Clemens Kamrath1, Michaela F Hartmann2, Stefan A Wudy2. 1. Steroid Research & Mass Spectrometry Unit, Laboratory for Translational Hormone Analytics, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany. Electronic address: clemens.kamrath@paediat.med.uni-giessen.de. 2. Steroid Research & Mass Spectrometry Unit, Laboratory for Translational Hormone Analytics, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany.
Abstract
PURPOSE: Primary adrenal insufficiency (PAI) is a rare and life-threatening disease. A recent Endocrine Society guideline argued against hormonal monitoring of glucocorticoid replacement. However, about 50% of adolescents and young adults (AYAs) with chronic diseases are non-adherent to their treatment regimens. Therefore, suitable hormonal monitoring of glucocorticoid replacement would be highly desirable in AYAs with PAI. We investigated whether quantitative targeted gas chromatography-mass spectrometry urinary steroid metabolome analysis would be suitable for monitoring glucocorticoid replacement in AYAs with autoimmune PAI. METHOD: Retrospective analysis of 21 urinary steroid profiles of four AYAs aged 15.6 ± 2.0 years with autoimmune PAI on hydrocortisone and fludrocortisone treatment. 24-hr cortisol metabolite excretion rates (CMERs) were calculated using the sum of major seven urinary cortisol metabolites. CMERs were transformed into z-scores according to reference values of healthy age- and sex matched subjects. RESULTS: Three patients showed good treatment adherence (17 of 21 samples). Mean CMER of these samples was 7.4 ± 1.8 mg/m2/d, corresponding to a z-score of 1.8 ± 1.1. CMER reflected 59.7 ± 14.5% of prescribed hydrocortisone dosages. A forth patient displayed clinical symptoms of PAI during treatment. CMER was only 0.3 mg/m2 (-3.4 z), reflecting only 3.1% of prescribed hydrocortisone dosage, compatible with lack of treatment adherence. Thereafter, the parents supervised the intake of tablets and treatment adherence improved. CONCLUSION: Quantitative targeted GCMS steroid metabolome analysis could support monitoring of glucocorticoid replacement treatment in patients with PAI.
PURPOSE:Primary adrenal insufficiency (PAI) is a rare and life-threatening disease. A recent Endocrine Society guideline argued against hormonal monitoring of glucocorticoid replacement. However, about 50% of adolescents and young adults (AYAs) with chronic diseases are non-adherent to their treatment regimens. Therefore, suitable hormonal monitoring of glucocorticoid replacement would be highly desirable in AYAs with PAI. We investigated whether quantitative targeted gas chromatography-mass spectrometry urinary steroid metabolome analysis would be suitable for monitoring glucocorticoid replacement in AYAs with autoimmune PAI. METHOD: Retrospective analysis of 21 urinary steroid profiles of four AYAs aged 15.6 ± 2.0 years with autoimmune PAI on hydrocortisone and fludrocortisone treatment. 24-hr cortisol metabolite excretion rates (CMERs) were calculated using the sum of major seven urinary cortisol metabolites. CMERs were transformed into z-scores according to reference values of healthy age- and sex matched subjects. RESULTS: Three patients showed good treatment adherence (17 of 21 samples). Mean CMER of these samples was 7.4 ± 1.8 mg/m2/d, corresponding to a z-score of 1.8 ± 1.1. CMER reflected 59.7 ± 14.5% of prescribed hydrocortisone dosages. A forth patient displayed clinical symptoms of PAI during treatment. CMER was only 0.3 mg/m2 (-3.4 z), reflecting only 3.1% of prescribed hydrocortisone dosage, compatible with lack of treatment adherence. Thereafter, the parents supervised the intake of tablets and treatment adherence improved. CONCLUSION: Quantitative targeted GCMS steroid metabolome analysis could support monitoring of glucocorticoid replacement treatment in patients with PAI.