PMID- 9828916
OWN - NLM
STAT- MEDLINE
DCOM- 19981203
LR  - 20190813
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 49
IP  - 2
DP  - 1998 Aug
TI  - Growth hormone replacement inhibits renal and hepatic 11 beta-hydroxysteroid 
      dehydrogenases in ACTH-deficient patients.
PG  - 257-63
AB  - OBJECTIVES: The commonest side-effects of GH replacement therapy relate to sodium 
      retention but its mechanism is unclear. In rats, GH inhibits renal and hepatic 11 
      beta-hydroxysteroid dehydrogenase (11 beta-HSD) activities. In man, this action 
      might impair inactivation of cortisol to cortisone in the distal nephron thereby 
      allowing cortisol to activate mineralocorticoid receptors. In this study, we 
      examined the effects of GH replacement on cortisol metabolism. DESIGN: A 
      randomized double-blind study comparing 6 months GH replacement with placebo in 
      adults with GH deficiency due to pituitary or hypothalamic disease. PATIENTS: 6 
      men and 8 women received placebo and 8 men and 9 women received GH. MEASUREMENTS: 
      Cortisol and its metabolites were measured in overnight urine samples and in a 
      fasting morning plasma sample at baseline and at 6 months. RESULTS: Five patients 
      withdrew from the study, 4 because of adverse effects of GH. Amongst those who 
      completed the study, the effects of GH on cortisol metabolism differed between 
      patients with and without ACTH deficiency. Amongst those receiving hydrocortisone 
      replacement (n = 18), GH had no effect on plasma cortisol/cortisone ratio, or 
      urine tetrahydrocortisols/tetrahydrocortisone ratio, but produced a substantial 
      reduction in total urinary cortisol metabolites (from 1326 +/- 191 to 777 +/- 229 
      micrograms/mmol creatinine; P < 0.01) and an increase in urinary free 
      cortisol/cortisone ratio (from 0.88 +/- 0.10 to 2.57 +/- 0.74; P < 0.02). By 
      contrast, GH had none of these effects in patients with normal ACTH secretion. 
      There were no changes in blood pressure or plasma electrolytes, aldosterone, or 
      renin activity with GH, and no changes in any variables with placebo. 
      CONCLUSIONS: The increase in cortisol/cortisone ratio in urine but not in plasma, 
      and the lack of effect on hepatic cortisol metabolites, suggests that GH inhibits 
      both the conversion of cortisol to cortisone by renal 11 beta-HSD2 and the 
      conversion of cortisone to cortisol by hepatic 11 beta-HSD1. It is unclear why 
      this action of GH only affects patients with ACTH deficiency. The reduction in 
      total cortisol metabolite excretion suggests that GH also affects bioavailability 
      of hydrocortisone tablets. These observations suggest that glucocorticoid 
      replacement therapy may need to be adjusted in hypopituitary patients who are 
      commenced on GH replacement.
FAU - Walker, B R
AU  - Walker BR
AD  - University of Edinburgh, Department of Medicine, Western General Hospital, UK. 
      B.Walker@ed.ac.uk
FAU - Andrew, R
AU  - Andrew R
FAU - MacLeod, K M
AU  - MacLeod KM
FAU - Padfield, P L
AU  - Padfield PL
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 9002-72-6 (Growth Hormone)
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  - Adrenocorticotropic Hormone/*deficiency
MH  - Adult
MH  - Cortisone/urine
MH  - Double-Blind Method
MH  - Female
MH  - Growth Hormone/*deficiency/*therapeutic use
MH  - Humans
MH  - Hydrocortisone/blood/therapeutic use/urine
MH  - Hydroxysteroid Dehydrogenases/*metabolism
MH  - Hypopituitarism/complications/drug therapy/metabolism
MH  - Hypothalamic Diseases/complications/drug therapy/metabolism
MH  - Kidney/*enzymology
MH  - Liver/*enzymology
MH  - Male
MH  - Middle Aged
EDAT- 1998/11/26 00:00
MHDA- 1998/11/26 00:01
CRDT- 1998/11/26 00:00
PHST- 1998/11/26 00:00 [pubmed]
PHST- 1998/11/26 00:01 [medline]
PHST- 1998/11/26 00:00 [entrez]
AID - 10.1046/j.1365-2265.1998.00575.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 1998 Aug;49(2):257-63. doi: 
      10.1046/j.1365-2265.1998.00575.x.