ESPE Yearbook of Paediatric Endocrinology

In Brief: These authors investigated patients referred to the UK National Prion Clinic (NPC) for suspected prion diseases. They identified 8 individuals with a history of receiving treatment with cadaveric pituitary-derived growth hormone (c-hGH) and referred to, or reviewed by, the NPC between 2017 and 2022. None had a diagnosis of iatrogenic Creutzfeldt–Jakob disease (CJD) (on the basis of clinical presentation, neuroimaging and biomarkers and, in two cases, by postmortem examination). Yet, 5 patients fulfilled the diagnostic criteria for Alzheimer’s disease (AD).

At least 1,848 patients in the UK were treated with c-hGH between 1959 and 1985. Of these, 80 cases of iatrogenic CJD were recorded, and worldwide there have been over 200 such cases. However, c-hGH resulted in the transmission not only of the CJD prion, but also of amyloid-beta (Abeta) and tau, which are characteristic features of Alzheimer’s disease (AD). On histology, these proteins are typically deposited in the brain parenchyma and blood vessels and in neurofibrillary tangles of hyperphosphorylated tau.

This study shows that tragically, the original c-hGH recipients who did not die from iatrogenic CJD may develop iatrogenic AD. The 5 patients with iatrogenic AD had progressive cognitive impairment in two or more domains severe enough to affect usual activities of daily living. Symptoms started between ages 38 and 55 years old and in some cases progression was rapid.

The study also provides compelling insights into the pathogenesis of AD, that Abeta and tau are indeed causal factors for AD, and also that AD is a transmissible disease due to human-human transmission of Abeta and tau proteins. Fortunately, there is no evidence for human-human transmission of Abeta in normal human interactions. However, it underlines the need to prevent iatrogenic transmission of AD (as is already recognised for CJD) during medical and surgical procedures. Furthermore, as AD is far more prevalent than CJD, the likelihood and public health impact of iatrogenic AD is likely to be far greater than that of iatrogenic CJD.