Growth Hormone Deficiency - Diagnosis

Diagnosis

Pediatric endocrinologists are the physicians who specialize in diagnosis and treatment of growth hormone deficiency and growth problems in children. Internist endocrinologists are the physicians with the most expertise in assessment and treatment of adult GH deficiency.

Although GH can be readily measured in a blood sample, testing for GH deficiency is constrained by the fact that levels are nearly undetectable for most of the day. This makes simple measurement of GH in a single blood sample useless for detecting deficiency. Physicians therefore use a combination of indirect and direct criteria in assessing GHD, including:

• Auxologic criteria (defined by body measurements)
• Indirect hormonal criteria (IGF levels from a single blood sample)
• Direct hormonal criteria (measurement of GH in multiple blood samples to determine secretory patterns or responses to provocative testing), in particular:
  • Subnormal frequency and amplitude of GH secretory peaks when sampled over several hours
  • Subnormal GH secretion in response to at least two provocative stimuli
  • Increased IGF1 levels after a few days of GH treatment
• Response to GH treatment
• Corroborative evidence of pituitary dysfunction

"Provocative tests" involve giving a dose of an agent that will normally provoke a pituitary to release a burst of growth hormone. An intravenous line is established, the agent is given, and small amounts of blood are drawn at 15 minute intervals over the next hour to determine if a rise of GH was provoked. Agents which have been used clinically to stimulate and assess GH secretion are arginine, levodopa, clonidine, epinephrine and propranolol, glucagon and insulin. An insulin tolerance test has been shown to be reproducible, age-independent, and able to distinguish between GHD and normal adults, and so is the test of choice

Severe GH deficiency in childhood additionally has the following measurable characteristics:

• Proportional stature well below that expected for family heights, although this characteristic may not be present in the case of familial-linked GH deficiency
• Below-normal velocity of growth
• Delayed physical maturation
• Delayed bone age
• Low levels of IGF1, IGF2, IGF binding protein 3
• Increased growth velocity after a few months of GH treatment

In childhood and adulthood, the diagnosing doctor will look for these features accompanied by corroboratory evidence of hypopituitarism such as deficiency of other pituitary hormones, a structurally abnormal pituitary, or a history of damage to the pituitary. This would confirm the diagnosis; in the absence of pituitary pathology, further testing would be required.