Growth Hormone (GH)
Sample for Growth Hormone (GH)
- This test is done on serum (clotted blood 3 to 5 ml).
- A serum sample is preferred.
- Plasma (EDTA) has lower values with some methods.
- The patient should be fasting and complete rest for at least 30 minutes before taking the blood.
- It is stable for 8 hours at 2 to 8 °C.
- It can be kept for a more extended period at -20 °C.
Precautions for Growth Hormone (GH) estimation
- Perform the test immediately because the half-life of GH is 20 to 25 minutes.
- Immediately refrigerate the serum.
- The patient should be fasting after midnight.
- The patient must be fasting and at complete rest, 30 min before the sample is taken because this may increase the level.
- Avoid stress, low blood glucose, and exercise during the sample collection.
- EDTA plasma gives lower values.
- Random measurement is not helpful because of episodic variation in the GH level.
- Drugs that may increase the level are Amphetamine, Estrogen, Dopamine, Insulin, Methyldopa, Levodopa, Histamine, and Nicotinic acid.
- Certain drugs that decrease GH levels are Phenothiazine and Corticosteroids.
Purpose of the test (Indications) for Growth Hormone (GH)
- Growth hormone (GH) is done to identify its deficiency in:
- Adults with short stature.
- Delayed sexual maturity.
- Or other growth abnormalities.
- To diagnose gigantism or acromegaly,
- This can be used to identify the pituitary hypofunction or hyperfunction.
Definition of Growth Hormone (GH):
- GH is a peptide secreted by the pituitary gland’s acidophilic cells.
- Growth hormone-releasing hormone (GHRH) stimulates GH release.
- Somatostatin inhibits the release of GH.
- The growth hormone is a single-chain polypeptide with a molecular weight of 21,500 Da and 191 amino acids.
- It has two intramolecular disulfide bridges.
- Its structure is similar to prolactin.
- This is one of the hormones involved in growth produced by the pituitary gland.
- This is also called Somatotropin, which is secreted by acidophilic cells of anterior pituitary glands.
- It is stored in the cells as intracellular granules.
- Growth hormone production is pulsatile.
Pathophysiology of growth hormone (GH)
- GH plays a role in growth from birth until the end of puberty.
- GH promotes protein synthesis and stimulates skeletal growth.
- Various factors increase GH secretion. While somatotropin is a man-made hormone.
- GH is produced by the acidophilic cells of the anterior pituitary gland and is stored within the intracellular molecules granules.
- GH secretion occurs predominantly during sleep in the form of irregular pulses or bursts.
Growth Hormone secretion:
- Anterior pituitary gland cells (acidophilic cells) secrete:
- Growth hormone.
- Thyroid-stimulating hormone (TSH).
- Follicle-stimulating hormone (FSH).
- Luteinizing hormone (LH).
- Hypoglycemia stimulates the pituitary gland to secrete GH. It is an antagonist to insulin. This was used as a stimulation test but was not safe.
- Arginine is used, which activates the secretion of GH.
- GH increases glucose by:
- Inhibiting the entry of glucose into the muscle cells.
- By inhibiting glycolysis.
- By inhibiting the formation of triglycerides from the glucose.
Growth hormone (GH) controlling mechanism:
- The growth hormone release is controlled by two hypothalamic factors secreted into portal circulation from nerve terminals in the median eminence.
- Growth hormone-releasing hormone (GH-RH). It will stimulate GH release into circulation.
- Somatotropin release-inhibitory factor (SRIF) will inhibit the GH release into circulation.
- SRIF is found in the pancreatic islets’ delta cells and other digestive tract sites.
- SRIF also has another important function of inhibiting insulin and glucagon release.
- GH affects many tissues through a group of peptides (Somatomedins).
- Increased level of Somatomedins leads to an increase in the production of Somatostatin which is released from the hypothalamus.
Growth hormone variation in the production:
- GH has diurnal variation in concentration. Stimuli leading to increase of GH:
- Physical and emotional stress.
