Cortisol production rate in children by gas chromatography/mass spectrometry using [l,2,3,4,- 13C]cortisol

Abstract

A urinary method of determining the cortisol production rate (CPR) in children was studied under physiologic conditions by administration of low amounts of [1,2,3,4- 13C]cortisol. The CPR in three patients with multiple pituitary deficiency ranged from 7 to 16 nmoles d −1 m −2, and the CPR in three patients with congenital adrenal hyperplasia (CAH) due to 11β-hydroxylase deficiency (11βOHD) and 17α-hydroxylase deficiency (17αOHD) from 0.1 to 2.11 μmmoles d −1 m −2. Results showed that with this method, very low CPRs can be reliably measured. The metabolism of [ 13C 4] cortisol or [9,12,12- 2H]cortisol was compared with that of native cortisol in adrenalectomized piglets. For the urinary cortisol metabolites, small to substantial differences in isotope dilution were noted relative to that in the original cortisol mixture. With [ 13C 4]cortisol, the so-called secondary isotope effects were approximately 2% to 3% for tetrahydrocortisone (THE) and tetrahydrocortisol (THF), and about 10% for the cortolones, relative to the cortisol mixture. When [ 2H 3] cortisol was used, the cortisol metabolites THE and THF contained only two deuterium atoms. Together with this apparent loss of one deuterium atom, the secondary isotope effects in these steroids amounted to 5% to 10%. It was concluded that [ 13C 4] cortisol was the better tracer to use for the measurement of urinary CPR.