Diagnostic Accuracy of Dehydroepiandrosterone Sulfate and Corticotropin in Autonomous Cortisol Secretion

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Abstract

Autonomous cortisol secretion (ACS) affects up to 50% of patients with adrenal adenomas. Despite the limited evidence, clinical guidelines recommend measurement of serum concentrations of dehydroepiandrosterone-sulfate (DHEA-S) and corticotropin (ACTH) to aid in the diagnosis of ACS. Our objective was to determine the accuracy of serum concentrations of DHEA-S and ACTH in diagnosing ACS. We conducted a retrospective single center study of adults with adrenal adenoma evaluated between 2000−2020. Main outcome measure was diagnostic accuracy of DHEA-S and ACTH. ACS was defined as post-dexamethasone cortisol >1.8 mcg/dL. Of 468 patients, ACS was diagnosed in 256 (55%) patients with a median post-DST cortisol of 3.45 mcg/dL (range, 1.9–32.7). Patients with ACS demonstrated lower serum concentrations of DHEA-S (35 vs. 87.3 mcg/dL, p < 0.0001) and ACTH (8.3 vs. 16 pg/mL, p < 0.0001) compared to patients with non-functioning adrenal tumors (NFAT). Serum DHEA-S concentration <40 mcg/dL diagnosed ACS with 84% specificity and 81% PPV, while serum ACTH concentration <10 pg/mL diagnosed ACS with 75% specificity and 78% PPV. The combination of serum concentrations of DHEA-S <40 mcg/dL and ACTH <10 pg/mL diagnosed ACS with the highest accuracy with 92% specificity and 87% PPV. Serum concentrations of DHEA-S and ACTH provide additional value in diagnosing ACS.

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

Martin Fassnacht, Wiebke Arlt, Irina Bancos … (2016)

: 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 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/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 with 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 incidentalomas.

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The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline.

Lynnette K Nieman, Beverly M K Biller, James Findling … (2008)

The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome. The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage the Task Force incorporated needed changes in response to written comments. After excluding exogenous glucocorticoid use, we recommend testing for Cushing's syndrome in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal incidentaloma. We recommend initial use of one test with high diagnostic accuracy (urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone suppression test). We recommend that patients with an abnormal result see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasone-CRH test. Patients with concordant abnormal results should undergo testing for the cause of Cushing's syndrome. Patients with concordant normal results should not undergo further evaluation. We recommend additional testing in patients with discordant results, normal responses suspected of cyclic hypercortisolism, or initially normal responses who accumulate additional features over time.

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Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing's syndrome: a 15-year retrospective study.

Guido Di Dalmazi, Valentina Vicennati, Silvia Garelli … (2014)

Incidental discovery of adrenal masses has increased over the past few years. Mild alterations in cortisol secretion without clinical signs of overt hypercortisolism (subclinical Cushing's syndrome) are a common finding in patients with these tumours. Although metabolic alterations and increased cardiovascular risk have been noted in patients with subclinical Cushing's syndrome, incidence of cardiovascular events and mortality in the long term have not been assessed. We aimed to ascertain the frequency of new cardiovascular events and mortality in patients with non-secreting adrenal incidentalomas, tumours of intermediate phenotype, or those causing subclinical Cushing's syndrome.

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Author and article information

Contributors

Danae Delivanis: Role: Academic Editor

Anna Angelousi: Role: Academic Editor

Journal

Journal ID (nlm-ta): Biomedicines

Journal ID (iso-abbrev): Biomedicines

Journal ID (publisher-id): biomedicines

Title: Biomedicines

Publisher: MDPI

ISSN (Electronic): 2227-9059

Publication date (Electronic): 28 June 2021

Publication date Collection: July 2021

Volume: 9

Issue: 7

Electronic Location Identifier: 741

Affiliations

[1 ]Department of Internal Medicine, May Clinic, Rochester, MN 55902, USA; carafone.lindsay@ 123456mayo.edu

[2 ]Division of Endocrinology, Mayo Clinic, Rochester, MN 55902, USA; zhang.catherine@ 123456mayo.edu (C.D.Z.); li.dingfeng@ 123456mayo.edu (D.L.); lazik.natalia@ 123456mayo.edu (N.L.); Oksana.Hamidi@ 123456UTSouthwestern.edu (O.H.); Hurtado.Mariadaniela@ 123456mayo.edu (M.D.H.); young.william@ 123456mayo.edu (W.F.Y.J.); thomas.melinda@ 123456mayo.edu (M.A.T.)

[3 ]Division of Endocrinology and Metabolism, UT Southwestern Medical Center, Dallas, TX 75390, USA

[4 ]Division of Endocrinology, Mayo Clinic Health System, La Crosse, WI 54601, USA

[5 ]Department of Surgery, Mayo Clinic, Rochester, MN 55902, USA; dy.benzon@ 123456mayo.edu (B.M.D.); Lyden.melanie@ 123456mayo.edu (M.L.L.); Foster.Trenton@ 123456mayo.edu (T.R.F.); mckenzie.travis@ 123456mayo.edu (T.J.M.)

Author notes

[* ]Correspondence: Bancos.Irina@ 123456mayo.edu

Author information

Oksana Hamidi https://orcid.org/0000-0002-7367-3885

Irina Bancos https://orcid.org/0000-0001-9332-2524

Article

Publisher ID: biomedicines-09-00741

DOI: 10.3390/biomedicines9070741

PMC ID: 8301396

PubMed ID: 34203283

SO-VID: fb6afc68-f6ac-4e62-bce1-e997973090f1

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

Diagnostic Accuracy of Dehydroepiandrosterone Sulfate and Corticotropin in Autonomous Cortisol Secretion

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Most cited references 15

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

The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline.

Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing's syndrome: a 15-year retrospective study.

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