growth%20hormone%20deficiency
GROWTH HORMONE DEFICIENCY
Growth hormone deficiency in adults reflects an absence of two hormones, growth hormone and insulin-like growth factor-1 (IGF-1), affecting the process of glucose-insulin metabolism, lipolysis and bone remodelling.
History may show pituitary adenoma, surgery &/or radiation treatment of pituitary adenomas or cranial radiation for other disorders, deficiency of other pituitary hormones that may occur concurrently with growth hormone deficiency, and previous childhood growth hormone deficiency.
Physical exam reveals reduced lean body mass with increased weight, body fat predominantly in the abdominal region, thin & dry skin, cool peripheries, poor venous access and blunt affect.

Growth%20hormone%20deficiency Treatment

Pharmacotherapy

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
Gonadotropin-Releasing Hormone (GnRH) Agonist
  • 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
Recombinant IGF-1/Mecasermin
  • 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
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