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A. Aproved Indications

  1. GH deficiency in children
  2. Idiopathic, non-GH deficiency in children with short stature (~1% shortest children) [11]
  3. Girls with Turner Syndrome
  4. End-stage renal disease in children [7]
  5. Growth hormone deficiency in adults
  6. HIV wasting syndrome in adults

B. Investigational Studies

  1. Pediatric renal or liver transplant patients
  2. Intrauterine growth retardation (IUGR) / small for gestational age (SGA) children
  3. Noonan Syndrome
  4. Down Syndrome
  5. Prader-Willi Syndrome [12]
  6. Achondroplasia
  7. Spina bifida
  8. Healthy Elderly - overall not recommended [3,8]
  9. Critically ill patients
  10. Dilated cardiomyopathy (adults)
  11. Insulin resistance syndromes
  12. Short bowel syndrome
  13. Infertility
  14. Crohn's Disease [5]

C. GH Therapy Not Indicated

  1. Constitutional growth delay
  2. Osteoporosis
  3. No consistent benefits and clear increased risks in athletes taking GH supplements [14]

D. GH Replacement

  1. Recombinant GH (rGH) may be beneficial in persons with hypopituitarism
  2. Begin deficient patients at 20-40µg/kg/day and increase over several weeks
  3. Standard dose is 40-80µg/kg/day for replacement therapy
  4. Metabolic Effects of GH
    1. Low dose rGH (10µg/kg/d) Increased bone mineral density in lumbar spine
    2. Significant improvement in markers of bone turnover
    3. Body fat was reduced as well and lean body mass increased
    4. No increase in muscle strength despite increase in lean body mass in athletes [14]
    5. rGH reduces levels of inflammatory cardiovascular risk markers and central fat in men with GH deficiency [6]
    6. rGH increases lipoprotein(a) and glucose levels without affecting other lipid levels [6]
    7. Long term treatment in children with chronic renal failure induces catch-up growth and most patients achieve normal adult height [7]
  5. Dose of rGH may be adjusted by following serum IGF-1 levels
  6. Recombinant GH releasing hormone (GHRH) [4]
    1. Stimulates release of GH
    2. GHRH is about 55% of the price of most rGH, but may be less effective
  7. Recombinant insulin-like growth factor (IGF-1) also available (see below)

E. GH in Elderly [3,8]

  1. GH levels reduced during normal aging
  2. Normal aging has been called "somatopause"
    1. Reduction in muscle mass
    2. Increase in fat mass
    3. Reduction in skeletal muscle strength
  3. GH with or without sex steroids in healthy men and women 65-88 years [8]
    1. Reduced fat mass
    2. Slightly increased muscle mass (lean body mass)
    3. Increased skeletal muscle strength and oxygen consumption
    4. Increased carpal tunnel syndrome (32%), arthralgias (41%), glucose intolerance
    5. Increased overall diabetes risk
  4. Meta-analysis has shown no overall benefit and is not recommended [3]

F. GH Antagonism [9,10]

  1. Mainly for treatment of acromegaly
  2. Pegvisomant (Somavert®) is genetically engineered analogue of hGH
    1. This analog has 9 amino acid substitutions which cause antagonist actions
    2. Conjugated to polyethylaene glycol (PEG) to reduce renal clearance and immunogenicity
  3. Pegvisomant 10-20mg per day for >12 months reduced serum IGF-1 levels ~50%
    1. Serum insulin and glucose concentrations significantly reduced
    2. Reduced soft tissue swelling, degree of perspiration and fatigue with 15-20mg/day
    3. Mean pituitary tumor volume decreased slightly
    4. Well tolerated with mild injection site reactions, some nausea, vomiting, chest pain
    5. Anti-GH Abs formed in 17% of patients

G. Recombinant Human GHs [11]

  1. Humatrope®
  2. Saizen®
  3. Norditropin®
  4. Nutropin® and Nutropin AQ®
  5. Genotropin®

H. Insulin-Like Growth Factor (IGF) [13]

  1. IGF-1 is the main mediator of growth promoting actions of GH
  2. GH stimulates synthesis of IGF-1 in liver, bone and other tissues
  3. Severe IGF-1 deficiency affects <10,000 children worldwide, causes severe growth failure
  4. Mecasermin (Increlex®) is recombinant human IGF-1
  5. Starting dose is 40-80µg/kg twice daily subcutaneously, to maximum 120µg/kg/dose
  6. Studied up to 8 years
  7. Main side effect is hypoglycemia in 50%, usually during first month of treatment
  8. Overgrowth of fat, facial bones, kidneys has been reported
  9. Contraindicated in patients with closed epiphyses
  10. Has also been used successfully in children with anti-GH antibodies

References

  1. Lee MM. 2006. NEJM. 354(24):2576 abstract
  2. Vance ML and Mauras N. 1999. NEJM. 341(16):1206 abstract
  3. Liu H, Bravata DM, Olkin I, et al. 2007. Ann Intern Med. 146(2):104 abstract
  4. Growth Hormone Releasing Factor for Growth Hormone Deficiency. 1999. Med Let. 41(1043):2 abstract
  5. Slonim AE, Bulone L, Damore MB, et al. 2000. JAMA. 355(22):1633
  6. Sesmilo G, Biller BMK, Llevadot J, et al. 2000. Ann Intern Med. 133(2):110
  7. Haffner D, Schaefer F, Nissel R, et al. 2000. NEJM. 343(13):923 abstract
  8. Blackman MR, Sorkin JD, Munzer T, et al. 2002. 288(18):2282 abstract
  9. Trainer PJ, Drake WM, Katznelson L, et al. 2000. NEJM. 342(16):1171 abstract
  10. Pegvisomant. 2003. Med Let. 45(1160):54
  11. Growth Hormone for Normal Short Children. 2003. Med Let. 45(1169):89 abstract
  12. Holland A, Whittington J, Hinton E. 2003. Lancet. 362(9)388):989 abstract
  13. Insulin-Like Growth Factor 1. 2007. Med Let. 49(1261):43 abstract
  14. Liu H, Bravata DM, Olkin I, et al. 2008. Ann Intern Med.148(10):747 abstract