A 50 nmol/L cortisol threshold may be too low for identifying hypercortisolism in adrenal incidentalomasNew data suggests lower cortisol thresholds may over-diagnose adrenal issues

Frontiers in Medicine Published September 9, 2026 DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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Key Takeaway

Note that the 50 nmol/L cortisol threshold may be too low for identifying hypercortisolism in adrenal incidentalomas.

This guideline evaluates the clinical utility of different cortisol cut-off values for the 1 mg overnight dexamethasone suppression test (DST) in patients with adrenal incidentalomas. The analysis compares a guideline-recommended threshold of 50 nmol/L against a control-derived threshold of 66 nmol/L (the 97.5th percentile of post-DST cortisol in controls).

Key findings indicate that the 50 nmol/L threshold identifies 44% of patients as having hypercortisolism, whereas the 66 nmol/L threshold identifies 26%. Additionally, pre-DST ACTH showed poor discrimination for post-DST cortisol >50 nmol/L with an AUC of 0.69. Post-DST cortisol was not associated with dexamethasone concentrations or patient comorbidities including diabetes, dyslipidaemia, hypertension, and osteoporosis.

The authors suggest that the 50 nmol/L threshold may be too low, indicating that higher thresholds might warrant further evaluation. However, this finding does not establish a new clinical standard. Clinical application should be approached with caution as the optimal threshold for identifying hypercortisolism in this population is not yet definitively established.

How this fits prior evidence

This guideline addresses the diagnostic criteria for hypercortisolism in patients with adrenal incidentalomas. It does not relate to the prior coverage of dexamethasone for pain management, multiple myeloma, or infections, as those cases involve different clinical indications and patient populations.

When doctors find an unexpected growth on the adrenal gland, called an incidentaloma, they must determine if the gland is overproducing cortisol. To do this, they use a dexamethasone suppression test. This test involves giving a patient a dose of medicine to see if their cortisol levels drop.

Researchers looked at 108 patients with these growths and 101 healthy people. They compared two different cutoff points for what is considered a high cortisol level. Using the current guideline of 50 nmol/L, 44% of patients were flagged as having high cortisol. However, when using a higher threshold of 66 nmol/L, that number dropped to 26%.

This suggests that the current standard might be set too low, which could lead to more people being flagged than necessary. Other factors like pre-test hormones or common health issues like high blood pressure did not change the results. While this doesn't change the rules today, it suggests that higher thresholds might need more study to ensure patients are only flagged when truly necessary.

What this means for you:

Current cortisol testing thresholds might be too low, potentially leading to more people being flagged than needed.

Common questions

What is an adrenal incidentaloma?

An adrenal incidentaloma is a growth on the adrenal gland that is found by chance while looking for something else. Doctors then use a dexamethasone suppression test to see if the growth is causing the body to produce too much cortisol, a hormone that can cause health problems if levels are too high.

How do the two different cortisol thresholds compare?

The study compared a guideline-recommended threshold of 50 nmol/L to a higher threshold of 66 nmol/L. Using the 50 nmol/L mark, 44% of patients were classified as having high cortisol. Using the 66 nmol/L mark, only 26% of patients were classified that way.

Do other health conditions affect the test results?

The study looked at whether conditions like diabetes, high blood pressure, and high cholesterol affected the results. It found that these comorbidities, as well as the amount of dexamethasone in the system, were not associated with the post-test cortisol levels.

Study Details

Study typeGuideline

EvidenceLevel 5

PublishedSep 2026

View Original Abstract ↓

PurposeAssessment of cortisol secretion in patients with adrenal incidentalomas remains challenging. We evaluated the guideline-recommended cortisol cut-off value for cortisol suppression (50 nmol/L) following a 1 mg overnight dexamethasone suppression test (DST) against a control-derived threshold and compared patient classification using the two thresholds. Secondary objectives included assessing associations of pre-DST ACTH, post-DST dexamethasone, and comorbidities with post-DST cortisol.MethodsIn this cross-sectional study (NCT07350031), pre- and post-DST plasma samples from patients with adrenal incidentalomas (N = 108) and matched controls (N = 101) were prospectively collected, and cortisol was analysed using immunoassay (Elecsys®Cort II) and LC–MS/MS. Post-DST dexamethasone ≥3 nmol/L defined appropriate dexamethasone exposure. The 97.5th percentile of LC–MS/MS-measured post-DST cortisol in controls defined the control-derived threshold. Associations between pre-DST ACTH, post-DST dexamethasone, and post-DST cortisol were assessed. The performance of pre-DST ACTH for identifying post-DST cortisol >50 nmol/L was evaluated using receiver operating characteristic analysis. Logistic regression examined associations between post-DST cortisol and diabetes, dyslipidaemia, hypertension, and osteoporosis.ResultsThe 97.5th percentile of post-DST cortisol in controls was 66 nmol/L. The 50 nmol/L threshold corresponded to the 90th percentile of controls and classified 44% of patients as having hypercortisolism, compared with 26% using the control-derived threshold (66 nmol/L). Pre-DST ACTH showed poor discrimination for post-DST cortisol >50 nmol/L (AUC 0.69). Post-DST cortisol was not associated with dexamethasone concentrations or comorbidities.Main conclusionsThe guideline-recommended post-DST cortisol threshold of 50 nmol/L may be too low, suggesting that higher thresholds warrant further evaluation.

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