Short-stature treatment reevaluated.

Since 1963, about 10,000 short-statured children in the United States have received extracts of human cadaver pituitaries, rich in growth hormone, to boost their growth. But within the last year three of them have died of Creutzfeldt-Jakob disease (CJD), a rare, infectious neurological condition; and the federal government in April stopped distribution of the hormone product, which over the years has been prepared by a variety of different techniques.

According to a report in the Aug. 3 LANCET, the type of purification in use since 1977--which purifies the growth hormone on the basis of its size and electrical charge--is capable of eliminating the infectious agent. Prior to 1977, the hormone was purified by solvent extraction and salt and alcohol fractionation, which resulted in a relatively impure product. In all three deaths, the victims had for years received the hormone prepared by the older method.

The epidemiological connection between the receipt of human growth hormone and CJD was first made last November, following the death of a 20-year-old man who had received growth hormone for 14 years. Since the average age of death from CJD is 57, the report from Stanford University researches was met with some concern. When two more hormone recipients died of CJD, the National Institutes of Health (NIH) stopped its growth hormone distribution through the National Hormone and Pituitary Program (NHPP), and the Food and Drug Administration (FDA) pressured the two commercial distributors into halting sales.

The growth hormone-CJD relationship is a thorny one, complicated by the enigmatic nature of CJD. Scientists have been unable to isolate the CJD causative agent--the only way to determine whether it is present is to inject a questioned tissue into monkeys and watch them for a couple of years to see if they develop the disease.

The new LANCET report, from the laboratory of A.G. Dickinson of the Medical Research Council's Neuropathogenesis Unit in Edinburgh, evaluates one of the current extraction methods by proxy. Because CJD-infected tissue presents a potential hazard to laboratory workers, the researchers used scrapie, which causes a similar disease in animals and is believed to share properties with the CJD agent. They added scrapie to human pituitary tissue, ran the result through the purification process, and injected it into mice. They found that, provided the material is handled with extreme care, the infectious agent can be eliminated.

"We feel it's very hopeful and encouraging, but not definitive," says judith Fradkin of NIH, whose office oversees the NHPP. But more research is needed before it can be assumed that a procedure that eliminates scrapie also eliminates the CJD agent, she says.

NIH has begun injecting monkeys with samples of all the pituitary extracts that have been used in U.S. children since its program was begun in 1963, and will try to locate all 10,000 people who have received the extracts to see whether any have died of CJD.

In the meantime, NIH is still providing the hormone to children who have medical problems related to growth hormone deficiency. And a handful of children are receiving genetically engineered hormone manufactured by Genentech in South San Francisco, which is awaiting FDA approval to market the product (SN: 2/11/84, p. 92).

Some scientists worry the moratorium will harm research. In the August ANNALs OF INTERNAL MEDICINE, Salvatore Raiti, head of the NHPP, comments, "The future of human pituitary research is at great risk at this time." Albert Parlow of Harbor-UCLA Medical Center in Torrance, Calif., who purifies pituitary hormones for NIH using a size-and-charge-type extraction process he developed, says he fears the stoppage will cause a loss of momentum, and that NIH will decrease funds for pituitary research. But Frandkin says the NIH will continue its support.