beta-endorphin and Cushing-Syndrome

Corticotroph adenoma is a benign tumor composed of adenohypophyseal cells; carcinoma with metastasis and ectopic adenoma have also been reported. In our pathological series, the frequency of this type of adenoma is 13% (250/1863 tumors removed between 1970 and 2001). Usually, corticotroph adenomas synthesize peptides derived from POMC maturation: ACTH, ss-endorphine, and ssLPH. In the great majority of cases, ACTH induces hypercorticism with clinical and biological signs of Cushing's disease. However, some tumors the pathologist identifies as corticotroph adenomas are not associated with clinical signs of hypercorticism (20% of the corticotroph adenomas in our series). Corticotroph adenoma is a basophilic or chromophobe tumor composed of cells which remain regulated by cortisol. This may explain the small size of this type of adenoma in 80% of the cases. In contrast, "silent" adenomas or macroadenonas which synthesize high-weight POMC are aggressive invasive tumors. Neurosurgery is indicated for the treatment of corticotroph adenoma. Recurrence is explained by incomplete removeal of the tumor. Peroperative studies may be necessary to find microadenomas. In some cases, the whole pituitary must be removed and cut in serial sections to find a tumor measuring<2 mm. In our opinion, the existence of corticotroph hyperplasia inducing Cushing's disease remains to be proven (we have never observed one). The pituitary origin of the tumor is based on its monoclonality. The general mechanism of tumorigenesis is known, but the specific factors involved and markers of aggressiveness remain to be discovered.

Topics: Adenoma; Adrenocorticotropic Hormone; Animals; beta-Endorphin; beta-Lipotropin; Biomarkers, Tumor; Cell Cycle Proteins; Corticotropin-Releasing Hormone; Cushing Syndrome; Cytokines; Growth Substances; Humans; Hyperplasia; Hypothalamo-Hypophyseal System; Mice; Mice, Knockout; Mice, Transgenic; Neoplasm Proteins; Pituitary Gland, Anterior; Pituitary Neoplasms; Pituitary-Adrenal System; Pro-Opiomelanocortin; Receptors, Glucocorticoid; Retrospective Studies

Substantial evidence now exists to indicate that the endogenous hypothalamic opioidergic mechanism(s) represents one of the important controlling systems for release of gonadotropin-releasing hormone. Modulations of frequency and amplitude of the secretory activity of gonadotropin-releasing hormone appears to be mediated through an inhibitory action of endogenous opioids, and the functional coupling of the opioidergic and gonadotropin-releasing hormone systems is an ovarian steroid-dependent event. There is also evidence to implicate suprahypothalamic mechanism(s) that enhance endogenous opioid inhibition of secretion of gonadotropin-releasing hormone. Although exogenous opioid peptides and their synthetic analogs consistently induce the secretion of prolactin, blockade of opioid receptors in humans by naloxone failed to elicit a decrement in the levels of prolactin under a variety of conditions. On the contrary, naloxone induced a remarkable increment in the secretion of prolactin via an increased frequency of pulsatile release which is synchronized with pulses of luteinizing hormone. These observations suggest that a common neuroendocrine mechanism is involved in the opioidergic control of the secretion of both luteinizing hormone and prolactin in women.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Cushing Syndrome; DNA, Recombinant; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Female; Gonadotropins; Humans; Hypothalamus; Luteinizing Hormone; Menstrual Cycle; Naloxone; Ovary; Pituitary Hormone-Releasing Hormones; Prolactin; Receptors, Opioid

Anterior pituitary corticotrophin cells secrete ACTH as part of a larger precursor molecule, pro-opiomelanocortin. Post-translational cleavage of this precursor yields three major peptides: ACTH, beta-LPH and N-POMC. Experiments both in vivo and in vitro suggest that N-POMC may act as a prohormone amplifier for ACTH-induced adrenal steroidogenesis and as regulator of adrenocortical cell growth. The secretion of POMC is under the control of CRF. These findings are discussed in relation to the pathophysiology of corticotrophinoma. The primary defect in this condition appears to reside at the level of the anterior pituitary cell and is readily amenable to treatment by trans-sphenoidal microsurgery. The estimation of plasma ACTH concentrations is proving useful in the monitoring of various clinical conditions including Addison's disease and congenital adrenal hyperplasia.

Topics: Adrenal Cortex; Adrenal Gland Diseases; Adrenocorticotropic Hormone; beta-Endorphin; beta-Lipotropin; Circadian Rhythm; Cushing Syndrome; Dexamethasone; Endorphins; Feedback; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Infant, Newborn; Male; Neurosecretion; Pituitary Hormones, Anterior; Pituitary-Adrenal System; Pro-Opiomelanocortin; Protein Precursors; Puberty

Ovine corticotropin-releasing factor (oCRF) stimulates increased plasma immunoreactive adrenocorticotropin (IR-ACTH) and IR-cortisol at threshold, half-maximal, and maximal doses of 0.01-0.03, 0.3-1, and 3-10 micrograms/kg, respectively. Side effects occur with increasing frequency, severity, and duration at doses above 1 microgram/kg. oCRF has a prolonged duration of action, at least in part because of the long circulating half-life of intact oCRF in plasma. Increasing doses of oCRF given in late afternoon progressively diminish the next morning's circadian rise in plasma IR-ACTH in normal subjects, but not in Addisonian patients or subjects receiving metyrapone, indicating that prolonged oCRF-induced hypercortisolemia is the cause. Plasma IR-lipotropins and IR-beta-endorphin rise and fall concomitantly with IR-ACTH after oCRF injection. Arginine vasopressin increases the IR-ACTH response to oCRF fourfold when given simultaneously with oCRF. Cushing's disease patients respond variably, suggesting that oCRF may not be a very useful diagnostic agent in Cushing's syndrome. However, the combination of oCRF with growth hormone-releasing factor, gonadotropin-releasing hormone, and thyrotropin-releasing hormone appears to provide a rapid and useful test of combined anterior pituitary function.

Topics: Adrenocorticotropic Hormone; Adult; Arginine Vasopressin; beta-Endorphin; beta-Lipotropin; Circadian Rhythm; Clinical Trials as Topic; Corticotropin-Releasing Hormone; Cushing Syndrome; Dose-Response Relationship, Drug; Double-Blind Method; Drug Synergism; Endorphins; Hemodynamics; Humans; Hydrocortisone; Kinetics; Male; Middle Aged; Pituitary Gland, Anterior; Time Factors

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

Topics: Adult; beta-Endorphin; Cognition; Cushing Syndrome; Emotions; Endorphins; Humans; Middle Aged; Naloxone; Nelson Syndrome; Nociceptors

The case of a 60-year-old female with severe and rapidly progressing Cushing's syndrome with fatal consequences is described. Both the clinical and the biochemical findings were consistent with ectopic ACTH production. A computed tomographic (CT) scan revealed intact pituitary and enlarged adrenal glands. Liver metastases were seen but the primary neoplasm was not found. Treatment with aminoglutethimide and other therapeutic measures were unsuccessful. A carcinoma of the right ovary was discovered on autopsy. The tumour cells showed immunoreactivity for neuron-specific enolase (NSE), ACTH and beta-endorphin with differing degree of intensity.

