Adrenocorticotropin-independent Macronodular Adrenal Hyperplasia: An Uncommon Cause of Primary Adrenal Hypercortisolism

Doppman, John L.; Chrousos, G. P.; Papanicolaou, Dimitris A.; Stratakis, Constantine A.; Alexander, H. Richard; Nieman, Lynnette K.

doi:10.1148/radiology.216.3.r00au40797

Cited by 98 publications

(55 citation statements)

References 27 publications

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“…Low attenuation value on unenhanced computed tomography scan confirmed the presence of fat within the masses, already suggesting their adrenocortical origin (21), and subtle dysregulation of cortisol secretion is a further evidence in support of an AIMAH.…”

Section: Discussionmentioning

confidence: 63%

Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: a frequent finding in a prospective study of 32 patients with overt or subclinical Cushing's syndrome

Libé¹,

Coste²,

Guignat³

et al. 2010

European Journal of Endocrinology

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Context: ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare and heterogeneous condition characterized by abnormal steroid production. Cortisol secretion can be regulated by aberrant hormone receptors. Objective: A large series of patients with AIMAH were evaluated to provide information on the prevalence and profile of aberrant regulations, in relation with the functional status. Design and patients: Thirty-two consecutive patients with AIMAH were prospectively studied: 10 had a Cushing's syndrome (CS), and 22 had a subclinical CS (SCS). Methods: A baseline endocrine evaluation was followed by an in vivo protocol in search of aberrant cortisol responses (seven provocative tests). An acute inhibition test with the somatostatin analog octreotide was also performed. Results: At least one aberrant cortisol response was identified in 28 of 32 (87%) patients. The overall prevalence of aberrant responses was independent of the functional status. Responses to the upright posture and to metoclopramide were frequently observed (67 and 56% respectively). A glucagon response was frequently observed in the SCS group (58%). A cortisol inhibition by octreotide was specifically found in the three CS patients who positively responded to the mixed meal, and was observed also in 12 of 13 (92%) patients with SCS. Conclusions: Cortisol responses indicative of aberrant receptor expression were highly prevalent in AIMAH. Thorough phenotyping of AIMAH may help uncover the underlying pathophysiology.

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Section: Discussionmentioning

confidence: 63%

Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: a frequent finding in a prospective study of 32 patients with overt or subclinical Cushing's syndrome

Libé¹,

Coste²,

Guignat³

et al. 2010

European Journal of Endocrinology

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“…The glands can demonstrate a signal dropout at chemical shift imaging, suggesting the presence of intracellular lipid (21). Doppman et al (22) described very similar characteristics in the adrenal glands of 12 patients with AIMAH (three men, nine women) and also found a bilateral uptake of Iodine-131-6β-iodomethyl-19-norcholesterol (NP-59). The asymmetric appearance of adrenal macronodules in AIMAH has been described and may lead to the erroneous diagnosis of unilateral pathology as the development of contralateral disease can occur several years later (4,23).…”

Section: Radiologymentioning

confidence: 95%

Cushing's syndrome secondary to ACTH-Independent macronodular adrenal hyperplasia

