Description [8, 9, 14]
Note the image below.
Growth hormone.
GH, or somatotropin, is produced and released by specialized cells (somatotrophs) in the anterior part of the pituitary gland. GH is required for growth and has important effects on protein, lipids, and carbohydrate metabolism. The functions of GH are accomplished directly as a result of GH binding to its receptor on target cells or indirectly primarily through IGF-1, a hormone secreted from the liver and other tissues in response to GH. A majority of the growth-promoting effects of GH are through IGF-1 acting on its target cells. IGF-1 is frequently measured in clinical practice. Produced primarily in the liver, IGF-1 plays a critical role in promoting cartilage growth and skeletal development. [1]
GH release in the pituitary is primarily determined by the balance of two antagonistic regulatory hormones secreted from the neurosecretory nuclei of the hypothalamus. These are GHRH — or somatocrinin — which is stimulatory, and GH-inhibiting hormone — or somatostatin, which is inhibitory. These two hypothalamic hormones in turn are modulated by many factors, including stress, exercise, nutrition, sleep, IGF-1, and GH itself (negative feedback loop).
Integration of all the factors that affect GH synthesis and secretion leads to a pulsatile pattern of release. The largest and most predictable GH peak occurs about an hour after the onset of deep sleep.
Indications/applications [8, 9, 15]
GH testing is primarily used to evaluate adolescents with a short stature, delayed puberty, or other features suggestive of GH deficiency. It also aids in confirming GH excess in patients with suspected gigantism or acromegaly. In addition, GH measurement can help detect ectopic hormone production by certain tumors and is frequently employed as a screening tool in the assessment of pituitary hypo- or hyperfunction. [1]
The following conditions suggest the possible need for GH testing:
Signs or symptoms of GH excess - Acromegaly in adults (e.g., soft tissue swelling and enlargement of extremities, coarsening of facial features, prognathism, macroglossia) and gigantism in children
Signs or symptoms of GH deficiency - A short stature in children (the child is significantly shorter than others of the same age) and changes in muscle mass, cholesterol levels, and bone strength in adults
History of a pituitary gland problem (e.g., trauma, surgery, radiation)
Adults with signs or symptoms suggestive of a deficiency in other pituitary hormones (e.g., thyroid, adrenal, gonads)
Follow-up for other abnormal hormone test results
Children who have had radiation treatment of the central nervous system or whole body irradiation (e.g., treatment for malignancy, prior to stem cell transplantation)
Monitor treatment in patients on GH replacement therapy. Assess the success of therapy for acromegaly or gigantism.
The landscape of GH replacement therapy is evolving with the introduction of LAGH preparations such as somapacitan. Unlike traditional daily recombinant human GH, these novel agents offer a less frequent dosing schedule, which is anticipated to enhance treatment adherence and consequently improve clinical outcomes. The use of LAGH formulations necessitates a revised monitoring protocol, including specific timing for IGF-I measurements, to accurately assess treatment response and guide dose titration. This shift in therapeutic strategy aims to optimize patient care by balancing efficacy with convenience. [16]
Considerations/precautions
GH levels in the blood change during the day and are affected by exercise, sleep, emotional stress, and diet. [8, 9]
To avoid interpretation dilemmas from variations in GH secretion, screening for IGF-1 or somatomedin C are mandated and can provide superior accuracy regarding the mean plasma levels of GH. [1]
GH is released in pulses. Because GH is secreted in a pulsatile manner, random GH measurements are unreliable for diagnosing GH deficiency. [16] A higher level may be normal if the blood was drawn during a pulse. A lower level may be normal if the blood was drawn around the end of a pulse. Because of this, random GH levels are generally not very useful; too much overlap occurs between abnormal GH results and normal daily variations. It is more useful to perform a GH stimulation test (if one suspects deficiency) and a GH suppression test (if one suspects excess) and to correlate GH levels with IGF-1 levels as IGF-1 levels integrate GH excesses and deficiencies and are stable throughout the day. [8, 9]
For the GH stimulation test, a sample of blood is drawn after 10-12 h of fasting. Then, under close medical supervision, a person is given an intravenous solution of insulin or arginine (or other stimulus). Blood samples are then drawn at timed intervals, and GH levels are tested in each sample to see if the pituitary gland was stimulated to produce the expected GH levels. If GH levels are not adequately stimulated during a GH stimulation test (usually on at least two tests) and the individual has symptoms of GH deficiency and a low IGF-1 level, then a GH deficiency is likely. [8, 9]
For the GH suppression test, a sample of blood is drawn after 10-12 h of fasting in the patient. They are then given a standard glucose solution to drink. Blood samples are drawn at timed intervals, and GH levels are tested. If GH levels are not adequately suppressed during a GH suppression test and the patient has symptoms of gigantism or acromegaly and a high IGF-1 level, then it is likely that they are producing excess of GH. If a mass shows up on a computed tomography or magnetic resonance imaging scan of the pituitary, then a pituitary tumor (usually benign) is likely present. [8, 9]
If the person has hypothyroidism, then GH testing for GH deficiency should not be performed until the individual's thyroid function has been evaluated and treated as thyroid deficiency can cause symptoms similar to GH deficiency. [8, 9]
GH abnormalities can usually be treated once the causes are identified, but to have a good outcome, they should be identified as soon as possible because some changes are not reversible. [14]
In younger children, IGFBP-3 is a superior screening test for GH deficiency than IGF-1 because it can determine low-normal levels of IGFBP-3 in this age group in contrast to truly low levels. [17, 6]