Topics: ACTH Syndrome, Ectopic; Adrenocorticotropic Hormone; beta-Endorphin; Cushing Syndrome; Fatal Outcome; Female; Humans; Liver Neoplasms; Lymphatic Metastasis; Middle Aged; Ovarian Neoplasms; Phosphopyruvate Hydratase

We report a case of a 25-year-old man with Cushing's syndrome due to an ACTH and CRH-producing thymic carcinoid. Immunohistology and radioimmunoassay demonstrated CRH and a lesser amount of ACTH in the resected primary tumor. After a symptom-free period, the tumor recurred and the patient died. Tumor obtained at autopsy contained mainly ACTH and lesser quantities of CRH. We conclude that this thymic carcinoid initially produced mainly CRH and then transformed to secrete mainly ACTH, suggesting that endocrine tumors may change their functional phenotype.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Carcinoid Tumor; Corticotropin-Releasing Hormone; Cushing Syndrome; Humans; Immunohistochemistry; Male; Neoplasm Recurrence, Local; Thymus Neoplasms

The effect of corticotropin (ACTH)-releasing hormone (CRH) administration on alpha-melanocyte-stimulating hormone (alpha-MSH), ACTH and beta-endorphin (beta-EPH) was evaluated in the inferior petrosal sinuses and in the periphery of 30 patients affected with Cushing's disease subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes. Baseline PRL levels, sensitivity to dexamethasone and surgery outcome were compared to alpha-MSH response. CRH bolus did not modify alpha-MSH concentrations either in the inferior petrosal sinuses or in the periphery in the 30 patients considered as a whole. In 7 of 30 patients, however, a greater than 50% increase over baseline alpha-MSH levels (from 50 to 115.5%) was recorded in the inferior petrosal sinus ipsilateral to the adenoma (from 42.9 +/- 1.7 to 76.4 +/- 4.6 ng/l; p < 0.001), whereas no change was found in the contralateral inferior petrosal sinus or in the periphery. Conversely, as expected, ACTH and beta-ELI significantly increased in all the patients after CRH both in the inferior petrosal sinuses and in the periphery (particularly in the inferior petrosal sinus ipsilateral to the adenoma). No difference in sensitivity to dexamethasone (urinary cortisol percent decrease: 66.4 +/- 4.9 vs. 67.8 +/- 3.4) and surgery outcome (chi 2 test: p = 0.7) was found between patients with alpha-MSH response to CRH and patients without such a response. By contrast, baseline PRL levels, although being normal in both groups, were significantly higher in patients with alpha-MSH response to CRH (18.1 +/- 1.6 vs. 10.1 +/- 0.7 micrograms/l; p < 0.001). In conclusion, the results of the present study suggest that in a subset of patients with Cushing's disease (23.3% of our series) alpha-MSH may be released after the administration of CRH together with ACTH and beta-EPH by adenomatous corticotrophs. In this subset of patients, PRL levels may be in the upper normal range.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; alpha-MSH; beta-Endorphin; Corticotropin-Releasing Hormone; Cushing Syndrome; Female; Humans; Male; Middle Aged; Petrosal Sinus Sampling; Prolactin

The aim of this study was to evaluate the effect of acute human corticotropin (ACTH)-releasing hormone (CRH) administration (100 micrograms, as i.v. bolus) on tumor necrosis factor-alpha (TNF alpha) levels in the inferior petrosal sinuses and in the peripheral blood of 7 patients with Cushing's disease subjected to diagnostic inferior petrosal sinus sampling. Blood samples for ACTH, beta-endorphin (beta-EPH) and TNF alpha were collected from inferior petrosal sinuses and periphery simultaneously. In addition, TNF alpha concentrations were measured after CRH administration (10 nmol/l, 100 nmol/l and 1 mumol/l) in culture medium from primary cultures obtained in 3 of 7 patients. At baseline, plasma ACTH and beta-EPH levels were significantly higher in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma than in the contralateral one and in the periphery (p < 0.001) whereas no significant difference was found as far as serum TNF alpha levels were concerned. CRH administration caused a significant increase of ACTH (p < 0.001), beta-EPH (p < 0.01) and TNF alpha (p < 0.01) levels greater in the ipsilateral inferior petrosal sinus than in the contralateral one and in the periphery. In addition, CRH increased ACTH, beta-EPH and TNF alpha levels in the culture medium of three ACTH-secreting tumors at the doses of 100 nmol/l and 1 mumol/l (greater than 300, 200 and 110% of baseline pretreatment incubation levels, respectively). These data suggest that CRH may increase TNF alpha concentrations in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma and in the peripheral blood as well. In addition, it stimulated TNF alpha release both in vivo and in vitro. These findings suggest the possibility that an imbalanced intrapituitary TNF alpha production can be detected in ACTH-secreting adenomas.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Corticotropin-Releasing Hormone; Cushing Syndrome; Female; Humans; Male; Middle Aged; Petrosal Sinus Sampling; Pituitary Neoplasms; Tumor Necrosis Factor-alpha

Hormones of the hypothalamic-pituitary-adrenal (HPA) axis are connected closely with immune measures. To investigate whether Cushing's syndrome (CS) is associated with immune dysregulation, we compared the percentage of specific lymphocyte subsets as well as natural cell activity (NKCA) in 48 patients with Cushing's syndrome and 48 age- and sex-matched normal controls. Lymphocyte subset analysis included the percentage of lymphocytes expressing CD3 (total T), CD4 (T helper/inducer), CD8 (T suppressor/cytotoxic) and CD56 (NK cell) antigens. Baseline plasma concentrations of cortisol, ACTH and beta-endorphin as well as 24 h urinary-free cortisol (UFC) levels also were determined. Results indicated a decrease in the percentage of CD4+ cells (p < 0.05), an increase in percentage of CD8+ cells (p < 0.05), a decrease in CD4/CD8 ratios (p < 0.01), and a reduction in NKCA (p < 0.05) in patients with CS compared to matched controls. We also found significant negative correlations between NKCA on the one hand and 24 h UFC (p < 0.05) and plasma beta-endorphin (p < 0.05) on the other. These results indicate there is immune dysregulation in CS patients which can be explained in part by an increase in HPA-axis hormones.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; CD4-CD8 Ratio; Cushing Syndrome; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Immune Tolerance; Immunophenotyping; Killer Cells, Natural; Lymphocyte Activation; Male; Middle Aged; Pituitary-Adrenal System; Psychoneuroimmunology; Reference Values; T-Lymphocyte Subsets

Topics: Adenoma; Adult; beta-Endorphin; Bromocriptine; Cushing Syndrome; Female; Humans; Hyperprolactinemia; Neoplasm Recurrence, Local; Pituitary Neoplasms; Time Factors

The endogenous opioid beta-endorphin, a derivative of proopiomelanocortin, stimulates the growth of cloned human small cell lung carcinoma. The present hypothesis states that mutations of the retinoblastoma gene (a tumor suppressor gene) associated to the malignant transformation of bronchial cells would trigger a cascade of biomolecular events leading to 'de novo' proopiomelanocortin expression in small cell lung carcinoma.

Topics: ACTH Syndrome, Ectopic; beta-Endorphin; Carcinoma, Small Cell; Cushing Syndrome; Female; Gene Expression Regulation, Neoplastic; Genes, fos; Genes, Retinoblastoma; Hormones, Ectopic; Humans; Lung Neoplasms; Models, Biological; Neoplasm Proteins; Pro-Opiomelanocortin; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-fos; Retinoblastoma Protein

In humans, proopiomelanocortin (POMC) and the peptides derived from it have been individually identified in plasma under differing conditions. However, direct quantitative comparison has proved difficult because of the limitations of RIAs. Using a panel of monoclonal antibodies recognizing different regions of POMC, we have developed specific two-site immunoradiometric assays (IRMAs) for the ACTH precursors (POMC and pro-ACTH), ACTH, beta-lipotropin (beta LPH), beta-endorphin (beta EP), and the N-terminal POMC fragment (N-POC). We have quantified these peptides directly in plasma from normal subjects under basal conditions and in response to different regulatory factors. Basal levels of ACTH precursors, 5-40 pmol/L, were greater than or equal to ACTH, less than 0.9-11.3 pmol/L; N-POC, 5.6-16.8 pmol/L; beta LPH, 2.5-6.7 pmol/L; and beta EP less than or equal to 1.7 pmol/L. ACTH, N-POC, beta LPH, and beta EP levels increased in parallel in response to metyrapone (n = 8) and decreased in response to dexamethasone (n = 8), whereas ACTH precursor concentrations did not respond. After human CRH administration, peripheral concentrations of ACTH, N-POC, and beta LPH showed similar increments (median increment, 163%, 145%, and 172%, respectively; n = 6). POMC peptide responses to human CRH were also assessed in inferior petrosal sinuses draining the pituitary in 20 patients with pituitary-dependent Cushing's disease. In these patients, the increment in ACTH after CRH exceeded that in ACTH precursors by 4-fold (median, 459% and 96%). An increase in the ratios of ACTH/N-POC and ACTH/beta LPH was also apparent after CRH stimulation. The increment in beta EP after CRH always exceeded the increments in POMC and beta LPH. In summary, these data suggest that significant concentrations of ACTH precursors are present in the circulation of normal subjects, that ACTH precursors are not regulated in the same way as the processed POMC peptides, and that ACTH and beta EP are preferentially released from the pituitary in response to CRH.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; beta-Lipotropin; Corticotropin-Releasing Hormone; Cushing Syndrome; Dimethyl Sulfoxide; Female; Humans; Immunoradiometric Assay; Male; Metyrapone; Middle Aged; Peptide Fragments; Pituitary Gland; Pro-Opiomelanocortin; Protein Precursors

