Oral Presentation ESA-SRB-AOTA 2019

Utility of Androstenedione and 17-hydroxyprogesterone for monitoring androgen excess in Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency – a local experience (#246)

Timothy Lin 1 , Ee Mun Lim 1 2 , Bronwyn Stuckey 1 3 4 , Jennifer Ng 4 , Simon Carrivick 1 2
  1. Sir Charles Gairdner Hospital, Nedlands, WA, Australia
  2. Pathwest, Perth
  3. University of Western Australia, Perth, Western Australia
  4. Keogh Institute, Perth

Background

Serum 17-hydroxyprogesterone (17-OHP) and Androstenedione are markers of adrenal androgen excess in patients with congenital adrenal hyperplasia (CAH). 17-OHP has considerably greater diurnal variation than Androstenedione, which may limit its clinical utility as a marker of overall androgen exposure.

Objective

To examine variability of longitudinal serum 17-OHP and Androstenedione measurements in patients with CAH.

Method

We conducted a retrospective case series on a small cohort of young adults with CAH requiring glucocorticoid replacement. We reviewed longitudinal measurements serum 17-OHP and Androstenedione by LCMS and correlated them with clinical records to evaluate variability of 17-OHP and Androstenedione.

Results

We analysed the results of 6 patients (1 male, 5 female) with CAH with a minimum of three synchronous measurements of serum 17-OHP and Androstenedione by LCMS over 16 to 58m months. All patients required glucocorticoid replacement with oral hydrocortisone or cortisone acetate.

Inter and intra patient serum 17-OHP was highly variable with peak levels exceeding the upper reference limit by a factor of 50 or more in four patients. Nadir serum 17-OHP in one patient fell within the reference range, whereas the remaining 5 patients had nadir levels which exceeded the upper reference limit by a factor of 1.5 to 31.

Serum Androstenedione levels were less variable. One patient had peak androstenedione levels exceeding 10x the upper reference limit. Nadir Androstenedione levels were within the reference range in four patients, and approximately twice the upper reference limit in the remaining two.

Conclusion

Our results demonstrate marked variability of serum 17-OHP results in a small cohort of patients with CAH. This likely reflects diurnal variation in response to glucocorticoid therapy. Clinical utility of intermittent measurements of serum 17-OHP is limited in the absence of standardised timing of sample collection in relation to glucocorticoid dosing.

 

  1. Kang MJ, Kim SM, Lee YA, Shin CH, Yang SW. Relationships of basal level of serum 17-hydroxyprogesterone with that of serum androstenedione and their stimulated responses to a low dose of ACTH in young adult patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Korean Med Sci. 2011 Nov;26(11):1454-60. doi:10.3346/jkms.2011.26.11.1454
  2. Debono M, Mallappa A, Gounden V, Nella AA, Harrison RF, Crutchfield CA, et al. Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: Identifying optimal monitoring times and novel disease biomarkers. Eur J Endocrinol. 2015 Dec;173(6):727/737. doi:10.1530/EJE-15-0064.
  3. Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, et al. Congenital Adrenal Hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018 Nov;103(11):4043-4088. doi:10.1210/jc.2018-01865.