Costa

Lacroix

2007

Arq Bras Endocrinol Metab

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ACTH-Independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of endogenous Cushing's syndrome (CS), in which clinical features usually become apparent only after several decades of life. This form of adrenal hyperplasia typically produces excess cortisol with overt or subclinical CS, but concurrent secretion of mineralocorticoids or sexual steroids can also occur. The diagnosis is suspected by bilateral adrenal nodules larger than 1 cm on incidental imaging studies or following the demonstration of ACTH-independent hormonal hypersecretion. The pathophysiology of this entity is heterogeneous and has been intensely explored in recent years. Several G-protein coupled receptors aberrantly expressed in the adrenal cortex have been implicated in the regulation of steroidogenesis and in the initial cell proliferation in AIMAH. Several familial cases of AIMAH have been recently described with the same pattern of aberrant hormone receptors in all affected members of the family. It is probable that additional somatic genetic events related to cell cycle regulation, adhesion and transcription factors occur in addition over time in the various nodules; other mechanisms, as Gsp or ACTH receptor mutations and paracrine adrenal hormonal secretion have been rarely identified as the molecular mechanism in some cases. When systematically screened, most patients with AIMAH exhibit an in vivo aberrant cortisol response to one or various ligands suggesting the presence of aberrant adrenal receptors. The identification of these receptors creates the possibility of a specific pharmacological treatment isolated or associated with adrenalectomy. A hiperplasia adrenal macronodular independente de ACTH (AIMAH) é uma causa rara de síndrome de Cushing (SC) endógena, na qual alguns aspectos clínicos só se tornam evidentes depois de várias décadas de vida. Esta forma de hiperplasia adrenal caracteristicamente produz excesso de cortisol resultando na síndrome de Cushing franca ou subclínica, embora a secreção concomitante de mineralocorticóide, estrógeno e andrógenos também possa ocorrer. A suspeita diagnóstica é feita pela presença de nódulos adrenais bilaterais maiores que 1 cm, como achado incidental em exames de imagem ou pela demonstração de hipersecreção hormonal independente de ACTH. A fisiopatologia desta doença é heterogênea e tem sido intensamente estudada nos últimos anos. Vários receptores acoplados à proteína G, com expressão aberrante no córtex adrenal, têm sido implicados na regulação da esteroidogênese e no início da proliferação celular que ocorre na AIMAH. Diversos casos familiais de AIMAH foram recentemente descritos, e um mesmo padrão de expressão anormal dos receptores aberrantes foi observado em todos os membros afetados das famílias investigadas. Ao longo do tempo, é provável que ocorram, nos nódulos, eventos genéticos adicionais relacionados à regulação do ciclo celular, adesão e fatores de transcrição. Outros mecanismos moleculares, como mutações nos genes da proteína Gsα e do receptor de ACTH, ou ...

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“…The remaining cases will be adrenocortical hyperplasias. Even in these cases it's important to distinguish adrenocorticotropin (ACTH)-dependent forms like Cushing's disease or CAH (due to 21-hydroxylase deficiency) from ACTHindependent ones as a primary step in the differential diagnosis of Cushing's syndrome due to adrenocortical bilateral hyperplasias (Doppman et al, 2000). Among the adrenal causes of Cushing's syndrome about 10-15% are due to bilateral adrenal lesions that include micronodular (particularly its most common variant the Primary Pigmented Nodular Adrenocortical Disease -PPNAD) and macronodular adrenal hyperplasias (ACTH-Independent Macronodular Adrenocortical Hyperplasia -AIMAH) and, more rarely, bilateral adenomas or carcinomas (Christopoulos et al, 2005;Stratakis & Boikos, 2007).…”

Section: Pediatric Adrenal Cortex Tumorsmentioning

confidence: 99%

“…The most common laboratory findings associated with AIMAH are the following:  Increased serum and urinary cortisol and undetectable plasma ACTH in the basal state (Doppman et al, 2000;Swain et al, 1998;Kirschner et al, 1964;Bourdeau et al, 2001, Lieberman et al, 1994.  As in any cause of adrenal cortisol hypersecretion, dexamethasone suppression test fails to suppress cortisol production (Christopoulos et al, 2005).…”

Section: Aimah Diagnosis and Clinical Presentationmentioning

confidence: 99%

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Adrenal Cortex Tumors and Hyperplasias

Pignatelli¹

2011

Contemporary Aspects of Endocrinology

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Adrenocorticotropin-independent Macronodular Adrenal Hyperplasia: An Uncommon Cause of Primary Adrenal Hypercortisolism

Abstract: AIMAH is a rare cause of ACTH-independent Cushing syndrome, with characteristic CT findings of massively enlarged multinodular adrenal glands. Bilateral adrenalectomy is indicated on the basis of clinical and CT findings.

Cited by 98 publications

References 27 publications

Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: a frequent finding in a prospective study of 32 patients with overt or subclinical Cushing's syndrome

Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: a frequent finding in a prospective study of 32 patients with overt or subclinical Cushing's syndrome

Cushing's syndrome secondary to ACTH-Independent macronodular adrenal hyperplasia

Adrenal Cortex Tumors and Hyperplasias

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