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

We wished to discriminate between the opioid peptide beta-endorphin (beta-EP) and its non-opioid precursor beta-lipotrophin (beta-LPH) in normal subjects and patients with ACTH-related disorders.. We produced monoclonal antibodies to beta-EP and beta-LPH for the development of two-site immunoradiometric assays (IRMAs) which specifically quantitate beta-EP and beta-LPH.. Samples were obtained from patients with a range of ACTH-related disorders and compared with 18 normal subjects. Peptide levels were also compared in six patients with Cushing's syndrome undergoing bilateral inferior petrosal sinus sampling with corticotrophin releasing hormone administration.. In the beta-EP IRMA, antibody 6B2, specific for beta-EP 18-27, is radiolabelled and antibody 2E10, recognizing beta-EP 1-5, is coupled to Sephacryl S-300 as solid phase. The IRMA is specific for beta-EP (beta-LPH cross-reacts < 0.02%), has a detection limit of 1.4 +/- 0.7 pmol/l (n = 7) and has a within-assay coefficient of variation of < 10% between 4.9 and 1200 pmol/l. In the beta-LPH IRMA, antibody 6B2, which recognizes an epitope common to beta-LPH and beta-EP, is radiolabelled and paired with solid-phase antibody 5C11 which recognizes beta-LPH 39-56. The binding site of this antibody ensures that beta-EP cannot be measured in the beta-LPH assay. The detection limit is 0.8 +/- 0.1 pmol/l (n = 9) and the within-assay coefficient of variation is < 10% at concentrations 1.7-870 pmol/l.. In normal subjects, beta-EP and beta-LPH levels were < 1.4-1.7 pmol/l (< 5-6 ng/l) and 2.5-6.7 pmol/l (29-77 ng/l) at 0930 h and < 1.4-1.7 pmol/l (< 5-6 ng/l) and 1.9-4.5 pmol/l (22-49 ng/l) at 1600 h, respectively. In patients with ACTH-related pathologies concentrations of beta-EP and beta-LPH paralleled those of ACTH. The ratio of beta-LPH:beta-EP in plasma varied between 3.2:1 and 38:1 in these patients demonstrating that beta-LPH is the major circulating peptide derived from the C-terminal of pro-opiomelanocortin in man. However, in two patients undergoing bilateral inferior petrosal sampling with corticotrophin releasing hormone for diagnosis of Cushing's disease beta-EP concentrations increased rapidly during the first 5 minutes of the test, resulting in a sharp decrease in the beta-LPH: beta-EP ratio. These results suggest that beta-EP is preferentially released in response to acute corticotrophin releasing hormone stimulation.. It is concluded that two-site IRMAs for beta-EP and beta-LPH provide an easy approach to study the dynamic changes in processing of beta-LPH to beta-EP.

Topics: ACTH Syndrome, Ectopic; Addison Disease; Adolescent; Adrenocorticotropic Hormone; Adult; Animals; Antibodies, Monoclonal; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Drug Stability; Endocrine System Diseases; Female; Humans; Immunoradiometric Assay; Male; Middle Aged; Nelson Syndrome; Reference Values; Sensitivity and Specificity

Recent reports suggest that, contrary to radioimmunoassays (RIA), immunoradiometric assays (IRMA) artifactually decrease plasma ACTH levels in patients with the ectopic ACTH syndrome. Discrepancies between RIA and IRMA results may provide a means of discriminating this entity from Cushing's disease. We have compared the results of these two techniques, together with those of a beta-endorphin assay, in 17 patients with Cushing's disease, 9 with the ectopic ACTH syndrome and 30 controls. ACTH-RIA and ACTH-IRMA levels in patients with Cushing's disease were similar (17.5 +/- 2.5 vs 15.1 +/- 2.8 pmol/l) and were correlated (rs = 0.59, p less than 0.01). ACTH-RIA levels in patients with the ectopic ACTH syndrome were higher than ACTH-IRMA levels (27.3 +/- 2.9 vs 14.5 +/- 2.5, p less than 0.01) and these did not correlate. The ACTH-RIA and ACTH-RIA/ACTH-IRMA ratio levels in patients with the ectopic ACTH syndrome were higher than those of patients with Cushing's disease (p less than 0.01), but they overlapped with these in 27 and 31% of cases respectively. Plasma beta-endorphin level was higher in patients with the ectopic ACTH syndrome than in patients with Cushing's disease (81.9 +/- 19.4 vs 26.4 +/- 5.6 pmol/l, p less than 0.01) and was correlated with ACTH only in patients with Cushing's disease. The overlap in beta-endorphin and beta-endorphin/ACTH-IRMA molar ratio levels between the two groups were 19 and 27% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Cushing Syndrome; Humans; Immunoradiometric Assay; Osmolar Concentration; Reagent Kits, Diagnostic

Bilateral simultaneous inferior petrosal sinus sampling, associated with the oCRH stimulation test (100 micrograms i.v. as a bolus) was performed in 22 patients with Cushing's syndrome and no signs of pituitary abnormalities. Catheters were inserted into both femoral veins. More than one site in the superior and inferior vena cava was sampled before reaching the inferior petrosal sinuses. Blood samples for ACTH and beta-endorphin were gently aspirated from both petrosal sinuses and from a peripheral vein simultaneously. Blood was drawn at 0, 5, 10 and 15 min after oCRH injection. Seventeen of 22 patients showed an ipsilateral to peripheral vein ratio higher than 1.5, and 12 patients showed a lateralization of ACTH levels after oCRH stimulation. Seventeen patients underwent transsphenoidal pituitary surgery. Nine patients had a pituitary adenoma at the expected side; 1 at the contralateral side, while in 2 it was central. Three of 4 patients in whom the ipsilateral/peripheral ratio was less than 1.5 had the highest ACTH levels at the superior or inferior vena cava, not responsive to oCRH stimulation. One of these had a mediastinal and one a pulmonary mass. The third one, with an occult ectopic source, is still under investigation. At immunohistochemical and biological in vitro studies, both tumors were shown to secrete ACTH. In 13 patients in whom both beta-endorphin and ACTH measurements were performed, these hormones showed similar patterns of response. In conclusion, simultaneous bilateral petrosal sinus catheterization is a useful tool in the differential diagnosis of Cushing's syndrome as concerning pituitary and ectopic forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: ACTH Syndrome, Ectopic; Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Cavernous Sinus; Corticotropin-Releasing Hormone; Cushing Syndrome; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Vena Cava, Inferior; Vena Cava, Superior

Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and beta-lipotropin/beta-endorphin (beta-LPH/beta-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean [+/- SD] depressed mood score = 0.17 +/- 0.4; modified Hamilton Depression scale score = 7.6 +/- 4.5) and five as severely depressed (mean depressed mood score = 2.4 +/- 0.5; modified Hamilton Depression scale score = 15 +/- 5.6) (p < 0.05). ACTH and beta-LPH/beta-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and beta-LPH/beta-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly depressed = 90.0 +/- 16.7; severely depressed = 34.6 +/- 8.7 (p < 0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0 mg dexamethasone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Depressive Disorder; Female; Humans; Hypothalamo-Hypophyseal System; Male; Metyrapone; Middle Aged; Neurocognitive Disorders; Personality Inventory; Pituitary-Adrenal System

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

This study explores the possibility of improving endocrinologic testing during petrosal sinus catheterization by determining both beta-endorphin and corticotropin (ACTH). We studied 14 patients with Cushing's disease, two with adrenal tumor, and three with ectopic tumors secreting ACTH. In patients with Cushing's disease, beta-endorphin concentrations paralleled those of ACTH in all basal plasma samples collected either from petrosal sinuses or peripheral veins. Individual responses of beta-endorphin and ACTH to corticotropin releasing hormone (CRH) were closely related to the presence of a corticotroph adenoma. In such patients, a consistently higher concentration of beta-endorphin over ACTH was observed in all samples collected either from petrosal sinuses or peripheral veins; the ratios were unchanged after the administration of CRH. In patients with ectopic ACTH secretion, the mean ratio of beta-endorphin over ACTH (with both values expressed in pmol/L) was significantly higher (3.5) than that of patients with Cushing's disease (2.9) or Cushing's syndrome due to adrenal tumor (2.7).

