Mild autonomous cortisol secretion, often abbreviated MACS, sits at the gray zone of adrenal medicine. It typically emerges when imaging performed for unrelated reasons reveals an incidental adrenal mass, prompting clinicians to ask whether that mass is quietly producing cortisol without the normal brakes of the hypothalamic–pituitary–adrenal axis. Unlike overt Cushing’s syndrome, with its dramatic constellation of weight gain, striae, muscle wasting, and metabolic derangement, MACS produces a whisper rather than a shout. Patients may carry only vague features such as hypertension, obesity, or insulin resistance, yet longitudinal data link even this low-grade cortisol excess to increased cardiovascular and metabolic risk. The European Society of Endocrinology has formalized diagnostic criteria, but the biochemical tests at the heart of those criteria share a common limitation: they capture hormone dynamics over hours or days, not the cumulative burden of exposure that may be driving long-term harm.

That limitation is precisely where hair cortisol analysis enters the picture. Cortisol circulating in the bloodstream diffuses into the growing hair follicle and becomes incorporated into the keratin matrix of the hair shaft as it grows at roughly one centimeter per month. Because the hormone remains embedded in the fiber, the proximal three centimeters of hair provide an integrated record of systemic glucocorticoid exposure over approximately the preceding three months. This is fundamentally different from a morning serum cortisol, a late-night salivary sample, or a 24-hour urinary collection, all of which reflect a snapshot of hypothalamic–pituitary–adrenal activity subject to circadian rhythm, acute stress, and collection error. Hair, by contrast, averages the noise. The technique has been validated in stress research, cardiology, and occupational health, but evidence in MACS had remained sparse, motivating the Turkish team to test whether the hair shaft could reveal what standard endocrine assays miss.

The study enrolled 73 patients diagnosed with mild autonomous cortisol secretion according to European Society of Endocrinology guidelines, alongside 60 healthy controls who underwent rigorous screening to exclude any hint of cortisol excess. Each participant’s diagnosis or exclusion rested on a battery of conventional assessments: the 1-milligram overnight dexamethasone suppression test, the 2-day 2-milligram dexamethasone suppression test, 24-hour urinary free cortisol, and late-night salivary cortisol. From every participant, researchers collected the proximal 3-centimeter hair segment and quantified cortisol concentration, expressed in nanograms per gram of hair. The design, approved by the ethics committee of Basaksehir Cam and Sakura City Hospital and conducted with written informed consent under the Declaration of Helsinki, allowed the investigators to pursue three linked questions: whether hair cortisol differs between the groups, how well it discriminates patients from controls, and whether it tracks with hormonal and metabolic markers within the patient group.

The headline result was a clear group difference. Median hair cortisol concentration in patients with mild autonomous cortisol secretion reached 3.6 nanograms per gram, roughly double the 1.75 nanograms per gram observed in healthy controls, a difference that was statistically significant at p less than 0.01. For a condition defined by subtle, subclinical hormone production, this doubling of the long-term exposure signal is biologically meaningful. It suggests that even the low-grade autonomous cortisol output characteristic of MACS leaves a measurable imprint in the growing hair shaft, supporting the idea that hair analysis captures an integrated dimension of glucocorticoid burden that point-in-time tests cannot.

Within the patient group, hair cortisol told a more nuanced story. Concentrations correlated positively with waist circumference, with a Spearman coefficient of 0.27 and a p-value of 0.02, hinting that cumulative cortisol exposure may travel with central adiposity, one of the hallmark cardiometabolic consequences of cortisol excess. Hair cortisol also correlated with late-night salivary cortisol, at a coefficient of 0.25 and p equal to 0.03, indicating partial concordance between the long-term hair signal and a standard test of circadian hormone dysregulation. Intriguingly, however, hair cortisol showed no significant relationship with dexamethasone suppression test results or with 24-hour urinary free cortisol. This dissociation is not necessarily a weakness; it may reflect the fact that suppression tests and urinary collections measure dynamic feedback behavior and short-term secretion, respectively, whereas hair integrates tonic exposure over months. Two instruments measuring different constructs need not agree perfectly.

