First Morning Pregnanetriol and 17-Hydroxyprogesterone Correlated Significantly in 21-Hydroxylase Deficiency

Abstract

BackgroundBiochemically monitoring 21-hydroxylase deficiency (21-OHD) is challenging. Serum/blood 17-hydroxyprogesterone (17OHP) measurements are normally 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 optimal first morning PT value fell in the range of 2.2–3.3 mg/gCr (95% confidence interval of the mean) and 0.59-6.0 mg/gCr (10th – 90th percentile) for monitoring 21-OHD treatment. No report thus far has directly compared the first morning urinary PT value with the 17OHP value at various times during the day.ObjectiveTo explore the correlation between the first morning urinary PT value before glucocorticoid administration and the serum/blood 17OHP value at three time points, namely, before and two and four hours after glucocorticoid administration.DesignThis was a prospective study done at two children’s hospitals.MethodsIn total, 25 patients with 21-OHD aged 3-25 years were recruited. Their urinary PT levels and 17OHP levels were measured for three days within a total period of one week. The first morning PT value was collected on all three days. Dried blood spots and serum were used to measure 17OHP.ResultsThe range for the first morning PT value for all the samples (n=69) was 0.10-56.1 mg/gCr. A significant, positive correlation was found between the first morning PT and 17OHP values before medication (r=0.87, p<0.01), and weaker correlation was observed between the first morning PT and 17OHP values after medication.ConclusionsThe first morning PT correlated more significantly with 17OHP before the morning medication. Measuring the first morning PT value may be more practical and useful for monitoring 21-OHD biochemically.

Clinical guidelines for the diagnosis and treatment of 21-hydroxylase deficiency (2021 revision)

“…In Japanese children with 21-OHD excluding neonatal and pubertal patients, the optimal range of urine PT was 1.2–2.1 mg/m 2 /d and 2.2–3.3 mg/gCr in the first morning sample based on auxological data ( 127 , 128 ). Measuring the first morning urine PT value would be more practical and useful for monitoring 21-OHD biochemically because the first morning PT correlated with 17-OHP before taking the morning dose of glucocorticoid ( 129 ). In addition to PT, total androgen and AD metabolites are also useful as indicators of treatment status ( 130 ).…”

Monitoring treatment in pediatric patients with 21-hydroxylase deficiency

“…In a recent, prospective study, the first morning PT levels before morning medication significantly correlated with the blood 17OHP value obtained from DBS on filter paper ( 59 ). Early morning urine collection, which provides urine data from late night to early morning, is more suitable for repetitive measurements than 24-hour urine collection ( Table 1 ).…”

Biochemical monitoring of 21-hydroxylase deficiency: a clinical utility of overnight fasting urine pregnanetriol

“…Recently, a significant correlation was found between LC–MS/MS 17-OHP and DBS 17-OHP. Moreover, the latter correlated well with the serum 17-OHP obtained by ELISA [3 ▪ ].…”

“…Following a decades-long research project exploring methods of controlling 21-hydroxylase deficiency (21-OHD) [1,2], we have published two, important studies [3 ▪ ,4 ▪▪ ], one of which is a review of methods of monitoring 21-OHD [3 ▪ ]. The optimal method of monitoring this disease is still uncertain.…”

“…If the challenges of monitoring are solved, the treatment for 21-OHD can be further improved. The present, brief review summarizes the current understanding of biochemical markers of GC treatment, focusing on the clinical utility of overnight fasting urinary P3 [3 ▪ ,4 ▪▪ ]. Other review articles [7,8] may be consulted for indices for managing mineralocorticoid (MC) treatment although the optimal dosage for MC substitution has been less critically studied than that for GC substitution.…”