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 is the major serum carrier protein for IGF-I [45-47] and the most GH dependent [48].
Their concentrations often reflect the integrated 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
●Moderately or severely reduced IGF-I and IGFBP-3 with delayed bone age:
•In most cases, the possibility of GHD should be explored by provocative GH testing, if other causes of low IGF-1 and IGFBP-3, such as poor nutrition, have been excluded.
•If the growth failure is severe, bone age is significantly delayed, and IGF-I and IGFBP-3 are definitively low (eg, <-2 SD), it is reasonable to make the diagnosis of GHD without performing GH stimulation testing, especially in the setting of known hypothalamic-pituitary disease and/or its treatment (eg, brain surgery and/or radiation)
●Clearly normal IGF-1 and IGFBP-3 (SD ≥0); ie, in the upper half of the normal range) – GHD is extremely unlikely, and no further testing is required.
GH stimulation tests
Indications
most patients to confirm a diagnosis of GHD. Because this testing has limitations, the results should not be used as the sole diagnostic criterion, and should be interpreted in the context of auxological findings, bone age, and IGF-1 and IGFBP-3 concentrations.
Provocative GH testing is not necessary for selected patients in whom other clinical criteria are sufficient to make the diagnosis of GHD, including those with the following conditions:
●Pituitary abnormality (secondary to a congenital anomaly, tumor, or irradiation), and a known deficiency of at least one other pituitary hormone, as well as auxological criteria [51].
●Newborn with a congenital pituitary abnormality (ectopic posterior pituitary and pituitary hypoplasia with abnormal stalk) or known deficiency of a pituitary hormone, along with hypoglycemia, at which time a simultaneous serum GH concentration is <5 mcg/L [51].
●Infant or young child with extreme short stature (eg, height <-3 SD), normal nutrition, significantly reduced IGF-I (eg, <-2 SD) and IGFBP-3 and delayed bone age. This is the classic presentation of congenital and severe GHD, and most experts agree that provocative testing is not required to make the diagnosis.
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. After the pharmacologic stimulus, serum samples are collected at intervals designed to capture the peak GH level; the expected time to this peak varies with the stimulus administered.
- that two different stimuli should be used for most patients [51].
- In a patient with a known pathology of the central nervous system, 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.
- It is administered at a dose of 5 mcg/kg (maximum 250 mcg), and serum GH is measured at 0, 30, 60 and 90 minutes; peak GH secretion typically occurs about one hour after the stimulus is given [60]. Clonidine may cause modest hypotension and hypoglycemia, so patients should be monitored for these problems during the test. Estimates of this test's sensitivity and specificity vary considerably [68,69].
- Arginine [60] There are no side effects from this test
- Glucagon — Administration of glucagon causes transient hyperglycemia, which in turn stimulates endogenous insulin secretion followed by controlled hypoglycemia, and consequent GH secretion [60,70].
- 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]
Limitations (table 1) [7]:
●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.
●Adiposity (as measured by the body mass index [BMI]) also influences GH response to the stimulation test, such that obese children show diminished GH responses to all stimuli [51,53,54].
●The tests rely upon GH assays of variable accuracy.
●The tests are expensive, uncomfortable and carry some risks.
●Test reproducibility has not been adequately documented.
●The ability of the tests to discriminate between normal short children and children with partial GHD is limited.
Because of these limitations, it is clear that there is no real "gold standard" for the diagnosis of GHD [32]. Nonetheless, GH stimulation tests are a valuable diagnostic tool when combined with auxological data and measurements of IGF-1 and IGFBP-3. The peak GH response to provocative testing is also a useful predictor of response during the first year of treatment with GH [55,56].