Search

Background Hydrocortisone therapy is based on a dosing regimen derived from estimates of cortisol secretion, but little is known of how the dose should be distributed throughout the 24 h. We have used deconvolution analysis of 24-h serum cortisol profiles to determine 24-h cortisol secretion and distribution to inform hydrocortisone dosing schedules in young children and older adults. Methods Twenty four hour serum cortisol profiles from 80 adults (41 men, aged 60-74 years) and 29 children (24 boys, aged 59 years) were subject to deconvolution analysis using an 80-min half-life to ascertain total cortisol secretion and distribution throughout the 24-h period. Results Mean daily cortisol secretion was similar between adults (6.3 mg/m2 body surface area/day, range 5.19.3) and children (8.0 mg/m2 body surface area/day, range 5.312.0). Peak serum cortisol concentration was higher in children compared with adults, whereas nadir serum cortisol concentrations were similar. Timing of the peak serum cortisol concentration was similar (07.0507.25), whereas that of the nadir concentration occurred later in adults (midnight) compared with children (22.48) (P = 0.003). Children had the highest percentage of cortisol secretion between 06.00 and 12.00 (38.4%), whereas in adults this took place between midnight and 06.00 (45.2%). Conclusions These observations suggest that the daily hydrocortisone replacement dose should be equivalent on average to 6.3 mg/m2 body surface area/day in adults and 8.0 mg/m2 body surface area/day in children. Differences in distribution of the total daily dose between older adults and young children need to be taken into account when using a three or four times per day dosing regimen.

International audience

Context Differences of sex development (DSD) represent a wide range of conditions presenting at different ages to various health professionals. Establishing a diagnosis, supporting the family, and developing a management plan are important. Objective We aimed to better understand the presentation and prevalence of pediatric DSD. Methods A retrospective, observational cohort study was undertaken in a single tertiary pediatric center of all children and young people (CYP) referred to a DSD multidisciplinary team over 25 years (1995-2019). In total, 607 CYP (520 regional referrals) were included. Data were analyzed for diagnosis, sex-assignment, age and mode of presentation, additional phenotypic features, mortality, and approximate point prevalence. Results Among the 3 major DSD categories, sex chromosome DSD was diagnosed in 11.2% (68/607) (most commonly 45,X/46,XY mosaicism), 46,XY DSD in 61.1% (371/607) (multiple diagnoses often with associated features), while 46,XX DSD occurred in 27.7% (168/607) (often 21-hydroxylase deficiency). Most children (80.1%) presented as neonates, usually with atypical genitalia, adrenal insufficiency, undescended testes or hernias. Those presenting later had diverse features. Rarely, the diagnosis was made antenatally (3.8%, n = 23) or following incidental karyotyping/family history (n = 14). Mortality was surprisingly high in 46,XY children, usually due to complex associated features (46,XY girls, 8.3%; 46,XY boys, 2.7%). The approximate point prevalence of neonatal referrals for investigation of DSD was 1 in 6347 births, and 1 in 5101 overall throughout childhood. Conclusion DSD represent a diverse range of conditions that can present at different ages. Pathways for expert diagnosis and management are important to optimize care.