Creutzfeldt–Jakob Disease in a Young Adult with Idiopathic Hypopituitarism

Koch, Thorsten; Berg, Bruce O.; Armond, S. J. De; Gravina, R F

doi:10.1056/nejm198509193131206

Cited by 150 publications

(19 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most observers have found especially with growth hormone, could potentiate the regrowth of tumors but such an effect has not been documented. Recently, it has been reported that some children treated with human growth hormone have developed a spongiform encephalopathy, possibly because of contamination of the growth hormone with CreutzfeldtJacob virus [67]. Hormone produced by recombinant DNA technology should overcome this problem.…”

Section: Neuroendocrinologic Deficitsmentioning

confidence: 99%

Long‐term sequelae of cancer treatment on the central nervous system in childhood

Packer¹,

Meadows²,

Rorke³

et al. 1987

Med. Pediatr. Oncol.

205

View full text Add to dashboard Cite

Increasing numbers of children with cancer, including those with acute lymphocytic leukemia and medulloblastoma, are experiencing long-term disease control. As survival increases, so does the recognition that the treatment used to prolong survival may have significant detrimental effects on the central nervous system (CNS). Because of the slow replication rate of most constituents of the CNS, these effects tend to be delayed. Radiotherapy, and to a lesser extent, chemotherapy (primarily methotrexate) have been implicated in the causation of such sequelae. The pathogenesis of CNS damage is only partially understood and evidence suggests that direct effects on intracranial endothelial cells and brain white matter and immunologic mechanism play a role. A spectrum of clinical syndromes may occur, including radionecrosis, necrotizing leukoencephalopathy, mineralizing microangiopathy with dystrophic calcification, cerebellar sclerosis and spinal cord dysfunction. The two most common forms of sequelae are neuropsychological and neuroendocrinologic damage. The frequency, degree of and etiology of neurocognitive dysfunction is less than completely elucidated. Radiotherapy has been implicated as the major cause of damage, but the relationship between radiotherapy and the type of damage caused and the volume and dose of radiotherapy and degree of cognitive damage is unclear. Cognitive deficits are progressive in nature. Younger children are more likely to suffer the severest damage; but no patient of any age is free of risk of damage. Growth hormone impairment is the most common form of neuroendocrinologic dysfunction. There is increasing evidence that children with cancer who are long-term survivors are at increased risk for the development of secondary CNS tumors; possibly due, in part, to previous treatment. Much work needs to be done to characterize the sequelae which may occur, develop means of earlier detection, investigate ways to ameliorate sequelae and devise less toxic treatment.

show abstract

Section: Neuroendocrinologic Deficitsmentioning

confidence: 99%

Long‐term sequelae of cancer treatment on the central nervous system in childhood

Packer¹,

Meadows²,

Rorke³

et al. 1987

Med. Pediatr. Oncol.

205

View full text Add to dashboard Cite

show abstract

“…In 1985, the first case report was published of a patient with CJD after administration of pituitary-derived human growth hormone [7,14,15]. In various countries (including the Netherlands), the treatment with pituitaryderived human growth hormone was instantly stopped [15].…”

Section: Introductionmentioning

confidence: 99%

A Nationwide Cohort Study on Creutzfeldt-Jakob Disease among Human Growth Hormone Recipients

Wientjens¹,

Rikken²,

Wit³

et al. 2000

Neuroepidemiology

View full text Add to dashboard Cite

Objective: In 1991, a Dutch patient who had been treated from 1963 to 1969 with human-derived growth hormone died of Creutzfeldt-Jakob disease (CJD). This study was performed to investigate whether among other Dutch human growth hormone recipients there were clinically suspected cases of iatrogenic CJD. Methods: In a retrospective cohort study, all patients (n = 564) treated with human-derived growth hormone before May 1985 and recorded in the Dutch National Growth Registry were followed up until January 1995 for a clinical diagnosis of CJD. For this purpose, all human growth hormone recipients were linked to a database of the Foundation for Health Care Information comprising hospital discharges with a clinical diagnosis of iatrogenic CJD. Linkage of the two databases was performed on the basis of date of birth and gender. Subsequently, verification of patient’s name and initials of the positively matched pairs took place. Results: Linkage provided 37 positively matched pairs concerning 29 individual patients. After verification, no name from the hospital discharge records corresponded to the names of the human growth hormone recipients. Conclusion: The follow-up of 564 Dutch human growth hormone recipients, who had been treated with human growth hormone until 1985 did not establish any clinically suspected case of iatrogenic CJD. Future cases, however, can still emerge due to the potentially long incubation period of prion diseases.

