Loading Calculator...
Please wait a moment
Please wait a moment
Evaluate growth hormone status using IGF-1 levels, growth velocity, and clinical symptoms
Growth hormone (GH) is secreted by the pituitary gland in a pulsatile manner, with peaks during deep sleep and exercise. Because GH levels fluctuate dramatically throughout the day, direct GH measurement is unreliable for screening. Instead, IGF-1 (insulin-like growth factor 1) is measured as a marker of integrated GH secretion.
IGF-1 is produced primarily in the liver in response to GH stimulation. It has a longer half-life and more stable levels than GH, making it an excellent screening tool for GH disorders. Low IGF-1 suggests GH deficiency, while elevated IGF-1 suggests GH excess. However, IGF-1 varies significantly with age, sex, and pubertal status, requiring age-specific reference ranges.
Normal IGF-1 levels are low in infancy, rise during childhood, peak during puberty (higher in females than males), and progressively decline with age. Factors other than GH also affect IGF-1, including nutrition (malnutrition lowers IGF-1), liver disease, diabetes, hypothyroidism, and chronic illness. Clinical context is essential for interpretation.
In children, GH deficiency presents with short stature (height <3rd percentile or >2 SD below mean), decreased growth velocity (<4 cm/year after age 3), delayed bone age, and characteristic features including central obesity and immature facial appearance. Causes include congenital defects, pituitary tumors, cranial radiation, or idiopathic.
Diagnosis requires demonstration of poor growth, low IGF-1, and failure to achieve adequate peak GH (<5-10 ng/mL) on stimulation testing. Multiple tests may be needed as single tests have poor specificity. Brain MRI evaluates pituitary anatomy. Treatment with recombinant GH improves growth velocity and final adult height, with better outcomes when started earlier.
Adult GH deficiency typically results from pituitary disease (tumors, surgery, radiation) or persists from childhood. Symptoms are non-specific: decreased energy, increased body fat (particularly abdominal), reduced muscle mass and strength, reduced bone density, impaired quality of life, and unfavorable lipid profile.
Diagnosis in adults requires history of pituitary disease or childhood GH deficiency, low IGF-1, and inadequate GH response to stimulation (typically insulin tolerance test; peak GH <5 ng/mL). GH replacement in adults improves body composition, bone density, exercise capacity, and quality of life, though cardiovascular and mortality benefits are uncertain.
GH excess before growth plate closure causes gigantism - excessive linear growth and tall stature. This is rare and almost always due to a pituitary adenoma. Children present with accelerated growth velocity, tall stature, and features of acromegaly. Early diagnosis and treatment prevent extreme height and complications.
GH excess after growth plate closure causes acromegaly, characterized by gradual acral enlargement (hands, feet, jaw), facial changes (prominent brow, nose, jaw), soft tissue swelling, enlarged organs, and multiple complications. Over 95% of cases are due to pituitary adenomas; rarely from ectopic GH or GHRH secretion.
Diagnosis requires elevated IGF-1 and failure of GH suppression to <1 ng/mL (ideally <0.4 ng/mL with modern assays) during oral glucose tolerance test. Pituitary MRI typically shows adenoma. Complications include diabetes, hypertension, cardiomyopathy, sleep apnea, arthritis, colon polyps, and increased cancer risk. Untreated acromegaly reduces life expectancy.
Treatment goals are biochemical control (normalize IGF-1, suppress GH), tumor mass reduction, and managing complications. Transsphenoidal surgery is first-line; cure rates are 70-90% for microadenomas but lower for macroadenomas. Medical therapy (somatostatin analogs, dopamine agonists, pegvisomant) is used for surgical failures or non-surgical candidates. Radiation is reserved for refractory cases.
Growth velocity (height gain per year) is one of the most sensitive indicators of growth disorders. Normal growth patterns vary by age: infants grow 20-25 cm/year in the first year, 10-12 cm in the second year, then 5-6 cm/year during childhood. Pubertal growth spurts peak at 8-9 cm/year for girls and 9-10 cm/year for boys.
