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)

We treated two men with Cushing's syndrome due to adrenocorticotropin (ACTH)-independent bilateral macronodular adrenocortical hyperplasia (AIMAH). In both patients, plasma ACTH was low and plasma cortisol was not suppressed by a high dose of dexamethasone (8 mg) but was remarkably responsive to exogenous ACTH. The adrenal glands were extremely enlarged and contained multiple nodules composed of large clear cells and small compact cells. The immunoreactivity of P-450(17) alpha was predominant in the small compact cells, while that of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was observed exclusively in the large clear cells. Among various adrenocortical disorders, differential expression of 3 beta-HSD and P-450(17) alpha in clear and compact cells has heretofore been demonstrated only in AIMAH. Total adrenalectomy was done for one patient, and partial adrenalectomy for the other. In the former patient, the normal diurnal rhythm of plasma ACTH was restored 11 months postoperatively. In the latter patient, the normal dynamics in the hypothalamic-pituitary-adrenal axis became evident 15 months after surgery. Thus AIMAH is apparently a primary adrenocortical disorder and is not due to abnormalities of the hypothalamus or pituitary.
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PMID:Adrenocorticotropin-independent bilateral macronodular adrenocortical hyperplasia: immunohistochemical studies of steroidogenic enzymes and post-operative course in two men. 866 79

We report a male Japanese with corticotropin (ACTH)-independent macronodular adrenocortical hyperplasia (AIMAH) associated with multiple colon adenomas/carcinomas. The plasma cortisol level was elevated with no diurnal rhythm and was not suppressed with dexamethasone. Basal plasma ACTH was unmeasurable but subnormally increased after administration of metyrapone or corticotropin releasing hormone. Both adrenals were resected and weighed 90g; the histopathologic findings were similar to those of AIMAH as previously reported. At least 21 colon lesions which were adenomas or carcinomas, were resected endoscopically or surgically. This is the second reported case of the association of AIMAH with multiple colon polyps. An APC gene point mutation was detected in the colon cancer tissue by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP)/direct sequencing analysis at the putative splice acceptor site consensus sequence. However, no abnormality of APC gene was detected in the adrenocortical hyperplastic tissue. The possible etiological coexistence of these two diseases is discussed.
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PMID:Adrenocorticotropin-independent macronodular adrenocortical hyperplasia associated with multiple colon adenomas/carcinomas which showed a point mutation in the APC gene. 926 Jul 67

We report a case of adrenocorticotropic hormone (ACTH)-independent macronodular adrenocortical hyperplasia (AIMAH). A 54-year-old Japanese man was admitted to our hospital for further examination of obesity and hypertension. Endocrinological studies showed that plasma cortisol was high (22.5 micrograms/dl) without diurnal rhythm, and plasma ACTH was low. Two or 8 mg of dexamethasone did not suppress the plasma cortisol levels. Abdominal computed tomography revealed nodular hyperplasia of bilateral adrenal glands. Adrenal scintigraphy showed the positive uptake of 131I-adosterol to bilateral adrenal glands. Brain magnetic resonance imaging revealed no abnormalities. He was diagnosed as having Cushing's syndrome with bilateral adrenal hyperplasia, and bilateral adrenalectomy was performed. Left and right adrenal glands were 52 g and 35 g, respectively, and were occupied by yellow nodular lesions. Histologically, hyperplastic lesions were composed of clear cells. Finally he was diagnosed with AIMAH.
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PMID:[ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH): a case report]. 1036 43

We report a case of adrenocorticotropic hormone (ACTH)-independent bilateral macronodular adrenocortical hyperplasia (AIMAH), which was successfully treated with mitotane. A 71-year-old man visited our hospital because of central obesity and enlarged bilateral adrenal glands. The endocrinological studies showed elevated plasma cortisol and undetectable levels of ACTH, a lack of suppression with high-dose dexamethasone and a hyper-response to exogenous ACTH. These clinical features were compatible with the diagnosis of AIMAH. In this patient, extra-adrenal multiple tumors were also detected. After treatment with mitotane, the plasma level of cortisol was decreased while that of ACTH was increased and the signs of Cushing's syndrome were resolved.
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PMID:Adrenocorticotropic hormone-independent bilateral adrenocortical macronodular hyperplasia treated with mitotane. 1062 36

With increasing case reports, it has been indicated that some cases with adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) show abnormal responses in cortisol to various stimulation tests. Here we report a case of AIMAH that showed an aberrant response to angiotensin II via AT1 receptor in cortisol hypersecretion. A 53-yr-old man was admitted to our division seeking further examinations for the possible diagnosis of Cushing's syndrome. He had hypertension, diabetes mellitus, and physical stigmata, such as moon face and central obesity. His plasma ACTH level was undetectable, and plasma cortisol level was high. Plasma cortisol showed no normal diurnal rhythm and was not suppressed after the administration of 8 mg of dexamethasone. Abdominal computed tomography demonstrated nodular enlargement of bilateral adrenal glands. He was diagnosed with Cushing's syndrome owing to AIMAH. An injection of arginine vasopressin (AVP) increased plasma cortisol and aldosterone levels, whereas ACTH remained undetectable. After 4 h in an upright position, plasma cortisol and aldosterone levels were increased. Pretreatment with candesartan, angiotensin II receptor AT1 antagonist, blocked the increase in plasma cortisol level. These results suggested a possibility of adrenal hypersensitivity to angiotensin II and AVP in cortisol secretion. Bilateral laparoscopic adrenalectomy was performed. The histological findings of the specimen were compatible with AIMAH. In summary, we have made the first report on a case of AIMAH with possible hypersensitivity to angiotensin II.
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PMID:Case of adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with possible adrenal hypersensitivity to angiotensin II. 1157 27

Corticotropin (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) is a heterogeneous condition in which cortisol secretion may be mediated by gastrointestinal peptide (GIP), vasopressin, catecholamines and other hormones. We studied the expression profile of AIMAH by genomic cDNA microarray analysis. Total RNA was extracted from eight tissues (three GIP-dependent) and compared to total RNA obtained from adrenal glands from 62 normal subjects. Genes had to be altered in 75% of the patients, and be up- or downregulated at a cutoff ratio of at least 2.0; 82 and 31 genes were found to be consistently up- and downregulated, respectively. Among the former were regulators of transcription, chromatin remodeling, and cell cycle and adhesion. Downregulated sequences included genes involved in immune responses and insulin signaling. Hierarchical clustering correlated with the two main AIMAH diagnostic groups: GIP-dependent and non-GIP-dependent. The genes encoding the 7B2 protein (SGNE1) and WNT1-inducible signaling pathway protein 2 (WISP2) were specifically overexpressed in the GIP-dependent AIMAH. For these, and six more genes, the data were validated by semiquantitative amplification in samples from a total of 32 patients (the original eight, six more cases of AIMAH, and 18 other adrenocortical hyperplasias and tumors) and the H295R adrenocortical cancer cell line. In conclusion, our data confirmed AIMAH's clinical heterogeneity by identifying molecularly distinct diagnostic subgroups. Several candidate genes that may be responsible for AIMAH formation and/or progression were also identified, suggesting pathways that affect the cell cycle, adhesion and transcription as possible mediators of adrenocortical hyperplasia.
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PMID:Gene array analysis of macronodular adrenal hyperplasia confirms clinical heterogeneity and identifies several candidate genes as molecular mediators. 1476 69

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

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

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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