OBJECTIVE: Currently available methods for endogenous cortisol monitoring in patients with hormonal insufficiency rely on measurements of plasma levels only at a single time point; thus, any kind of chronic exposure to cortisol is challenging to evaluate because it requires collecting samples at different time points. Hair cortisol levels acquired longitudinally better reflected chronic exposure (both cortisol synthesis and deposition) and may significantly contribute to better outcomes in glucocorticoid replacement therapies. DESIGN: Twenty-two patients on cortisol substitution therapy were monitored for plasma, urinary, and hair cortisol levels for 18 months to determine whether hair cortisol may serve as a monitoring option for therapy setting and adjustment. METHODS: Plasma and urinary cortisol levels were measured using standardized immunoassay methods, and segmented (∼1 cm) hair cortisol levels were monitored by liquid chromatography coupled to mass spectrometry. A log-normal model of the changes over time was proposed, and Bayesian statistics were used to compare plasma, urinary, and hair cortisol levels over 18 months. RESULTS AND CONCLUSIONS: Hair cortisol levels decreased over time in patients undergoing substitutional therapy. The residual variance of hair cortisol in comparison to plasma or urinary cortisol levels was much lower. Thus, longitudinal monitoring of hair cortisol levels could prove beneficial as a noninvasive tool to reduce the risk of overdosing and improve the overall patient health.

Department of Biochemistry Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pharmacology and Toxicology Pharmaceutical Faculty Faculty of Medicine Masaryk University Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Psychiatry Faculty of Medicine Masaryk University and University Hospital Brno Brno Czech Republic ; and

Endocrinology Ambulance St Anne's University Hospital Brno Czech Republic

Ther Drug Monit. 2022 Aug 01;44(4):597. doi: 10.1097/FTD.0000000000001001. PubMed

See more in PubMed

Burton C, Cottrell E, Edwards J. Addison's disease: identification and management in primary care. Br J Gen Pract. 2015;65:488–490.

Bensing S, Brandt L, Tabaroj F, et al. Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency. Clin Endocrinol. 2008;69:697–704.

Erichsen MM, Lovas K, Fougner KJ, et al. Normal overall mortality rate in Addison's disease, but young patients are at risk of premature death. Eur J Endocrinol. 2009;160:233–237.

Forss M, Batcheller G, Skrtic S, et al. Current practice of glucocorticoid replacement therapy and patient-perceived health outcomes in adrenal insufficiency - a worldwide patient survey. BMC Endocr Disord. 2012;12:8.

Murray RD, Ekman B, Uddin S, et al. Management of glucocorticoid replacement in adrenal insufficiency shows notable heterogeneity—data from the EU-AIR. Clin Endocrinol. 2017;86:340–346.

Feelders RA, Pulgar SJ, Kempel A, et al. The burden of Cushing's disease: clinical and health-related quality of life aspects. Eur J Endocrinol. 2012;167:311–326.

Clayton RN, Raskauskiene D, Reulen RC, et al. Mortality and morbidity in Cushing's disease over 50 years in stoke-on-trent, UK: audit and meta-analysis of literature. J Clin Endocrinol Metab. 2011;96:632–642.

Huguet I, Aguirre M, Vicente A, et al. Assessment of the outcomes of the treatment of Cushing's disease in the hospitals of Castilla-La Mancha. Endocrinol Nutr. 2015;62:217–223.

Oksnes M, Ross R, Lovas K. Optimal glucocorticoid replacement in adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2015;29:3–15.

Stalder T, Kirschbaum C. Analysis of cortisol in hair - state of the art and future directions. Brain Behav Immun. 2012;26:1019–1029.

Cirimele V, Kintz P, Dumestre V, et al. Identification of ten corticosteroids in human hair by liquid chromatography-ion spray mass spectrometry. Forensic Sci Int. 2000;107:381–388.