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Catheterization; Corticotropin-Releasing Hormone; Cranial Sinuses; Cushing Syndrome; Humans

Topics: Addison Disease; Adult; beta-Endorphin; Cushing Syndrome; Female; Humans; Hypopituitarism; Infant, Newborn; Male; Nelson Syndrome; Pituitary Function Tests; Pregnancy; Radioimmunoassay; Radioligand Assay; Reference Values

The combined intravenous injection of TRH and GnRH elicited paradoxical responses of plasma beta-endorphin in active and successfully treated pituitary dependent Cushing's disease as well as in ectopic ACTH syndrome and in congenital adrenal hyperplasia. No response was observed in Cushing's syndrome due to adrenal tumours. It is concluded that an abnormal response to inappropriate releasing hormones cannot verify the existence of a pituitary corticotrophic microadenoma.

Topics: Adenoma; Adolescent; Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Cushing Syndrome; Female; Humans; Male; Pituitary Hormone-Releasing Hormones; Thyrotropin-Releasing Hormone

Equine Cushing's disease is caused by an adenomatous hyperplasia of the intermediate pituitary which secretes high levels of beta-endorphin, ACTH, and other peptide derivatives of POMC. In the present study we found that plasma and cerebrospinal fluid immunoreactive beta-endorphin (i beta-endorphin) levels were 60- and 120-fold higher than control values in horses with Cushing's disease. There were no significant differences in intermediate lobe i beta-endorphin concentrations, although anterior lobe i beta-endorphin was significantly reduced in Cushing's horses, presumably because high levels of circulating glucocorticoids inhibit POMC biosynthesis in corticotrophs. Although the i beta-endorphin concentration of the tumors was not different from that in normal tissue, the posttranslational processing of beta-endorphin in the two tissues differed significantly. In controls, beta-endorphin-(1-31) was extensively processed to N-acetyl-beta-endorphin-(1-31), -(1-27), and -(1-26) and des-acetyl beta-endorphin-(1-27). N-Acetyl-beta-endorphin-(1-27) was the predominant form, constituting 57% of the total i beta-endorphin, whereas beta-endorphin-(1-31) was quantitatively minor (less than 7% of the total immunoreactivity. In adenomatous pituitaries, the processing of beta-endorphin was restricted, significantly increasing the proportions of beta-endorphin-(1-31) and N-acetyl-beta-endorphin-(1-31) and lowering the amounts of N-acetyl-beta-endorphin-(1-27) and -(1-26). These changes in peptide processing were associated with markedly reduced levels of dopamine, suggesting that the dopaminergic neurons that normally control intermediate lobe secretion no longer innervate the hyperplastic tissue. These findings are consistent with evidence that the dopaminergic innervation of the intermediate pituitary regulates the posttranslational processing and release of beta-endorphin.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; beta-Endorphin; Cushing Syndrome; Dopamine; Female; Horse Diseases; Horses; Hydroxyindoleacetic Acid; Male; Orchiectomy; Pituitary Gland; Pituitary Neoplasms; Protein Processing, Post-Translational; Reference Values; Serotonin

The purpose of this study was to evaluate the effect of clonidine--an alpha 2-adrenergic agonist--and naloxone--an opiate antagonist--on pituitary hormone release. The study involved 43 women: 20 menopausal women, 9 untreated women with ACTH-dependent Cushing's disease, and 14 healthy women. Serum GH, ACTH, LH, FSH, TSH, cortisol, and plasma beta-endorphin concentrations were measured with RIA methods. A significant increase in GH and a significant decrease in ACTH and in cortisol was observed after clonidine injection in healthy women. Clonidine caused a significant decrease in LH concentration in the luteal phase of the menstrual cycle. However, naloxone induced the opposite effect on pituitary hormone release. In Cushing's disease, ACTH significantly decreased in response to clonidine. In postmenopausal women with hypertension a decrease in blood pressure, a marked decrease in the number of hot flashes, as well as a diminution in amplitude and frequency of LH pulsatility was found. Conclusions are as follows: (1) Clonidine may be useful in the treatment of hypertensive menopausal women; and (2) a diminution in ACTH, beta-endorphin, and cortisol release in response to clonidine was observed in Cushing's disease.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Clonidine; Cushing Syndrome; Female; Growth Hormone; Humans; Hydrocortisone; Hypertension; Luteinizing Hormone; Menopause; Middle Aged; Naloxone; Pituitary Gland, Anterior; Pituitary Hormones, Anterior

An ACTH-producing thymic carcinoid tumour was diagnosed in a 10-year-old girl, 8 years after bilateral adrenalectomy for Cushing's syndrome. The peptides produced by the tumour were characterised thoroughly. High circulating levels of beta-endorphin and other peptides may have contributed to mood and behaviour disturbances.

Topics: ACTH Syndrome, Ectopic; beta-Endorphin; Carcinoid Tumor; Child; Cushing Syndrome; Female; Humans; Paraneoplastic Endocrine Syndromes; Potassium; Thymus Neoplasms

Topics: Addison Disease; Adrenalectomy; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Cushing Syndrome; Female; Humans; Injections, Intravenous; Male; Middle Aged; Naloxone; Radioimmunoassay

Topics: Adolescent; Adult; Anorexia Nervosa; beta-Endorphin; Cushing Syndrome; Endorphins; Humans; Middle Aged; Nelson Syndrome; Radioimmunoassay

We measured basal plasma concentrations of the immunoreactive (IR) proopiomelanocortin (POMC)-derived peptides ACTH, beta-lipotropin (beta LPH), beta-endorphin (beta END), and alpha MSH in 160 normal dogs, 32 dogs with Addison's disease, 42 dogs with adrenocortical tumors causing Cushing's syndrome, and 169 dogs with pituitary-dependent Cushing's disease. In normal dogs, plasma IR-POMC peptide levels were similar to those in man, except that IR-alpha MSH, a pars intermedia POMC product, was readily detected. In Addisonian dogs, plasma cortisol was decreased, and the IR-POMC peptides were increased, except for IR-alpha MSH, which was normal. In 7 Addisonian dogs given dexamethasone, elevated plasma IR-ACTH, beta LPH, and beta END levels fell dramatically. In dogs with Cushing's syndrome due to adrenal tumors, plasma IR-ACTH, beta LPH, and beta END were decreased, and cortisol was increased, but IR-alpha MSH was normal. Dogs with Cushing's disease due to pars distalis tumors had elevated plasma IR-ACTH, beta LPH, beta END, and cortisol, but normal IR-alpha MSH; their plasma cortisol was suppressed by dexamethasone. There appeared to be 2 types of pars intermedia tumors causing Cushing's disease: 1 dexamethasone nonsuppressible and with disproportionately high plasma IR-alpha MSH levels, the other relatively dexamethasone suppressible and with normal to slightly elevated IR-alpha MSH levels. These 2 pars intermedia tumor types may arise from 2 distinct normal canine pars intermedia cell types. Canine Cushing's disease may provide a useful model for variants of the disorder in man.

Topics: Addison Disease; Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Animals; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Dexamethasone; Disease Models, Animal; Dogs; Endorphins; Female; Hydrocortisone; Male; Melanocyte-Stimulating Hormones; Pituitary Hormones, Anterior; Pituitary Neoplasms

Tissues from 12 human corticotropin-secreting adenomas, obtained during surgery for Cushing's disease (CD, ten cases) or Nelson's Syndrome (NS, two cases), were exclusively mechanically dispersed. Single cells and cell aggregates were plated on extracellular matrix derived from bovine corneal endothelia. Functional responses to physiological stimuli were analyzed by measuring human beta-endorphin (beta h-EP) immunoreactivity (IR) by radioimmunoassay in the culture medium. All adenomas responded with stimulated secretory activity to arginine vasopressin (AVP), corticotropin-releasing factor (CRF), or both. Cortisol higher than 10(-8) M suppressed basal secretion and CRF- or AVP-stimulated beta h-EP-IR secretion. There was no consistent difference in response of the cells when cultured in medium containing 10% fetal calf serum (FCS) or in serum-free conditions. A change of cells from serum to serum-free conditions usually resulted in 10%-50% reduction in the basal secretion level that remained stable for at least 2 weeks and, in one case (NS), 10 weeks. In cells maintained in medium supplemented with 5% serum obtained from the respective patients 40 min after adenoma removal, basal secretion was suppressed to 60% of the baseline level in a 10% FCS control. Long-term incubation with CRF (10(-9) M) showed sustained stimulation of hormone secretion. No remarkable cell proliferation was observed under basal conditions or during long-term, low-dose incubation with cholera toxin (10(-12) M) in two cases (CD), or CRF (10(-9) M) in two cases (NS, CD). Parallel beta-EP-IR and adrenocorticotropin secretion was verified in selected cases.

