Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients
Open accessAbstract
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. Study design 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.
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More than half of the unexpected deaths in that cohort were thought to have undiagnosed secondary adrenal insufficiency.
“In addition, more than half of the unexpected deaths were thought to have undiagnosed secondary adrenal insufficiency (9).”
From Hypoglycaemia in adrenal insufficiency (2023) · cites this paper as [9]
The Results report that 59 of 106 sudden, unexpected deaths (56%) had a clinical course strongly suggestive of adrenal insufficiency. The paper does not say that more than half had *undiagnosed secondary* adrenal insufficiency; it also describes deaths involving inadequate treatment of adrenal insufficiency. (LLM, conf=0.89)
Experimental — accuracy not yet measured74% of these unexpected deaths were associated with multiple pituitary hormone deficiencies and hypoglycaemia was highlighted in 31% of these 106 deaths.
“74% of these unexpected deaths were associated with multiple pituitary hormone deficiencies and hypoglycaemia was highlighted in 31% of these 106 deaths.”
From Hypoglycaemia in adrenal insufficiency (2023) · cites this paper as [9]
In a large cohort study of patients who received growth hormone in the United States, 24.5% (106 out of 433) deaths recorded were sudden and unexpected.
“In a large cohort study of patients who received growth hormone in the United States, 24.5% (106 out of the 433) deaths recorded were found to be sudden and unexpected.”
From Hypoglycaemia in adrenal insufficiency (2023) · cites this paper as [9]
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References 13 · Cited by 118
Research works printed but not linked: 12
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- Hintz RL. Eternal vigilance-mortality in children with growth hormone deficiency. J Clin Endocrinol Metab 1996;81:1691-2.
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- Authors
- Mills, J. L., Schonberger, L. B., Wysowski, D. K., Brown, P., Durako, S. J., Cox, C., Kong, F., & Fradkin, J. E.
- Affiliations
- Centers for Disease Control and Prevention (US)
- Corresponding author
- Mills, James L
- Venue
- The Journal of Pediatrics
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 144
- Issue
- 4
- Pages
- 430-436
- ISSN
- 0022-3476 (ISSN-L)
- OpenAlex
- W2089651359
- Cited by
- 118
- References
- 13
- Citations by year
- 2023: 4 · 2022: 2 · 2021: 5 · 2020: 6 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 5 · 2014: 9 · 2013: 8 · 2012: 6
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Pediatrics (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- pituitary-derived growth hormone, mortality, Creutzfeldt-Jakob disease, hypoglycemia, adrenal insufficiency, panhypopituitarism, growth hormone deficiency, recombinant human growth hormone, sudden unexpected death
- MeSH terms
- Adrenal Insufficiency, Age Factors, Child, Child, Preschool, Death Certificates, Death, Sudden, Epilepsy, Female, Humans, Hypoglycemia, Creutzfeldt-Jakob Syndrome, Male, Neoplasms, Risk Factors, United States, Cohort Studies, Survival Rate, Age Distribution, Human Growth Hormone
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