PMID- 1911435
OWN - NLM
STAT- MEDLINE
DCOM- 19911108
LR  - 20190828
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 39
IP  - 4A
DP  - 1991 Oct
TI  - A possible defect in the inter-conversion between cortisone and cortisol in 
      prepubertal patients with congenital adrenal hyperplasia receiving cortisone 
      acetate therapy.
PG  - 461-70
AB  - Oral administration of cortisone acetate is widely used to treat prepubertal 
      patients with congenital adrenal hyperplasia (CAH). However, efficient 'first 
      pass' hepatic conversion of the biologically inactive cortisone (E) to cortisol 
      (F) by the 11-reductase component of the 11 beta-hydroxysteroid dehydrogenase (11 
      beta-HSD) system is required for suppression of the 
      hypothalamic-pituitary-adrenal (HPA) axis. 11-beta-HSD activity can be assessed 
      by measurement of urinary tetrahydroderivatives of E (tetrahydrocortisone, THE) 
      and F (tetrahydrocortisol, THF), formed in separate hepatic compartments by 
      reduction of the A ring. Inadequate HPA axis suppression is frequently 
      encountered in peripubertal CAH patients receiving cortisone acetate therapy. In 
      this paper, we describe THE and THF concentration in 24 h urine samples collected 
      every 3-6 months from 14 prepubertal patients with simple virilizing CAH. The 
      patients had been receiving cortisone acetate and 9 alpha-fluorohydrocortisone 
      since diagnosis and were investigated for 2-4 years during which there was marked 
      intra- and inter-individual variation in the level of suppression. Good and poor 
      control of HPA axis suppression were defined on the basis of a profile of early 
      morning serum 17-hydroxyprogesterone, androstenedione, plasma renin activity and 
      24 h urinary excretion of pregnanetriol, pregnanetriolone and 5 beta, 17 
      alpha-hydroxypregnanolone. Serum steroids were measured by RIA and urinary 
      metabolites quantitated as methyloxime-trimethylsilylimidazole derivatives by gas 
      chromatography and GC-mass spectrometry. There were no significant differences in 
      the THE/THF ratio between male (n = 9) and female (n = 5) patients during either 
      good or poor therapeutic control. The data were therefore analyzed without 
      consideration of patient sex. Urinary THE/THF (mean +/- SD) was significantly 
      higher in patients during periods of poor control (6.56 +/- 2.51, P less than 
      0.001) compared with periods of good control (3.73 +/- 0.96) in the same 
      patients. THE/THF levels were also significantly (P less than 0.001) higher in 
      CAH patients, irrespective of the level of control, than those for the normal 
      subjects (1.79 +/- 0.20). Furthermore, THE excretion was significantly higher 
      during periods of poor control compared with good control at all doses of 
      cortisone acetate administered (10-50 mg/day). There were no significant 
      differences in THF excretion. THE levels also rose significantly (P less than 
      0.001) in response to increasing total dose during periods of poor control. The 
      increase in THF excretion was slight and significant only at doses greater than 
      40 mg/day compared with doses less than 15 mg/day.(ABSTRACT TRUNCATED AT 400 
      WORDS)
FAU - Whorwood, C B
AU  - Whorwood CB
AD  - Department of Clinical Biochemistry, Royal Children's Hospital, Parkville, 
      Victoria, Australia.
FAU - Warne, G L
AU  - Warne GL
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Steroids)
RN  - V27W9254FZ (Cortisone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Adolescent
MH  - Adrenal Hyperplasia, Congenital/drug therapy/*metabolism
MH  - Child
MH  - Child, Preschool
MH  - Cortisone/*analogs & derivatives/*metabolism/therapeutic use
MH  - Female
MH  - Humans
MH  - Hydrocortisone/*metabolism
MH  - Hypothalamo-Hypophyseal System/drug effects
MH  - Male
MH  - Pituitary-Adrenal System/drug effects
MH  - Reference Values
MH  - Steroids/blood/urine
EDAT- 1991/10/01 00:00
MHDA- 1991/10/01 00:01
CRDT- 1991/10/01 00:00
PHST- 1991/10/01 00:00 [pubmed]
PHST- 1991/10/01 00:01 [medline]
PHST- 1991/10/01 00:00 [entrez]
AID - 10.1016/0960-0760(91)90239-2 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 1991 Oct;39(4A):461-70. doi: 
      10.1016/0960-0760(91)90239-2.