Growth hormone Creutzfeldt-Jakob disease

P. Brown, C. C. Gajdusek, C. J. Gibbs, and D. N. Asher, Potential epidemic of Creutzfeldt-Jakob disease from human growth hormone therapy, N. Engl. J. Med., 313(12), 728 (1985). 

It overcomes problems of product safety. Direct extraction of product from some native biological sources has, in the past, led to the unwitting transmission of disease. Examples include the transmission of blood-borne pathogens such as hepatitis B and C and human immunodeficiency virus (HIV) via infected blood products and the transmission of Creutzfeldt-Jakob disease to persons receiving human growth hormone (GH) preparations derived from human pituitaries. 

Hintz, R.L., The prismatic case of Creutzfeldt-Jakob disease associated with pituitary growth hormone treatment. J Clin Endocrinol Metab, 1995. 80(8) 2298-301. 

Growth hormone is a 191-amino-acid peptide with two sulfhydryl bridges. Its structure closely resembles that of prolactin. In the past, medicinal GH was isolated from the pituitaries of human cadavers. However, this form of GH was found to be contaminated with prions that could cause Creutzfeldt-Jakob disease. For this reason, it is no longer used. Somatropin, the recombinant form of GH, has a 191-amino acid sequence that is identical with the predominant native form of human GH. 

Somatropin extracted from cadaveric human pituitaries was used to treat growth hormone-deficient patients until several cases of the fatal degenerative neurological disorder Creutzfeldt-Jakob disease were reported in the mid-1980s. Of 267 cases of iatrogenic Creutzfeldt-Jakob disease, 139 were caused by human cadaver-derived somatropin (SEDA-25, 479). 

This disease develops when an abnormal prion protein present in the cadaveric material induces a cascade of conformational changes in host protein. Creutzfeldt-Jakob disease in recipients of somatropin differs from the sporadic form, in that it usually presents with cerebellar signs rather than cognitive impairment, and also in the prominence of prion protein amyloid plaques in nervous tissue (18). In a review, 139 cases of Creutzfeldt-Jakob disease were identified worldwide in people treated with cadaveric somatropin before recombinant human growth hormone became available in the mid-1980s (19). The prevalence of this fatal neurodegenerative condition in recipients of somatropin ranges from 0.3% in the USA to 4.4% in France. Creutzfeldt-Jakob disease has been reported to start at 4-30 years after therapy with cadaveric somatropin (18), so that further cases are anticipated and continue to be reported (20). 

Caboclo LO, Huang N, Lepski GA, Livramento JA, Buchpiguel CA, Porto CS, Nitrini R. Iatrogenic Creutzfeldt-Jakob disease following human growth hormone therapy case report. Arq Neuropsiquiatr 2002 60(2-B) 458-61. 

Huillard d Aignaux J, Alperovitch A, Maccario J. A statistical model to identify the contaminated lots implicated in iatrogenic transmission of Creutzfeldt-Jakob disease among French human growth hormone recipients. Am J Epidemiol 1998 147(6) 597-604. 

Before 1985, GH was obtained from human cadaver pituitary glands. A small number of individuals who received cadaver-derived pooled growth hormone preparations developed Creutzfeldt-Jakob disease, a fatal neurodegenerative disease that presented many years after GH treatment. (This... 

A few cases of Creutzfeldt-Jakob disease have been transmitted by corneal transplantation, dural transplantation, surgical equipment, and human growth hormone extracted from human pituitary glands (195). This has of course raised concern that Creutzfeldt-Jakob disease might prove to be transmissible by blood and blood products (196). The concern has been further accentuated by recent fears of transmission bovine spongiform encephalopathy through food consumption by humans. Some manufacturers of plasma products have reacted by recalling products from the market (197). 

Creutzfeldt-Jakob disease foUowmg human growth hormone therapy case report. Arq Nemopsiquiatr... 

Fatal viral infections resulting from the use of contaminated human tissue or fluids as components of medicines are well recorded. Examples of this include human immunodeficiency virus (HIV) infection of haemophiliacs by contaminated and inadequately treated factor VIII products made from pooled human blood, and Creutzfeldt-Jakob disease (CJD) from injections of human growth hormone derived from human pituitary glands, some of which were infected. 

Somatotropin (growth hormone GH) is a pituitary somatotrophic linear peptide hormone of 191 residues. The name somatotropin is used for human growth hormone (HGH), which was isolated from the pituitary glands of cadavers. This when used to treat short stature (dwarfism) brought with it the risk of acquiring Creutzfeldt-Jakob disease through contamination. It is now replaced in many countries by somatropin, which is a biosynthetic form of human growth hormone without this liability. 

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