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.

History

Adults

  • Pituitary adenoma
  • Surgery &/or radiation treatment of pituitary adenomas or cranial radiation for other disorders
  • Deficiency of other pituitary hormones may occur concurrently w/ growth hormone deficiency (GHD)
  • Previous childhood GHD

Children

  • Any of the following may indicate GHD:
    • In the neonate: Hypoglycemia, prolonged jaundice
    • History of microphallus or traumatic delivery
    • Head trauma, central nervous system (CNS) infection or cranial radiation
    • Consanguinity &/or affected family member
    • Craniofacial midline abnormalities

Physical Examination

Adults

  • Reduced lean body mass w/ increased weight, body fat predominantly in the abdominal region
  • Thin & dry skin
  • Cool peripheries
  • Poor venous access
  • Blunt affect

Children

  • Height & weight evaluation
    • Plot weight & height measurements on growth charts which will graphically depict changes in growth & growth velocity
  • Short stature may suggest growth hormone deficiency (GHD) & immediate investigation should be conducted if any of the following criteria based on 2003 American Association of Clinical Endocrinologists (AACE) are present:
    • Severe short stature [defined as height >2-3 standard deviation (SD) below population mean]
    • Height >2 SD below population mean w/ 1-year height velocity >1 SD below mean for chronological age or (in child age >2 year), a 1-year decrease of >0.5 SD in height
    • In the absence of short stature, a 1-year height velocity >2 SD below the mean or a 2-year height velocity >1.5 SD below the mean (esp GH manifesting during infancy or in organic acquired GHD)
    • Ht >1.5 SD below midparental height (average of father’s & mother’s)
    • Signs indicative of an intracranial lesion
    • Signs of multiple pituitary hormone deficiencies (MPHD)
    • Neonatal signs & symptoms of GHD
  • Other clinical features/findings of growth hormone deficiency (GHD) in children
    • Increased subcutaneous fat, esp around the trunk
    • Lower body mass index (BMI) & waist-to-hip ratio compared w/ adult onset growth hormone deficiency (AOGHD)
    • Immature facies, w/ a prominent forehead & depressed midfacial development
    • Delayed dentition
    • Delayed average age of pubertal onset
    • In males, the phallus may be small
    • Lower serum insulin-like growth factor 1 (IGF-1) & insulin-like growth factor binding protein (IGFBP-3) levels compared w/ AOGHD
    • More reduced muscle & bone mass, & reduced cardiac function as compared w/ AOGHD
Other
  • Evaluate for possible causes of GHD: Congenital, genetic or acquired causes (pituitary tumor, cranipharyngioma Langerhans cell histiocytosis, etc)

Laboratory Tests

Adults

  • Diagnosis of growth hormone deficiency (GHD) is based on subnormal growth hormone (GH) secretion in response to a stimuli
    • There are various stimulation tests available for the diagnosis of GHD
  • Insulin tolerance test (ITT)
    • Gold standard test for diagnosing adult GHD
    • Insulin-induced hypoglycemia provides strong stimulus for GH secretion
    • Contraindicated in seizures, coronary artery disease, elderly >60 years
    • Should only be performed in specialized endocrine units
  • Acceptable alternative stimulation tests include:
    • Growth hormone–releasing hormone (GHRH) + Arginine (ARG) test
      • Traditionally, the alternative test of choice
      • In cases of hypothalamic GHD (where GHRH + ARG test may produce false-negative result), a normal test result warrants further testing (test of choice would be ITT, followed by glucagon or possibly, ARG alone)
    • Glucagon test
      • Recommended alternative test when ITT is undesirable or when GHRH + ARG test is unavailable
      • In recent years, has been increasingly used in US & Europe as alternative test of choice due to unavailability of GHRH + Arg test in these regions
      • Other advantages include safety, reproducibility, lack of influence by gender & hypothalamic cause of GHD & relatively few contraindications
    • ARG test alone
      • Alternative when ITT & glucagon tests are unavailable
      • Use w/ caution since fewer data are available about its accuracy in GHD diagnosis
      • It should be limited to non-obese adolescents as it is very dependent on body mass index
  • The following conditions are considered GH deficient & do not require further GH stimulation tests: serum insulin-like growth factor (IGF-1) levels below the age- and sex-appropriate reference range when off GH therapy, irreversible hypothalamic-pituitary structural lesions & those w/ evidence of panhypopituitarism (at least 3 pituitary hormone deficiencies)
    • It is important to note that severe GHD may also be associated w/ normal serum IGF-1 levels (nearly always <50th percentile)
    • Clinicians should therefore consider GHD in a patient w/ an IGF-1 <50th percentile & perform further testing
  • Body mass index (BMI) should be used w/ GHRH + ARG test since BMI has a well-validated effect on GH responses to GHRH & ARG stimulation
  • Aneurysmal subarachnoid hemorrhage & traumatic brain injury may cause transient GHD; GH stimulation testing is therefore recommended to be done at least 12 months after the event

Children

  • Stimulation tests w/ Arginine, glucagon, insulin (use w/ caution in young children), Levodopa or Clonidine
    • Patients need to fast overnight
    • Should be performed & monitored by experienced medical experts
  • Diagnostic range:
    • Peak serum GH <10 mcg/L [revise values when newer monoclonal based assays & human growth hormone (hGH) reference preparations are used in the tests]
    • IGF-1 & insulin-like growth factor binding protein-3(IGFBP-3) >2 standard deviation (SD) below mean reference ranges standardized for age & sex suggest abnormality in GH axis when other causes of low IGF are excluded
  • GH measurement after physiologic stimulation (eg exercise)

Imaging

Children

  • Magnetic resonance imaging or computed tomography (MRI or CT) scans of the brain
    • Performed in children diagnosed w/ growth hormone deficiency (GHD) to detect presence of pituitary tumors, intracranial tumors, optic nerve hypoplasia
  • Radiograph studies to estimate bone age
    • In children >4 years, delay of bone age of at least 2 years compared to chronological age
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