Decreased growth velocity (<4 cm/year after age 3, or crossing down major percentile lines) warrants evaluation even if the child isn't yet below the 3rd percentile. Serial height measurements over 6-12 months provide more useful information than a single height measurement. Growth velocity should be interpreted in context of bone age and pubertal status.
Many conditions cause poor growth besides GH deficiency: genetic short stature, constitutional delay, hypothyroidism, chronic illness (IBD, celiac disease, renal disease), malnutrition, Turner syndrome, and psychosocial deprivation. Comprehensive evaluation includes growth curve analysis, bone age, screening labs, and focused testing based on clinical findings.
GH is secreted in pulses with peaks during sleep and after meals, so a random GH level is meaningless - a low level could be normal between pulses, and a high level could be a normal pulse. IGF-1 has a much longer half-life (12-15 hours vs. 20 minutes for GH) and stable levels, making it a reliable integrated marker of 24-hour GH secretion. However, GH stimulation or suppression testing is still needed to confirm GH disorders.
IGF-1 can be falsely low in malnutrition, poorly controlled diabetes, hypothyroidism, liver disease, chronic illness, and certain medications. It may be falsely elevated in pregnancy and puberty (physiologic). Proper interpretation requires clinical context and consideration of these factors. If IGF-1 is abnormal but clinical suspicion is low, repeat testing after addressing potential confounders may be appropriate.
Indications include: height <3rd percentile or >2 SD below mid-parental height, growth velocity <4 cm/year (age 3-puberty), crossing down 2+ major percentile lines, or short stature with suggestive clinical features (central obesity, hypoglycemia, micropenis). Not all short children have GH deficiency - most have familial short stature or constitutional delay. Screening includes IGF-1, bone age, thyroid function, and celiac screening.
Various provocative agents stimulate GH release: insulin-induced hypoglycemia (gold standard but requires careful monitoring), arginine, glucagon, clonidine, or combination protocols. GH is measured at baseline and multiple time points. Peak GH <5-10 ng/mL (cutoff varies by assay and protocol) indicates deficiency. At least two different tests showing inadequate response are recommended due to high false-positive rates. Testing requires experienced staff and emergency preparedness.
GH is FDA-approved only for specific conditions: GH deficiency, Turner syndrome, Prader-Willi syndrome, chronic renal insufficiency, SGA (small for gestational age) without catch-up growth, and idiopathic short stature (ISS) in very short children. In ISS, GH produces modest height gains (4-7 cm on average) with significant cost and daily injections for years. Response is unpredictable, and long-term benefits/risks are debated. Use in children without approved indications is controversial.
GH therapy is generally well-tolerated. Common side effects include injection site reactions, joint/muscle pain, edema, and headaches. Rare but serious concerns include benign intracranial hypertension, slipped capital femoral epiphysis, scoliosis progression, and possible increased diabetes risk. In children with resolved cancer, GH doesn't appear to increase recurrence risk but should be avoided during active malignancy. Long-term cardiovascular safety appears reassuring in deficient patients.
Surgery (transsphenoidal resection of pituitary adenoma) is first-line treatment, with cure rates of 70-90% for microadenomas but only 40-50% for macroadenomas. Medical therapy includes somatostatin analogs (octreotide, lanreotide, pasireotide) which suppress GH/IGF-1 in 50-70%, dopamine agonists (cabergoline) for dual secreting tumors, and pegvisomant (GH receptor antagonist) which normalizes IGF-1 in >90%. Radiation therapy is used for refractory disease but has delayed effects and causes hypopituitarism.
Yes, GH replacement is FDA-approved for adult GH deficiency confirmed by stimulation testing in patients with known pituitary disease or childhood-onset deficiency. Benefits include improved body composition (increased lean mass, decreased fat), bone density, exercise capacity, and quality of life. However, effects on cardiovascular outcomes and mortality are uncertain. Treatment is expensive, requires daily injections, and should be individualized based on symptoms and monitoring of IGF-1 levels.