Fat content in liver and skeletal muscle changes in a reciprocal manner in patients with acromegaly during combination therapy with a somatostatin analog and a GH receptor antagonist: a randomized clinical trial.
BACKGROUND
Pegvisomant is a GH antagonist, which is used for the treatment of acromegalic patients. It effectively blocks the hepatic and peripheral effects of GH, but transient elevations in circulating liver enzymes of unknown pathogenesis may occur, which seems to be more prevalent when the treatment is combined with a somatostatin analog (SA). Accumulation of intrahepatic lipid is a known cause of elevated liver enzymes, and there is evidence to suggest that GH impacts lipid content in liver and skeletal muscle.


OBJECTIVE
Our objective was to measure lipid content in liver and skeletal muscle in acromegalic patients before and after cotreatment with pegvisomant and SA as compared with SA monotherapy.


METHODS
Eighteen acromegalic patients well controlled on SA monotherapy were randomized in a parallel study over 24 wk to 1) unchanged SA monotherapy, or 2) cotreatment with pegvisomant (15-30 mg twice a week) and SA (half the usual dosage).


METHODS
This was an investigator-initiated study in a single tertiary referral center.


METHODS
Intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) was assessed by ¹H magnetic resonance spectroscopy.


RESULTS
IHL increased in the cotreatment group compared with SA only (P = 0.002). The increase was positively correlated to weekly pegvisomant dose (r² = 0.52; P = 0.01). By contrast, IMCL decreased in the cotreatment group compared with SA only (P = 0.01). These changes related neither to insulin sensitivity nor inflammatory markers.


CONCLUSIONS
Cotreatment with pegvisomant and a reduced SA dose increase IHL and decrease IMCL compared with SA monotherapy. The clinical implications remain unclear, but increased IHL may be causally linked to the transient elevations in liver enzymes observed during pegvisomant treatment.
Department of Internal Medicine and Endocriniology (MEA), Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark. michael.madsen@ki.au.dk
Michael
M
Madsen
Thomas
T
Krusenstjerna-Hafstrøm
Louise
L
Møller
Britt
B
Christensen
Mikkel Holm
MH
Vendelbo
Steen B
SB
Pedersen
Jan
J
Frystyk
Niels
N
Jessen
Troels Krarup
TK
Hansen
Hans
H
Stødkilde-Jørgensen
Allan
A
Flyvbjerg
Jens Otto L
JO
Jørgensen
D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001707:Biopsy, Needle; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D048550:Hepatic Insufficiency / Q000139:chemically induced; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D015187:Lipectomy; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D013004:Somatostatin; C406545:pegvisomant