What labs should be included to check for Cushing's syndrome in a secondary hypertension workup?

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From the Guidelines

To evaluate for Cushing's syndrome during a secondary hypertension workup, I recommend starting with a 24-hour urinary free cortisol measurement or a low-dose dexamethasone suppression test, as suggested by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. When considering the diagnosis of Cushing's syndrome, it's crucial to prioritize tests that can accurately identify excess cortisol production. The following labs should be included to check for Cushing's syndrome:

  • 24-hour urinary free cortisol measurement
  • Low-dose dexamethasone suppression test These tests are essential for assessing cortisol secretory status and can help diagnose Cushing's syndrome, which is a critical step in managing secondary hypertension. According to the consensus on diagnosis and management of Cushing's disease, a guideline update published in The Lancet Diabetes and Endocrinology in 2021, the sensitivity of these tests is above 90%, with the highest rates seen with the dexamethasone suppression test and the lowest with urinary free cortisol 1. It's also important to note that if any screening test is positive, confirmation with a second test is recommended, and for patients with confirmed hypercortisolism, additional tests to determine the cause include plasma ACTH levels, a high-dose dexamethasone suppression test, and imaging studies such as pituitary MRI or adrenal CT scan 1. By prioritizing these tests and following the recommended diagnostic algorithm, clinicians can effectively evaluate for Cushing's syndrome and develop an appropriate management plan to improve patient outcomes.

From the Research

Labs to Check for Cushing's Syndrome

To check for Cushing's syndrome in a secondary hypertension workup, the following labs can be included:

  • 1-mg dexamethasone suppression test (DST) 2, 3, 4, 5
  • Late-night salivary cortisol (LNSC) measurement 2, 6, 3, 4, 5
  • 24-hour urinary free cortisol (UFC) excretion 2, 6, 3, 4, 5
  • Scalp-hair cortisol/cortisone analysis to assess long-term glucocorticoid exposure 3
  • Plasma ACTH concentrations to differentiate between ACTH-dependent and ACTH-independent causes of Cushing's syndrome 3

Considerations for Lab Selection

When selecting labs to check for Cushing's syndrome, consider the following:

  • The Endocrine Society's Clinical Practice Guidelines recommend a single test with high diagnostic accuracy, such as 1-mg DST, LNSC, or 24-hour UFC 4
  • LNSC may be the most discriminatory test, but its availability should be considered 5
  • 1-mg DST is recommended as the screening test for hypertensive patients with an adrenal incidentaloma 5
  • UFC levels can reflect the integrated tissue exposure to free cortisol over 24 hours and provide a picture of endogenous hypercortisolism 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Screening Tests for Cushing's Syndrome: Urinary Free Cortisol Role Measured by LC-MS/MS.

The Journal of clinical endocrinology and metabolism, 2015

Research

Approach to the Patient: Diagnosis of Cushing Syndrome.

The Journal of clinical endocrinology and metabolism, 2022

Research

Cushing's Syndrome: Screening and Diagnosis.

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

Research

Hypertension and Cushing's syndrome: hunt for the red flag.

Journal of endocrinological investigation, 2025

Research

Late-night salivary cortisol as a screening test for Cushing's syndrome.

The Journal of clinical endocrinology and metabolism, 1998

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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