01 and p < 0.05, respectively). In patients with other pituitary diseases only ACTH and beta-endorphin, but not alpha-melanocyte-stimulating hormone levels in both inferior petrosal sinuses were significantly higher than in the periphery (p < 0.01). Furthermore, no difference was found in the peripheral blood among patients with Cushing's disease, patients with other pituitary diseases and normal subjects for ACTH and beta-endorphin level. By contrast, in patients with Cushing's disease peripheral alpha-melanocyte-stimulating hormone levels were significantly higher than in patients with other pituitary diseases and in normal subjects (p < 0.05). In conclusion, the results of the present study suggest that only in patients with Cushing's disease, but not in patients with other pituitary diseases, alpha-melanocyte-stimulating hormone is released by adenomatous pituitary corticotrophs together with ACTH and beta-endorphin.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; alpha-MSH; beta-Endorphin; Cushing Syndrome; Female; Humans; Male; Middle Aged; Petrosal Sinus Sampling; Pituitary Diseases; Radioimmunoassay

Aim of the present study was the evaluation of ACTH and beta-endorphin-like-immunoreactivity (beta-ELI) in the inferior petrosal sinuses (IPS's) and in the peripheral blood of patients with Cushing's disease (Group 1), with GH- or PRL-secreting adenomas or nontumoral hyperprolactinemia (Group 2). These patients had undergone selective and bilateral simultaneous IPS sampling for diagnostic purposes or for neurosurgical indications. In the patients of Group 1, ACTH and beta-ELI levels were higher in the IPS ipsilateral than in the contralateral to the adenoma and in the periphery (p < 0.001). In the patients of Group 2 ACTH and beta-ELI levels were higher in the IPS's than in the peripheral blood (p < 0.001) and, in the 9 patients with GH- or PRL-secreting adenomas, they were higher in the IPS ipsilateral than in the contralateral to the adenoma and in the periphery (p < 0.05). A significant correlation exists between ACTH and beta-ELI in the periphery (p < 0.01; r = 0.72), in the IPS ipsilateral (p < 0.05; r = 0.54) and contralateral (p < 0.01; r = 0.66) to the adenoma in Group 1, but not in Group 2. In conclusion, higher beta-ELI levels were detected in the IPS's than in the peripheral blood not only in patients with Cushing's disease but also in those with other pituitary diseases not involving ACTH secretion. The absence of correlation between ACTH and beta-ELI in patients not bearing Cushing's disease suggests that in these conditions corticotrophs release ACTH and beta-endorphin in an independent manner.

Topics: Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Cranial Sinuses; Cushing Syndrome; Female; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Middle Aged; Phlebography; Pituitary Diseases; Pituitary Neoplasms; Tomography, X-Ray Computed

Topics: Adrenal Gland Diseases; Adrenocorticotropic Hormone; beta-Endorphin; Endorphins; Humans; Hypothalamic Diseases; Methods; Pituitary Diseases