Background: Autoimmune primary adrenal insufficiency (PAI) is a rare and life-threatening disease. Standard replacement therapy consists of multiple daily doses of hydrocortisone combined with fludrocortisone. 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 prescribed treatment regimens. Pervasive nonadherence places patients with PAI at an increased risk for morbidity and mortality. As a consequence, useful hormonal monitoring of glucocorticoid replacement would be mandatory in AYAs with PAI.
Objective and hypotheses: The suitability of 24 h urinary steroid metabolites analysis for treatment monitoring for AYAs with autoimmune PAI.
Method: We retrospectively analyzed 21 daily urinary steroid hormone metabolite profiles obtained by GC-MS of four AYAs aged 15.6±2.0 years with autoimmune PAI on hydrocortisone and fludrocortisone treatment. Urine was collected over a period of 1.54.2 years, with 49 collected urines each patient. Urinary glucocorticoid metabolites (GCM) were summed and were transformed into z-scores using references of healthy children.
Results: Mean oral hydrocortisone replacement dosage was 12.1±1.1 mg/m2 BSA/d. Three patients showed good treatment adherence (17 of 21 samples). Daily urinary GCM excretion of these samples was 7.36±1.78 mg/m2 BSA/d, consistent with a GCM z-score of 1.77±1.08. In these samples, urinary GCM reflected 59.7±14.5% of orally prescribed hydrocortisone dosages. The forth patient initially showed an adequate treatment-adherence (GCM 5.20 mg/m2 BSA/d; 0.83 z; 49.4% of the prescribed hydrocortisone dosage). However, later the patient showed clinically symptoms of PAI, but assured regular treatment adherence. In this 24-h urine sample, GCM excretion was only 0.32 mg/m2 BSA (−3.36 z), reflecting only 3.1% of orally prescribed hydrocortisone dosage. The patient later confirmed that treatment was stopped. During the next visits treatment adherence was better, but still inadequate. The morning dose was taken regularly under parental control, but the following dosages were taken inconsistently. Accordingly, urinary GCM excretion in the following two samples were 3.57 mg/m2 BSA/d (−0.34 z; 27.4%) and 1.88 mg/m2 BSA/d (−1.63 z; 17.2%).
Conclusion: We could demonstrate that analysis of 24-h urinary hydrocortisone metabolite excretions rates were suitable to monitor glucocorticoid replacement treatment in patients with autoimmune Addisons disease. It allows assessment of treatment adherence and helps to avoid overtreatment.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology