Cadaveric Human Growth Hormone-Associated Creutzfeldt-Jakob Disease with Long Latency Period, United States

Abstract

We report a case of iatrogenic Creutzfeldt-Jakob disease (iCJD) after a 48.3-year incubation period in a patient treated with cadaveric human growth hormone. iCJD was pathologically confirmed; genetic analysis was negative for pathogenic mutations. Clinicians should consider iCJD in patients with progressive neurologic signs who had received cadaveric human growth hormone treatment.

Keywords: CJD; Creutzfeldt-Jakob disease; PrPSc proteins; United States; human growth hormone; myoclonus; prions and related diseases; sporadic.

Figure 1

Magnetic resonance imaging of the brain from a case of cadaveric human growth hormone–associated Creutzfeldt-Jakob disease with long latency period, United States. A, B) Images obtained at initial clinical examination were unremarkable. C, D) Images obtained 3 months later demonstrated subtle areas of symmetric T2 hyperintensity in the insulae and frontotemporal lobes (C) and deep gray structures with diffusion restriction along the bilateral insulae and caudate heads without gadolinium enhancement (D).

Figure 2

Comparison of latency estimates among US cases in a study of chGH-associated CJD with long latency period, United States. The patient in this report (current CJD case) was treated with chGH for 9.3 years starting in late 1971 at 7 years of age, and neurologic symptoms developed when she was 58 years of age. We used data from all 36 US cases of chGH-associated CJD to compare estimates of CJD latency periods via 4 methods: first dose of chGH to symptom onset (red), midpoint of chGH treatment to symptom onset (green), last dose of chGH to symptom (blue), and midpoint of pre-1978 chGH to symptom onset (purple). Using those 4 methods, we believe the last (purple box plot) to be the most accurate, giving a best estimate of 48.3 years for our patient’s latency period. Black dots indicate other CJD cases, box top and bottoms indicate 25th and 75th percentiles, horizontal lines inside boxes indicate medians, and whiskers extend to the furthest observed points within 1.5 times the interquartile range from the 25th and 75th percentiles. chGH, cadaveric human growth hormone; CJD, Creutzfeldt-Jakob disease.