PMID- 8977758
OWN - NLM
STAT- MEDLINE
DCOM- 19970110
LR  - 20190813
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 45
IP  - 5
DP  - 1996 Nov
TI  - Urinary free cortisone and the assessment of 11 beta-hydroxysteroid dehydrogenase 
      activity in man.
PG  - 605-11
AB  - OBJECTIVE: Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) 
      catalyse the interconversion of cortisol to hormonally inactive cortisone; 
      defects in the 11 beta-HSD2 isoform result in hypertension. The kidney, 
      expressing high levels of 11 beta-HSD2, is the principal source of cortisone in 
      man. We have validated the measurement of urinary free cortisone (UFE) excretion 
      in normals and in patients with disorders of the pitultary-adrenal axis in an 
      attempt to more accurately measure the activity of 11 beta-HSD2 in vivo. 
      SUBJECTS: Forty-one normal adults, 12 normal children < 12 years of age, 15 
      patients with Cushing's syndrome, 12 with hypopitultarism on replacement 
      hydrocortisone, 12 with the syndrome of apparent mineralocorticoid excess (AME) 
      and 7 volunteers consuming liquorice. MEASUREMENTS: A complete 24-hour urine 
      collection was analysed by gas chromatography/mass spectrometry for "A-ring' 
      reduced cortisol and cortisone metabolites, i.e. tetrahydrocortisols (THF and 
      allo-THF) and tetrahydrocortisone (THE). In addition, urinary free cortisol (UFF) 
      and urinary free cortisone were quantified using deuterium-labelled internal 
      standards. RESULTS: In normal adults and children, UFE excretion exceeded that of 
      UFF (UFF 30.4 +/- 2.4 micrograms/24h (mean +/- SE), UFE 54.6 +/- 4.1 
      micrograms/24h, adults) (for conversion to nmol/24h multiply E by 2.78 and F by 
      2.76 respectively). Thus the normal UFF/UFE ratio was 0.54 +/- 0.05 in contrast 
      to the (THF + allo-THF)/THE ratio of 1.21 +/- 0.06. UFE excretion was normal in 
      hypopituitary patients on replacement hydrocortisone. Although UFE was elevated 
      in all forms of Cushing's syndrome, the UFF/UFE ratio was grossly elevated in 
      patients with the ectopic ACTH syndrome (14.0 +/- 6.7, n = 6). UFE was below the 
      lower limit of the assay (< 1 microgram/24h) in most patients with the so-called 
      type 1 variant of AME and significantly reduced in 4 patients described as having 
      the type 2 variant of AME (10.5 +/- 3.5 micrograms/h, P < 0.05) and in 7 
      volunteers consuming liquorice (26.8 +/- 10.0 micrograms/24h, P < 0.01). In 
      ectopic ACTH syndrome, AME, and liquorice ingestion the UFF/UFE ratio was more 
      deranged than the (THF + allo-THF)/THE ratio. CONCLUSION: In normals the 
      discrepant THF + allo-THF/ THE and UFF/UFE ratio suggests that much more of the 
      UFE is derived from the kidney. Reduction in UFE excretion is seen following 
      liquorice ingestion and in both variants of AME, though it is more profound in 
      AME1. The high UFF/UFE ratio in the mineralocorticoid excess state seen in the 
      ectopic ACTH syndrome is compatible with substrate-saturation of renal 11 
      beta-HSD2. The measurement of UFE and the UFF/UFE ratio is a significant advance 
      in the analysis of human 11 beta-HSD activity in vivo; in particular, the UFF/UFE 
      ratio appears to be a more sensitive index than the (THF + allo-THF)/THE ratio of 
      renal 11 beta-HSD2 activity.
FAU - Palermo, M
AU  - Palermo M
AD  - Children's Hospital Oakland Research Institute, CA 94609, USA.
FAU - Shackleton, C H
AU  - Shackleton CH
FAU - Mantero, F
AU  - Mantero F
FAU - Stewart, P M
AU  - Stewart PM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (Mineralocorticoids)
RN  - 5HF9TM2D15 (Tetrahydrocortisone)
RN  - 7P2O6MFN8O (Tetrahydrocortisol)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - V27W9254FZ (Cortisone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Adult
MH  - Child
MH  - Cortisone/*urine
MH  - Cushing Syndrome/enzymology/urine
MH  - Female
MH  - Gas Chromatography-Mass Spectrometry
MH  - Glycyrrhiza
MH  - Humans
MH  - Hydrocortisone/*urine
MH  - Hydroxysteroid Dehydrogenases/*metabolism
MH  - Hypopituitarism/enzymology/urine
MH  - Male
MH  - Middle Aged
MH  - Mineralocorticoids/blood
MH  - Pituitary-Adrenal System/*metabolism
MH  - Plants, Medicinal
MH  - Tetrahydrocortisol/urine
MH  - Tetrahydrocortisone/urine
EDAT- 1996/11/01 00:00
MHDA- 1996/11/01 00:01
CRDT- 1996/11/01 00:00
PHST- 1996/11/01 00:00 [pubmed]
PHST- 1996/11/01 00:01 [medline]
PHST- 1996/11/01 00:00 [entrez]
AID - 10.1046/j.1365-2265.1996.00853.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 1996 Nov;45(5):605-11. doi: 
      10.1046/j.1365-2265.1996.00853.x.