Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Research Articles

A Marked Difference in the Vasopressin Responsiveness Between the Adrenal Glands in a Patient with Adrenocorticotropin-independent Macronodular Adrenal Hyperplasia

We herein present the case of a 53-year-old patient with adrenocorticotropin-independent macronodular adrenocortical hyperplasia (AIMAH), which is a rare form of Cushing syndrome. He had hypercortisolemia and bilateral macronodular adrenal glands with a left side predominance. The administration of vasopressin significantly increased the plasma cortisol level (1.9-fold). Following left adrenalectomy, the patient's hypercortisolemia significantly improved and vasopressin responsiveness was lost, suggesting that the responsiveness originated from the resected left adrenal gland. The marked difference in vasopressin responsiveness between the adrenals corresponded with their asymmetrical size and function. Evaluating the differences in the vasopressin sensitivity may therefore be helpful for understanding the progression of AIMAH.

ACTH-independent macronodular adrenal hyperplasia: report of 12 cases

Objective To explore the diagnosis and treatment of adrenocorticotropin-independent macronodular adrenal hyperplasia (AIMAH). Methods The clinical symptoms, endocrinological and radiological characteristics, treatment modalities, and postoperative clinical course of 12 AIMAH patients were retrospectively reviewed. There were 5 men and 7 women with an average age of 48 years old. Results All cases had some clinical features and biochemical evidence of Cushing's syndrome. The circadian rhythm of serum cortisol was abnormal. Low- and high-dose dexamethasone suppression tests failed to suppress cortisol secretion. CT or MRI scan showed bilateral enlargement of the adrenal glands with multiple macronodules. Bilateral adrenalectomy was performed in three patients and unilateral adrenalectomy combined with contralateral subtotal adrenalectomy was performed in one patient. Seven patients underwent unilateral adrenalectomy of the larger gland. The removed adrenal glands weighted within 8-96 g range and pathologic diagnoses were nodular or adenomatoid hyperplasia of adrenal cortex. The duration of postoperative follow-up was 14 to 124 months. Clinical symptoms of Cushing's syndrome disappeared after surgery in all cases and there was no Nelson's syndrome after bilateral adrenalectomy. Urinary free cortisol and serum cortisol were within normal ranges. No further enlargement of the contralateral gland has been noticed in patients who received unilateral adrenalectomy during the follow-up.Conclusions AIMAH had unique endocrinological and pathological features. Unilateral adrenalectomy appears to be an effective and safe alternative treatment for AIMAH. Bilateral adrenalectomy or unilateral adrenalectomy combined with contralateral subtotal adrenalectomy may be performed if the symptoms had not been improved or recurred after unilateral adrenalectomy. Key words: Cushing's syndrome; Corticotropin; Macronodular adrenal hyperplasia

Clinical and genetic heterogeneity, overlap with other tumor syndromes, and atypical glucocorticoid hormone secretion in adrenocorticotropin-independent macronodular adrenal hyperplasia compared with other adrenocortical tumors

Clinical and genetic heterogeneity, overlap with other tumor syndromes, and atypical glucocorticoid hormone secretion in adrenocorticotropin-independent macronodular adrenal hyperplasia compared with other adrenocortical tumors

Clinical and Genetic Heterogeneity, Overlap with Other Tumor Syndromes, and Atypical Glucocorticoid Hormone Secretion in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Compared with Other Adrenocortical Tumors

