Adult HGH Deficiency

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Adult Human Growth Hormone Deficiency

Source: Indian J Endocrinol Metab. 2011 Sep; 15(Suppl3): S197–S202.
doi: 10.4103/2230-8210.84865

Abstract

Adult growth hormone deficiency (AGHD) is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD) has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1). It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.

Introduction

Adult onset growth hormone deficiency (AGHD) may represent two distinct clinical situations:

Children with growth hormone (GH) deficiency transitioning to adulthood or
GH deficiency acquired during adulthood (structural/trauma or idiopathic).
Over the past decade, there has been an increasing recognition of premature mortality associated with hypopituitarism. There is a two- to three-fold increase in standardized mortality in these patients with hypopituitarism.[1] The increased mortality is probably related to macrovascular disease (cardiovascular and cerebrovascular).[2] The fact that these patients with increased mortality were replaced with steroids, thyroxine and a majority were on male hormone replacement, led some experts to believe that GHD may have contributed to the increased mortality.

GH is the first hormone to deplete following any pituitary insult. It was not until 1995 that the concept of growth hormone replacement became popular and recognized.

Historical Review

In 1922 Evans and Long[3] injected the beef pituitary extract to animals (rats) and reported excessive growth. Smith,[4] a few years later, showed the opposite effect of growth cessation following hypophysectomy in rats with re-growth following implantation of pituitary tissue. This suggested the possibility of a substance in the pituitary responsible for growth.

In 1908, it was further thought that this pituitary factor promoting growth might be diabetogenic.[5] It was only after 1950 that the combined effects were explained by one single substance, growth hormone. Houssay’s was awarded the Nobel Prize in 1947 for his extensive work on the hypophysis and carbohydrate metabolism.[6] Salmon and Daughaday[7] suggested that GH action was mediated via a factor, named sulfation factor, only later to be identified as somatomedin. This was given a new name: insulin-like growth factor-1 (IGF-1) to indicate its chemical similarity to (pro)insulin. The complete structure with 70 amino acids was reported in 1978.

In 1944, Li and Evans were the first to claim that bovine GH had been isolated.[8,9] Berson and Yalow engineered a radioimmunoassay for GH that was later used to determine plasma IGF-1.[10,11]

The first results of treating children with GH were published in 1932.[12] The report by Raben[13] is quoted as the first successful example of the use of GH extracted from human pituitaries. The patient was a young hypopituitary man who responded to GH treatment with an accelerated growth.

As the source of GH (human pituitaries) was limited, in most countries, distribution and use of GH was regulated and supervised by official bodies, for example in the United States by the National Pituitary Agency (NPA). Creutzfeldt–Jakob’s disease was a dreaded complication of GH therapy obtained from human pituitary, resulting in death of patients.[14] In 1979, a commercial company (Genentech) decided to produce GH by inserting the gene controlling GH synthesis into bacteria.[15] From around 1985, pharmaceutical companies started manufacturing recombinant GH.

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