Hair Cortisol Measurement Not Effective for Identifying Autonomous Cortisol Secretion in Adrenal Incidentalomas

Diseased adrenal glands, conceptual computer illustration.
A team of investigators measured concentrations of 5 corticosteroid hormones in the keratin matrix of patients with adrenal incidentalomas with or without cortisol autonomy.

No statistically significant differences in hair cortisol, cortisone, and 20b-dihydrocortisol concentrations were identified in patients with adrenal incidentalomas compared with individuals without incidentalomas, according to the results of a study published in Frontiers in Endocrinology.

Researchers sought to determine whether measurement of 5 corticosteroid hormones with ultra-high performance liquid chromatography-tandem mass spectrometry in the keratin matrix could help stratify patients with adrenal incidentaloma by the presence of autonomous cortisol secretion (serum cortisol after 1-mg dexamethasone suppression test [DST] >138 nmol/L) or possible autonomous cortisol secretion (serum cortisol after 1-mg DST >50 nmol/L but ≤138 nmol/L).

Eligible participants with adrenal incidentaloma were identified from a hospital in Italy between March 2019 and February 2020. All patients were diagnosed with cortical adrenal adenoma, with specific computed tomographic characteristics such as size <4 cm, well-defined margins, and homogeneous and hypodense content.

A total of 67 patients with adrenal incidentaloma (median age, 68 years; 55.2% women) and 81 control individuals without adrenal incidentaloma (median age, 64 years; 40.7% women) were included in the study. No statistically significant differences were observed in the hair concentrations of cortisol (median 3.40, interquartile range [IQR] 1.80-6.88 vs 2.72, 1.24-6.78 pg/mg), 20b-dihydrocortisol (median 1.55, 0.51-2.63 vs 1.63, 0.98-3.36 pg/mg), and cortisone (median 13.21, 9.94-22.00 vs 10.53, 6.43-22.91 pg/mg) between the control group and patients with adrenal incidentaloma, respectively. In all samples, levels of 6b-hydroxycortisol and 11-deoxycortisol were undetectable.

In the patients with adrenal incidentaloma, 35 participants had cortisol values ≤50 nmol/L, excluding cortisol autonomy. The remaining patients had biochemical evidence of cortisol autonomy, either autonomous cortisol secretion (n=3) or possible autonomous cortisol secretion (n=29).

Hair concentrations of cortisol, 20b-dihydrocortisol, and cortisone were comparable among patients with adrenal incidentaloma with serum cortisol after 1-mg DST ≤50 nmol/L and in patients with adrenal incidentaloma and serum cortisol after 1-mg DST >50 nmol/L. No correlation was observed in the 3 compounds in the keratin matrix with serum cortisol after 1-mg DST, 24-hour urinary free cortisol, plasma adrenocorticotropic hormone, or midnight salivary cortisol.

In addition, no correlation was found between cortisol and cortisone concentrations in the keratin matrix and body mass index, or among normal weight, overweight, or obese patients.

Study limitations include the retrospective nature of the study and the limited sample size. Also, although the monocentric nature avoided bias owing to interlaboratory variability, it may limit the validity of the results to a specific population.

“Our findings do not support the use of hair glucocorticoid measurement as a diagnostic test for cortisol autonomy in patients with [adrenal incidentaloma],” concluded the researchers.


Puglisi S, Leporati M, Amante E, et al. Limited role of hair cortisol and cortisone measurement for detecting cortisol autonomy in patients with adrenal incidentalomas. Front Endocrinol (Lausanne). Published online February 8, 2022. doi:10.3389/fendo.2022.833514