Possible Link Between Growth Hormone Treatment and Creutzfeldt-Jakob Disease

A report from the University of California, published in Emerging Infectious Diseases, outlines the case of a 58-year-old woman who passed away from iatrogenic Creutzfeldt-Jakob disease (iCJD) after receiving cadaver-derived human growth hormone nearly 48 years prior. This patient had sought medical help due to balance issues and tremors that developed two weeks earlier. She had been treated with contaminated human growth hormone for over nine years, beginning when she was seven years old. Prion diseases, which lead to severe neurological decline, are caused by infectious misfolded proteins.

The cadaver-derived hormone is a known healthcare-related cause of this variant of CJD. From the 1960s to the 1980s, the National Hormone Pituitary Program (NHPP) administered this hormone to approximately 7,700 patients in the U.S. An outbreak of chGH-related iCJD was first identified in the U.S. in 1985, leading to the cessation of its production and administration.

Following this, recombinant human growth hormone took its place, yet cases of iCJD continued. This persistence is partly due to the long latency periods associated with prion diseases, which can vary based on several factors—such as the dose of infectious material, the exposure route, and individual genetic factors.

Rapid Clinical Decline

As of January 2024, this woman represented the 36th case of iCJD among U.S. patients treated with chGH and the 254th globally.

Upon her arrival for treatment, her medical history included depression, spinal fusion surgery, and idiopathic panhypopituitarism, a condition in which the pituitary gland fails to produce adequate hormones. During her initial neurologic examination, she displayed involuntary movements of her head and limbs, though other aspects appeared normal.

Brain imaging showed no abnormalities, and tests for autoimmune movement disorders and HIV were negative, with levels of vitamins and minerals also normal. The patient was referred to a movement disorders specialist, advised to begin physical therapy, and continue psychological support.

Within a month, her condition worsened, leading to urinary incontinence, increased tremors, and trouble speaking. She was subsequently admitted to the hospital again, presenting with rapid breathing, an exaggerated startle reflex, and stiffness in her limbs.

Her mental alertness diminished, culminating in intubation. A few days later, she developed myoclonus and remained comatose.

Diagnosis and Death

Two months after her first visit, a repeat brain MRI pointed to lesions, and an EEG indicated abnormal brain activity. Her antinuclear antibody tests were mildly positive, while other tests failed to reveal any significant pathological findings. Testing of her cerebrospinal fluid showed no signs of viral or autoimmune disturbances.

However, prion testing at the National Prion Disease Pathology Surveillance Center confirmed a high level of tau protein and 14-3-3 protein, indicative of prion disease. Following her documented wishes, she was extubated and subsequently died.

An autopsy confirmed the diagnosis of CJD through specialized analysis of brain tissue, which indicated no inherited mutations related to genetic CJD, affirming it as iCJD tied to her past treatment with chGH.

Notably, she carried a polymorphism in the PRNP gene associated with longer incubation times for prion diseases.

Estimating Latency

Determining the exact latency period for iCJD cases linked to chGH is often complex due to prolonged exposure. Researchers noted that estimates could be gauged by the time between the initial chGH dose and the onset of symptoms, among other methods.

It’s crucial to note that none of the 36 former U.S. cases received exclusively post-1977 chGH. This is likely because a new extraction method was adopted by the NHPP that year, which greatly reduced prion contamination.

Potential for New Cases

As part of this investigation, four calculations were made for latency estimates. They identified that while the ongoing outbreak in the U.S. had slowed, new cases could still arise, particularly among those with certain genetic variants.

Medical professionals should be aware of the potential for new instances of chGH-related CJD and remain vigilant in cases of new neurologic symptoms, especially in individuals previously treated with chGH before the updated purification method was implemented in 1977.