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Whither Recombinant Human Growth Hormone?
- Christos S. Mantzoros, MD, DSc; and
- Alan C. Moses, MD
- Beth Israel Deaconess Medical Center, Boston, MA 02215. Requests for Reprints: Alan C. Moses, MD, GZ 800, General Clinical Research Center, Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215. Current Author Addresses: Drs. Mantzoros and Moses: GZ 800, General Clinical Research Center, Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215.
Growth hormone and insulin-like growth factor 1 (IGF-1) are important anabolic hormones. They enhance intestinal absorption of calcium and phosphate and may play a direct role in DNA synthesis in bone, proliferation of osteoblasts, and accumulation of procollagen messenger RNA [1, 2]. Although the actions of growth hormone were thought to be caused by circulating IGF-1 alone, recent evidence [1, 2] suggests that growth hormone and other hormones stimulate local production of IGF-1, which acts in a paracrine-autocrine fashion in some tissues.
Starvation and cachexia (including that seen in patients with wasting associated with the acquired immunodeficiency syndrome [AIDS]) are associated with functional resistance to growth hormone and IGF-1 [1, 2]. In addition, secretion of growth hormone substantially declines with age and results in concentrations of IGF-1 that are approximately 50% lower in elderly men than in younger men [1, 3] and are associated with clinical manifestations of the insulin resistance syndrome [4].
Since the introduction of recombinant human growth hormone, impressive data have accrued on its ability to promote linear growth in children with growth hormone deficiency or advanced renal failure [1, 4, 5]. The embracing of recombinant human growth hormone as a therapeutic tool in pediatric endocrinology has been accompanied by a search for further indications for its use. Although parenteral injection of recombinant human growth hormone by athletes and body builders is acknowledged as abuse [6], recent studies have explored its use (and that of IGF-1) as medically appropriate therapy in adults with acquired growth hormone deficiency, in older adults with physiologic deficiency of growth hormone, in patients in severely catabolic states (such as those who have had trauma, burns, or extensive surgery) [1, 3, 7, 8] and in persons with AIDS-associated wasting [9]. What is the rationale for these treatments, …