Topics: Adenoma; Adrenocorticotropic Hormone; Arginine Vasopressin; beta-Endorphin; Corticotropin-Releasing Hormone; Culture Techniques; Cushing Syndrome; Endorphins; Extracellular Matrix; Humans; Hydrocortisone; Nelson Syndrome; Pituitary Neoplasms

To further elucidate the site of action of opioids on the pituitary-adrenal axis, we studied the effect of D-Ala2,MePhe4,met-(O)enkephalin-ol (Sandoz, FK 33-824) on plasma ACTH and beta-endorphin immunoreactivity and serum cortisol in 7 normal subjects and 11 patients with Cushing's syndrome (Cushing's disease, n = 7; adrenal adenoma, n = 2; ectopic Cushing's syndrome, n = 2) after administration of human corticotropin-releasing hormone (hCRH). hCRH (0.1 mg; Bachem) was injected iv after pretreatment with 0.5 mg FK 33-824, im, or 0.9% saline. In normal subjects, the hCRH-induced ACTH, beta-endorphin, and cortisol increases were almost completely abolished by pretreatment with FK 33-824. Mean peak (+/- SEM) hormone concentrations were significantly reduced (ACTH, 16.7 +/- 3.5 vs. 45.3 +/- 7.8 pg/ml; beta-endorphin, 151 +/- 25 vs. 277 +/- 51 pg/ml; cortisol, 8.1 +/- 1.2 vs. 19.5 +/- 2.6 micrograms/dl; P less than 0.02), as were secretory areas (P less than 0.02). These results indicate a direct pituitary action of the synthetic met-enkephalin. In contrast, in patients with Cushing's disease, FK 33-824 did not inhibit hCRH-induced hormone release. Instead, maximum ACTH and beta-endorphin concentrations were slightly but not significantly higher after the administration of FK 33-824 (ACTH, 292 +/- 143 vs. 131 +/- 32 pg/ml; beta-endorphin, 2409 +/- 763 vs. 1921 +/- 600 pg/ml). These findings indicate a defect in inhibitory opiodergic control of ACTH secretion in patients with Cushing's disease, which may contribute to the pathological ACTH hypersecretion. In patients with Cushing's syndrome due to an adrenal adenoma or ectopic ACTH secretion, neither hCRH nor FK 33-824 altered hormone concentrations.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Corticotropin-Releasing Hormone; Cushing Syndrome; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Female; Humans; Hydrocortisone; Male; Middle Aged; Time Factors

Pituitary carcinoma is defined as a malignant pituitary tumour associated with blood- or lymph-borne metastases. Cushing's disease is frequently present in patients with this condition. After adrenalectomy for Cushing's disease, a 37-year-old man developed Nelson's syndrome resulting from a pituitary carcinoma with metastases to the spinal cord, cauda equina, heart, liver, and pancreas. The primary tumour and its metastases showed immunocytochemical staining for ACTH, beta-lipotrophin, and variably for beta-endorphin and alpha-melanocyte stimulating hormone (alpha-MSH). A coincidental glioblastoma was also present. Nine cases of Cushing's disease associated with pituitary carcinoma, including the present patient, are documented in the literature. The case reported is only the second in which immunohistochemical staining of the primary pituitary tumour and its metastases was performed, and the first in which ACTH-related peptides, in addition to ACTH itself, were demonstrated in the carcinoma cells.

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Brain Neoplasms; Cushing Syndrome; Endorphins; Glioma; Humans; Male; Melanocyte-Stimulating Hormones; Nelson Syndrome; Neoplasms, Multiple Primary; Pituitary Neoplasms; Pro-Opiomelanocortin

In order to clarify the diurnal pattern of secretion of plasma immunoreactive (IR) proopiomelanocortin (POMC)-derived peptides, IR-N-terminal peptide (Nt), IR-beta-endorphin (Ep), IR-beta-lipotropin (LPH), and IR-ACTH (ACTH) in normal subjects and in patients with Addison's disease and Cushing's disease, we measured these 4 peptides in the same plasma obtained at 0900 h and then every three hours until 0600 h at the next day. All four peptides showed diurnal rhythms with the peaks at 0600 h, and the nadirs of ACTH, LPH, Ep and Nt were at 0000 h, 0000 h, 1800 h and 0300, respectively in normal subjects. In patients with Addison's disease, these four peptides also showed diurnal rhythms with the peaks at 0600 h for ACTH and Ep and at 0900 h for LPH and Nt, and the nadirs at 2100 h for ACTH and Ep and at 0000 h for LPH and Nt. The molar ratios of Ep/ACTH, LPH/ACTH and Nt/ACTH in plasma also presented diurnal variations in normal subjects and in patients with Addison's disease. On the other hand, in patients with Cushing's disease, ACTH, LPH and Nt showed no rhythmicity or change in molar ratios of Ep/ACTH, LPH/ACTH or Nt/ACTH. Only Ep showed diurnal variation. The molar ratios of Ep/ACTH, LPH/ACTH and Nt/ACTH in patients with Cushing's disease were significantly higher than those in normal subjects and in patients with Addison's disease at 0000 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Addison Disease; Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Circadian Rhythm; Cushing Syndrome; Endorphins; Female; Humans; Male; Middle Aged; Peptide Fragments; Pro-Opiomelanocortin

Sixty-one pituitary corticotroph adenomas from 47 patients with Cushing's disease, 10 with Nelson's syndrome, and four eucorticoid patients were studied by light microscopy, immunoperoxidase, and electron microscopy. Seventy nine percent of all tumors and 70% of Nelson's cases were microadenomas, sometimes minute. A contiguity between the posterior lobe and the adenoma was seen in ten cases. Spontaneous infarction of the tumor with remission of Cushing's syndrome occurred in one case. Light microscopy revealed that the adenoma cells were basophilic and contained PAS-positive granules also staining with Herlant tetrachrome and lead-hematoxylin. The granules stained positively with antiserum to adrenocorticotrophic hormone (ACTH), beta-lipotropic hormones (beta-LPH) and beta-endorphin. The most characteristic ultrastructural finding was the presence of perinuclear bundles of microfilaments found in all our cases. Oncocytic changes were seen in three tumors. Four silent corticotroph adenomas, two of them originally microadenomas that had enlarged to enclosed adenomas while being treated with bromocriptine for hyperprolactinemia and one a large diffuse invasive tumor, did not differ in their microscopic, immunocytological, or ultrastructural features.

Topics: Adenoma, Basophil; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; beta-Lipotropin; Child; Cushing Syndrome; Endorphins; Female; Humans; Hydrocortisone; Male; Microscopy, Electron; Middle Aged; Nelson Syndrome; Pituitary Gland; Pituitary Neoplasms

Release of immunoreactive ACTH and beta-endorphin (beta-EP) in response to corticotrophin-releasing factor (CRF) and dopaminergic agents was studied in vivo and in vitro in a patient with Cushing's disease. Iv administration of synthetic ovine (o) CRF significantly stimulated plasma ACTH release, accompanied by increase of plasma cortisol levels. Oral administration of bromocriptine significantly suppressed plasma cortisol levels. Although reduced responses of plasma ACTH and cortisol to o-CRF was observed 1 month after removal of the pituitary adenoma, these normalized 6 months after operation. In vitro perifusion of the pituitary adenoma obtained by surgery revealed that o-CRF also stimulated ACTH and beta-EP release in a dose-responsive manner (10(-9)M 10(-5)M) and that dopamine suppressed their basal secretion. Gel exclusion chromatography of the perfusates showed that the predominant component of ACTH and beta-EP before and after o-CRF stimulation coeluted with standard ACTH and beta-EP, respectively. The present data suggest that o-CRF is a potent secretagogue for ACTH and beta-EP release from the human pituitary adenoma causing Cushing's disease and that ACTH secretion from certain adenomas, possibly originating from the intermediate lobe of the pituitary gland, is partly regulated by a dopaminergic mechanism.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Animals; beta-Endorphin; Bromocriptine; Corticotropin-Releasing Hormone; Cushing Syndrome; Dexamethasone; Dopamine; Endorphins; Humans; Male; Metyrapone; Pituitary Neoplasms; Receptors, Dopamine; Sheep

