What is the screening method for hyperadrenalism (Cushing's syndrome)?

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Last updated: February 15, 2025View editorial policy

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From the Guidelines

The screening method for hyperadrenalism (Cushing's syndrome) is the overnight 1-mg dexamethasone suppression test (DST), late night salivary cortisol (LNSC), or 24-hour urinary free cortisol (UFC), with the highest sensitivity and specificity seen with DST and LNSC 1.

Screening Tests

  • Late night salivary cortisol (LNSC): measures cortisol levels in saliva at night, with abnormal results indicating Cushing's syndrome 1
  • Overnight 1-mg dexamethasone suppression test (DST): measures cortisol levels after taking a dose of dexamethasone, with abnormal results indicating Cushing's syndrome 1
  • 24-hour urinary free cortisol (UFC): measures cortisol levels in urine over 24 hours, with abnormal results indicating Cushing's syndrome 1

Clinical Considerations

When interpreting test results, consider factors such as sex, body mass index (BMI), age, urinary volume, and sodium intake, as they can influence UFC levels 1. For patients with renal impairment or significant polyuria, LNSC may be preferred over UFC 1.

Distinguishing between Cushing's Syndrome and Pseudo-Cushing's Syndrome

In cases where non-neoplastic hypercortisolism (pseudo-Cushing's syndrome) is suspected, the combined LDDT-CRH (Dex-CRH) test or desmopressin test may be used to distinguish between ACTH-dependent Cushing's syndrome and pseudo-Cushing's syndrome 1.

From the Research

Screening Methods for Hyperadrenalism (Cushing's Syndrome)

The screening methods for hyperadrenalism (Cushing's syndrome) include:

  • 1-mg dexamethasone suppression test (1-mg DST) 2, 3, 4, 5, 6
  • Late night salivary cortisol (LNSC) 2, 3, 4, 5, 6
  • 24-hour urinary free cortisol (UFC) 2, 3, 4, 5, 6

Characteristics of Each Screening Test

  • 1-mg DST: explores the normal feedback reaction from the hypothalamic-pituitary-adrenal axis (HPA), simple dynamic test, usually performed in outpatients 2
  • LNSC: measures cortisol values at night, easy to measure in saliva, suitable for outpatients 2, 3
  • UFC: reflects the integrated tissue exposure to free cortisol over 24 hours, provides a picture of endogenous hypercortisolism, used to diagnose and monitor CS 2, 4

Considerations for Each Test

  • 1-mg DST: some drugs can interfere with the test, false-positive or false-negative results may occur 2
  • LNSC: false-positive or false-negative results may be due to inadequate soaking of the device or cyclic CS 2
  • UFC: important to ensure complete urine collections with appropriate total volumes, measuring cortisol with antibody-based immunoassays can generate false-positive results due to cross-reactivity 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cushing's Syndrome: Screening and Diagnosis.

High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension, 2016

Research

Biochemical diagnosis of Cushing's disease: Screening and confirmatory testing.

Best practice & research. Clinical endocrinology & metabolism, 2021

Research

Diagnostic workup of Cushing's syndrome.

Journal of neuroendocrinology, 2022

Research

Recent Updates on the Diagnosis and Management of Cushing's Syndrome.

Endocrinology and metabolism (Seoul, Korea), 2018

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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