Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nelson's syndrome is a specific form of Cushing's disease treated by bilateral adrenalectomy, presenting with a deep hyperpigmentation caused by a pituitary adenoma (corticotropinoma). These ACTH-secreting tumors are frequently aggressive, so early diagnosis is of prime importance. We have studied 33 patients with Nelson's syndrome, 28 women and 5 men, aged 14-56 yr at the time of adrenalectomy and 16-58 yr at the time of Nelson's syndrome diagnosis (observed for 5-32 yr). Methods of examination included simultaneous adrenocorticotropic hormone (ACTH) and cortisol measurements during routine hydrocortisone replacement therapy, computed tomography (CT), pituitary magnetic resonance imaging (MRI), and visual field examination. The results obtained in a group of six patients diagnosed in the last 3 yr were compared with those obtained in a group of 27 patients examined before 1992. High plasma ACTH levels accompanied by normal serum cortisol concentration were characteristic for a late stage of the disease. Absolute temporal scotomas were an early finding. MRI, especially with the gadolinium enhancement, was superior to CT in demonstrating pituitary microadenomas in Nelson's syndrome. Thus, MRI diagnosis allowed for an early neurosurgical treatment of the patients with Nelson's tumors.
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PMID:Early diagnosis of Nelson's syndrome. 887 92

The long-acting analogues of somatostatin have an established place in the medical treatment of patients with neuroendocrine tumours. They act through binding with specific, high-affinity membrane receptors. Somatostatin analogue therapy is an effective and safe treatment for most growth hormone and thyrothropin-secreting pituitary adenomas. The potential therapeutic consequences of the presence of somatostatin receptors on clinically 'nonfunctioning' pituitary tumours are still uncertain. Somatostatin analogues are not useful in the treatment of patients with prolactinomas, or adrenocorticotropin (ACTH)-secreting adenomas. However, the somatostatin analogue octreotide suppressed pathological ACTH release in some patients with Nelson's syndrome and ACTH and cortisol secretion in several patients with Cushing's syndrome caused by ectopic ACTH secretion. Somatostatin analogues are effective in the sympatomatic treatment of most (metastatic) pancreatic islet cell tumours and most (metastatic) carcinoids. In some of these patients, they also induce tumour stabilisation or reduction. In some patients with (metastatic) medullary thyroid carcinomas, continuous treatment with very high doses of octreotide can be of temporary relief. The clinical effectiveness of somatostatin analogues in patients with small cell lung cancer is currently under investigation. Long-term therapy with somatostatin analogues of catecholamine-secreting (malignant) paragangliomas and phaeochromocytomas has not shown clinical benefits.
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PMID:Somatostatin analogue treatment of neuroendocrine tumours. 893 99

Patients with Cushing's syndrome (137 total) who underwent adrenalectomy from 1957 through 1999 were reviewed for survival and complications. Of the 137 patients, 83 had adrenocortical adenoma, 30 Cushing's disease, seven primary pigmented nodular adrenocortical disease (PPNAD), eight adrenocorticotropin (ACTH)-independent macronodular hyperplasia, five adrenocortical carcinoma, and four ectopic ACTH syndromes. Seventy-eight patients with adrenocortical adenoma are alive, and their survival rate was equal to the age-matched control population, when patients who died of postoperative complications were excluded. Of the patients with Cushing's disease, 20 are alive, and ten of 16 patients (63%) who were followed and evaluated, had skin pigmentation. Four of 16 patients (25%) developed Nelson's syndrome. Five PPNAD patients and six with ACTH-independent macronodular hyperplasia are alive. All five adrenocortical carcinoma patients and four with ectopic ACTH syndrome died within two years after operation. The prognosis for patients with adrenocortical adenoma after unilateral adrenalectomy is excellent, though it is important to avoid operative complications. The rapid disappearance of signs and symptoms of glucocorticoid excess after total adrenalectomy is assured, and the prognosis is satisfactory under careful glucocorticoid replacement, making total adrenalectomy an alternative treatment for Cushing's disease.
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PMID:Surgical management of Cushing's syndrome. 1091 11

Bilateral adrenalectomy is an acceptable alternative treatment in salt-wasting 21-hydroxylase deficiency when conventional steroid replacement therapy fails to control hyperandrogenism. Objections to surgical adrenalectomy have been based on surgical risk, possible loss of protective adrenal function, and the risk of ACTH-induced activation of adrenal rest tissue. We report a young female with salt-wasting CAH, who underwent bilateral adrenalectomy and developed severe hyperpigmentation, progressively marked corticotropin hypersecretion to concentrations seen in Nelson's syndrome (5,000-7,000 pg/ml), a pituitary microadenoma 5 years postoperatively, and probable ectopic adrenal rest tissue. Corticotropin concentrations failed to respond to ovine corticotropin-releasing hormone (oCRH) (1 microg/kg given as an i.v. bolus), but did suppress following both hydrocortisone administration (100 mg given as an i.v. bolus) and a low dose (0.5 mg given orally every 6 h for 48 h) dexamethasone suppression test. Patients with CAH have hyperactivity of the hypothalamic-pituitary-adrenal axis and are at risk for pituitary tumor formation.
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PMID:Adrenocorticotropin hypersecretion and pituitary microadenoma following bilateral adrenalectomy in a patient with classic 21-hydroxylase deficiency. 1567 75

