Growth hormone deficiency laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Laboratory Findings

GH secretion is pulsatile and its secretion is regulated by two hypothalamic factors; growth hormone releasing hormone and somatostatin. [33]

So, measurement of a random serum GH level alone is not helpful and usually other tests used with it:

  • Insulin-like growth factor I (IGF-I)
  • Insulin-like growth factor binding protein-3 (IGFBP-3) levels: it is the major serum carrier protein for IGF-I [45-47] and the most GH dependent [48].
  • Their concentrations often reflect the concentration of secreted GH.[35-38].They are better tests than GH level because they are stable during the day and not pulsatile. [34]

Limitations

Serum IGF-I levels may be low in conditions other than GHD, such as growth hormone insensitivity (GHI), hypothyroidism [41], diabetes [42], renal failure [41,43], and cancer [44].

Interpretation

  • Reduced level of IGF-I and IGFBP-3 with delayed bone age: provocative GH testing is needed.
  • If the growth failure is severe and IGF-I and IGFBP-3 are severely low, there is no need to perform GH stimulation testing.

Normal IGF-1 and IGFBP-3: no further testing is required.

GH stimulation tests

  • It is indicated for most patients suspected to have GHD.
  • The results should be interpreted in the context of auxological findings, bone age, and IGF-1 and IGFBP-3 concentrations.
  • If the clinical and other laboratory criteria are sufficient to make the diagnosis of GHD, there is no need to perform the test. 
  • A serum GH concentration of >10 mcg/L, but a cutoff of 7.5 mcg/L is often used for modern assays.
  • The stimulation tests are performed after an overnight fast. Serum samples are collected at intervals to capture the peak GH level.
  • Two different stimuli should be used for most patients [51].
  • In a patient with other pituitary hormone defects or a genetic defect, one test is sufficient to establish the diagnosis [32,60].
  • Pharmacologic stimuli include clonidine [62] glucagon [63], arginine [64], and insulin-induced hypoglycemia: [65-67].
  • Clonidine stimulates GH by several mechanisms, including the stimulation of GHRH via alpha-adrenergic pathways. Side effects of clonidine are hypotension and hypoglycemia. So, blood pressure and blood glucose level need to be measured during the test.[68,69]
  • Arginine: [60] There are no side effects from this test.
  • Glucagon: side effects of glucagon are transient hyperglycemia. [60,70]It is a good choice for infants and young children. Side effects include nausea, vomiting, sweating, or headaches.
  • Insulin-induced hypoglycemia is a potent stimulant of GH release this test is less commonly used in children because of safety concerns. [32]

The interpretation of the test results depends upon age and sex hormone concentrations [52]. Children with constitutional delay of growth and puberty may have low GH results on provocative testing in the absence of true GHD (ie, false-positive results). Administration of sex steroids for a few days prior to the provocative GH testing (known as "priming") reduces the chance of a false-positive result, as discussed below.

References

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