ESPE Abstracts

Background: Biochemically monitoring 21-hydroxylase deficiency (21OHD) treatment is challenging. Serum/blood 17-hydroxyprogesterone (17OHP) measurements, especially in the early morning before medication, are traditionally used for this purpose. Urinary pregnanetriol (PT), a urinary metabolite of 17OHP, may also be used. Based on auxological data, we previously reported that the first morning PT value in the range of 2.2–3.3 mg/gCr is optimal for monitoring 21OHD treatment. No report thus far has compared urinary PT and 17OHP values.

Objective: To explore the correlation between first morning urinary PT value before glucocorticoid administration (0h-PT) and the serum/blood 17OHP value at three time points, namely, before (0h-17OHP) and two and four hours after glucocorticoid administration (2h-17OHP, 4h-17OHP).

Design: This was a prospective study done at two children's hospitals.

Methods: In total, 24 patients with 21OHD aged 3-25 years were recruited. The urinary PT levels and 17OHP levels were measured for three days within a week. The 0h-PT (n=69) values were collected on all three days. Enzyme immunoassay (ELISA) of dried blood spots (DBS) was done for 2h-17OHP (n=22) and 4h-17OHP (n=22) on day 1 and for 0h-17OHP on days 2 and 3 (n=45). Serum 17OHP levels were also measured on day 1 by ELISA and LC-MS/MS (n=24).

Results: All 24 patients received both gluco- and mineralocorticoids. The 0h-PT value for the total samples was 0.12-56.1 mg/gCr (n=54). DBS 0h-, 2h-, and 4h-17OHP levels were 0.28- 100, 0.44-77.1, and 0.54-87.2 ng/ml, respectively. A significant, positive correlation was found between the 0h-PT and DBS 0h-17OHP values (r=0.961, P<0.01), but none was observed between the 0h-PT and DBS 2h- or 4h-17OHP values. When the 95% confidence intervals of the mean 0h-PT level obtained during a period of good disease control (2.2-3.3 mg/gCr) in our previous study were applied, the DBS and serum ELISA for 0h-17OHP yielded a value of 14.2-19.1 ng/ml and 29.5-37.2 ng/ml, respectively. The day-to-day variation in 0h-PT (n=51) was 24.7 +/- 22.3%. We confirmed a significant correlation between ELISA and LC-MS/MS in terms of 17OHP level.

Conclusions: First morning PT correlated significantly only with DBS 17OHP before morning medication. Since early morning serum/blood 17OHP measurements are impractical for patients and caregivers and the levels do not reflect a long period of disease control, first morning PT measurements may be more useful for biochemical monitoring of 21OHD.