{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:55:13Z","timestamp":1753883713652,"version":"3.41.2"},"reference-count":37,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human growth hormone (hGH) has been in clinical use for children with GH deficiency (GHD) since the late 1950s. The original formulations were considered very safe with few adverse events reported. That changed remarkably in 1985 when the first patients with GHD, who had been treated with cadaveric hGH, were diagnosed with Creutzfeldt-Jakob disease (CJD).<\/jats:p>\n               <jats:p>Fortunately, that same year a robust supply of recombinant hGH was released to the market whose adverse event profile did not include CJD. Patients who had received National Hormone and Pituitary Program hGH have been continuously followed since 1985.<\/jats:p>\n               <jats:p>It is clear that prions are causative for CJD. Within the last 10 years there have been reports that similar preparations of cadaveric hGH may have been contaminated with amyloid \u03b2 (A\u03b2) protein, a material that is related to Alzheimer disease. Eight patients in the United Kingdom, who had received cadaveric hGH extracted in an analogous manner to that in the United States, had conditions compatible with Alzheimer disease, although they did not fulfill all of the requirements for that diagnosis. In this report we discuss the findings of both CJD and Alzheimer disease, especially as they relate to a possible transmission of the diseases by prions and A\u03b2 protein.<\/jats:p>","DOI":"10.1210\/jendso\/bvaf029","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T09:27:20Z","timestamp":1739870840000},"source":"Crossref","is-referenced-by-count":1,"title":["The Unfolding Story of Protein Misfolding Causing Alzheimer Disease in Recipients of Human Pituitary Growth Hormone"],"prefix":"10.1210","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9959-9230","authenticated-orcid":false,"given":"Evan G","family":"Graber","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Pediatrics Nemours Children's Health, Wilmington , DL 19803, USA, and Sidney Kimmel Medical College, Philadelphia, PA 19107 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5186-7008","authenticated-orcid":false,"given":"Sayed M Hadi","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Computational Brain Research and Intervention (C-Brain) Laboratory, Department of Psychiatry and Behavioral Science, Stanford University , Palo Alto, CA 94304 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9589-6011","authenticated-orcid":false,"given":"Darrell M","family":"Wilson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Pediatrics, Stanford University , Palo Alto, CA 94304 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7526-3142","authenticated-orcid":false,"given":"Alan D","family":"Rogol","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Pediatrics, University of Virginia , Charlottesville, VA 22903 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"issue":"8","key":"2025022605371589700_bvaf029-B1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1590\/S0004-27302011000800009","article-title":"Adverse effects of growth hormone replacement therapy in children","volume":"55","author":"Souza","year":"2011","journal-title":"Arq Bras Endocrinol Metab"},{"issue":"12","key":"2025022605371589700_bvaf029-B2","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1056\/NEJM198509193131206","article-title":"Creutzfeldt-Jakob disease in a young adult with idiopathic hypopituitarism: possible relationship to administration of cadaveric human growth hormone","volume":"313","author":"Koch","year":"1985","journal-title":"N Engl J 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Clinical use of human growth hormone","volume":"266","author":"Raben","year":"1962","journal-title":"N Engl J Med"},{"issue":"3253","key":"2025022605371589700_bvaf029-B12","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1126\/science.125.3253.884","article-title":"Metabolic effects of human and monkey growth hormone in man","volume":"125","author":"Beck","year":"1957","journal-title":"Science"},{"issue":"5","key":"2025022605371589700_bvaf029-B13","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1210\/jcem-46-5-853","article-title":"Isolation and purity of human pituitary hormones","volume":"46","author":"Raiti","year":"1978","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2025022605371589700_bvaf029-B14","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1128\/jcm.20.3.323-329.1984","article-title":"Human leukocytic pyrogen test for detection of pyrogenic material in growth hormone produced by recombinant Escherichia coli","volume":"20","author":"Dinarello","year":"1984","journal-title":"J Clin Microbiol"},{"issue":"1","key":"2025022605371589700_bvaf029-B15","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/02648725.1988.10647845","article-title":"Secretion and folding of human growth hormone in Escherichia coli","volume":"6","author":"Hsiung","year":"1988","journal-title":"Biotechnol Genet Eng Rev"},{"issue":"1","key":"2025022605371589700_bvaf029-B16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s00441-022-03676-z","article-title":"Prion strains viewed through the lens of cryo-EM","volume":"392","author":"Manka","year":"2023","journal-title":"Cell Tissue Res"},{"issue":"8","key":"2025022605371589700_bvaf029-B17","first-page":"2298","article-title":"The prismatic case of Creutzfeldt\u2013Jakob disease associated with pituitary growth hormone treatment","volume":"80","author":"Hintz","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2025022605371589700_bvaf029-B18","first-page":"49","article-title":"Growth hormone as a therapeutic agent","volume":"21","author":"Blizzard","year":"2005","journal-title":"Growth Genet Horm"},{"key":"2025022605371589700_bvaf029-B19","first-page":"85","article-title":"Human growth hormone therapy and Creutzfeldt-Jakob disease: a drama in three acts","volume":"81","author":"Brown","year":"1988","journal-title":"Pediatrics"},{"issue":"1","key":"2025022605371589700_bvaf029-B20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S0022-3476(85)80604-1","article-title":"Degenerative neurologic disease in patients formerly treated with human growth hormone. 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