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الانزيمات
Laboratory Investigations of Growth Hormone
المؤلف:
Marcello Ciaccio
المصدر:
Clinical and Laboratory Medicine Textbook 2021
الجزء والصفحة:
p320-321
2025-09-11
66
Basal Measurement
GH
The basal serum GH assay is indicated in diagnosing GH excess (acromegaly and gigantism) and controlling the pathologies mentioned above after pharmacological therapy; however, it has little diagnostic value in GH deficiency. Since GH is released in a pulsatile manner, performing the test at a single time of day is usually not clinically indicative. The most commonly used GH assay methods are based on mono clonal antibodies with enzymatic, fluorescent, and chemiluminescent tracers.
The whole blood sample should be taken in the morning on an empty stomach, in the patient in clinostat, and at rest for 30 minutes; exercise or stress conditions can significantly alter GH levels. Reference values in the healthy population are reported in Table 1, although it is not always possible to measure GH levels in healthy subjects.
Table1. Normal values of GH
In contrast to the healthy subject, in patients with acromegaly, GH is always measurable, although it may be at nor mal limits in some cases.
IGF-1
IGF-1 reflects GH deficiency or excess, but unlike GH, its levels are stable throughout the day. Therefore, measuring IGF-1 levels is a helpful estimate of average GH levels. Normal IGF-1 values vary with age and sex and depend on the assay method used. The most commonly used assay methods are radioimmunoassays and those based on chemiluminescent tracers.
Testing for the IGF-1 measurement may be required in conjunction with the measurement of other pituitary hormones (PRL, FSH, or LH) to diagnose pituitary disorders. Normal levels of IGF-1 indicate, with high probability, the absence of GH abnormalities. However, the patient’s clinical context must be always considered; some people may have normal IGF-1 levels in the presence of GHD. Conversely, decreased IGF-1 levels are strongly indicative of GHD. Noteworthy, a decrease in IGF-1 can result from nutritional deficits (anorexia nervosa), chronic kidney or liver dis ease, production of inactive forms of GH, and intake of high doses of estrogen. Usually, elevated IGF-1 levels indicate increased GH production.
During puberty and pregnancy, it is normal to detect increased concentrations of GH and IGF-1; otherwise, they are very often due to pituitary tumors.
Finally, IGF-1 measurement helps monitor the treatment of GH-secreting tumors. If the tumor is surgically removed, measurement of IGF-1 and GH is an estimate of the actual complete tumor removal. If IGF-1 is still elevated after surgical removal of a pituitary tumor, then it may be that the surgery was not fully effective. Decreasing concentrations of IGF-1 during subsequent drug therapy and/or radiation therapy indicate that the treatment is lowering GH production. Increased IGF-1 levels may indicate pituitary tumor recurrence when a patient undergoes long-term monitoring.
Dynamic Measurement
The secretion of GH is pulsatile and episodic. Therefore, the finding of a basal value close to zero is not diagnostic, as it is also evident in normal subjects. In order to assess GH deficiency, it is preferable to use a stimulus test by different drugs administered alone or in combination.
The stimulation test is performed by collecting a blood sample after fasting for 10–12 hours. Then, under medical supervision, a solution that stimulates the release of GH by the pituitary gland is administered intravenously to the patient. Subsequently, following stimulation, multiple blood samples are collected at regular intervals to assess GH pro duction by the pituitary gland.
The insulin-induced hypoglycemia test is the gold standard for diagnosing GH in adults because of its high sensitivity. When the hypoglycemic condition is reached, healthy subjects have a GH peak within 60 minutes, which persists for the next 2 hours; GHD in adults is diagnosed when GH peak response to hypoglycemia below 5 ng/mL. Although the induced hypoglycemia test is safe when performed under close medical supervision, it is contraindicated in elderly subjects and patients at high cardiovascular risk. In addition, obese normoglycemic or hyperglycemic patients with insulin resistance may not achieve an adequate hypoglycemic state. Finally, although it has good sensitivity, it has poor reproducibility. A viable alternative to the induced hypoglycemia test is the glucagon stimulus test. Other tests using arginine or clonidine as the stimulating agent are available. However, they present poor diagnostic accuracy. Glucagon is more potent than other agents in inducing GH secretion. Additionally, glucagon stimulates GH release more effectively when administered intramuscularly or subcutaneously than intravenously.
Finally, enhanced stimulus tests are based on administering GHRH with other agents, most commonly arginine. GHRH stimulates the synthesis and pituitary release of GH, whereas arginine potentiates the stimulatory effect of GHRH by inhibiting hypothalamic somatostatin release. The peak GH response depends not on age or sex but on body mass index (BMI) and central adiposity. Its main advantages are its reproducibility and high discriminatory power.
GH threshold values vary depending on the stimulus test used. Table 2 shows the main characteristics of the most common stimulus tests.
Table2. Characteristics of the main GH stimulus tests
The GH suppression test is indicated for the diagnosis of GH excess and monitoring patients undergoing treatment. The oral Glucose Tolerance Test (OGTT) is performed by collecting a blood sample after fasting for 10–12 hours. The patient is then given a solution containing 75 g of glucose dissolved in 300 mL of water. Subsequent blood samples, collected at regular time intervals (30, 60, 90, and 120 minutes), make it possible to assess whether the release of GH by the pituitary gland is correctly inhibited (the inhibitory action is linked to the activation of endogenous secretion of somatostatin by glucose). In healthy subjects, after 1 hour, GH is less than 1 ng/mL, in patients with GH hypersecretion, levels never fall below this value. However, it should be kept in mind that the limit of normality for GH values after OGTT varies according to the sensitivity of the assay method used (1 ng/mL for conventional methods and 0.3–0.4 ng/mL for ultrasensitive methods). In addition, it should be considered that the following conditions may give false-positive results for lack of GH inhibition: malnutrition, depression, renal or hepatic insufficiency, diabetes mellitus, and obesity.
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