The diagnostic performance data tempered enthusiasm. Receiver operating characteristic analysis yielded an area under the curve of 0.60, with a 95 percent confidence interval of 0.51 to 0.70 and a p-value of 0.025, indicating discrimination only modestly better than chance. A cut-off of 2.7 nanograms per gram, chosen from the analysis, delivered limited sensitivity and specificity, meaning the threshold would miss a substantial share of true cases while misclassifying a meaningful number of controls. In other words, a clinician armed only with a hair cortisol value could not reliably separate a patient with MACS from a healthy person, particularly given the well-documented influence of obesity, psychological stress, and other factors on hair cortisol in the general population.

Multivariable analysis drove the point home further. When the researchers adjusted for age, sex, and body mass index in a logistic regression model, hair cortisol concentration was no longer independently associated with mild autonomous cortisol secretion. Because adiposity itself elevates hair cortisol, and because MACS is closely entangled with obesity and metabolic syndrome, the apparent group difference partly overlaps with body composition rather than standing as an independent disease signature. The authors therefore concluded that hair cortisol should be regarded as a complementary biomarker, one that adds longitudinal context to the standard biochemical workup, rather than a replacement for dexamethasone suppression testing, urinary free cortisol, or late-night salivary cortisol in establishing the diagnosis.

The clinical implications cut in two directions. On one hand, the study provides the strongest signal yet that hair cortisol can quantify chronic glucocorticoid exposure in MACS, opening the possibility of tracking cumulative burden over time in patients followed conservatively for incidentalomas, or of correlating hair-based exposure metrics with the progression of hypertension, diabetes, and cardiovascular risk in prospective cohorts. On the other hand, the modest diagnostic performance and the loss of independence after adjustment for demographic and anthropometric variables argue against any near-term role for hair cortisol as a screening or confirmatory test. The cross-sectional design further limits causal inference, and the single-center enrollment of 73 patients and 60 controls leaves open questions about generalizability across populations with different hair types, cosmetic treatment practices, and baseline stress exposures, all of which are known to modulate hair cortisol measurements.

What the Istanbul team has delivered, ultimately, is a careful calibration of expectations for an appealing technology. Hair cortisol genuinely reflects something real about chronic hormone exposure in mild autonomous cortisol secretion, doubling in patients and tracking with waist circumference and late-night salivary cortisol, yet it cannot stand alone against the diagnostic rigor that endocrinology guidelines demand. The authors call for further prospective studies to clarify whether the hair shaft’s three-month hormonal archive can earn a defined place in clinical practice, perhaps as a risk-stratification tool or a research endpoint for cumulative exposure. Until then, the strand of hair remains a promising witness rather than a verdict, and the diagnosis of this subtle adrenal condition will continue to rest on the established, if snapshot-limited, arsenal of suppression tests and timed hormone collections.

Subject of Research: Hair cortisol measurement as a long-term biomarker of chronic glucocorticoid exposure in mild autonomous cortisol secretion

Article Title: Hair cortisol as a complementary marker of chronic glucocorticoid exposure in mild autonomous cortisol secretion

Article References: Korkmaz Yilmaz, M., Tek, S., Pekmezci, A., Niyazoglu, M., & Hatipoglu, E. (2026). Hair cortisol as a complementary marker of chronic glucocorticoid exposure in mild autonomous cortisol secretion. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02607-1

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02607-1

Keywords: hair cortisol, mild autonomous cortisol secretion, adrenal incidentaloma, cortisol excess, HPA axis, dexamethasone suppression test, late-night salivary cortisol, chronic glucocorticoid exposure, endocrinology, biomarker, cardiometabolic risk, BMC Endocrine Disorders