Congenital growth hormone (GH) deficiency and atherosclerosis: effects of GH replacement in GH-naive adults.
BACKGROUND
GH deficiency (GHD) in adults is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein cholesterol, and C-reactive protein.


METHODS
We have studied the effects of 6-month GH replacement therapy in 20 adult members of a large Brazilian kindred with lifelong severe and isolated GHD due to a homozygous mutation in GHRH receptor gene (46 +/- 14.5 yr; 122 +/- 7.7 cm; 36.7 +/- 5.4 kg; 10 men). Subjects were studied at baseline, after 6-month bimonthly depot GH injections (Nutropin Depot; Genentech, Inc., South San Francisco, CA) [post GH (pGH)], and after 6- and 12-month washout.


RESULTS
Despite modest trough serum IGF-I increase, GH replacement therapy caused a decrease in skinfolds and in waist-hip ratio, with a rebound increase at 12 months. Total and low-density lipoprotein cholesterol were reduced pGH and returned to baseline at 6 months. High-density lipoprotein cholesterol increased pGH, but at 12 months was lower than baseline. A progressive increase in left ventricular mass index, posterior wall, and septum thickness occurred from pGH to 12 months, and of carotid intima-media thickness, from 6 to 12 months. Individuals were 6, 16, and 52 times more likely to have an atherosclerotic carotid plaque at pGH, 6 and 12 months, respectively, when compared with baseline.


CONCLUSIONS
In patients with lifetime isolated GHD, 6-month treatment with GH has reversible beneficial effects on body composition and metabolic profile, but it causes a progressive increase in intima-media thickness and in the number of atherosclerotic carotid plaques.
Oliveira
Joselina L M
JL
Department of Endocrinology, Federal University of Sergipe, Aracaju, SE Brazil 49060-100.
Aguiar-Oliveira
Manuel H
MH
D'Oliveira
Argemiro
A
Pereira
Rossana M C
RM
Oliveira
Carla R P
CR
Farias
Catarine T
CT
Barreto-Filho
José A
JA
Anjos-Andrade
Fernando D
FD
Marques-Santos
Celi
C
Nascimento-Junior
Adão C
AC
Alves
Erica O
EO
Oliveira
Francielle T
FT
Campos
Viviane C
VC
Ximenes
Roberto
R
Blackford
Amanda
A
Parmigiani
Giovanni
G
Salvatori
Roberto
R
D000328:Adult; D000886:Anthropometry; D050197:Atherosclerosis / Q000139:chemically induced* / Q000453:epidemiology* / Q000473:pathology; D001794:Blood Pressure / Q000502:physiology; D002339:Carotid Arteries / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003692:Delayed-Action Preparations; D004452:Echocardiography; D015444:Exercise / Q000502:physiology; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D006339:Heart Rate / Q000502:physiology; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency*; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003692:Delayed-Action Preparations; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone