Growth%20hormone%20deficiency Treatment

Somatropin

• A synthetic polypeptide human growth hormone of recombinant deoxyribonucleic acid (DNA) origin

Factors Affecting Dosing

• Physiologic factors
  
  • Pubertal girls and premenopausal women secrete more growth hormone (GH) than their male counterpart mainly due to the underlying estrogen-antagonistic effects on GH action in women
    • Higher GH doses are therefore required among female patients

• Concomitant medications
  
  • Use of oral estrogen as replacement therapy or for contraception purposes in women renders them more GH-resistant than men, thus, requiring a higher dose to achieve equivalent insulin-like growth factor-1 (IGF-1) responses
  • Use of transdermal estrogen patches may help lower the GH dose needed to achieve equivalent IGF-1I response

• Obesity
  
  • Characterized by marked decrease in both spontaneous and stimulated GH secretion but with normal or low-normal serum IGF-1 levels which is probably secondary to enhanced hepatic responsiveness to exogenous GH
    
    • Obese GH-deficient patients may be started on low doses (0.1-0.2 mg/day) to reduce risk of worsening glucose tolerance

• Compliance
  
  • Patients may at times find it difficult to comply with daily injections
  • Using the same total weekly dose, patients may administer his/her injections on an alternate day or thrice-weekly basis

• Other factors that may increase GH dose: Low serum IGF-1 levels, young patients regardless of type
• Others factors that may decrease GH dose: High serum IGF-1 levels, elderly patients, worsening glucose tolerance, side effects

Growth Hormone (GH) Replacement Therapy

Adults

• Indicated for growth hormone deficiency (GHD) due to pituitary diseases from known causes (eg pituitary tumor, irradiation, trauma, reconfirmed childhood GHD, etc)
• Treatment must be individualized independent of body weight, starting with a low dose and gradually titrating up until serum IGF-1 levels are normal with minimal side effects
• Serum IGF-1 is the recommended biomarker for GH dose adjustments
• Aim for serum IGF-1 levels in the middle of the normal range appropriate for age and sex, except when side effects are significant
  
  • Consider a trial of higher GH doses as long as serum IGF-1 levels remain within the normal range

• Effects:
  
  • Increase in bone density
  • Increase in lean tissue
  • Decrease in adipose tissue
  • Modulate lipoprotein metabolism [eg decreased serum low-density lipoprotein (LDL)]
  • Improved mood and motivation
  • Improved exercise capacity
  • Increase in cardiac contractility

• Use lower GH doses (0.1-0.2 mg/day) in all patients with diabetes or who are susceptible to glucose intolerance & elderly >60 years old
• It is recommended to retest patients transitioning from pediatric to adult care (especially those with isolated GHD)

Children

• Indicated for GHD in children, Turner syndrome, Prader-Willi syndrome, Noonan syndrome, short children small for gestational age, children with short stature homeobox-containing gene (SHOX) deficiency, and children with impaired growth due to chronic kidney disease
• May also be used for children with ISS shorter than -2.25 SD score whose epiphyses are not closed, and with expected adult height below the normal range [160 cm (<63 inches) for males, 150 cm (<59 inches) for females]
• Effects:
  
  • Induce normal statural growth
  • Correction of hypoglycemia

• Target for treatment:
  
  • Satisfactory response is defined as an increase in height velocity of at least 2-2.5 cm/year above pretreatment velocity
  • Achieve acceptable adult height

• Replacement is continued until attainment of bone age of 14 years (girls) and 16 years (boys) or if the child has achieved at least 10th percentile of adult height
• In certain patients, surgical therapy may also be needed for congenital anomalies and pituitary tumors

• Studies found GnRH agonists to be effective when given concurrently with recombinant GH
• May delay epiphyseal fusion and prolong growth during puberty
• Increases height and velocity in some growth hormone-deficient pediatric patients

• Alternative treatment for patients with GH receptor abnormalities, STAT5b gene defects, and those with severe GH deficiency unresponsive to therapy due to development of antibodies against GH
• Further studies are needed to prove its efficacy in GHD