0800 ENDO LAB (36 36 52) [email protected] The Role of Plasma Measurements of Growth Hormone and IGF-1 in Assessing Growth Hormone Secretion in Humans Growth hormone is a peptide hormone synthesised by the anterior pituitary gland. Growth hormone controls expression of insulin-like growth factor 1 (IGF-1) in a wide variety of tissues. Most circulating IGF-1 is derived from the liver and there exists a feedback mechanism by which IGF-1 feeds back to the hypothalamus and pituitary to regulate growth hormone secretion. Currently the two main clinical indications for assessing the growth hormone axis are short stature in children and when there are clinical signs of growth hormone excess such as excessively tall stature in children or the possibility of acromegaly in adult patients. A random plasma growth hormone is of no value whatsoever in the assessment of short stature in children. Growth hormone is normally secreted in a pulsatile fashion and in normal individuals may be undetectable for much of the day. Similarly a readily detectable level of growth hormone does not imply normal secretory dynamics. Therefore a stimulation test is required. In Christchurch the most frequently used screening test is a clonidine test where clonidine (an alpha-2 receptor agonist) is given at a dose of 0.15mg/m2. Growth hormone is measured before and afterwards and a normal response is for the growth hormone level to rise to above 7µg/L. Other pharmacological stimulation tests include the insulin tolerance test, arginine infusion and growth hormone releasing hormone. Physiological tests of growth hormone secretion include exercise and stage 3/4 sleep. In New Zealand the Growth Hormone Committee require two independent tests of growth hormone secretion with peak levels of less than 7µg/L in order to qualify for exogenous growth hormone. Plasma IGF-1 is often low in the setting of growth hormone deficiency and may be a useful initial screening test. However many patients who are growth hormone deficient on dynamic testing have a normal IGF-1 level. Therefore a level of IGF-1 within the normal range should not dissuade the clinician from embarking on a dynamic test of growth hormone secretion. Because growth hormone is secreted in a pulsatile fashion, normal individuals may have quite high levels if by chance the blood sample was taken during a secretory pulse. In addition some patients with acromegaly have levels within the normal range but secreted at constant amounts without the usual peaks and troughs seen in normal individuals. Therefore a single random growth hormone is of no value in the work-up for acromegaly. The most useful screening test is a single IGF-1 level. In the setting of adequate nutrition, acromegaly will be characterised by an elevated IGF-1 level. At Endolab we have developed a local reference interval for IGF-1 which is age dependent. If the IGF-1 is elevated for age then referral to the Department of Endocrinology for further assessment is indicated. 0800 ENDO LAB (36 36 52) [email protected] The Role of Plasma Measurements of Growth Hormone and IGF-1 in Assessing Growth Hormone Secretion in Humans Sample Aliquot Requirements: Laboratory Endolab, Christchurch Hospital Anticoagulant EDTA, heparin Volume 0.5ml plasma or serum, minimum 150µL Transport Ambient Storage Frozen after separation Species Human, equine, bovine, porcine, canine, guinea-pig, deer. Test Details: Frequency: Weekly Standard: Recombinant IGF-1 Method: RIA after extraction and cryoprecipitation Reference Interval: Age dependant, see graph
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