Correlations of Radiographic and Hormonal Indices of Disease Control in a Cohort of Children and Adults with Classic 21-Hydroxylase Deficiency

Presentation Number: SUN 428
Date of Presentation: April 2nd, 2017

Adina F. Turcu*1, Ashwini Mallappa2, Meredith Elman3, Nilo A Avila4, Alexander Tsodikov5, Richard J. Auchus6 and Deborah P. Merke7
1The University of Michigan, Ann Arbor, MI, 2National Institutes of Health, Clinical Center, Bethesda,, MD, 3National Institutes of Health, Bethesda, MD, 4Radiology Service, Washington D. C. Veterans Affairs Medical Center, Cardiovascular and Pulmonary Branch, NHLBI, NIH, Washington, D.C., DC, 5University of Michigan, 6University of Michigan, Ann Arbor, MI, 7NIH, Bethesda, MD


Background: Patients with 21-hydroxylase deficiency (21OHD) suffer from numerous long-term complications, which might result from poor disease control and/or overtreatment with glucocorticoids. The complex relationships amongst biomarkers and clinical outcomes challenge efforts to individualize therapy and to predict long-term outcomes in patients with 21OHD.

Objective: To assess the relation between radiographic and hormonal indices of disease control in patients with classic 21OHD. 

Setting and participants: Cross-sectional study of 114 patients (70 males), ages 2 to 67 years (median, 15; 59% younger than 18), seen in a tertiary referral center. 

Methods: Clinical evaluation included: bone age in children, adrenal volume in adults, glucocorticoid equivalent (GCE) medication dose and pituitary hormones. Using liquid chromatography-tandem mass spectrometry, we quantified 23 steroids from early morning serum, obtained before the first medication dose. The nonparametric Spearman correlation test assessed the relation between pairs of continuous variables. Logistic regression was employed to find the best multivariate correlation model. Statistical significance was accepted for p<0.05.

Results: The median GCE daily dose was 13.7/m2 for children and 17.5/m2 for adults. Of the pediatric patients, 32 (48%), 10 (15%), 5 (7.5%), 7 (10.5%) and 13 (19%) were in Tanner stages 1, 2, 3, 4 and 5, respectively. In children, no steroid biomarkers correlated well with bone age. Of the 23 steroid biomarkers measured, 21 correlated directly with ACTH. The tightest correlation with ACTH was observed for 17α-hydroxyprogesterone (17OHP) and 16a-hydroxyprogesterone (16OHP) (r=0.7, p < 0.0001), followed by 21-deoxycortisol (21dF), and three 11-oxygenated 19-carbon (11oxC19) steroids: 11β-hydroxy- and 11keto-androstenedione (11OHAD, 11KAD), and 11-keto-testosterone (11KT) (r≈0.6, p< 0.0001). 11KT and 11KAD correlated positively with testosterone (T) in boys in Tanner stages 1-2 (r=0.6-0.8, p<0.001), but negatively in males in Tanner stage 5 (r=-0.3, p<0.05). In females, there was direct correlation between all four 11oxC19 steroids and T for all Tanner stages (r=0.75-0.84, p< 0.0001). In adults and children >16 years with fused epiphyses, total adrenal volume correlated positively with 18/23 steroids, including 11OHAD, 11KAD, 11β-hydroxytestosterone (11OHT), 11KTand 21dF (r≈0.7, p<0.0001, for all). Total adrenal volume also correlated directly with ACTH (r=0.4, p=0.005), but inversely with LH (r=-0.5, p<0.001).

Conclusion: Although steroids immediately proximate to the enzymatic block correlate best with ACTH, 11oxC19 steroids correlate best with adrenal volume. These results suggest that the 11oxC19 steroids might serve as useful biomarkers of long-term disease control in patients with 21OHD.


Disclosure: DPM: Principal Investigator, Diurnal, Principal Investigator, Millendo Therapeutics. Nothing to Disclose: AFT, AM, ME, NAA, AT, RJA