Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone.
OBJECTIVE
We aimed to determine whether growth hormone (GH) resistance is present in patients with chronic heart failure (CHF) and whether it may be linked to the biochemical response to GH treatment.


BACKGROUND
Acquired GH resistance is a feature of severe illness, in particular, cachexia. In patients with CHF, the response to GH therapy appears to be variable.


METHODS
Biochemical markers of the GH-insulin-like growth factor-I (IGF-I) axis were compared in 21 cachectic patients with CHF, 51 noncachectic patients and 26 healthy control subjects. In separate studies, the predictive value of baseline biochemical variables for the IGF-I response to GH treatment was analyzed.


RESULTS
Cachectic patients showed an increase of total GH and immunologically intact GH (p < or = 0.0002) and a decrease of GH-binding protein (BP) (p = 0.005), IGF-BP3 (p = 0.01) and IGF-I (p = 0.06), compared with noncachectic patients. Similar changes were found when the cachectic group was compared with the control group. No differences were found between noncachectic patients and control subjects. Levels of GH-BP correlated with the IGF-I/GH ratio in all subgroups (all p < or = 0.002). Baseline GH-BP levels were related to the increase of IGF-I levels in response to GH treatment in patients with CHF after 24 h (r = 0.83, p = 0.005; n = 9; study 2), 44 days (r = 0.52, p = 0.007; n = 25; study 3) and 96 days (r = 0.54, p = 0.006; n = 24; study 3).


CONCLUSIONS
Most cachectic and some noncachectic patients with CHF show features of acquired GH resistance. The principal predictors of the biochemical features of GH resistance and of the poor biochemical response to short-term and longer-term GH treatment are GH-BP plasma levels. The presence of GH resistance is potentially a major factor determining the response to GH therapy in patients with CHF.
Anker
S D
SD
Franz-Volhard-Klinik, Max Delbrück Centrum for Molecular Medicine, Charité, Berlin, Germany. s.anker@ic.ac.uk
Volterrani
M
M
Pflaum
C D
CD
Strasburger
C J
CJ
Osterziel
K J
KJ
Doehner
W
W
Ranke
M B
MB
Poole-Wilson
P A
PA
Giustina
A
A
Dietz
R
R
Coats
A J
AJ
D015415:Biomarkers / Q000097:blood; D001823:Body Composition; D002100:Cachexia / Q000097:blood / Q000188:drug therapy; D002352:Carrier Proteins / Q000097:blood; D002908:Chronic Disease; D004361:Drug Tolerance; D005215:Fasting; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors
D015415:Biomarkers; D002352:Carrier Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein