ESPE Abstracts

Background: There exists no gold standard for adjustment of treatment in congenital adrenal hyperplasia. Clinicians try to avoid over-and undertreatment by considering various indicators. We aimed to investigate the sampling times of 17-hydroxyprogesterone (17-OHP) and the use of sex hormone-binding globulin (SHBG) as a monitoring parameter, the association of which was not studied with clinical features. Materials and Methods: This cross-sectional study included 16 children (9 girls, 7 boys; median age 7 years) with salt-wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency. In addition to standard clinical evaluation, serum levels of 17-OHP, cortisol, androstenedione, SHBG were obtained between 07.00 and 08.00 a.m., prior to morning dose of hydrocortisone and fludrocortisone, and 17-OHP and cortisol levels 1, 2, and 4 hours after the morning dose. Serum samples of 17-OHP and cortisol were assayed using high-performance liquid chromatography-tandem mass spectrometry. Subjects were divided into good and poor control subgroups according to the presence of hyperandrogenic state, considered when (i) bone age SD score ⩾2, (ii) annual change in height SD score was ⩾ 0.3, or (iii) androstenedione >3.3 ng/ml for girls and >3.1 ng/ml for boys. The results are reported as median (interquartile range).

Results: Premedication 17-OHP levels were strongly correlated with 17-OHP levels 1, 2, and 4 hours after the morning dose (r_s=0.929, P < 0.01; r_s=0.943, P < 0.01; r_s=0.835, P < 0.01, respectively). Clinical features, indicators of hyperandrogenic state, and the ratio of reduction of 17-OHP levels after medication were similar in children with premedication serum 17-OHP level >10 ng/ml (n = 9) vs. <10 ng/ml (n = 7) while hydrocortisone dose was significantly lower in children with high 17-OHP levels [11 (8) vs. 19 (11) mg/m²/day, P = 0.017). Subgroup analyses revealed that clinical and biochemical features were not different except significantly higher SHBG values [92 (59) mmol/l vs. 40 (22), P = 0.036] in the growth acceleration group (n = 8) and significantly lower daily hydrocortisone doses in children with growth acceleration [7 (7) vs. 15 (9) mg/m²/day, P = 0.036] and in those with elevated androstenedione levels [9 (6) vs. 19 (9) mg/m²/day, P = 0.039].

Conclusions: When over-or undertreatment is suspected, the levels of 17-OHP should not be trusted, it misses the hyperandrogenic state or may falsely suggest unnecessary dose increments. A 4-hour profile of 17-OHP does not add significant data over early morning premedication 17-OHP levels. In general, low doses of hydrocortisone should be avoided. SHBG can be considered as an indicator of hyperandrogenemia.