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is often associated with subclinical cortisol secretion or atypical Cushing's syndrome (CS). We characterized a large series of patients of AIMAH and compared them with patients with other adrenocortical tumors. We recruited 82 subjects with: 1) AIMAH (n = 16); 2) adrenocortical cortisol-producing adenoma with CS (n = 15); 3) aldosterone-producing adenoma (n = 19); and 4) single adenomas with clinically nonsignificant cortisol secretion (n = 32). Urinary free cortisol (UFC) and 17-hydroxycorticosteroid (17OHS) were collected at baseline and during dexamethasone testing; aberrant receptor responses was also sought by clinical testing and confirmed molecularly. Peripheral and/or tumor DNA was sequenced for candidate genes. AIMAH patients had the highest 17OHS excretion, even when UFCs were within or close to the normal range. Aberrant receptor expression was highly prevalent. Histology showed at least two subtypes of AIMAH. For three patients with AIMAH, there was family history of CS; germline mutations were identified in three other patients in the genes for menin (one), fumarate hydratase (one), and adenomatosis polyposis coli (APC) (one); a PDE11A gene variant was found in another. One patient had a GNAS mutation in adrenal nodules only. There were no mutations in any of the tested genes in the patients of the other groups. AIMAH is a clinically and genetically heterogeneous disorder that can be associated with various genetic defects and aberrant hormone receptors. It is frequently associated with atypical CS and increased 17OHS; UFCs and other measures of adrenocortical activity can be misleadingly normal.

Diagnosis and surgical management of adrenocortical hyperplasia disease (report of 180 cases)

Objective To review the diagnosis and surgical therapeutic methods of adrenocorti-cal hyperplasia disease. Methods One hundred and eighty adrenocortical hyperplasia patients (74 males and 106 females with a mean age of 40 years) were retrospectively analyzed. The patients were divided into hypereortisolism (n=152) and aldosteronism (n=28) according to secretion. Data of clinical characteristic, endocrine and image examination were collected. All patients were treated by operation. Results Of these patients, 107 had Cushing disease (CD), 28 had adrenocorticotropin independent macronodular adrenal hyperplasia (AIMAH), 19 had ectopic adrenocorticotropin adrenal hyperplasia (EAAH), 4 had primary pigmented nodular adrenocortical hyperplasia (PPNAH), 28 had DOI: 10.3760/cma.j.issn. 1000-6702.2009.05.002idiopathic hyperaldosteronism (IHA). 24 h urinay free cortisol (24hUFC) excretion of CD, AIMAH, EAAH and PPNAH were 95.2-535.7 μg (mean, 287.6 μg), 24.8-808.2 μg (mean, 307.9 μg), 102.5-3127.0 μg (mean, 852.5 μg), 243.8-1124.6 μg (mean. 564.3 μg). The proportion loss of the serum cortisol circadian rhythm were 99% (102/103), 92% (11/12), 100% (17/17), 100% (4/ 4), respectively. Low- and high-dose dexamethasone suppression tests (DDST) failed to suppress cor-tisol secretion in AIMAH, PPNAH and EAAH groups, but HDDST was suppressed in CD group. Of the 28 IHA cases, 17 had hypokalemia and 15 had high urine kalium (>30 mmol/24 h). The results of plasma renin activity and serum aldosterone accorded with the diagnosis. Unilateral adrenalectomy were operated in 102 hypercortisolism cases, and 24hUFC of CD, AIMAH, EAAH and PPNAH were 56.2-233.5 μg (mean, 157.4 μg), 22.5-418.5 μg (mean, 117.9 μg), 116.5-1137.0 μg (mean, 756.7 μg), 124.6-422.6 μg (mean, 164.3 μg) 1 week after operation. The blood pressure was nor-mal in 8 paitents and droped in 13 patients for IHA after unilateral adrenalectomy. 24hUFC were nor-mal in 55 patients after bilateral adrenalectomy for hypercortisolism. One hundred and six patients were followed up for 4-158 months, the Cushing syndrome ameliorated and blood pressure dropped. Conclusions Unilateral adrenalectomy is the first choice for adrenocortical hyperplasia disease which needs operation. The operation mode of the contralateral adrenal gland is based on the hyperplasia types and clinical observation. Key words: Adrenocortical hyperplasia; Diagnosis; Surgical procedure, elective

51: Surgical Strategies in the Treatment of Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia

You have accessJournal of UrologyPodium 1, Saturday, May 19, 2007 1:00 - 3:00 pm1 Apr 200751: Surgical Strategies in the Treatment of Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Hanzhong Li, and Xuebin Zhang Hanzhong LiHanzhong Li More articles by this author , and Xuebin ZhangXuebin Zhang More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)30316-1AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "51: Surgical Strategies in the Treatment of Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia." The Journal of Urology, 177(4S), p. 18 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 177Issue 4SApril 2007Page: 18 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Hanzhong Li More articles by this author Xuebin Zhang More articles by this author Expand All Advertisement Loading ...