- Ingestion of protein.
- In hypoglycemia.
- Spike occurs after 3 hours of meals or exercise.
- The level is low during the day and is around 5 ng/mL (another reference says <2 ng/mL).
- In adults and children in the evening, it shows the highest level.
- The secretion of GH is episodic and variable; sometimes, the level may reach 40 ng/ml in a healthy subject.
- The highest values are noted during the deepest sleep level. So its level is increased during sleep.
- So the best time is 60 to 90 minutes after deep sleep.
- Or do the exercise for 30 minutes and get the GH sample, which will be at the highest level.
- The GH may increase ten times the normal level during sleep.
- So the best time is 60 to 90 minutes after deep sleep.
- GH test may be used to monitor the acromegaly treatment.
- Obesity reduces the release of GH and response to insulin.
- Hypoglycemia stimulates the pituitary to secret GH.
- The ability to secrete GH to conventional challenges decreases with age.
- GH is tested in case of retarded growth or short stature.
The stimuli for the growth hormone (GH) secretion:
|The stimulus for the secretion of Growth hormone (GH)||Time of peak level of Growth hormone (GH)|
|Insulin injection (0.1 0.15 U/Kg body weight)||
|Glucagon injection (0.3 mg/Kg body weight I/M or subcut)||
|l-Dopa (o.5 g/1.73 m2, given with lunch)||
|Arginine hydrochloride (0.5 g/Kg body weight I/V in 30 minutes)||
|Diazepam 0.15 mg/Kg body weight, orally)||
|Pentagstrin (1.5 mg/Kg/hour, I/V infusion)||
|Clonidine (0.15 mg/m2)||
Growth hormone (GH) functions:
- GH insufficient amount leads to:
- Limited growth.
- Its deficiency leads to dwarfism.
- Delay in maturity.
- GH overproduction leads to :
- Its excess leads to gigantism.
- Acromegaly. (Increase in bone thickness and width).
- It promotes protein synthesis in muscles.
- It promotes the synthesis of protein in the liver.
- It stimulates skeletal muscle growth.
- It directly stimulates amino acid uptake.
- GH is important for anabolic and repair functions and proper skeletal growth.
- GH has an anti-insulin effect on carbohydrate metabolism.
- In fasting, insulin secretion decreases and GH secretion increases, stimulating the body to use fatty acids instead of glucose.
Clinical presentation of growth hormone (GH) excess:
- Excess GH is seen in the eosinophilic or chromophobe adenomas of the pituitary gland.
- 75% of these tumors can be diagnosed on CT scans or MRIs.
- Prolonged exposure to GH leads to overgrowth of the skeleton, muscles, and soft tissues.
- It is usually seen in adults and is called Acromegaly.
- This condition is called Pituitary gigantism when excess GH is seen before long bone growth is complete.
Various types of growth hormone (GH) tests:
- A growth stimulation test can be done to evaluate the deficiency.
- An exercise stimulation test can be advised for GH.
- Brick exercise increases GH.
- This test can be done in the morning after an overnight fast or at any time.
- The patient is advised to exercise for 20 minutes vigorously.
- Collect the blood immediately after the termination of exercise.
- If GH is >7 ng/ml, less likely for deficiency.
- 3 to 6 ng/mL is an intermediate response, and consider it a suspected case.
- The growth suppression test is done in gigantism and acromegaly in adults.
- An oral glucose tolerance test is very helpful for a rise in glucose levels. Normally GH is suppressed. But in acromegalic patients, there is a slight or no decrease in GH.
- Give glucose 75 to 100 grams in 5 minutes, then get the sample for GH at 30, 60, 90, and 120 minutes.
- Insulin-induced hypoglycemia stimulation test where hypoglycemia triggers the release of GH and ACTH from pituitary glands in the normal person.
- Give I/V insulin in overnight fasting patients.
- Insulin 0.1 to 0.15 U/Kg body weight is injected I/V.
- Collect the blood sample after 30 minutes rest period for GH, ACTH, and cortisol.
