Scalp hair cortisol and testosterone levels in patients with sarcoidosis

Abstract

Background: Patients with sarcoidosis often experience fatigue and psychological distress, but little is known about the etiology of these conditions. While serum and saliva steroid hormones are used to monitor acute steroid levels, scalp hair analysis is a relatively new method enabling measurement of long-term steroid levels, including hair cortisol reflecting chronic stress. We investigated whether scalp hair cortisol and testosterone levels differ between sarcoidosis patients both with and without fatigue and general population controls. Additionally, we studied if these hormones could serve as objective biomarkers for psychological distress in patients with sarcoidosis.

Methods: We measured hair steroid levels using liquid chromatography-tandem mass spectrometry in glucocorticoid naïve sarcoidosis patients. Patients completed the Perceived Stress Scale, Fatigue Assessment Scale, Hospital Anxiety and Depression Scale and Short Form 36 (SF-36). Hair steroid levels from 293 participants of the population-based Lifelines cohort study served as controls.

Results: Thirty-two patients (14 males) were included. Hair cortisol, but not testosterone, concentrations were significantly higher in patients with sarcoidosis than in general population controls (mean 6.6 versus 2.7 pg/mg, p<0.001). No differences were found in hair cortisol and testosterone levels between fatigued and non-fatigued patients with sarcoidosis. Hair cortisol of sarcoidosis patients correlated significantly with anxiety (r = 0.47, p = 0.01), depression (r = 0.46, p = 0.01), and SF-36 mental domain (r = -0.38, p = 0.03), but not with fatigue.

Conclusions: Patients with sarcoidosis have chronically higher levels of the stress hormone cortisol than the normal population, while testosterone levels in hair did not differ. Hair cortisol levels were positively related to subjective measures of psychological distress, but not to fatigue. Our study shows that hair cortisol is a promising non-invasive biomarker for psychological distress in patients with sarcoidosis.

Trial registration: ClinicalTrials.gov: NCT03108547. Registered 31 March 2017, retrospectively registered.

Conflict of interest statement

MM, ER, VW, LT, KD, and YR declare that they have no competing interests. MW reports grants and other financial support from Intermune/Hoffman la Roche and Boehringer Ingelheim, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Scalp hair analysis: Hair sample collection, pre-treatment and analysis.

LC-MS/MS, liquid chromatography-tandem mass spectrometry. Modified from [21] with permission from the publisher.

Fig 2. Hair cortisol, cortisone and testosterone levels in patients with sarcoidosis and general population controls [23, 24].

Cortisol and cortisone were measured in 32 sarcoidosis patients and in 293 general population controls. Testosterone was measured in 13 male sarcoidosis patients and in 62 male general population controls. Data are shown as geometric mean (95% CI), and corrected for age and gender. General Linear model–Univariate (ANCOVA) was used for analysis.

Fig 3. Hair cortisol, cortisone and testosterone levels in sarcoidosis patients with and without fatigue.

Cortisol and cortisone were measured in 23 sarcoidosis patients with fatigue and in 9 patients without fatigue. Testosterone was measured in 10 male sarcoidosis patients with fatigue and in 4 male patients without fatigue. Data are shown as geometric mean (95% CI). Independent sample t-test was used for analysis.

Fig 4. Interaction network showing all significant correlations between hair steroid levels, psychological distress and fatigue scores, and pulmonary function tests in sarcoidosis patients (n = 32).

Each node of the network corresponds to a questionnaire score, and its size is proportional to the % of the total score of the questionnaire. Two nodes are linked if they significantly correlate, the wider the string the better the correlation. EQ5D5L; Euroqol-5D 5-level; FAS, Fatigue Assessment Scale; SF-36, Short Form-36; MH, mental health domain; GH, general health domain; KSQ; King's Sarcoidosis Questionnaire; GHS, General Health Status domain; HADS, Hospital Anxiety and Depression Scale; PSS, Perceived Stress Scale; TLCOc, transfer factor for carbon monoxide corrected for hemoglobin; FVC, forced vital capacity; Test, testosterone.

Fig 5. Hair cortisol, cortisone and testosterone levels in sarcoidosis patients with and without active disease.

Cortisol and cortisone were measured in 24 sarcoidosis patients with active disease and in 8 patients without active disease. Testosterone was measured in 9 male sarcoidosis patients with active disease and in 4 male patients without active disease. Data are shown as geometric mean (95% CI). Independent sample t-test was used for analysis.