Acth-Independent Macronodular Adrenal Hyperplasia

An endogenous form of adrenal Cushing syndrome characterized by multiple bilateral adrenocortical nodules that cause a striking enlargement of the ADRENAL GLANDS. Although some familial cases have been reported, the vast majority of AIMAH cases are sporadic. Patients typically present in the fifth and sixth decades of life, approximately 10 years later than most patients with other causes of Cushing syndrome. Somatic mutations in the GNAS gene have been identified. OMIM: 219080

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Networked: 166 relevant articles (12 outcomes, 17 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Acth-Independent Macronodular Adrenal Hyperplasia
2.	Cushing Syndrome
3.	Insulin Resistance
4.	Hypoglycemia (Reactive Hypoglycemia)
5.	Hyperglycemia

Experts

1.	Bourdeau, Isabelle: 16 articles (01/2015 - 06/2002)
2.	Lacroix, André: 16 articles (01/2015 - 01/2003)
3.	Stratakis, Constantine A: 12 articles (01/2019 - 06/2002)
4.	Bertherat, Jérôme: 9 articles (11/2013 - 05/2002)
5.	Groussin, Lionel: 8 articles (11/2013 - 05/2002)
6.	Sasano, Hironobu: 7 articles (09/2017 - 04/2002)
7.	Bertagna, Xavier: 6 articles (11/2013 - 05/2002)
8.	Lefebvre, Hervé: 6 articles (10/2010 - 05/2002)
9.	Fragoso, Maria Candida Barisson Villares: 5 articles (01/2015 - 05/2003)
10.	Horvath, Anelia: 4 articles (10/2015 - 06/2008)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Acth-Independent Macronodular Adrenal Hyperplasia:

1.	Hydrocortisone (Cortisol)FDA LinkGeneric 01/01/2015 - "Twenty-four-hour urinary free cortisol (24 h UFC) excretion of CD, EAAH, AIMAH and PPNAH patients were 95.2~535.7 µg (average 287.6 µg), 24.8~808.2 µg (average 307.9 µg), 102.5~3127.0 µg (average 852.5 µg), and 243.8~1124.6 µg (average 564.3 µg). " 09/13/2013 - "Short- and long-term incubation with AVP increased cortisol secretion in cultures of AIMAH cells. " 09/13/2013 - "Positive serum cortisol responses to stimuli were detected in 27/35 AIMAH patients tested, with multiple responses within individual patients occurring for up to four stimuli. " 09/01/2013 - "Based on clinical manifestations and serum cortisol, we divide AIMAH into three types, subclinical AIMAH, clinical AIMAH and high-risk AIMAH, with varied treatment methods being adapted to different subtypes. " 02/01/2011 - "Although a feasible method is still needed for determining the lateralization of cortisol secretion of bilateral adrenal masses, ultrasonography and computed tomography scan are useful for the diagnosis and differentiated diagnosis of AIMAH. "
2.	Adrenocorticotropic Hormone (ACTH)FDA Link 03/01/2022 - "Metabolic profile differences in ACTH-dependent and ACTH-independent Cushing syndrome." 04/01/2019 - "However, adrenal (ACTH-independent) Cushing syndrome was established using ACTH(AIA) or ACTH(Cobas) and proved surgically. " 03/21/2019 - "Biochemical investigation was suggestive of corticotropin (ACTH)-independent Cushing syndrome. " 09/01/2015 - "Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. " 05/01/2014 - "The diagnosis of adrenocorticotrophic hormone (ACTH)-independent Cushing syndrome was established. "
3.	Vasopressins (Vasopressin)IBA 01/01/2013 - "Evaluating the differences in the vasopressin sensitivity may therefore be helpful for understanding the progression of AIMAH." 01/01/2007 - "We describe a familial case of AIMAH with in vivo and in vitro demonstration of aberrant 5-HT4 and vasopressin adrenal receptors. " 01/01/2009 - "A high expression level of V1a receptor mRNAs was observed in the resected adrenal glands of vasopressin responders with AIMAH and unilateral adenomas. " 02/01/2004 - "Vasopressin responsiveness of subclinical Cushing's syndrome due to ACTH-independent macronodular adrenocortical hyperplasia." 06/01/2009 - "Familial vasopressin-sensitive ACTH-independent macronodular adrenal hyperplasia (VPs-AIMAH): clinical studies of three kindreds."
4.	Gastric Inhibitory Polypeptide (Glucose Dependent Insulinotropic Peptide)IBA 01/01/2011 - "Overexpression of the glucose-dependent insulinotropic peptide receptor has been shown to promote adrenocortical tumorigenesis in a mice model and has also been associated with ACTH-independent Cushing syndrome in humans. " 05/01/2013 - "In contrast, in a meal-responsive patient with apparent gastric inhibitory polypeptide (GIP) dependent AIMAH, did not achieve remission under somatostatin analogues." 08/01/1997 - "The elucidation of gastric inhibitory polypeptide-dependent Cushing's syndrome suggested that ectopic expression or increased responsiveness of other adrenal hormone receptors may underlie ACTH-independent macronodular adrenal hyperplasia (AIMAH) or adrenocortical tumors. " 12/01/1997 - "Food intake, gastric inhibitory polypeptide (GIP), or octreotide administration, which were reported to regulate cortisol release in patients with AIMAH, failed to affect plasma cortisol levels. " 11/01/2006 - "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. "
5.	Somatostatin (Somatotropin Release-Inhibiting Factor)IBA 05/01/2013 - "In contrast, in a meal-responsive patient with apparent gastric inhibitory polypeptide (GIP) dependent AIMAH, did not achieve remission under somatostatin analogues." 05/01/2013 - "We focused on the efficacy of somatostatin analogues in a patient with food-dependent AIMAH and of leuprolide acetate in a patient with AIMAH due to aberrant LH/hCG receptor expression. " 12/01/2012 - "somatostatin, dopamine, and epidermal growth factor receptors) and the adrenal gland (ectopically expressed receptors in ACTH-independent macronodular adrenal hyperplasia). "
6.	LH Receptors (LH Receptor)IBA 12/01/2007 - "GIP and LH-receptor expression may coexist in AIMAH, influencing the functional and morphological phenotype. " 05/01/2013 - "We focused on the efficacy of somatostatin analogues in a patient with food-dependent AIMAH and of leuprolide acetate in a patient with AIMAH due to aberrant LH/hCG receptor expression. "
7.	MetyraponeFDA Link 12/01/2001 - "Treatment with metyrapone thus appears a good therapy for AIMAH, but its effectiveness has not, to our knowledge, been studied. " 02/01/2012 - "Assessment of long-term efficacy and safety of metyrapone monotherapy in a patient with ACTH-independent macronodular adrenal hyperplasia." 12/01/2001 - "We treated a 59-year-old man with AIMAH with metyrapone. " 12/01/2001 - "Therapy using metyrapone thus appears effective in treating AIMAH, and can be recommended for high risk AIMAH patients as an alternative therapy." 12/01/2001 - "Rational, effective metyrapone treatment of ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH)."
8.	Leuprolide (Lupron)FDA LinkGeneric 05/01/2013 - "We focused on the efficacy of somatostatin analogues in a patient with food-dependent AIMAH and of leuprolide acetate in a patient with AIMAH due to aberrant LH/hCG receptor expression. " 05/01/2013 - "A luteinizing hormone/human chorionic gonadotropin (LH/hCG) responsive patient with AIMAH sustained long-term control of cortisol excess on leuprolide acetate. "
9.	Insulin (Novolin)FDA Link 01/01/2009 - "Evidence for cortisol stimulation by upright posture and insulin-induced hypoglycemia in a patient with CS related to AIMAH led us to try beta-blockers as a therapeutic test and then as a first line treatment. "
10.	Hormones (Hormone)IBA 08/01/2010 - "The design of the study includes clinical case description, and biochemical and immunohistochemical analysis to demonstrate aberrant expression of multiple hormone receptors in AIMAH. " 08/01/2010 - "We aimed to determine aberrant expression of multiple hormone receptors in vivo and in vitro in adrenal tissue of a patient with AIMAH. " 07/01/2010 - "In recent years, cases of familial AIMAH have been identified, and specific aberrant hormone receptors are functional in the adrenal of affected members. " 08/01/2009 - "AIMAH is a clinically and genetically heterogeneous disorder that can be associated with various genetic defects and aberrant hormone receptors. " 04/01/2009 - "In several familial cases of AIMAH, specific aberrant hormone receptors are functional in the adrenal of affected members. "

