Journal Scan Dr NSMani Nov 2011

Robert M. Blizzard, History of Growth Hormone Therapy, Indian Journal of Pediatrics

Volume 3 / 1936 - Volume 78 / 2011

The first human to receive GH therapy was in 1956; it was of bovine origin and was given for 3 wk for metabolic balance studies revealing no effects. By 1958, three separate laboratories utilizing different extraction methods retrieved hGH from human pituitaries, purified it and used for clinical investigation. By 1959 presumed GHD patients were being given native hGH collected and extracted by various methods. Since 1 mg of hGH was needed to treat one patient per day, >360 human pituitaries were needed per patient per year. Thus, the availability of hGH was limited and was awarded on the basis of clinical research protocols approved by the National Pituitary Agency (NPA) established in 1961. hGH was dispensed and injected on a milligram weight basis with varied concentrations between batches from 0.5 units/mg to 2.0 units/mg of hGH. By 1977 a centralized laboratory was established to extract all human pituitaries in the US, this markedly improved the yield of hGH obtained and most remarkably, hGH of this laboratory was never associated with Creutzfeld-Jacob disease (CJD) resulting from the injection of apparently prior- contaminated hGH produced years earlier. However, widespread rhGH use was not possible even if a pituitary from each autopsy performed in the US was collected, this would only permit therapy for about 4,000 patients. Thus, the mass production of rhGH required the identification of the gene structure of the hormone, methodology that began in 1976 to make insulin by recombinant technology. Unexpectedly  in 1985 patients who had received hGH years ago were reported to have died of CJD. This led to the discontinuation of the distribution and use of hGH, at a time when a synthetic rhGH became available for clinical use. The creation of a synthetic rhGH was accompanied by unlimited supplies of hGH for investigation and therapy. The appropriate use and the potential abuse of this hormone are to be made clear. The illegitimate use of rhGH, that is abuse by athletes is of primary concern and should be halted. The abuse of prescribing rhGH in an attempt to retard the aging process also should receive attention.

Raphaël Rappaport , Indian Journal of Pediatrics,

Volume 3 / 1936 - Volume 78 / 2011

 Growth Hormone Deficiency: Optimizing Therapy and New Issues

 Some Simple Rules Should Help Optimize the rhGH Treatment in Patients with Documented Growth Hormone Deficiency:

• Early diagnosis of GHD

•Onset of treatment several years before puberty

• Evaluation of responsiveness after the first treatment year

• Continuous treatment until final height unless demonstration of normalization of GH response to stimulation test if retested during puberty

• IGF1 circulating levels maintained in the normal range all along the treatment period

• Appropriate treatment of associated pituitary deficiency

• Information of the parents and the patient about expected height improvement and safety issues, including a post-treatment follow-up

• Late diagnosed and severely retarded cases will benefit from postponing onset of puberty with a LHRH analog. Aromatase inhibitors, although promising, are still being investigated for safety and efficacy.