Young and mature, genetically obese and non-obese, spontaneously hypertensive rats (SHR) were injected with saline (controls) or naloxone for 12 weeks. Naloxone stilled the hyperphagia to a normal intake in the obese SHR (Obese/SHR) so that young Obese/SHR did not develop their usual massive obesity and mature Obese/SHR that had become massively obese were reduced to leanness. The naloxone-treated young, obese and non-obese SHR (controls) exhibited marked reduction of the weight of their pituitary and adrenal glands, whereas the pituitary and adrenal glands of naloxone-treated mature, obese and non-obese/SHR were greatly increased in weight. The elevated systolic blood pressure of the obese and non-obese rats was reduced after chronic treatment with naloxone. Naloxone treatment caused reduction of blood ACTH, corticosterone, and beta endorphin levels but elevated growth hormone levels. The characteristic hyperinsulinemia, hyperlipidemia, hyperglycemia, elevated BUN levels, and the Cushingoid spectrum of degenerative changes found in Obese/SHR did not appear in naloxone-treated rats.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Blood Pressure; Body Weight; Corticosterone; Cushing Syndrome; Disease Models, Animal; Endorphins; Female; Growth Hormone; Male; Naloxone; Obesity; Organ Size; Pituitary Gland; Rats; Rats, Inbred SHR; Rats, Inbred Strains

In the present paper evidences are provided for the changes occurring in blood opioid neuropeptides in patients with Itsenko-Cushing's disease), who were treated with an antiserotonin drug, cyproheptadine (peritol). An increase in the plasma contents of beta-endorphin and beta-lipotrophin in the above patients has been found to be one of the factors conditioning an enhanced activity of the hypothalamic-pituitary-adrenal system. Treatment of the patients suffering from Itsenko-Cushing's disease with cyproheptadine (peritol) resulted in a decrease of the plasma beta-endorphin and beta-lipotropin, as well as a display in 60% of cases of clinical and laboratory remission. Absence of the clinical remission in some patients treated with peritol indicated a need for intervention in the metabolism of other monoamines involved in the modulation of the action of opioid neuropeptides on the activity of the hypothalamic-pituitary system.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Cyproheptadine; Endorphins; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System

The profile of endogenous opioid peptides in the peptide-rich fraction obtained from a homogenate of an ACTH-secreting human pituitary tumor is presented. Gradient RP-HPLC is used to separate the mixture into peptide constituents. A preparation of opioid receptors is used in a radioreceptor assay with ethorphine - a relatively non-specific ligand that is used as a screen because it interacts with mu, sigma, and delta receptors - as the HPLC detector to detect a range of peptides that derive from proenkephalin A and POMC.

Topics: Adrenocorticotropic Hormone; beta-Endorphin; beta-Lipotropin; Chromatography, High Pressure Liquid; Cross Reactions; Cushing Syndrome; Endorphins; Female; Humans; Middle Aged; Pituitary Neoplasms; Radioligand Assay

Endogenous opiates may be important in the control of ACTH secretion in men. The effect of opiate receptor blockade by naloxone on ACTH, beta-endorphin-like substance and cortisol release was studied in healthy women and in 9 patients with Cushing's disease. In the healthy subjects, ACTH, beta-endorphin and cortisol levels were increased in response to naloxone. However, in 3 our of the 9 patients with Cushing's disease, a paradoxical decrease in serum ACTH, cortisol and beta-endorphin concentrations was observed after naloxone administration. In the patients with a paradoxical response to naloxone, transsphenoidal microadenomectomy was ineffective.

Topics: 17-Hydroxycorticosteroids; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Cushing Syndrome; Endorphins; Female; Humans; Hydrocortisone; Naloxone; Receptors, Opioid

Pituitary adenomas are usually classified according to the nature of their proper hormonal production. Silent adenomas of the pituitary are tumors without clinical and biochemical evidence of overproduction of any known adenohypophyseal hormones. The proportion of such seemingly nonfunctioning tumors is 20 to 30%. Silent corticotropic adenomas are able to synthesize some normal or abnormal sequences of proopiomelanocortin precursor without any signs of hypercorticism. These tumors were divided into basophilic adenomas with strong periodic acid-Schiff (PAS) positivity and chromophobic adenomas with moderate or no PAS positivity. All of our cases were chromophobic adenomas. Two of the cases were positive for beta-endorphin by immunofluorescence. ACTH immunoreactivity was not present in the cells. Electron microscopic study of the adenoma cells showed small secretory granules with a halo. The diameter of these granules varied from 50 to 250 nm. Automated morphometric and densitometric investigations of silent corticotropic adenomas and adenomas from patients with Cushing's disease gave different karyometric results. The most important practical problem arising from the present investigation was the high frequency of recurrence of silent corticotropic tumors.

Topics: Adenoma, Chromophobe; Adult; beta-Endorphin; Cell Nucleus; Cushing Syndrome; Cytoplasmic Granules; Endorphins; Fluorescent Antibody Technique; Humans; Hypophysectomy; Male; Microscopy, Electron; Neoplasm Recurrence, Local; Pituitary Neoplasms

In 14 cases of ACTH-producing pituitary adenomas (8 cases of Cushing's disease and 6 cases of Nelson's syndrome) dispersed cells prepared from adenoma tissue were incubated in a superfusion or static incubation system and investigated for ACTH, beta-endorphin (beta-EP) and beta-lipoprotein (beta-LPH) production. Effects of cortisol and lysine vasopressin (LVP) were evaluated. During the superfusion a qualitatively parallel secretory pattern is obtained for all hormones. Quantitatively, however, the response to LVP stimulation is more pronounced for beta-endorphin-like immunoreactivity (beta-LPH/beta-EP-IR) causing ACTH/beta-LPH/beta-EP-IR ratios to change throughout single experiments. beta-EP/beta-LPH ratios, however, which were estimated by means of Sephadex G-50 gel chromatography at various key points of the superfusion, were constant for each tumor, although variable between different adenomas, ranging from 0.68 to 2.0. The results suggest neither a differential control for the secretion of the peptides investigated within individual tumors nor a direct effect of cortisol or LVP on pro-opiomelanocortin processing. Summarizing clinical data and in vitro findings such as secretory behavior or hormone ratios, we can find no characteristic differences between Nelson's syndrome and Cushing's disease.

Topics: Adenoma; Adrenocorticotropic Hormone; beta-Endorphin; Cushing Syndrome; Endorphins; Humans; In Vitro Techniques; Lipoproteins, LDL; Lypressin; Nelson Syndrome; Pituitary Neoplasms; Pro-Opiomelanocortin

beta-Endorphin31, beta-endorphin1-27, and their alpha-N-acetyl derivatives were specifically separated by ion exchange chromatography from human beta-endorphin-'like' material obtained from extracts and culture media of corticotropic adenomas and extract of plasma from Nelson's syndrome and ectopic ACTH/LPH syndrome. Studies with pituitary-derived materials have shown that human beta-endorphin1-31 was the major form and human beta-endorphin1-27 a minor form. No other peptide was detected. In plasma from the ectopic ACTH-LPH syndrome human beta-endorphin1-31 was the only detected peptide. In 2 such patients with chronic elevation of human beta-endorphin1-31 the pain sensitivity threshold was normal and naloxone induced no modification, suggesting that circulatory human beta-endorphin has no effect on the central nervous system.

Topics: ACTH Syndrome, Ectopic; Adenoma; beta-Endorphin; beta-Lipotropin; Chemical Phenomena; Chemistry; Chromatography, Ion Exchange; Cushing Syndrome; Endorphins; Humans; Nelson Syndrome; Paraneoplastic Endocrine Syndromes; Pituitary Neoplasms

The authors provide the data on the changes in the blood content of opioid neuropeptides in patients with Icenko-Cushing's disease treated with an antiserotonin drug peritol. The high content of beta-endorphine and beta-lipotropin in the patients' blood was one of the factors determining activation of the hypothalamus-pituitary-adrenal system. The treatment of patients with Icenko-Cushing's disease by peritol led to a decrease in the blood content of beta-endorphine and beta-lipotropin, promoting a clinical and laboratory remission in 60% of patients. Some patients treated with peritol did not develop a clinical remission. This indicates the necessity of acting on the metabolism of other monoamines involved in the modulation of the action of neuropeptides on the hypothalamus-pituitary system.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Cyproheptadine; Drug Therapy, Combination; Endorphins; Female; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Middle Aged; Mitotane

The tissue-specific processing of proopiomelanocortin (POMC), the precursor of ACTH, beta-endorphin, and their related peptides, is currently of considerable interest. We report a patient with a large aggressive pituitary tumor, Cushing's syndrome, and hyperpigmentation managed by transsphenoidal hypophysectomy, bilateral adrenalectomy, and sellar irradiation. Preoperatively, plasma levels of immunoreactive ACTH (ir-ACTH; 280 ng/liter) and beta-endorphin (ir-beta EP; 520 ng/liter) were moderately elevated. Chromatography of the plasma showed two peaks of ACTH immunoreactivity, with the major peak eluting in the void volume, and two major peaks of ir-beta EP, corresponding to the elution positions of beta-lipotropin and beta-endorphin standards. Plasma ir-ACTH and ir-beta EP were not suppressed by high doses of glucocorticoid or bromocriptine, a degree of autonomy more commonly found with POMC production from ectopic sources than that from pituitary tumors. Tissue removed at operation was enzymatically dispersed, and the cells were cultured in suspension, propagated, and passaged sequentially for over 20 passages. Using this cell line, we demonstrated that the biosynthesis of POMC, its pattern of processing, and the release of POMC/ir-beta EP/ir-ACTH in vitro were consistent with the in vivo evidence of autonomous secretion and abnormal processing of POMC by this pituitary tumor.

Topics: Adenoma; Adrenocorticotropic Hormone; Autoradiography; beta-Endorphin; Cell Division; Cells, Cultured; Chromatography, Gel; Cushing Syndrome; Electrophoresis; Endorphins; Fluorescent Antibody Technique; Humans; Hydrocortisone; Male; Middle Aged; Peptide Fragments; Pituitary Hormones, Anterior; Pituitary Neoplasms; Pro-Opiomelanocortin; Protein Precursors

The effects of ovine CRF, lysine vasopressin (LVP), and their interrelationships, and rat hypothalamic extract (HME), on ACTH and beta-endorphin release by human pituitary tumor cells from two patients with Nelson's syndrome and one with Cushing's disease and on ACTH and cortisol secretion in vivo were studied. In cultured pituitary tumor cells, both LVP and CRF greatly stimulated ACTH and beta-endorphin release at maximally active concentrations of 0.1 microM and 10 nM, respectively. At these concentrations, the combination of the two substances had an additive or synergistic effect on hormone release. Low concentrations of HME potentiated and/or were synergistic with CRF-mediated ACTH release. In vivo, the combination of CRF (1 microgram/kg) and LVP (10 pressor units) induced greater ACTH release than the sum of the responses to CRF and LVP alone. This synergistic effect of CRF plus LVP concerned only ACTH release, while cortisol release after CRF plus LVP was equivalent to the sum of the maximal increments in this hormone after CRF and LVP alone. The peak levels of cortisol after a combination of CRF and LVP probably reflect the maximum stimulatory capacity of the adrenal cortex. These data support the concept that in man, both ovine CRF and vasopressin are corticotropin-releasing factors which act synergistically. Both substances might well regulate, at the pituitary level, the responsiveness of the pituitary-adrenal axis to stimuli reaching the hypothalamus. A test using ovine CRF and LVP together might provide a better index of total pituitary ACTH reserve than one using the two compounds separately.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Corticotropin-Releasing Hormone; Cushing Syndrome; Drug Synergism; Endorphins; Female; Humans; Hydrocortisone; Hypothalamus; In Vitro Techniques; Lypressin; Nelson Syndrome; Pituitary Gland; Pituitary Neoplasms; Rats; Sheep; Tissue Extracts

Male and female, young (2 months old) and mature (10 months old), obese and nonobese, spontaneously hypertensive rats (SHR) were treated with dexamethasone, 5 micrograms/rat and 10 micrograms/rat, respectively, subcutaneously (SC) 2 times daily for 5 months. Steroid treatment stilled the voracious appetite of the obese SHR, and the massively obese, mature animals were reduced to almost normal size. The young, steroid-treated, obese SHR did not develop their genetically programmed corpulency. The untreated, young and mature, obese SHR ate voraciously, became massively obese, and developed their characteristic Cushing's disease-like spectrum of degenerative changes, eg, hypertension, hyperlipidemia, hyperglycemia, muscle wasting, kidney stones, thin skin, and accelerated aging. The blood pressure of the steroid-treated animals was lowered concomitant with reduced levels of circulating ACTH, beta endorphin, insulin, triglycerides, and cholesterol. Dexamethasone caused hyperlipidemia, hyperglycemia, and increased BUN levels in young obese and nonobese SHR only. The mature obese SHR had giant-sized thymus glands that were further enlarged with steroid treatment; dexamethasone was thymolytic in young, obese and nonobese SHR. Dexamethasone caused severe reduction of pituitary and adrenal gland size, simulating the condition of hypophysectomy. These findings demonstrate that dexamethasone suppression of the pituitary-adrenal axis palliates and prevents the spontaneous development of Cushingoid degenerative changes in these genetically obese and hypertensive rats.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Blood Glucose; Blood Urea Nitrogen; Cushing Syndrome; Dexamethasone; Disease Models, Animal; Endorphins; Female; Hypertension; Insulin; Lipids; Male; Obesity; Organ Size; Pituitary Gland; Rats; Rats, Inbred Strains

Using rapid and reusable affinity columns, we established a method to measure beta-endorphin (beta END) and beta-lipotropin (beta LPH) separately in human plasma. One column contained antibodies against the N-terminal portion of beta LPH, and the other contained antibodies against beta END. The first column separated beta LPH from beta END and concentrated beta LPH as well, and the second separated beta LPH from concentrated beta END. Mean plasma levels (at 0830-0930 h) of beta END and beta LPH in 10 normal subjects were 1.1 +/- 0.1 (+/- SE) and 4.1 +/- 0.4 fmol/ml, respectively; both were markedly elevated in patients with ACTH/LPH hypersecretory states. The molar ratios of plasma levels of beta END and beta LPH were fairly constant in normal subjects (0.28 +/- 0.01), unchanged in patients with Cushing's disease and Cushing's disease after adrenalectomy, lower in patients with Addison's disease (P less than 0.001), higher in patients with chronic bone pain (P less than 0.001), and variable in patients with the ectopic ACTH syndrome. These data indicate that beta END and beta LPH can be measured separately in plasma by simple and reproducible procedures.

Topics: ACTH Syndrome, Ectopic; Addison Disease; Adrenalectomy; Antibody Specificity; beta-Endorphin; beta-Lipotropin; Chromatography, Affinity; Cushing Syndrome; Endorphins; Female; Humans; Male; Radioimmunoassay

The response of pituitary adenomas obtained surgically from patients with Cushing's disease of Nelson's syndrome to synthetic ovine corticotropin-releasing factor (CRF), vasopressins, somatostatin-28, dexamethasone, 3-isobutylmethylxanthine or high [K+] was examined in vitro by measuring the amount of pro-opiomelanocortin (POMC)-derived peptides secreted into the culture medium. CRF did not stimulate the secretion of adrenocorticotropin-, beta-endorphin-, or gamma 3-melanotropin-like peptides from the pituitary adenomas at concentrations ranging from 1 x 10(-13) M to 1 x 10(-7) M whereas vasopressins, 3-isobutyrl-methylxanthine and high [K+] increased, while somatostatin-28 and dexamethasone suppressed, the secretion of these POMC-derived peptides. These findings suggest that either the pituitary ACTH-producing tumors have lost their receptors to CRF or their post-receptor mechanism to CRF is not functional.

