Prospective safety surveillance of GH-deficient adults: comparison of GH-treated vs untreated patients.
BACKGROUND
In clinical practice, the safety profile of GH replacement therapy for GH-deficient adults compared with no replacement therapy is unknown.


OBJECTIVE
The objective of this study was to compare adverse events (AEs) in GH-deficient adults who were GH-treated with those in GH-deficient adults who did not receive GH replacement.


METHODS
This was a prospective observational study in the setting of US clinical practices.


METHODS
AEs were compared between GH-treated (n = 1988) and untreated (n = 442) GH-deficient adults after adjusting for baseline group differences and controlling the false discovery rate. The standardized mortality ratio was calculated using US mortality rates.


RESULTS
After a mean follow-up of 2.3 years, there was no significant difference in rates of death, cancer, intracranial tumor growth or recurrence, diabetes, or cardiovascular events in GH-treated compared with untreated patients. The standardized mortality ratio was not increased in either group. Unexpected AEs (GH-treated vs untreated, P ≤ .05) included insomnia (6.4% vs 2.7%), dyspnea (4.2% vs 2.0%), anxiety (3.4% vs 0.9%), sleep apnea (3.3% vs 0.9%), and decreased libido (2.1% vs 0.2%). Some of these AEs were related to baseline risk factors (including obesity and cardiopulmonary disease), higher GH dose, or concomitant GH side effects.


CONCLUSIONS
In GH-deficient adults, there was no evidence for a GH treatment effect on death, cancer, intracranial tumor recurrence, diabetes, or cardiovascular events, although the follow-up period was of insufficient duration to be conclusive for these long-term events. The identification of unexpected GH-related AEs reinforces the fact that patient selection and GH dose titration are important to ensure safety of adult GH replacement.
Lilly Research Laboratories, Indianapolis, Indiana 46285, USA.
Mark L
ML
Hartman
Rong
R
Xu
Brenda J
BJ
Crowe
Leslie L
LL
Robison
Eva Marie
EM
Erfurth
David L
DL
Kleinberg
Alan G
AG
Zimmermann
Whitney W
WW
Woodmansee
Gordon B
GB
Cutler
John J
JJ
Chipman
Shlomo
S
Melmed
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000188:drug therapy* / Q000401:mortality*; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects* / Q000172:deficiency*; D006801:Humans; D015994:Incidence; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality; D011159:Population Surveillance; D011446:Prospective Studies; D012307:Risk Factors; D012893:Sleep Wake Disorders / Q000401:mortality
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I