- Collect blood samples at 30, 60, and 90 minutes intervals.
- Estimate glucose, GH, ACTH, and cortisol.
- The patients may become symptomatic and develop hypoglycemia <40 mg/dL.
- This test is contraindicated in patients with seizures and ischemic heart disease.
- GH level reaches a peak level of >10 ng/mL.
- Cortisol level reaches a peak value of >20 µg/dL.
- Direct GH can be measured by bioassay, receptor assay, and immunoassay.
- The excess of GH leads to Acromegaly.
- Pituitary gigantism is seen before the long bone growth is complete.
- This can be diagnosed by the physical appearance of the patient.
- There is an overgrowth of soft tissue and bone.
- There is coarse oily skin.
- There is a large tongue.
- There are prominent supraorbital ridges.
- The teeth spacing is increased.
- Hands are thick spade-like.
- The patient will have arthralgia and kyphosis.
- Voice is coarse.
- The patient may develop proximal muscle weakness.
- Sweating and headache are common.
- The patient will have progressive heart failure.
- The reversibility of the physical changes depends upon the duration of the disease.
- Acromegaly may lead to severe disability or death due to cardiac or neurological complications.
- There is an abnormal response of GH to oral glucose administration.
- The normal person shows <1 ng/ mL of GH after an oral dose of glucose.
- Complications of Acromegaly are:
- The patient may develop diabetes mellitus.
- The patient will have hypertension and cardiomegaly.
- There is obstructive sleep apnea.
- Diagnosis of Acromegaly:
- Acromegaly diagnosis depends upon the increased level of GH.
- Advise the glucose tolerance test and collect a blood sample at 0, 30 min, 60 min, 90 min.
- Estimate both glucose and GH.
- The values will be suppressed at around <1.0 ng/mL.
- Another test is IGF-1 (insulin-like growth factor-1), where its concentration increases in acromegaly.
Treatment of Acromegaly:
- For acromegaly due to adenoma is transsphenoidal resection of the tumor.
- Another method is gamma knife multiport irradiation.
- Somatostatin (SST) long-acting needs only one dose per month.
Clinical presentation of deficiency of growth hormone:
- This is usually seen in hypothalamic and pituitary tumors.
- Growth is a dwarf and short-stature in the child.
- Advice Two stimulating tests like insulin hypoglycemia or arginine.
- Measure GH at 30, 60, and 90 minutes.
- Normal patients show an increase of GH >8.0 ng/mL.
Normal growth hormone (GH)
|Cord blood||8 to 41|
|One day||5 to 53|
|One week||5 to 27|
|Children 1 to 12 months||2 to 10|
|Male||0 to 4|
|Female||0 to 18|
|> 60 years|
|Male||1 to 9|
|Female||1 to 16|
- To convert into SI units x 1.0 = µg/L
|Men||<5 ng/mL or <5 µg/L)|
|Women||<10 ng/mL or <10µg/L)|
|Newborn||10 to 40 ng /ml|
|Child||0 to 10 ng/ml|
- The random level of GH provides little diagnostic information.
- The single estimation may not be helpful because of the variation in the level of GH during the day.
The increased Growth hormone (GH) level is seen in the following:
- Pituitary gigantism (Acromegaly = up to 400 ng/ml).
- Ectopic GH secretion, e.g., Stomach neoplasm, lung.
- Renal failure.
- Stress, exercise, prolonged fasting.
- Uncontrolled diabetes mellitus.
- Anorexia nervosa.
- Starvation and malnutrition.
- Major surgery.
The decreased growth hormone (GH) level is seen in the following:
- Pituitary dwarfism, hypopituitarism.
- Adrenocortical hyperfunction.
- Delayed sexual maturity.
- Growth hormone deficiency.
Questions and answers:
Question 1: When is the peak level of GH?
GH is secreted during deep sleep at night.
Question 2: What are the complications of acromegaly?
Patients with acromegaly may develop diabetes mellitus, hypertension, and cardiomegaly.