Topics: Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Cells, Cultured; Corticotropin-Releasing Hormone; Cushing Syndrome; Dexamethasone; Endorphins; Female; Humans; Male; Melanocyte-Stimulating Hormones; Nelson Syndrome; Pituitary Neoplasms; Somatostatin; Somatostatin-28; Vasopressins

Direct effects of cyproheptadine, reserpine, synthetic ovine corticotropin-releasing factor (CRF), dexamethasone, and lysine-8-vasopressin (LVP) on the secretion of immunoreactive ACTH and beta-endorphin from the adenoma and the nonadenomatous tissue of patients with Cushing's disease were examined using a superfusion system. Cyproheptadine and reserpine (10(-9)-10(-7) M of each) suppressed immunoreactive ACTH and beta-endorphin secretion from both tissues. CRF (10(10)-10(7) M) stimulated the secretion of both peptides from the nonadenomatous tissue, but only a high dose of CRF could stimulate the secretion of these peptides from some adenomas. Such CRF-induced secretion was partially suppressed by dexamethasone. LVP (10(-9)-10(-7) M) stimulated peptide secretion from both types of tissue. These results suggest direct inhibitory effects of cyproheptadine and reserpine on the secretion of these peptides from the pituitary of patients with Cushing's disease, a different stimulatory mechanism of LVP from that of CRF in these tissues, and low sensitivity of the adenoma to CRF.

Topics: Adenoma; Adrenocorticotropic Hormone; beta-Endorphin; Corticotropin-Releasing Hormone; Cushing Syndrome; Cyproheptadine; Dose-Response Relationship, Drug; Endorphins; Humans; In Vitro Techniques; Peptides; Pituitary Gland; Radioimmunoassay; Reserpine

Human ACTH-producing tumor and plasma have been examined by gel filtration and ion exchange chromatography to detect the possible presence of reported multiple forms of immunoreactive beta-endorphin (I-EP) Ion exchange chromatography of I-EP obtained from gel filtration showed four components of I-EP [two major peaks in the positions of EP-(1-31) and EP-(1-27) and two minor peaks in the positions of N-acetyl EP-(1-31) and N-acetyl EP-(1-27)] in two ectopic ACTH-producing lung cancers, and two components of I-EP [the major peak in the position of EP-(1-31) and minor peak in the position of N-acetyl EP-(1-31) in an ectopic ACTH-producing thyroid cancer. Only a single peak in the position of EP-(1-31) was present in plasma from a patient with Nelson's sindrome and a patient with Addison's disease, in the pituitary adenomas from six patients with Cushing's disease, and in the nontumorous pituitary tissues from a patient with Cushing's disease and a patient with acromegaly. These data suggest that the posttranslational processing of EP in human pituitary is different from that in the ectopic ACTH-producing tumor.

Topics: Addison Disease; Adenoma; Adrenocorticotropic Hormone; beta-Endorphin; Chromatography, Gel; Chromatography, Ion Exchange; Cushing Syndrome; Endorphins; Humans; Lung Neoplasms; Nelson Syndrome; Pituitary Gland; Pituitary Neoplasms; Radioimmunoassay; Thyroid Neoplasms

Topics: Adult; Antigens; beta-Endorphin; Cushing Syndrome; Endorphins; Female; Humans; Insulin; Male; Middle Aged; Physical Exertion; Pituitary Neoplasms

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; beta-Endorphin; Circadian Rhythm; Corticotropin-Like Intermediate Lobe Peptide; Cushing Syndrome; Dexamethasone; Dopamine; Endorphins; Female; Glucose Tolerance Test; Horse Diseases; Horses; Hydrocortisone; Insulin; Male; Melanocyte-Stimulating Hormones; Peptide Fragments; Pituitary Hormones, Anterior; Pro-Opiomelanocortin; Protein Precursors; Radioimmunoassay

Topics: Adolescent; Adult; beta-Endorphin; Cushing Syndrome; Endorphins; Humans; Lipoproteins, LDL; Middle Aged; Obesity; Radioimmunoassay

ACTH and lipotropins (beta- and gamma-LPH) are synthesized from a common precursor by the pituitary corticotropic cell. We have measured LPH plasma levels under physiological and pathological conditions and we have compared them with ACTH plasma levels in the same circumstances. Spontaneous variations (nycthemeral rhythm) in LPH, ACTH and cortisol plasma levels were parallel, while responses to Dexamethasone freination test and stress (Insulin induced hypoglycemia) or more specific stimulation (Metopirone, lysine-vasopressin) were parallel and superimposable. LPH levels were always higher than ACTH levels in two pathological circumstances: chronic renal failure and Cushing's syndromes with ectopic ACTH producing tumors. The determination of both ACTH and LPH levels assists the diagnosis of corticotropic insufficiency and etiologic investigation of Cushing's syndrome, after hypercorticolism had been established. Although unable to confirm the presence of corticotropic adenoma in patients with Cushing's disease, or the predict effectiveness of pituitary surgery, these determination bring good arguments for treated Cushing's diseases follow up.

Topics: Adenoma; Adrenocorticotropic Hormone; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Endorphins; Humans; Hypopituitarism; Kidney Failure, Chronic; Pituitary Neoplasms; Pituitary-Adrenal Function Tests

A pituitary tumor from a patient with severe Cushing's disease and marked hyperprolactinemia was extensively studied by immunohistochemical techniques. Tissues from two separate areas of the adenoma were found to contain similar cell proportions of PRL as well as ACTH and related peptides (beta-lipotropin, beta-endorphin, and alpha MSH). The tumor was composed of approximately 70% immunoreactive PRL cells and 5% ACTH-containing cells. Double immunostaining revealed that PRL or ACTH and related peptides were found in two distinct populations of tumor cells. These results document for the first time inappropriate synthesis and secretion of an unusual combination of pituitary hormones from a mixed pituitary adenoma.

Topics: Adenoma; Adrenocorticotropic Hormone; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Endorphins; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Melanocyte-Stimulating Hormones; Microscopy, Electron; Middle Aged; Pituitary Neoplasms; Prolactin

Pituitary adenomas were found in 21 (84%) of 25 dogs with spontaneous pituitary-dependent hyperadrenocorticism. Six dogs had pars intermedia adenomas, whereas 15 had tumours of the pars distalis. Diffuse corticotroph cell hyperplasia was found in 1 of the 4 pituitaries without adenoma; in 2 dogs with pituitary adenoma, coexisting hyperplasia of the surrounding corticotrophs was also present. Immunocytochemical staining of the pituitaries revealed positive staining for ACTH, beta-lipotrophin, and beta-endorphin in the majority of both pars distalis and pars intermedia adenomas. The most frequent and intense staining was found with anti-beta-endorphin. In most part intermedia tumours, many cells stained strongly for alpha-MSH; double immunostaining of one pars intermedia adenoma for ACTH and alpha-MSH showed that some tumour cells stained only for ACTH or alpha-MSH whereas others contained both peptides. Only occasional cells stained for alpha-MSH in pars distalis adenomas.

Topics: Adenoma; Adrenocorticotropic Hormone; Animals; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Dogs; Endorphins; Female; Fluorescent Antibody Technique; Hyperplasia; Male; Melanocyte-Stimulating Hormones; Pituitary Gland; Pituitary Neoplasms

Thirteen patients with either Addison's disease, or Cushing's disease treated by bilateral adrenalectomy, were infused with the long-acting met-enkephalin analogue DAMME. In patients with Addison's disease significant and pronounced falls in ACTH and N- and C-terminal beta-LPH were seen; chromatography suggested that beta-endorphin fell concomitantly. Three out of four patients with Cushing's disease who had not received pituitary irradiation, also showed a decrease in plasma ACTH and N- and C-terminal beta-LPH; however, no change was seen in any of the irradiated patients. The changes were naloxone reversible. The levels of plasma met-enkephalin were normal and did not change after DAMME in any group of patients. These results are interpreted as suggesting that there are inhibitory opiate receptors controlling the release of ACTH, beta-LPH, and beta-endorphin.

Topics: Addison Disease; Adrenalectomy; Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Enkephalin, Methionine; Enkephalins; Female; Hormones; Humans; Male; Middle Aged; Naloxone

Topics: Addison Disease; Adrenalectomy; Adrenocorticotropic Hormone; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Dexamethasone; Endorphins; Enkephalin, Methionine; Enkephalins; Humans; Hydrocortisone; Insulin; Kidney Failure, Chronic; Male

Topics: Adolescent; Adrenalectomy; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Cushing Syndrome; Endorphins; Humans; Hydrocortisone; Middle Aged; Peptide Fragments