Wennig R. Potential problems with the interpretation of hair analysis results. Forensic Sci Int. 2000;107:5–12.

Greff MJE, Levine JM, Abuzgaia AM, et al. Hair cortisol analysis: an update on methodological considerations and clinical applications. Clin Biochem. 2019;63:1–9.

Kirschbaum C, Tietze A, Skoluda N, et al. Hair as a retrospective calendar of cortisol production-Increased cortisol incorporation into hair in the third trimester of pregnancy. Psychoneuroendocrinology. 2009;34:32–37.

Stalder T, Steudte S, Miller R, et al. Intraindividual stability of hair cortisol concentrations. Psychoneuroendocrinology. 2012;37:602–610.

Wester VL, Reincke M, Koper JW, et al. Scalp hair cortisol for diagnosis of Cushing's syndrome. Eur J Endocrinol. 2017;176:695–703.

Thomson S, Koren G, Fraser L-A, et al. Hair analysis provides a historical record of cortisol levels in Cushing's syndrome. Exp Clin Endocrinol Diabetes. 2010;118:133–138.

Manenschijn L, Koper JW, van den Akker ELT, et al. A novel tool in the diagnosis and follow-up of (cyclic) Cushing's syndrome: measurement of long-term cortisol in scalp hair. J Clin Endocrinol Metab. 2012;97:E1836–E1843.

Maimon L, Milo T, Moyal RS, et al. Timescales of human hair cortisol dynamics. iScience. 2020;23:101501.

Gow R, Koren G, Rieder M, et al. Hair cortisol content in patients with adrenal insufficiency on hydrocortisone replacement therapy. Clin Endocrinol. 2011;74:687–693.

Staufenbiel SM, Andela CD, Manenschijn L, et al. Increased hair cortisol concentrations and BMI in patients with pituitary-adrenal disease on hydrocortisone replacement. J Clin Endocrinol Metab. 2015;100:2456–2462.

Noppe G, van Rossum EFC, Vliegenthart J, et al. Elevated hair cortisol concentrations in children with adrenal insufficiency on hydrocortisone replacement therapy. Clin Endocrinol. 2014;81:820–825.

Quax RA, Manenschijn L, Koper JW, et al. Glucocorticoid sensitivity in health and disease. Nat Rev Endocrinol. 2013;9:670–686.

Kostolanska K, Novotna L, Taborska E, et al. Online solid-phase extraction liquid chromatography-mass spectrometry of hair cortisol using a surrogate analyte. Chem Pap. 2019;73:151–158.

Binz TM, Braun U, Baumgartner MR, et al. Development of an LC-MS/MS method for the determination of endogenous cortisol in hair using C-13(3)-labeled cortisol as surrogate analyte. J Chromatogr B Analyt Technol Biomed Life Sci. 2016;1033:65–72.

Cooper GAA, Kronstrand R, Kintz P. Society of Hair Testing guidelines for drug testing in hair. Forensic Sci Int. 2012;218:20–24.

Kruschke JK. Doing Bayesian Data Analysis: A Tutorial with R, JAGS, and Stan. Sea Harbor Drive Orlando, FL: Academic Press; 2014.

McElreath R. Statistical Rethinking: A Bayesian Course with Examples in R and Stan. Boca Raton, FL: Chapman & Hall/CRC; 2015.

Jiro N, Minoru Y. Age- and sex-related differences in urinary cortisol level. Clin Chim Acta 1984;137:77–80.

Van Kampen M, Fuchs E. Age-related levels of urinary free cortisol in the tree shrew. Neurobiol Aging 1998;19:363–366.

Albar WF, Russell EW, Koren G, et al. Human hair cortisol analysis: comparison of the internationally-reported ELISA methods. Clin Invest Med. 2013;36:E312–E316.

Casals G, Hanzu FA. Cortisol measurements in Cushing's syndrome: immunoassay or mass spectrometry? Ann Lab Med. 2020;40:285–296.