Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients.
OBJECTIVE
Patients who received pituitary-derived growth hormone (GH) are at excess risk of mortality from Creutzfeldt-Jakob disease. We investigated whether they were at increased risk of death from other conditions, particularly preventable conditions.


METHODS
A cohort (N=6107) from known US pituitary-derived GH recipients (treated 1963-1985) was studied. Deaths were identified by reports from physicians and parents and the National Death Index. Rates were compared with the expected rates for the US population standardized for race, age, and sex.


RESULTS
There were 433 deaths versus 114 expected (relative risk [RR], 3.8; 95% confidence interval [CI], 3.4-4.2; P<.0001) from 1963 through 1996. Risk was increased in subjects with GH deficiency caused by any tumor (RR, 10.4; 95% CI, 9.1-12.0; P<.0001). Surprisingly, subjects with hypoglycemia treated within the first 6 months of life were at extremely high risk (RR, 18.3; 95% CI, 9.2-32.8; P<.0001), as were all subjects with adrenal insufficiency (RR, 7.1; 95% CI, 6.2-8.2; P<.0001). A quarter of all deaths were sudden and unexpected. Of the 26 cases of Creutzfeldt-Jakob disease, four cases have died since 2000.


CONCLUSIONS
The death rate in pituitary-derived GH recipients was almost four times the expected rate. Replacing pituitary-derived GH with recombinant GH has eliminated only the risk of Creutzfeldt-Jakob disease. Hypoglycemia and adrenal insufficiency accounted for far more mortality than Creutzfeldt-Jakob disease. The large number of potentially preventable deaths in patients with adrenal insufficiency and hypoglycemia underscores the importance of early intervention when infection occurs in patients with adrenal insufficiency, and aggressive treatment of panhypopituitarism.
Mills
James L
JL
National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, 6100 Building Room 7B03, Bethesda, MD 20892, USA. jamesmills@nih.gov
Schonberger
Lawrence B
LB
Wysowski
Diane K
DK
Brown
Paul
P
Durako
Stephen J
SJ
Cox
Christopher
C
Kong
Fanhui
F
Fradkin
Judith E
JE
D000309:Adrenal Insufficiency / Q000188:drug therapy / Q000209:etiology / Q000401:mortality*; D017677:Age Distribution; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D007562:Creutzfeldt-Jakob Syndrome / Q000139:chemically induced / Q000401:mortality*; D003644:Death Certificates; D003645:Death, Sudden / Q000453:epidemiology; D004827:Epilepsy / Q000401:mortality; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects* / Q000172:deficiency*; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy / Q000209:etiology / Q000401:mortality*; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000401:mortality; D012307:Risk Factors; D015996:Survival Rate; D014481:United States / Q000453:epidemiology
D019382:Human Growth Hormone