Lowering the dexamethasone suppression test cut-off: is it time yet?

Area of Science:

• Endocrinology
• Internal Medicine
• Oncology

Background:

• Cushing's syndrome (CS) involves overt hypercortisolism, while mild autonomous cortisol secretion (MACS) is subclinical cortisol excess, often linked to adrenal incidentalomas (AI).
• MACS is more common than CS, especially in older adults.
• The diagnostic standard, the 1 mg overnight dexamethasone suppression test (F-1mgDST) with a 1.8 µg/dL cut-off, is debated for accuracy.

Purpose of the Study:

• To review literature on the diagnostic accuracy of the current F-1mgDST cut-off for identifying comorbidities in patients with non-functioning adrenal incidentalomas (NFAI).
• To assess if the 1.8 µg/dL threshold adequately identifies patients with cortisol-related health issues.

Main Methods:

• Literature review of studies published between January 1990 and March 2025.
• Searched PubMed, Web of Science, and Scopus using keywords related to adrenal incidentalomas and subclinical hypercortisolism.
• Analysis focused on identifying comorbidities in NFAI patients relative to F-1mgDST results.

Main Results:

• NFAI patients often exhibit metabolic, cardiovascular, bone, and muscle issues associated with cortisol excess, even with F-1mgDST below 1.8 µg/dL.
• Studies suggest a lower F-1mgDST threshold of approximately 1.2 µg/dL may identify more at-risk individuals.
• However, a lower threshold could decrease specificity and increase false positives.

Conclusions:

• Current diagnostic criteria for MACS may require enhanced sensitivity, potentially incorporating biomarkers or pharmacological tests.
• The concept of a cortisol "milieu" suggests normal cortisol activity or altered rhythms can contribute to chronic conditions.
• Closer monitoring of AI patients with F-1mgDST > 1.2 µg/dL is recommended, pending further research.