Endocrine Abstracts

Introduction: The most common cause of CAH is 21-hydroxylase deficiency, which is divided into classic (salt-wasting or simple virilising) and non-classic forms. Patients with classic CAH require lifelong hormone replacement. Optimisation of treatment requires close monitoring of biomarkers. Both under- and over-treatment are associated with impaired linear growth and gonadal function and increased cardiometabolic risk.

Aims & methods: This retrospective cross-sectional study aimed to comprehensively phenotype a large single-centre cohort of 21-hydroxylase deficiency patients (n = 168), aged 0 – 18 years. It formed part of a registered service evaluation. CAH patient data were collected retrospectively from patient records for patients seen between 1/6/2022 – 1/6/2024.

Results: 51.8% (43 females, 44 males) had salt-wasting CAH, 35.1% (42 females, 17 males) had simple virilising CAH and 13.1% (16 females, 6 males) had non-classic CAH. 82% (n = 137) had genetic testing. 32.3% had a large deletion/conversion within the CYP21A2 gene. 60% carried point mutations, with the I2 splice mutation found in 46.2% of affected alleles. There was no significant difference in mean height SDS by disease subtype (P value = 0.13). 84.8% (n = 28) of patients at final height were within 1.5 SDS of their mid-parental height SDS. Fourteen patients had required GnRH agonist treatment to arrest early puberty. Fifty-three patients (31.5%) were obese (+2 BMI SDS), and fifty-two patients (31%) were overweight (+1 BMI SDS) (BMI SDS range –4.33 to +4.12). On average, patients were insulin insensitive (mean HOMA-IR 3.31). Insulin insensitivity was notable in pre-pubertal patients of healthy weight. Assessment of biomarkers by pubertal stage revealed mean morning ACTH and 17-OHP concentrations above the reported reference range in each pubertal group (ACTH > 49 ng/l and 17-OHP >36 nmol/l). Statistically significant differences in average hydrocortisone dose, morning 17-OHP and androstenedione concentrations by pubertal group were found (P<0.05). 19% (n = 31) received hydrocortisone (or equivalent) doses >15 mg/m²/day. There was no significant difference between hydrocortisone dose equivalent by disease subtype (P value = 0.08).

Discussion: We report a high incidence of insulin insensitivity in our single-centre cohort of paediatric patients with 21-hydroxylase deficiency, with high rates of overweight/obesity. Biomarkers were elevated in some pre-pubertal patients, highlighting early difficulties with biochemical control. However, despite mean morning ACTH and 17-OHP concentrations outside the recommended ranges, our data suggest that few children required intervention for short stature or early puberty. Clearly longitudinal assessment of growth parameters is required, as is the reporting of long-term outcomes for this cohort.

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