Growth Hormone (GH)

Sample

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 the GH levels are Phenothiazine and Corticosteroids.

Purpose of the test (Indications)

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.

Various types of growth hormone 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 the GH.
   2. This test can be done in the morning after an overnight fast or at any time.
   3. The patient is advised for vigorous exercise for 20 minutes.
   4. Collect the blood immediately after the termination of exercise.
   5. If GH is >7 ng/ml, less likely for the 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 the 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.

Definition of Growth Hormone

1. 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.
2. This is one of the hormones involved in growth produced by the pituitary gland.
3. 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 the 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.

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).
      

      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 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 the circulation.
   2. Somatotropin release-inhibitory factor (SRIF) will inhibit the GH release into the circulation.
      1. SRIF is found in the delta cells of the pancreatic islets and other sites in the digestive tract.
      2. SRIF also has another important function of inhibition of the release of insulin and glucagon.

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 the 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 the 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 than the normal level during sleep.
         

         Growth Hormone fluctuations

6. This 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 secretes GH.
   2. The ability to secrete GH to conventional challenges decreases with age.

The stimuli for the growth hormone (GH) secretion:

The stimulus for secretion of  Growth hormone (GH)	Time of peak level of Growth hormone (GH)
Sleep	Usually, one hour after a deep sleep The sample was taken in stage III or VI of sleep
Meal	The sample was taken after 3 hours of the meal
Excercise	The sample was taken 20 minutes after the start of the exercise
Insulin injection (0.1 0.15 U/Kg body weight)	Take sample after 45 to 75 minutes of insulin injection Keep an eye on hypoglycemia
Glucagon injection (0.3 mg/Kg body weight I/M or subcut)	Take sample after 10 to 180 minutes of glucagon injection
l-Dopa (o.5 g/1.73 m2, given with lunch)	Take sample after 30 to 120 minutes of the dose
Arginine hydrochloride (0.5 g/Kg body weight I/V in 30 minutes)	Take sample after 60 to 120 minutes of injection
Diazepam 0.15 mg/Kg body weight, orally)	Take a sample after 60 minutes of the dose
Pentagstrin (1.5 mg/Kg/hour, I/V infusion)	Take a sample after 75 minutes of the injection
Clonidine (0.15 mg/m2)	Take a sample after 90 minutes of the dose

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, and it stimulates 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 MRI.
   2. Prolonged exposure to GH leads to overgrowth of the skeleton, muscles, and soft tissues.
   3. It is usually seen in adults and called Acromegaly.
   4. When excess GH is seen before long bones growth is complete, this condition is called Pituitary gigantism.

Acromegaly:

1. The excess of GH leads to Acromegaly.
   1. When seen before the long bone growth is complete, it is called Pituitary gigantism.
   2. This can be diagnosed with the physical appearance of the patient.
2. There is an overgrowth of the 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 are:
   1. The patient may develop diabetes mellitus.
   2. The patient will have hypertension and cardiomegaly.
   3. There is obstructive sleep apnea.
7. Diagnosis:
   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.

Clinical presentation of deficiency of growth hormone:

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

Normal growth hormone (GH)

Source 1

Age	ng/mL
Cord blood	8 to 41
Newborn
One day	5 to 53
One week	5 to 27
Child  1 to 12 months	2 to 10
Adult
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

Source 2

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:

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:

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

Treatment

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

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