Expression of Serotonin7Receptor and Coupling of Ectopic Receptors to Protein Kinase A and Ionic Currents in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Causing Cushing’s Syndrome

In ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing Cushing's syndrome, cortisol secretion is controlled by illegitimate membrane receptors. The aim of the present study was to characterize the pharmacological properties and the transduction mechanisms of illegitimate receptors, i.e. receptors for serotonin (5-HT), gastric inhibitory polypeptide (GIP), and LH/human chorionic gonadotropin (hCG), expressed by AIMAH tissues to evaluate the role of ectopic receptors in the physiopathology of Cushing's syndrome. We used in vitro studies on cultured adrenal hyperplasia cells. The setting was a university research laboratory. AIMAH tissues (H1-H3) were removed from three patients previously screened for illegitimate receptors. The main outcome measures were steroidogenic and electrical activities of cultured adrenal hyperplasia cells. In vitro studies showed that the corticotropic effect of 5-HT was mediated by ectopic 5-HT7 receptors in H1 and H2. GIP and hCG stimulated cortisol production via activation of cAMP-dependent protein kinase A in H2. On the contrary, the protein kinase A inhibitor H-89 did not affect hCG-induced cortisol production in H3. Activation of 5-HT7 or GIP receptors enhanced T-type calcium current in H1 or H2 and H3, respectively. In addition, GIP reduced the amplitude of transient and sustained potassium currents in H2. Conversely, hCG did not modify T-type calcium current in H3. These data show that, besides their coupling to the cAMP pathway, illegitimate adrenal receptors can activate additional transduction mechanisms, including modulation of membrane channels.

17q22–24 Chromosomal Losses and Alterations of Protein Kinase A Subunit Expression and Activity in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia

Primary adrenocortical hyperplasias leading to Cushing syndrome include primary pigmented nodular adrenocortical disease and ACTH-independent macronodular adrenal hyperplasia (AIMAH). Inactivating mutations of the 17q22-24-located PRKAR1A gene, coding for the type 1A regulatory subunit of protein kinase A (PKA), cause primary pigmented nodular adrenocortical disease and the multiple endocrine neoplasia syndrome Carney complex. PRKAR1A mutations and 17q22-24 chromosomal losses have been found in sporadic adrenal tumors and are associated with aberrant PKA signaling. The objective of the study was to examine whether somatic 17q22-24 changes, PRKAR1A mutations, and/or PKA abnormalities are present in AIMAH. We studied fourteen patients with Cushing syndrome due to AIMAH. Fluorescent in situ hybridization with a PRKAR1A-specific probe was used for investigating chromosome 17 allelic losses. The PRKAR1A gene was sequenced in all samples, and tissue was studied for PKA activity, cAMP responsiveness, and PKA subunit expression. We found 17q22-24 allelic losses in 73% of the samples. There were no PRKAR1A-coding sequence mutations. The RIIbeta PKA subunit was overexpressed by mRNA, whereas the RIalpha, RIbeta, RIIalpha, and Calpha PKA subunits were underexpressed. These findings were confirmed by immunohistochemistry. Total PKA activity and free PKA activity were higher in AIMAH than normal adrenal glands, consistent with the up-regulation of the RIIbeta PKA subunit. PRKAR1A mutations are not found in AIMAH. Somatic losses of the 17q22-24 region and PKA subunit and enzymatic activity changes show that PKA signaling is altered in AIMAH in a way that is similar to that of other adrenal tumors with 17q losses or PRKAR1A mutations.

Abnormal Adrenal and Vascular Responses to Vasopressin Mediated by a V1-Vasopressin Receptor in a Patient with Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia, Cushing's Syndrome, and Orthostatic Hypotension

Abnormal Adrenal and Vascular Responses to Vasopressin Mediated by a V1-Vasopressin Receptor in a Patient with Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia, Cushing's Syndrome, and Orthostatic Hypotension