Comparison of cortisol exposures and pharmacodynamic adrenal steroid responses to hydrocortisone suspension vs. commercial tablets

Normal to decreased final height (FH) has been reported in patients with congenital adrenal hyperplasia (CAH). The objective was to determine FH outcome and influences of steroid treatment. The effects of glucocorticoid treatment for classical CAH were retrospectively studied in 125 patients (77 females). Growth pattern, FH, and pubertal development were recorded. Corrected FH was in the lower range of genetic potential [females with simple virilizing (SV)-CAH, -0.6 +/- 1.0 sd score (SDS) vs. females with salt-wasting (SW)-CAH, -0.6 +/- 0.9 SDS; males with SV-CAH, -1.1 +/- 0.9 SDS vs. males with SW-CAH, -0.9 +/- 0.9 SDS]. Total pubertal growth was significantly reduced in comparison with a reference population (females with SV-CAH, 11.9 +/- 6.5 cm, and females with SW-CAH, 13.8 +/- 7.6 cm vs. reference 20.3 +/- 6.8 cm, P < 0.01; and males with SV-CAH, 15.4 +/- 6.6 cm, and males with SW-CAH, 18.5 +/- 6.9 cm vs. reference 28.2 +/- 8.2 cm, P < 0.01). Thirty-three patients had been treated with prednisone, which resulted in reduced FH compared with patients (n = 92) treated with hydrocortisone (-1.0 +/- 0.9 SDS vs.-0.6 +/- 0.9 SDS; P < 0.05). FH correlated negatively with hydrocortisone dose given at the start of puberty (r = -0.3; P < 0.05). Pubertal development started early in boys [9.8 +/- 2.3 yr (SV) and 10.6 +/- 1.9 yr (SW)] and was timely in girls [9.8 +/- 1.9 yr (SV) and 10.3 +/- 1.5 yr (SW), menarche at 13.3 +/- 1.7 yr (SV) and 13.7 +/- 1.5 yr (SV)]. Patients with CAH are able to achieve adequate FH with conventional therapy. Total pubertal growth is significantly decreased, and treatment with prednisone results in decreased FH. In addition to biochemical analysis, treatment should be adjusted to normal growth velocity, especially during puberty.

Patients with classical congenital adrenal hyperplasia (CAH) receive lifelong, often supraphysiological, glucocorticoid therapy. Pharmacological doses of glucocorticoids are an established risk factor for osteoporosis. Our objective was to evaluate bone mineral density (BMD), fracture prevalence, and markers of bone metabolism in adult females with CAH. This was a cross-sectional observational study. Tertiary care referral centers were used in this study. We studied 61 women, aged 18-63 yr, with genetically verified CAH due to 21-hydroxylase deficiency. They were patients with salt wasting (n = 27), simple virilizing (n = 28), and nonclassical 21-hydroxylase deficiency (n = 6). A total of 61 age-matched women were controls. History of fractures was recorded. Total body, lumbar spine, and femoral neck BMD were measured by dual-energy x-ray absorptiometry. The World Health Organization criteria for osteopenia and osteoporosis were used. Serum marker of bone resorption, beta-C telopeptide was studied. The mean glucocorticoid dose in hydrocortisone equivalents was 16.9 +/- 0.9 mg/m2. Patients had lower BMD than controls at all measured sites (P < 0.001). In patients younger than 30 yr old, 48% were osteopenic vs. 12% in controls (P < 0.009). In patients 30 yr or older, 73% were osteopenic or osteoporotic vs. 21% in controls (P < 0.001). BMD was similar in the two classical forms and had no obvious relationship to genotypes. beta-C-telopeptide was decreased in older patients. More fractures were reported in patients than controls (P < 0.001). The number of vertebrae and wrist fractures almost reached significance (P = 0.058). Women with CAH have low BMD and increased fracture risk. BMD should be monitored, adequate prophylaxis and treatment instituted, and glucocorticoid doses optimized from puberty.

In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a tendency for obesity, high insulin, and high 24-h blood pressure levels has been reported in children and adolescents. Increased intima-media thickness (IMT) is considered a measure of subclinical atherosclerosis and a predictor of myocardial infarction and stroke. The objective of the study was to evaluate glucose metabolism, lipid profile, IMT of the abdominal aorta, right and left common carotids, carotid bulbs, and common femoral arteries in adult CAH patients. Nineteen (10 females, nine males; 28 +/- 3.5 yr) patients (12 salt wasting and seven simple virilizing) and 19 (10 females, nine males) healthy subjects matched for anthropometric parameters (age, sex, body mass index, smoking habit, waist to hip ratio, and blood pressure). Glucose metabolism was studied using the oral glucose tolerance test and the homeostasis model assessment-insulin resistance. The echo-Doppler was used for arterial ultrasound. 17-Hydroxyprogesterone, androstenedione, testosterone, ACTH, plasma renin activity, total and high-density lipoprotein cholesterol, and triglycerides were measured. CAH patients had significantly higher fasting plasma insulin (11.6 +/- 6.20 microU/ml vs 5.18 +/- 2.4 microU/ml; P < 0.0001) and homeostasis model assessment-insulin resistance than controls (2.46 +/- 1.92 vs 1.12 +/- 0.58; P = 0.0033). IMT of the studied arteries was higher in CAH patients than controls. There was no correlation between IMT and cumulative glucocorticoid doses and androgen levels. A reduced insulin sensitivity and increased IMT were demonstrated in adults with CAH, who consequently need a follow-up for cardiovascular risk.