Will Dehydroepiandrosterone sulfate (DHEAS) and norepinephrine be elevated in Cushing's syndrome versus adrenal disorders?

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Last updated: April 10, 2025View editorial policy

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From the Guidelines

In patients with Cushing's syndrome versus adrenal disorders, DHEAS levels are typically normal or low, and norepinephrine levels are generally normal, unless there is a concurrent pheochromocytoma, as evidenced by recent guidelines 1. When testing for Cushing's versus adrenal disorders, it is essential to consider the specific condition and the underlying pathophysiology.

  • In Cushing's syndrome, DHEAS levels are typically normal or low, not high, as cortisol excess suppresses ACTH and subsequently DHEAS production.
  • Norepinephrine levels are generally normal in Cushing's syndrome unless there is concurrent pheochromocytoma. In contrast, certain adrenal disorders like adrenal adenomas or carcinomas may produce elevated DHEAS, particularly if they are androgen-secreting tumors.
  • Pheochromocytomas, which are catecholamine-producing adrenal tumors, cause elevated norepinephrine levels. The diagnostic approach should include a comprehensive panel including 24-hour urinary free cortisol, overnight dexamethasone suppression test, and midnight salivary cortisol for Cushing's, while plasma or urinary metanephrines and catecholamines are used to diagnose pheochromocytoma, as recommended by recent consensus guidelines 1. These tests help differentiate between various adrenal pathologies and guide appropriate treatment, ultimately improving patient outcomes in terms of morbidity, mortality, and quality of life.

From the Research

Diagnostic Tests for Cushing's Syndrome

  • The diagnosis of Cushing's syndrome involves a complex diagnostic assessment, and several studies have suggested that the prevalence of Cushing's syndrome is higher than previously thought 2, 3, 4.
  • The recommended diagnostic tests for Cushing's syndrome include 24-h urinary free cortisol, 1-mg overnight dexamethasone suppression test, and late-night salivary cortisol 2, 3, 4.
  • Once the diagnosis of Cushing's syndrome is established, the next step is the measurement of plasma ACTH to differentiate between ACTH-dependent and ACTH-independent causes 2, 4.

DHEAS and Norepinephrine Levels

  • There is no direct evidence in the provided studies to suggest that DHEAS and norepinephrine levels would be high in patients with Cushing's syndrome versus adrenal disorders.
  • However, it is known that Cushing's syndrome is associated with supraphysiological exposure to glucocorticoids, which can affect the levels of various hormones and biomarkers, including DHEAS and norepinephrine 4.
  • Further studies would be needed to determine the specific effects of Cushing's syndrome on DHEAS and norepinephrine levels and to differentiate between Cushing's syndrome and adrenal disorders.

Diagnostic Challenges

  • The diagnosis of Cushing's syndrome can be challenging due to the resemblance of its clinical features with those of common diseases found in the general population 2, 3, 4.
  • The choice of test, the modality of specimen collection, and the quality of measurement are key factors for optimal care of patients with suspected Cushing's syndrome 2.
  • The use of combined diagnostic tests, such as the 1-mg dexamethasone suppression test and 24-hour urinary free cortisol excretion, can help improve the accuracy of diagnosis 3, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Approach to the patient with possible Cushing's syndrome.

The Journal of clinical endocrinology and metabolism, 2009

Research

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

The Journal of clinical endocrinology and metabolism, 2008

Research

Approach to the Patient: Diagnosis of Cushing Syndrome.

The Journal of clinical endocrinology and metabolism, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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