Growth hormone use and abuse
Growth hormone plays an essential role in human growth and development; deficiency results in short stature and other defects, whereas high levels can cause excessive growth and acromegaly. In addition to recognized medical indications for replacement, growth hormone has come to public attention because of its use by athletes to enhance performance (doping). This chapter covers the latest evidence about growth hormone physiology, therapeutic use, abuse, and detection.
Growth hormone (GH) is the most abundant hormone in the anterior pituitary gland; it is a single-chain peptide hormone produced and secreted by somatotroph cells in the anterior pituitary gland in two molecular forms; 22-kilodalton (kDa) GH is more abundant than the 20-kDa form, but their biologic activities are similar. Measuring individual GH isoforms plays a key role in detection of doping by athletes. Endogenous GH production is highest during puberty, decreasing by middle age to only about 15% of peak levels.
2. How does GH secretion occur?
GH is secreted in a pulsatile fashion, mostly at night. Factors that increase secretion include sleep, exercise, trauma, and sepsis. Obesity and increasing age reduce GH secretion.
3. How is the release of GH regulated?
GH secretion is stimulated by GH-releasing hormone (GH-RH) and inhibited by somatostatin, both from the hypothalamus. Ghrelin, a gastric peptide, also stimulates GH release. Another major regulator of GH production is insulin-like growth factor-1 (IGF-1), which acts at the pituitary to directly inhibit GH production and at the hypothalamus to inhibit the production of GH-RH and to stimulate somatostatin.
As its name implies, GH stimulates both linear growth and growth of internal organs (Table 26-1).
TABLE 26-1.
ACTIONS OF GROWTH HORMONE AT SPECIFIC SITES
| TARGET SYSTEM | ACTIONS |
| Liver and muscle | Increases nitrogen retention, amino acid uptake, and protein synthesis |
| Cardiovascular | Increases cardiac muscle mass and cardiac output at rest and during maximal exercise |
| Hematologic | Increases plasma volume and red cell mass |
| Skeletal tissue | Increases bone mineral density and bone turnover |
| Connective tissue | Increases collagen turnover at nonskeletal sites, including tendons |
| Metabolism | Increases rates of sweating and thermal dispersion during exercise |
| Endocrine: | |
| Acute | Increases the uptake and utilization of glucose by muscle; antagonizes the lipolytic effect of catecholamines on adipose tissue |
| Chronic | Reduces glucose utilization, enhances lipolysis, and increases lean body mass |
5. Does GH exert all of its effects directly?
No. Many of the effects are mediated by IGF-1, which is also called somatomedin C. GH stimulates the production of IGF-1 in peripheral tissues, particularly the liver. In patients with GH resistance, which is often due to GH receptor mutations, some effects of GH can be achieved by IGF-1 administration; IGF-1 has been approved for treatment of GH-resistant patients.
6. What causes excessive GH secretion, and what are the consequences?
The major cause of excessive GH secretion is a GH-producing pituitary tumor. GH excess during childhood results in gigantism. Numerous historical examples have been noted, including Robert Wadlow, the “Alton giant,” who reached a height of just over 8 feet 11 inches and wore size 37AA shoes. GH excess after epiphyseal closure results in acromegaly.
7. What conditions are associated with GH deficiency?
GH deficiency can be congenital (genetic mutations) or may result from damage to the pituitary gland by intracranial tumors, surgery, radiation therapy, trauma, and a variety of infiltrative and infectious diseases. Adult-onset GH deficiency is much less common than onset during infancy and childhood and is often related to a preceding event such as radiation exposure or trauma.
8. What are some common signs and symptoms of GH deficiency?
GH deficiency in childhood results in short stature; similar effects are seen in GH resistance. GH deficiency in adults causes greater adiposity and decreases in lean body mass, bone density, extracellular water, cardiac function, muscle force and strength, and exercise performance. Patients have reduced exercise capacity and strength levels and often complain of lethargy and fatigue. Quality of life may be diminished, with manifestations of depression, anxiety, mental fatigue, and decreased self-esteem. Excessive intraabdominal fat is associated with an increased risk of cardiovascular disease, which is the predominant cause of death in GH-deficient patients.
9. Where do we get the GH used therapeutically?
Historically, GH was derived from human cadavers; however, modern techniques have allowed for abundant production of biosynthetic GH, which is identical to the endogenous form.
10. Besides availability, what problem was associated with GH derived from human cadavers?
