Overview
Growth Hormone (GH), also known as somatotropin, is a peptide hormone secreted by the anterior pituitary gland. It is composed of 191 amino acids with two disulfide bonds forming four helices. GH plays a crucial role in regulating linear growth, bone length, muscle development, and overall body composition.
Although GH is essential during childhood and adolescence for normal growth, it continues to have significant physiological functions throughout adulthood. Its actions are mediated directly and indirectly through insulin-like growth factor-1 (IGF-1), which is primarily produced in the liver in response to GH stimulation.
Regulation and Secretion
The secretion of GH is regulated by a complex interaction between the hypothalamus, anterior pituitary gland, and liver. It operates through positive and negative feedback mechanisms involving GH itself and IGF-1.
GH release is stimulated by growth hormone-releasing hormone (GHRH) and ghrelin, while it is inhibited by somatostatin. Secretion occurs in a pulsatile pattern, with peak levels seen during deep (slow-wave) sleep and puberty. Because of this pulsatility, random note: basal GH levels alone are unreliable for diagnosis.
Functions
GH primarily promotes growth through stimulation of IGF-1 production, leading to increased bone growth and muscle mass. It also influences fat distribution, metabolism, tissue repair, and organ function.
Key metabolic effects include stimulation of protein synthesis, enhancement of lipolysis, and modulation of glucose metabolism. GH increases the release of fatty acids and glycerol from adipose tissue, which are used as energy sources.
A deficiency of GH results in increased body fat, reduced muscle mass, and elevated blood glucose levels, while excess GH leads to abnormal tissue growth.
Indications for GH Testing
GH testing is indicated in both pediatric and adult populations. In children, it is used to evaluate growth delay, short stature, delayed puberty, and abnormal bone development. In adults, indications include fatigue, reduced bone density, adverse lipid changes, and reduced exercise tolerance.
Testing is also used to detect excess GH production, such as in acromegaly or gigantism, and to monitor treatment response. GH assessment helps evaluate pituitary function in suspected hypopituitarism or pituitary tumors and is used to track the efficacy of GH therapy over time.
Sample Collection and Testing Methods
Blood samples for GH testing are collected in the fasting state and after administration of specific stimuli that provoke GH release. Because random GH measurements are unreliable, dynamic tests are preferred.
Common GH stimulation tests include the insulin tolerance test (ITT), arginine stimulation test, clonidine stimulation test (pediatric use), and glucagon stimulation test when ITT is contraindicated.
For suspected GH excess, a GH suppression test using the oral glucose tolerance test (OGTT) is performed. In normal individuals, glucose suppresses GH secretion; failure of suppression indicates GH excess.
Reference Ranges
Normal GH levels vary by age and physiological state. Infants have the highest levels, while adults have lower baseline concentrations. Fasting adult reference values are generally <5 ng/mL in males and <10 ng/mL in females, though interpretation must consider stimulation or suppression responses rather than single measurements.
Causes of GH Deficiency
GH deficiency may be congenital, acquired, idiopathic, systemic, or adult-onset. Congenital causes include genetic mutations (such as GH1, GHRHR, and PROP1) and pituitary developmental defects.
Acquired causes include pituitary or hypothalamic tumors, traumatic brain injury, infections, cranial irradiation, and neurosurgical complications. Systemic illnesses, malnutrition, psychosocial deprivation, and hypothyroidism may also reduce GH secretion. Adult-onset deficiency can occur following pituitary surgery, pituitary apoplexy, radiation therapy, or infiltrative diseases.
Causes of Raised GH
Physiological elevations occur during exercise, deep sleep, stress, hypoglycemia, and puberty.
Pathological causes include GH-secreting pituitary adenomas, leading to gigantism in children and acromegaly in adults, as well as ectopic GHRH-secreting tumors.
Raised GH levels may also be seen in chronic renal failure, liver disease, uncontrolled diabetes mellitus, and as a result of recombinant GH therapy or drugs that stimulate GH release.
