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.