Quantitative targeted GC-MS-based urinary steroid metabolome analysis for treatment monitoring of adolescents and young adults with autoimmune primary adrenal insufficiency

Abstract

PurposePrimary 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. MethodRetrospective 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. ResultsThree 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. ConclusionQuantitative targeted GCMS steroid metabolome analysis could support monitoring of glucocorticoid replacement treatment in patients with PAI.