Variation in serum adrenal hormones in female 21-hydroxylase deficient patients

Abstract

Background: There is no consensus regarding markers of optimal treatment or timing between glucocorticoid intake and assessment of hormone levels in the follow-up of female 21-hydroxylase deficient patients.

Objective: To examine visit-to-visit repeatability in levels of adrenal hormones in adult female patients, to identify predictors of repeatability in hormone levels and to examine concordance between levels of different adrenal hormones.

Method: All patients with confirmed 21-hydroxylase deficiency treated with glucocorticoids, were included. The two most recent blood samples collected on a stable dose of glucocorticoid replacement were compared. Complete concordance was defined as all measured adrenal hormones either within, below or above normal range evaluated in a single-day measurement.

Results: Sixty-two patients, median age of 35 (range 18-74) years were included. All hormone levels showed moderate to excellent repeatability with an intraclass correlation coefficient between 0.80 and 0.99. Repeatability of hormone levels was not affected by the use of long-acting glucocorticoids or time of day for blood sample collection. The median difference in time between the two sample collections was 1.5 (range 0-7.5) h. Complete concordance between 17-hydroxyprogesterone, androstenedione, and testosterone was found in 21% of cases.

Conclusion: During everyday, clinical practice hormone levels in adult female patients with 21-hydroxylase deficiency showed a moderate to excellent repeatability, despite considerable variation in time of day for blood sample collection. We found no major predictors of hormone level variation. Future studies are needed to address the relationship between the timing of glucocorticoid intake vs adrenal hormone levels and clinical outcome in both adults and children.

Keywords: 17-hydroxyprogesterone; 21-hydroxylase deficiency; CAH; DHEAs; androstenedione; testosterone.

Figure 1

Repeatability of hormone levels in the two samples. Comparison of hormone levels in the two samples. For s-androstenedione, s-testosterone and s-DHEAs the shaded areas represent hormone levels below, within or above normal range in both measurements. For s-17-hydroxyprogesterone the shaded areas represent hormone levels within and above normal range for both measurements. The ICC is reported with the 95% CI. ICC, intraclass correlation coefficient; LLN, lower limit of normal; ULN, upper limit of normal.

Figure 2

Bland–Altman plots. Bland–Altman plots displaying agreement between serum hormone levels in the first and second blood sample.

Figure 3

Difference in time of sample collection vs difference in hormone levels. Difference in time (hours) of sample collection vs difference in levels of s-adrenal hormones between the two blood samples.

Figure 4

Concordance between levels of s-17-hydroxyprogesterone, s-androstenedione and stestosterone at the first sampling day. Concordance between levels of 17-hydroxyprogesterone, androstenedione and testosterone at the first sampling day. Group 1: the highest degree of concordance with all three hormones either below, within, or above the normal range. Group 2: two hormones either below, within, or above the normal range and one hormone differing. Group 3: two hormones below normal range and one above, or hormones distributed both below, above and within the normal range.