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

Libé, Rossella; Coste, Joël; Guignat, Laurence; Tissier, Frédérique; Lefebvre, Henri; Barrande, Gaëlle; Ajzenberg, C.; Tauveron, Igor; Clauser, Éric; Dousset, B.; Bertagna, Xavier; Bertherat, Jérôme; Groussin, Lionel

doi:10.1530/eje-10-0195

Cited by 88 publications

(73 citation statements)

References 36 publications

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“…CS in PBMAH is often mild and insidious, even if serious forms can be encountered. PBMAH seems to be predominant in females as observed with other causes of CS (9,10,11). Finally, the exact prevalence of PBMAH in the general population is unknown and dependent of the diagnosis criteria.…”

Section: Introductionmentioning

confidence: 87%

Genetics of primary bilateral macronodular adrenal hyperplasia: a model for early diagnosis of Cushing's syndrome?

Drougat

Espiard

Bertherat

2015

European Journal of Endocrinology

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Long-term consequences of cortisol excess are frequent despite appropriate treatment after cure of Cushing's syndrome. This might be due to diagnostic delay, often difficult to reduce in rare diseases. The identification of a genetic predisposing factor might help to improve early diagnosis by familial screening. Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing's syndrome. Hypercortisolism in PBMAH is most often diagnosed between the fifth and sixth decades of life. The bilateral nature of the adrenocortical tumors and the occurrence of rare clear familial forms suggest a genetic origin. Indeed, a limited subset of PBMAH can be observed as part of multiple tumors syndromes due to alterations of the APC, Menin or Fumarate Hydratase genes. Rare variants of the phosphodiesterases PDE11A have been associated with PBMAH. The recent identification of ARMC5 germline alterations in 25-50% of PBMAH patients without obvious familial history or associated tumors opens new perspectives. ARMC5 alterations follow the model of a tumor suppressor gene: a first germline inactivating mutation of this 16p located gene is followed by a somatic secondary hit on the other allele (inactivating mutation or allelic loss). Functional studies demonstrate that ARMC5 controls apoptosis and steroid synthesis. The phenotype of index cases patients with the mutation seems more severe than the one of WT index cases. However, phenotype variability within a family is often observed. This review summarizes the genetics of PBMAH, focusing on ARMC5, which offer new perspectives for early diagnosis of Cushing's syndrome.

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Section: Introductionmentioning

confidence: 87%

Genetics of primary bilateral macronodular adrenal hyperplasia: a model for early diagnosis of Cushing's syndrome?

Drougat

Espiard

Bertherat

2015

European Journal of Endocrinology

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“…However, routine assessment by the complex testing (27,209,210,211,212,213,214,215) needed to establish the presence of these receptors is hard to justify based on the fact that in the majority of patients, long-term management will not be based on knowledge of receptor activity, and, therefore, we suggest that these tests should be confined to clinical studies.…”

Section: Reasoningmentioning

confidence: 99%

Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors

Fassnacht

Arlt

Bancos

et al. 2016

European Journal of Endocrinology

1,237

1,424

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By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected recommendations: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1 mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50 nmol/L (1.8 µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1 mg dexamethasone >138 nmol/L (>5 µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with 'autonomous cortisol secretion' who also have comorbidities that are potentially related to cortisol excess. (vi) In principle, the appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. (vii) Surgery is not usually indicated in patients www.eje-online.org European Journal of Endocrinology175:2 G2 Clinical Practice Guideline M Fassnacht and others ESE and ENSAT guideline on adrenal incidentalomawith an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. Furthermore, we offer recommendations for the follow-up of patients with adrenal incidentaloma who do not undergo adrenal surgery, for those with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses and for young and elderly patients with adrenal inciden...

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“…73 The growth hormone inhibitor octreotide, GCG, and insulin suppressed cortisol production in some patients with Cushing's syndrome and 92% of the patients with subclinical Cushing's syndrome in this study. 68,72 Human chorionic gonadotropin stimulated cortisol production in vivo 48 and in AIMAH cell cultures, 42,47 demonstrating that an effect coupled to AC/PKA pathway. 44 Luteinizing hormone (LH) stimulated cortisol production in vivo 48 and LH receptors were identified in cultured cells, 40,47,48 which can be indirectly induced by gonadotropin-releasing hormone in vivo.…”

Section: Other Hormonesmentioning

confidence: 98%

“…72 Aberrant expression of GCG receptors in adrenal glands were detected in a patient with Cushing's syndrome and AIMAH. The results showed abnormally high levels of serum cortisol after stimulation with GCG.…”

Section: Other Hormonesmentioning

confidence: 98%

ACTH-Independent Hypercorticism in Adrenal Tumors and Adrenocortical Hyperplasia

Li¹,

Hanna²

2016

Cell Communication Insights

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Cortisol production is normally under the regulation of adrenocorticotropic hormone (ACTH). Hypercortisolism or Cushing's syndrome, characterized by excessive cortisol levels, may be caused by ACTH-independent mechanisms. The present work aims to review the current knowledge on ACTH-independent mechanisms through aberrant expression of hormone receptors in adrenal tumors and adrenocortical hyperplasia. In particular, the effects of epinephrine, norepinephrine, serotonin, arginine vasopressin, and gastric inhibitory polypeptide are discussed.KEY WORDS: hypercorticism, adrenal tumors, adrenocortical hyperplasia, Cushing's syndrome, ACTH-independent CITATION: liu and hanna. aCth-independent hypercorticism in adrenal tumors and adrenocortical hyperplasia.

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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

Cited by 88 publications

References 36 publications

Genetics of primary bilateral macronodular adrenal hyperplasia: a model for early diagnosis of Cushing's syndrome?

Genetics of primary bilateral macronodular adrenal hyperplasia: a model for early diagnosis of Cushing's syndrome?

Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors

ACTH-Independent Hypercorticism in Adrenal Tumors and Adrenocortical Hyperplasia

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