Growth Hormone Deficiency

Childhood growth hormone deficiency

• Epidemiology
  • Prevalence – not uncommon
  • Age – recognized early by slow linear growth <first percentile
  • Sex – M>F
• Etiology
  • Growth hormone deficiency
  • Inborn errors of the Pit-1 gene
  • Prop-1 mutations
  • Growth hormone releasing hormone (GHRH) gene defects
    • Genetic insensitivity to GH
• Pathophysiology
  • GH is secreted by the anterior pituitary
  • Binding of GH to the transmembrane receptor leads to the production of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3)
  • Secreted in a pulsatile fashion, natural impetus for secretion is sleep (rises at night and sporadically during the day, may be related to meals)
  • GH levels increase in response to hypoglycemia
• Clinical Presentation
  • Short stature (defined as height more than 2 standard deviations below the mean), severe growth failure, delayed bone age
• Diagnosis
  • Must rule out all other causes of short stature
    • Hypothyroidism
    • Chromosomal disorders
      • Prader-Willi syndrome
        • Genetic disorder involving deletion of long arm of chromosome 15
        • Incidence – 1/15,000
        • Infants – hypotonic with poor feeding
        • Age 2 – hyperphagic, short stature
        • Adults – prone to diabetes mellitus type 2 and morbid obesity, hypogonadism
      • Turner syndrome
        • Chromosomal abnormality (XO)
        • Incidence – 1/2000 live births
        • Short stature and infertility
      • Chronic systemic disease
        • Renal failure is most common
        • Malabsorption (celiac disease)
    • Skeletal disorders
    • Idiopathic short stature
  • Evaluation for growth hormone (GH) deficiency may be initiated in a child whose height is more than 2 standard deviations below the mean  
  • Laboratory testing
    • GH levels after stimulation (low)
    • Best test is insulin-induced hypoglycemia
      • Method – 0.1 units of insulin/kg of body weight and measure GH at 0, 15, 30, 60 and 90 minutes
      • Other agents are L dopa, arginine, clonidine and glucagon
        • GHRH plus arginine
      • Normal stimulation result is GH >10 ng/mL in children, >5 ng/mL in adults
    • IGF-1 measurements – normal
    • IGFBF-3 – low
• Disease monitoring
  • Linear height velocity usually accelerates with GH replacement
    • May not occur in ISS
  • Repeat GH testing – only necessary after puberty to assess if lifelong GH supplementation is necessary  
• Treatment
  • FDA indications for GH replacement
    • GH deficiency  
    • No GH deficiency but other indications
      • Idiopathic (ISS) short stature – most controversial indication
      • Small for gestational age (SGA) infants
        • 90% SGA infants catch up in growth by age 2 years and do not require GH supplementation
      • Chronic renal insufficiency
        • Causes in children – structural (usually congenital), metabolic (oxalosis, cystinosis), acquired (infection)
        • The younger the age of onset, the greater the stature loss
        • Dialysis/transplant often do not normalize growth
      • Turner syndrome
      • Prader-Willi syndrome

Adult GH deficiency

• Epidemiology – uncommon
• Etiology
  • Acquired pituitary damage – surgery, tumor, granulomas, cranial irradiation, trauma
  • Acquired hypothalamic damage
  • Usually a sequential loss in anterior pituitary function – loss of GH, follicle stimulating hormone and leuteinizing hormone (FSH and LH) may be followed by loss of thyroid stimulating hormone (TSH) and loss of adrenocorticotropic hormone (ACTH)
• Pathophysiology
  • Almost always acquired damage to pituitary or rarely hypothalamus
• Clinical Presentation
  • Constitutional – fatigue, low self esteem
  • Increased body fat
  • Reduced exercise capacity
  • Dyslipidemia
• Diagnosis
  • Laboratory testing
    • GH stimulation (low) – insulin-induced hypoglycemia or GHRH and arginine stimulation are the best test for adults (do not perform in patients >50 years)
    • Arginine stimulation test
      • 0.5 g/kg body weight IV given over 30 minutes with serum GH at 0, 30, 60, 90 minutes
    • IGF-1 (normal to low), IGFBP-3 (normal to low)
    • Consider testing other anterior pituitary hormones (LH/FSH, TSH, ACTH)
  • Imaging studies
    • If no obvious etiology of deficiency, then do CT or MRI to rule out tumor
• Treatment
  • GH replacement

Hypopituitarism  

Indications for Ordering

• Tests generally appear in the order most useful for common clinical situations
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• Click on number for test-specific information in the ARUP Laboratory Test Directory