Therapies and Procedures

1.	Adrenalectomy 09/01/2013 - "Unilateral adrenalectomy appears to be an effective and safe alternative treatment for AIMAH. " 01/01/2017 - "We conclude that unilateral adrenalectomy is a safe and effective treatment for certain cases of AIMAH." 05/01/2008 - "Unilateral adrenalectomy of the largest gland can be an effective and safe treatment for AIMAH in case of asymmetric involvement. " 02/01/2015 - "Diagnosis of AIMAH is usually derived from pathological examination and long term remission may be achieved by unilateral adrenalectomy. " 07/01/2013 - "At a median follow-up of 69 months (range: 23-120 months) for AIMAH and 47 months (range: 16-113 months) for PPNAD, 25 patients were cured by unilateral adrenalectomy. "
2.	Therapeutics 09/01/2013 - "To our knowledge, this is the first article discussing classification, diagnosis and treatment of this disease and should be useful for future therapy of AIMAH. " 12/01/2009 - "Improvement of hypercortisolism by β-blocker therapy in subclinical Cushing's syndrome associated with ACTH-independent macronodular adrenocortical hyperplasia." 01/01/2010 - "These results suggest that unilateral adrenalectomy of the larger gland can be an alternative therapy for infantile onset Cushing' s syndrome caused by AIMAH with MAS, when asymmetric involvement is evident and the smaller gland is not markedly enlarged." 01/01/2010 - "Unilateral adrenalectomy can be an alternative therapy for infantile onset Cushing' s syndrome caused by ACTH-independent macronodular adrenal hyperplasia with McCune-Albright syndrome." 12/01/2001 - "Therapy using metyrapone thus appears effective in treating AIMAH, and can be recommended for high risk AIMAH patients as an alternative therapy."
3.	Autologous Transplantation 06/01/2001 - "However, autotransplantation of adrenal fragments failed in this patient with AIMAH." 06/01/2001 - "The case is reported of a 56-year-old woman who underwent simultaneous bilateral laparoscopic adrenalectomy for adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasia (AIMAH), followed by autotransplantation of resected adrenal gland fragments. "
4.	Cholecystectomy 12/01/2001 - "We performed cholecystectomy and partial adrenalectomy of right adrenal gland as a biopsy, and diagnosed him as preclinical Cushing's syndrome due to adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) based on endocrinological and histological examinations. "
5.	Glycemic Control 01/01/2012 - "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. " 01/01/2012 - "Usefulness and limitations of unilateral adrenalectomy for ACTH-independent macronodular adrenal hyperplasia in a patient with poor glycemic control."