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)

The successful treatment of Cushing syndrome depends on specific therapy directed against the etiology of hypercortisolism. In addition to surgical procedures, various drugs have been employed in the management of this difficult disease. Compounds with neuromodulatory properties have been effective in only a limited number of cases of hypothalamic-pituitary-dependent Cushing disease, the most common form of Cushing syndrome. These agents include serotonin antagonists (cyproheptadine, ketanserin, ritanserin), dopamine agonists (bromocriptine, cabergoline), GABA agonists (valproic acid [sodium valproate]), and somatostatin analogs (octreotide). Interesting new avenues at the pituitary level involve the potential use of thiazolidinedione compounds, such as rosiglitazone, and of retinoic acid, which are ligands of different nuclear hormone receptors involved in hypothalamic-pituitary regulation. The most exciting news, however, in the pharmacologic approach to Cushing syndrome refers to the adrenal corticotropin (adrenocorticotropic hormone; ACTH)-independent forms, in which aberrant adrenal receptors, through the binding of their respective ligands, could lead to chronic cortisol overproduction. They include receptors for gastric inhibitory peptide (GIP), beta-adrenergic agonists, luteinizing hormone (LH)/human chorionic gonadotropin, serotonin (5-HT(4) receptor), vasopressin (V(1) receptor), and angiotensin II (AT(1) receptor). In GIP-dependent Cushing syndrome, the most frequent subtype of ACTH-independent macronodular adrenal hyperplasia associated with the presence of aberrant adrenocortical hormone receptors described so far, octreotide administration before each meal showed clinical efficacy only in the first few months, probably because of somatostatin receptor downregulation in GIP-secreting cells. Long-term medical treatments with propranolol and the gonadotropin-releasing hormone analog leuprorelin (leuprolide acetate) were effective in patients with catecholamine-dependent and LH-dependent Cushing syndrome, respectively. The oral vasopressin V(1) receptor antagonist OPC-21268 and the angiotensin II (AT(1)) receptor antagonist candesartan cilexetil were also able to decrease cortisol levels during the few days of administration of the drugs in patients with specific receptor abnormalities. These adrenal forms of Cushing syndrome are rare, and clinical data are scarce. Moreover, the real clinical significance of aberrant hormone receptors is still under investigation, as is the possibility of avoiding surgery by pharmacologic manipulation. Patients in whom these intriguing syndromes are suspected require detailed investigation protocols, which should be carried out in specialized centers. While awaiting further developments, the use of traditional medical treatment at the adrenal level with adrenal steroid inhibitors is still valuable in several instances.
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PMID:Pharmacologic management of Cushing syndrome : new targets for therapy. 1578 46

Corticotropin (ACTH)-independent bilateral macronodular adrenal hyperplasia (AIMAH) and primary pigmented nodular adrenocortical disease (PPNAD) are responsible for approximately 10% of adrenal Cushing's syndrome. AIMAH also can be present as subclinical bilateral incidentalomas in sporadic or familial forms. Diverse aberrant hormone receptors have been found to be implicated in the regulation of steroidogenesis and pathophysiology of AIMAH. PPNAD can be found alone or in the context of Carney complex, a multiple endocrine neoplasia syndrome. Additionally, it can be secondary to mutations of type 1 alpha-regulatory subunit of cAMP-dependent protein kinase A (PRKARIA). Strategies for the investigation and treatment of AIMAH and PPNAD are discussed.
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PMID:Bilateral adrenal Cushing's syndrome: macronodular adrenal hyperplasia and primary pigmented nodular adrenocortical disease. 1585 Aug 52

Cushing's syndrome caused by adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) is an extremely rare disease, which shows bilateral macronodular adrenal hypertrophy and autonomous cortisol production. We herein report a case of AIMAH treated successfully by minimally invasive simultaneous bilateral laparoscopic adrenalectomy. A 73-year-old woman with hypertension, diabetes mellitus, and osteoporosis was referred to our hospital because of an incidentally found huge bilateral adrenal mass. An abdominal computed tomography scan showed large bilateral adrenal glands with multiple nodules. A diagnosis of AIMAH was made and a simultaneous bilateral laparoscopic adrenalectomy was thus performed. The total operation time was 310 min and blood loss was 70 g. Both glands were hypertrophic (right 5 x 3 cm, 48.5 g and left 4 x 2 cm, 39.2 g) and consisted of multiple golden yellow macronodules. The postoperative course was uneventful. A simultaneous bilateral adrenalectomy for AIMAH performed by an experienced surgical team is therefore considered to be a safe and minimally invasive procedure.
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PMID:Simultaneous bilateral laparoscopic adrenalectomy for adrenocorticotropic hormone-independent macronodular adrenal hyerplasia: report of a case. 1679 2