Endogenous Cushing's syndrome can result from excess adrenocorticotropic hormone (ACTH; corticotropin) production by a pituitary adenoma (Cushing's disease) or by ectopic tumors secreting ACTH or corticotro- pin-releasing hormone (CRH). ACTH-independent Cushing's syndrome is caused by adrenocortical tumors or hyperplasias. Initial diagnosis is performed using 24-hour urinary free cortisol, low-dose dexamethasone tests, salivary cortisol, or night-time plasma cortisol values. A dexamethasone CRH test can discriminate between Cushing's syndrome and pseudo-Cushing's syndrome. If ACTH is elevated, combinations of high-dose dexamethasone tests, CRH/desmopressin tests, and pituitary magnetic resonance imaging can indicate a pituitary source. Discrimination from an ectopic ACTH tumor often requires inferior petrosal sinus sampling to confirm the ACTH source. If ACTH is low, adrenal computed tomography scan will identify the adrenal lesion(s) implicated. Some cortisol-producing adrenal tumors or, more frequently, bilateral macronodular hyperplasias, are under the control of aberrant membrane hormone receptors, or altered activity of eutopic receptors. The initial therapy of choice for patients with Cushing's disease is the selective transsphenoidal removal of the corticotroph adenoma; this induces remission in approximately 80% of patients, but long-term relapse occurs in up to 30% of these cases. The choice of second-line therapy remains controversial. Repeat surgery can be successful when residual tumor is detectable on magnetic resonance imaging, but carries a high risk of hypopituitarism. Bilateral adrenalectomy may be a better choice in patients without visible residual tumors, particularly in women desiring fertility. Radiotherapy combined with ketoconazole or radiosurgery was recently found effective, but longer-term evaluation of hypopituitarism and brain function is required. Current studies do not support the systematic use of prophylactic radiotherapy after bilateral adrenalectomy to decrease the risk of Nelson's syndrome; however, as soon as the residual tumor progresses, surgery and radiotherapy should be initiated. Various drugs which inhibit steroid synthesis (ketoconazole, metyrapone, aminoglutethimide, mitotane) are often effective for rapidly controlling hypercortisolism either in preparation for surgery, after unsuccessful removal of the etiologic tumor, or while awaiting the full effect of radiotherapy or more definitive therapy. Surgery is usually the treatment of choice for removal of cortisol-secreting adrenal tumors or ectopic ACTH/CRH-secreting tumors. The identification of aberrant adrenal receptors has recently allowed normalization of cortisol secretion by specific ligand receptor antagonists in limited cases of Cushing's syndrome secondary to bilateral macronodular adrenal hyperplasia. The long-term follow-up of patients treated for Cushing's syndrome should include the adequate replacement of glucocorticoids and other hormones, treatment of osteoporosis, and detection of long-term relapse of Cushing's syndrome.
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PMID:Classic and recent etiologies of Cushing's syndrome: diagnosis and therapy. 1576 24

We report the results of long-term (6-year) treatment of Nelson's syndrome with the long-acting dopamine agonist, cabergoline, in a 55-year-old woman. The disease presented 26 years after bilateral adrenalectomy and radiation treatment for Cushing's disease, followed by glucocorticoid and mineralocorticoid replacement therapy. Signs of Nelson's syndrome included skin and mucosal hyperpigmentation accompanied by elevated plasma levels of adrenocorticotropic hormone (ACTH) (984 pmol/l; normal, 2.0-11.5 pmol/l). Magnetic resonance imaging of the pituitary demonstrated sellar enlargement with a 15 mm macroadenoma. The patient was initially treated with bromocriptine (10 mg/d) which had no effect on either ACTH level or tumor mass. Because of visual loss, transsphenoidal surgery was performed, with partial excision of the adenoma and chiasmal decompression, followed by radiosurgery. However, ACTH levels improved only temporarily, and then increased to previous levels. Therefore, cabergoline treatment (1.5 mg/week) was initiated. ACTH levels decreased dramatically from 1050 to 132 pmol/l, accompanied by clinical improvement. Repeated imaging studies demonstrated a stable residual pituitary tumor. This case demonstrates that long-term cabergoline treatment may be efficient in patients with Nelson's syndrome.
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PMID:Clinical and biochemical stabilization of Nelson's syndrome with long-term low-dose cabergoline treatment. 1684