show abstract

“…Finally, pit-hGH therapy was often discontinued when a height of 152 cm was attained; a bar later raised to 165 cm for boys. Between 1962 and 1985 when the Creutzfeldt-Jakob disease disaster struck [3, 4, 5], the number of GH-deficient patients treated with pit-hGH had increased from about 150 to over 3,000, an increase attributable to the establishment in 1963 of the NIH-sponsored National Pituitary Agency in the United States [6]; similar bodies established in Canada and Europe led to comparable increases in the number of pit-hGH-treated children [6]. Recombinant human GH (rhGH) for the treatment of GHD gained approval by the US Food and Drug Administration in 1985. rhGH was the first example of efficient total synthesis of a natural mammalian polypeptide by bacteria [7].…”

Section: Introductionmentioning

confidence: 99%

The Growth Hormone Cascade: Progress and Long-Term Results of Growth Hormone Treatment in Growth Hormone Deficiency

Grumbach¹,

Bin-Abbas²,

Kaplan³

1998

Horm Res Paediatr

View full text Add to dashboard Cite

The growth hormone (GH) cascade and the remarkable advances over the past four decades in our knowledge of its components are considered. It is now over 40 years since human pituitary GH (pit-hGH) was purified and the first GH-deficient patient, a 17-year-old male, was successfully treated with pit-hGH. However, the shortage of pit-hGH limited its use and the dose, the biopotency of preparations varied, strict criteria of GH deficiency (GHD) were used for patient selection including peak plasma immunoreactive GH levels after provocative stimuli of <3.5–5 ng/ml, treatment was not infrequently interrupted, the mean age for initiating treatment was often late in childhood (12–13 years) and the growth deficiency severe (height –4 to –6 SDS), and finally pit-hGH therapy was often discontinued when girls attained a height of 5′ and boys 5′5′′. Nonetheless, the effects of pit-hGH were dramatic; the final height SDS increased in isolated GHD to about –2 SDS in boys and –2.5 to –3.0 SDS in girls, and in multiple pituitary hormone deficiencies to between –1 and –2 SDS. Between 1962 and 1985 when the Creutzfeldt-Jakob disease crisis struck, the number of GH-deficient patients treated with pit-hGH increased from about 150 to over 3,000. The advent of biosynthetic GH (rhGH) and its availability to treat large numbers of idiopathic GH-deficient children (the minimum prevalence rate of which in the USA and UK is between 1 in 3,400 and 4,000) dramatically changed this picture in 1985. It is estimated that more than 60,000 patients have been or are now on treatment. With rhGH treatment the attained mean adult height SDS is now about –1.0, and in our experience with the treatment of patients under 4 years of age, final height may exceed the target height. It is now recognized that (a) the replacement dose of rhGH ranges from 0.175 to 0.35 mg/kg/week and should be individualized; (b) dividing this dose into 6 or 7 daily subcutaneous injections is more effective than giving the same total dose in three weekly portions, and (c) final height correlates significantly with pretreatment chronologic age, height SDS and predicted adult height, duration of therapy, birth length, in some studies height SDS and age at start of puberty, weight, and serum GHBP (an indicator of GH receptor mass). Early recognition of GHD is essential for an optimal height outcome. rhGH treatment should not be delayed in children with documented GHD; the greater the height deficit, the lower the probability that target height will be reached. GHD needs to be detected earlier in children with organic hypopituitarism whether due to a developmental defect, neoplasm, radiation, head trauma, or a CNS infection. Early rhGH therapy in neonatal hypopituitarism has resulted in excellent growth responses. As the height prognosis in isolated GHD is not as good (especially in girls) as in GHD associated with gonadotropin deficiency, the use of LHRH agonists to delay puberty or potent aromatase inhibitors to delay skeletal maturation should be considered in selected patients ...

show abstract

Creutzfeldt–Jakob Disease in a Young Adult with Idiopathic Hypopituitarism

Cited by 150 publications

References 19 publications

Long‐term sequelae of cancer treatment on the central nervous system in childhood

Long‐term sequelae of cancer treatment on the central nervous system in childhood

A Nationwide Cohort Study on Creutzfeldt-Jakob Disease among Human Growth Hormone Recipients

The Growth Hormone Cascade: Progress and Long-Term Results of Growth Hormone Treatment in Growth Hormone Deficiency

Contact Info

Product

Resources

About