We describe the case of a 2-year-old girl with opsoclonus-myoclonus syndrome treated with chronic adrenocorticotropic hormone (ACTH) in which a metaiodobenzylguanidine scan showed abnormal radiotracer uptake in the left adrenal gland region, interpreted as the site of an occult neuroblastoma. As this finding was not corroborated by previous or subsequent metaiodobenzylguanidine scans or by computed tomography (CT) or magnetic resonance imaging (MRI), we attribute the finding to being a false-positive result from adrenal hyperplasia owing to chronic use of ACTH and not to neuroblastoma. Metaiodobenzylguanidine scintigraphy is an extremely important nuclear medicine examination tool used for the evaluation and staging of pediatric neuroblastoma. We highlight the need for cautious interpretation of metaiodobenzylguanidine as a screening tool for neuroblastoma in patients treated with ACTH.
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PMID:False-positive metaiodobenzylguanidine scan for neuroblastoma in a child with opsoclonus-myoclonus syndrome treated with adrenocorticotropic hormone (acth). 1697 Aug 54

Several new therapeutic options both medicinal and surgical, have emerged for the treatment of Cushing's syndrome. In Cushing's disease caused by an adrenocorticotropin (ACTH) secreting pituitary adenoma, the introduction ofendoscopic pituitary surgery offers better visualization of the sella than does the traditional explorative surgery. However, at present it is unclear whether this will result in a better outcome. New drugs under investigation include universal somatostatin analogues such as SOM230, and a combination of a somatostatin analogue and dopamine agonist known as dopastatin. These agents may also be effective for the medicinal treatment of ectopic ACTH-secretion. Treatment with radioactive-labelled somatostatin-analogues such as 177lutetium octreotate is another option for these patients. The primary treatment for ACTH-independent Cushing's syndrome is laparoscopic adrenalectomy. In rare cases of bilateral adrenal hyperplasia, medicinal treatment aimed at new regulatory pathways of cortisol secretion can be applied.
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PMID:[Cushing's syndrome. II. New forms of treatment]. 1732 80

Adrenocorticotropic hormone- (ACTH-)independent macronodular adrenal hyperplasia (AIMAH) is an infrequent cause of Cushing's syndrome (CS). AIMAH presents as incidental radiological finding or with subclinical or overt CS, occasionally with secretion of mineralocorticoids or sex steroids. The pathophysiology of this entity is heterogeneous. The aberrant adrenal expression and function of one or several G-protein-coupled receptors can lead to cell proliferation and abnormal regulation of steroidogenesis. In several familial cases of AIMAH, specific aberrant hormone receptors are functional in the adrenal of affected members. Additional somatic genetic events related to cell cycle regulation, adhesion and transcription factors occur in addition in the various nodules over time. Other mechanisms, such as Gsp or ACTH receptor mutations and paracrine adrenal hormonal secretion, have been rarely identified in other cases of AIMAH. The identification of aberrant receptors can offer a specific pharmacological approach to prevent progression and control abnormal steroidogenesis; alternatively, unilateral or bilateral adrenalectomy becomes the treatment of choice.
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PMID:ACTH-independent macronodular adrenal hyperplasia. 1950 Jul 67

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive hereditary diseases. The impairment of cortisol synthesis leads to excessive stimulation of the adrenal glands by adrenocorticotropic hormone (ACTH), adrenal hyperplasia, and excessive androgen synthesis. The syndrome is characterised by a considerable correlation between the genotype and the phenotype with the type of CYP21A2 gene mutation affecting the severity of 21-hydroxylase deficiency. The clinical manifestations of CAH in adults result from adrenocortical and adrenomedullary insufficiency, hyperandrogenism, and the adverse effects of glucocorticosteroids used for the treatment of the condition. Non-classic CAH may sometimes be asymptomatic. In patients with classic CAH obesity, hyperinsulinaemia, insulin resistance, and hyperleptinaemia are more often seen than in the general population. These abnormalities promote the development of metabolic syndrome and its sequelae, including endothelial dysfunction, and cardiovascular disease. Long-term glucocorticosteroid treatment is also a known risk factor for osteoporosis. Patients with CAH require constant monitoring of biochemical parameters (17a-hydroxyprogesterone [17-OHP] and androstenedione), clinical parameters (body mass, waist circumference, blood pressure, glucose, and lipids), and bone mineral density by densitometry. The principal goal of treatment in adults with CAH is to improve quality of life, ensure that they remain fertile, reduce the manifestations of hyperandrogenisation in females, and minimise the adverse effects of glucocorticosteroid treatment. Patients with classic CAH require treatment with glucocorticosteroids and, in cases of salt wasting, also with a mineralocorticosteroid. Radical measures, such as bilateral adrenalectomy, are very rarely needed. Asymptomatic patients with non-classic CAH require monitoring: treatment is not always necessary. Medical care for patients with CAH should be provided by reference centres, as the management of such patients requires collaboration between an endocrinologist, diabetologist, gynaecologist, andrologist, urologist, and psychologist.
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PMID:Congenital adrenal hyperplasia due to 21-hydroxylase deficiency - management in adults. 2020 17