The appearance of an adrenocorticotropic hormone (ACTH)-producing tumor after bilateral adrenalectomy for Cushing disease was first described by Nelson in 1958. The syndrome that now bears his name was characterized by hyperpigmentation, a sellar mass, and increased plasma ACTH levels. The treatment of Cushing disease has changed drastically since the 1950s, when the choice was adrenalectomy. Thus, the occurrence, diagnosis, and treatment of Nelson syndrome have changed as well. In the modern era of high-resolution neuroimaging, transsphenoidal microneurosurgery, and stereotactic radiosurgery, Nelson syndrome has become a rare entity. The authors describe the history of the diagnosis and treatment of Nelson syndrome. In light of the changes described, the authors believe this disease must be reevaluated in the contemporary era and a modern paradigm adopted.
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PMID:Nelson syndrome: historical perspectives and current concepts. 1796 Oct 24

Nelson syndrome (NS) is a rare clinical manifestation of an enlarging pituitary adenoma that can occur following bilateral adrenal gland removal performed for the treatment of Cushing disease. It is characterized by excess adreno-corticotropin secretion and hyperpigmentation of the skin and mucus membranes. The authors present a comprehensive review of the pathophysiology, diagnosis, and management of NS. Corticotroph adenomas in NS remain challenging tumors that can lead to significant rates of morbidity and mortality. A better understanding of the natural history of NS, advances in neurophysiology and neuroimaging, and growing experience with surgical intervention and radiation have expanded the repertoire of treatments. Currently available treatments include surgical, radiation, and medical therapy. Although the primary treatment for each tumor type may vary, it is important to consider all of the available options and select the one that is most appropriate for the individual case, particularly in cases of lesions resistant to intervention.
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PMID:Nelson syndrome: comprehensive review of pathophysiology, diagnosis, and management. 1796 Oct 28

Cushing's disease caused by pituitary corticotroph adenoma in dogs is usually treated by medical treatment, and the efficacy of this treatment has been reported. However, controversy remains as to whether reduced negative feedback through the inhibition of cortisol secretion, similar to Nelson's syndrome, may appear as an adverse effect. The purpose of this study was to investigate the effect of reduced negative feedback through the inhibition of cortisol secretion by daily trilostane administration on the pituitary-adrenal axis in clinically normal dogs. Dogs were administered 5mg/kg trilostane twice a day every day for 8 weeks (n=8) or 16 weeks (n=3). After the initiation of trilostane administration, plasma adrenocorticotropic hormone (ACTH) concentrations were increased remarkably. As assessed by magnetic resonance imaging (MRI) during administration, the pituitary became enlarged. After trilostane administration, the cytoplasmic areas of the pituitary corticotrophs were increased and the ratio of pituitary corticotrophs to all cells in the anterior lobe was greater in the trilostane-treated dogs than that in untreated animals. In addition, histological examinations revealed bilateral adrenal cortical hyperplasia. Using real-time PCR quantification, the expression of proopiomelanocortin (POMC) mRNA in the pituitary and ACTH receptor (ACTH-R) mRNA in the adrenal gland was greater in the dogs treated with trilostane than in untreated dogs. These results indicate that reduced negative feedback induced hyperfunction of the pituitary corticotrophs and pituitary enlargement in healthy dogs. These changes suggest that the inhibition of cortisol secretion by trilostane may increase the risk for accelerating the growth of corticotroph adenomas in dogs with Cushing's disease.
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PMID:Trilostane-induced inhibition of cortisol secretion results in reduced negative feedback at the hypothalamic-pituitary axis. 1904 2

Normal and tumoral pituitary corticotropic cells express sst(2) and sst(5), of which sst(5) is the predominantly expressed receptor subtype. Somatostatin (SS) inhibits pituitary adrenocorticotropin hormone (ACTH) secretion in vitro, but the sensitivity to SS is strongly regulated by glucocorticoids. In pathological conditions of a low endogenous cortisol level, i.e. in patients with adrenal insufficiency and in patients with Nelson's syndrome, SS and sst(2)-preferring SS analogs (SSA), such as octreotide, are able to lower circulating ACTH and cortisol levels. On the other hand, sst(2)-preferring SSA seem not effective in lowering ACTH and cortisol levels in patients with untreated Cushing's disease (CD), in which circulating cortisol levels are high. This is likely due to the downregulation of sst(2) receptors by glucocorticoids. sst(5) receptor expression is more resistant to the inhibitory effect of glucocorticoids. In recent years, novel sst subtype-selective and universal SSA have been developed. In particular, SSA with a high sst(5)-binding affinity are potent inhibitors of ACTH secretion by pituitary corticotropic adenoma cells. This knowledge has initiated clinical trials evaluating the efficacy of these novel SSA in patients with CD, with the aim to lower circulating ACTH and cortisol levels by targeting multiple ssts on the corticotropic adenoma cells. In this minireview, the effects of SS in the regulation of normal and tumoral ACTH secretion, the role of sst subtypes involved herein, as well as the potentials of novel SSA in the treatment of patients with recurrent or persisting CD are discussed.
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PMID:Role of somatostatin receptors in normal and tumoral pituitary corticotropic cells. 2082 12


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