Growth Hormone (GH)

Sample for Growth Hormone (GH)

1. This test is done on serum (clotted blood 3 to 5 ml).
   1. A serum sample is preferred.
2. Plasma (EDTA) has lower values with some methods.
3. The patient should be fasting and complete rest for at least 30 minutes before taking the blood.
4. It is stable for 8 hours at 2 to 8 °C.
5. It can be kept for a more extended period at -20 °C.

Precautions for Growth Hormone (GH) estimation

1. Perform the test immediately because the half-life of GH is 20 to 25 minutes.
2. Immediately refrigerate the serum.
3. The patient should be fasting after midnight.
4. The patient must be fasting and at complete rest, 30 min before the sample is taken because this may increase the level.
5. Avoid stress, low blood glucose, and exercise during the sample collection.
6. EDTA plasma gives lower values.
7. Random measurement is not helpful because of episodic variation in the GH level.
8. Drugs that may increase the level are Amphetamine, Estrogen, Dopamine, Insulin, Methyldopa, Levodopa, Histamine, and Nicotinic acid.
9. Certain drugs that decrease GH levels are Phenothiazine and Corticosteroids.

Purpose of the test (Indications) for Growth Hormone (GH)

1. Growth hormone (GH) is done to identify its deficiency in:
   1. Adults with short stature.
   2. Delayed sexual maturity.
   3. Or other growth abnormalities.
2. To diagnose gigantism or acromegaly,
3. This can be used to identify the pituitary hypofunction or hyperfunction.

Definition of Growth Hormone (GH):

1. GH is a peptide secreted by the pituitary gland’s acidophilic cells.
2. Growth hormone-releasing hormone (GHRH) stimulates GH release.
3. Somatostatin inhibits the release of GH.
4. The growth hormone is a single-chain polypeptide with a molecular weight of 21,500 Da and 191 amino acids.
   1. It has two intramolecular disulfide bridges.
   2. Its structure is similar to prolactin.

5. This is one of the hormones involved in growth produced by the pituitary gland.
6. This is also called Somatotropin, which is secreted by acidophilic cells of anterior pituitary glands.
   1. It is stored in the cells as intracellular granules.
   2. Growth hormone production is pulsatile.

Pathophysiology of growth hormone (GH)

1. GH plays a role in growth from birth until the end of puberty.
   1. GH promotes protein synthesis and stimulates skeletal growth.
2. Various factors increase GH secretion. While somatotropin is a man-made hormone.
3. GH is produced by the acidophilic cells of the anterior pituitary gland and is stored within the intracellular molecules granules.
4. GH secretion occurs predominantly during sleep in the form of irregular pulses or bursts.

Growth Hormone secretion:

1. Anterior pituitary gland cells (acidophilic cells) secrete:
   1. Growth hormone.
   2. Prolactin.
   3. Thyroid-stimulating hormone (TSH).
   4. Follicle-stimulating hormone (FSH).
   5. Luteinizing hormone (LH).

Growth Hormone (GH): Anterior pituitary gland hormones and Growth hormone (GH)

2. 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.
3. Arginine is used, which activates the secretion of GH.
4. GH increases glucose by:
   1. Inhibiting the entry of glucose into the muscle cells.
   2. By inhibiting glycolysis.
   3. By inhibiting the formation of triglycerides from the glucose.

Growth hormone (GH) controlling mechanism:

1. The growth hormone release is controlled by two hypothalamic factors secreted into portal circulation from nerve terminals in the median eminence.
   1. Growth hormone-releasing hormone (GH-RH). It will stimulate GH release into circulation.
   2. Somatotropin release-inhibitory factor (SRIF) will inhibit the GH release into circulation.
      1. SRIF is found in the pancreatic islets’ delta cells and other digestive tract sites.
      2. SRIF also has another important function of inhibiting insulin and glucagon release.

Growth hormone production

2. GH affects many tissues through a group of peptides (Somatomedins).
3. 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:

1. GH has diurnal variation in concentration. Stimuli leading to increase of GH:
   1. Exercise.
   2. Physical and emotional stress.
   3. Ingestion of protein.
   4. In hypoglycemia.
   5. Spike occurs after 3 hours of meals or exercise.
2. The level is low during the day and is around 5 ng/mL (another reference says <2 ng/mL).
3. In adults and children in the evening, it shows the highest level.
4. The secretion of GH is episodic and variable; sometimes, the level may reach 40 ng/ml in a healthy subject.
5. The highest values are noted during the deepest sleep level. So its level is increased during sleep.
   1. So the best time is 60 to 90 minutes after deep sleep.
      1. Or do the exercise for 30 minutes and get the GH sample, which will be at the highest level.
      2. The GH may increase ten times the normal level during sleep.

Growth Hormone fluctuations

6. GH test may be used to monitor the acromegaly treatment.
7. Obesity reduces the release of GH and response to insulin.
   1. Hypoglycemia stimulates the pituitary to secret GH.
   2. The ability to secrete GH to conventional challenges decreases with age.
8. GH is tested in case of retarded growth or short stature.

The stimuli for the growth hormone (GH) secretion:

Growth hormone (GH) functions:

1. GH insufficient amount leads to:
   1. Limited growth.
   2. Its deficiency leads to dwarfism.
   3. Delay in maturity.
2. GH overproduction leads to :
   1. Its excess leads to gigantism.
   2. Acromegaly. (Increase in bone thickness and width).
3. It promotes protein synthesis in muscles.
4. It promotes the synthesis of protein in the liver.
5. It stimulates skeletal muscle growth.
6. It directly stimulates amino acid uptake.
7. GH is important for anabolic and repair functions and proper skeletal growth.
8. GH has an anti-insulin effect on carbohydrate metabolism.
   1. In fasting, insulin secretion decreases and GH secretion increases, stimulating the body to use fatty acids instead of glucose.

Growth hormone functions

Clinical presentation of growth hormone (GH) excess:

1. Excess GH is seen in the eosinophilic or chromophobe adenomas of the pituitary gland.
   1. 75% of these tumors can be diagnosed on CT scans or MRIs.
   2. Prolonged exposure to GH leads to overgrowth of the skeleton, muscles, and soft tissues.
   3. It is usually seen in adults and is called Acromegaly.
   4. This condition is called Pituitary gigantism when excess GH is seen before long bone growth is complete.

Various types of growth hormone (GH) tests:

1. A growth stimulation test can be done to evaluate the deficiency.
2. An exercise stimulation test can be advised for GH.
   1. Brick exercise increases GH.
   2. This test can be done in the morning after an overnight fast or at any time.
   3. The patient is advised to exercise for 20 minutes vigorously.
   4. Collect the blood immediately after the termination of exercise.
   5. If GH is >7 ng/ml, less likely for deficiency.
   6. 3 to 6 ng/mL is an intermediate response, and consider it a suspected case.
3. The growth suppression test is done in gigantism and acromegaly in adults.
4. 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.
   1. Give glucose 75 to 100 grams in 5 minutes, then get the sample for GH at 30, 60, 90, and 120 minutes.
5. Insulin-induced hypoglycemia stimulation test where hypoglycemia triggers the release of GH and ACTH from pituitary glands in the normal person.
   1. Give I/V insulin in overnight fasting patients.
   2. Insulin 0.1 to 0.15 U/Kg body weight is injected I/V.
   3. Collect the blood sample after 30 minutes rest period for GH, ACTH, and cortisol.
   4. Collect blood samples at 30, 60, and 90 minutes intervals.
   5. Estimate glucose, GH, ACTH, and cortisol.
   6. The patients may become symptomatic and develop hypoglycemia <40 mg/dL.
   7. This test is contraindicated in patients with seizures and ischemic heart disease.
      1. GH level reaches a peak level of >10 ng/mL.
      2. Cortisol level reaches a peak value of >20 µg/dL.
6. Direct GH can be measured by bioassay, receptor assay, and immunoassay.

Acromegaly:

1. The excess of GH leads to Acromegaly.
   1. Pituitary gigantism is seen before the long bone growth is complete.
   2. This can be diagnosed by the physical appearance of the patient.
2. There is an overgrowth of soft tissue and bone.
   1. There is coarse oily skin.
   2. There is a large tongue.
   3. There are prominent supraorbital ridges.
   4. The teeth spacing is increased.
   5. Hands are thick spade-like.
   6. The patient will have arthralgia and kyphosis.
   7. Voice is coarse.
   8. The patient may develop proximal muscle weakness.
   9. Sweating and headache are common.
   10. The patient will have progressive heart failure.
3. The reversibility of the physical changes depends upon the duration of the disease.

Acromegaly characteristic features

4. Acromegaly may lead to severe disability or death due to cardiac or neurological complications.
5. There is an abnormal response of GH to oral glucose administration.
   1. The normal person shows <1 ng/ mL of GH after an oral dose of glucose.
6. Complications of Acromegaly are:
   1. The patient may develop diabetes mellitus.
   2. The patient will have hypertension and cardiomegaly.
   3. There is obstructive sleep apnea.
7. Diagnosis of Acromegaly:
   1. Acromegaly diagnosis depends upon the increased level of GH.
   2. Advise the glucose tolerance test and collect a blood sample at 0, 30 min, 60 min, 90 min.
      1. Estimate both glucose and GH.
      2. The values will be suppressed at around <1.0 ng/mL.
   3. Another test is IGF-1 (insulin-like growth factor-1), where its concentration increases in acromegaly.

8. Treatment of Acromegaly:

   1. For acromegaly due to adenoma is transsphenoidal resection of the tumor.
   2. Another method is gamma knife multiport irradiation.
   3. Somatostatin (SST) long-acting needs only one dose per month.

Clinical presentation of deficiency of growth hormone:

1. This is usually seen in hypothalamic and pituitary tumors.
2. Growth is a dwarf and short-stature in the child.
3. Diagnosis:
   1. Advice Two stimulating tests like insulin hypoglycemia or arginine.
   2. Measure GH at 30, 60, and 90 minutes.
      1. Normal patients show an increase of  GH >8.0 ng/mL.

Normal growth hormone (GH)

Source 1

• To convert into SI units x 1.0 =  µg/L

Source 2

• 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:

1. Pituitary gigantism (Acromegaly = up to 400 ng/ml).
2. Ectopic GH secretion, e.g., Stomach neoplasm, lung.
3. Renal failure.
4. Cirrhosis.
5. Stress, exercise, prolonged fasting.
6. Uncontrolled diabetes mellitus.
7. Anorexia nervosa.
8. Starvation and malnutrition.
9. Hypoglycemia.
10. Major surgery.
11. Exercise.

The decreased growth hormone (GH) level is seen in the following:

1. Pituitary dwarfism, hypopituitarism.
2. Adrenocortical hyperfunction.
3. Hyperglycemia.
4. Delayed sexual maturity.
5. Growth hormone deficiency.

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