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive hereditary diseases. The impairment of cortisol synthesis leads to excessive stimulation of the adrenal glands by adrenocorticotropic hormone (ACTH), adrenal hyperplasia, and excessive androgen synthesis. The syndrome is characterised by a considerable correlation between the genotype and the phenotype with the type of CYP21A2 gene mutation affecting the severity of 21-hydroxylase deficiency. The clinical manifestations of CAH in adults result from adrenocortical and adrenomedullary insufficiency, hyperandrogenism, and the adverse effects of glucocorticosteroids used for the treatment of the condition. Non-classic CAH may sometimes be asymptomatic. In patients with classic CAH obesity, hyperinsulinaemia, insulin resistance, and hyperleptinaemia are more often seen than in the general population. These abnormalities promote the development of metabolic syndrome and its sequelae, including endothelial dysfunction, and cardiovascular disease. Long-term glucocorticosteroid treatment is also a known risk factor for osteoporosis. Patients with CAH require constant monitoring of biochemical parameters (17a-hydroxyprogesterone and androstenedione), clinical parameters (body mass, waist circumference, blood pressure, glucose, and lipids), and bone mineral density by densitometry. The principal goal of treatment in adults with CAH is to improve quality of life, ensure that they remain fertile, reduce the manifestations of hyperandrogenisation in females, and minimise the adverse effects of glucocorticosteroid treatment. Patients with classic CAH require treatment with glucocorticosteroids and, in cases of salt wasting, also with a mineralocorticosteroid. Radical measures, such as bilateral adrenalectomy, are very rarely needed. Asymptomatic patients with non-classic CAH require monitoring: treatment is not always necessary. Medical care for patients with CAH should be provided by reference centres, as the management of such patients requires collaboration between an endocrinologist, diabetologist, gynaecologist, andrologist, urologist, and psychologist.
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PMID:[Congenital adrenal hyperplasia due to 21-hydroxylase deficiency--management in adults]. 2212 31

Hirsutism is excess terminal hair that commonly appears in a male pattern in women. Although hirsutism is generally associated with hyperandrogenemia, one-half of women with mild symptoms have normal androgen levels. The most common cause of hirsutism is polycystic ovary syndrome, accounting for three out of every four cases. Many medications can also cause hirsutism. In patients whose hirsutism is not related to medication use, evaluation is focused on testing for endocrinopathies and neoplasms, such as polycystic ovary syndrome, adrenal hyperplasia, thyroid dysfunction, Cushing syndrome, and androgen-secreting tumors. Symptoms and findings suggestive of neoplasm include rapid onset of symptoms, signs of virilization, and a palpable abdominal or pelvic mass. Patients without these findings who have mild symptoms and normal menses can be treated empirically. For patients with moderate or severe symptoms, an early morning total testosterone level should be obtained, and if moderately elevated, it should be followed by a plasma free testosterone level. A total testosterone level greater than 200 ng per dL (6.94 nmol per L) should prompt evaluation for an androgen-secreting tumor. Further workup is guided by history and physical examination, and may include thyroid function tests, prolactin level, 17-hydroxyprogesterone level, and corticotropin stimulation test. Treatment includes hair removal and pharmacologic measures. Shaving is effective but needs to be repeated often. Evidence for the effectiveness of electrolysis and laser therapy is limited. In patients who are not planning a pregnancy, first-line pharmacologic treatment should include oral contraceptives. Topical agents, such as eflornithine, may also be used. Treatment response should be monitored for at least six months before making adjustments.
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PMID:Hirsutism in women. 2233 16

Adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) is a rare disease which causes Cushing's syndrome. Bilateral adrenalectomy has been recommended as the treatment of choice for AIMAH. However, bilaterally adrenalectomized patients require lifelong steroid replacement therapy. Therefore, an increasing number of patients have undergone unilateral adrenalectomy for AIMAH. We report a case of AIMAH due to refractory diabetes in whom unilateral adrenalectomy initially yielded good diabetes control, but in whom poor glycemic control developed after 5 years, requiring eventual additional contralateral adrenalectomy. In elderly patients with AIMAH, one-stage bilateral adrenalectomy may be the treatment of choice.
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PMID:Usefulness and limitations of unilateral adrenalectomy for ACTH-independent macronodular adrenal hyperplasia in a patient with poor glycemic control. 2279 Jan 31


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