Growth Hormone

Growth hormone (GH) secretion by the pituitary is controlled both by growth hormone releasing hormone (GHRH) and somatostatin, an inhibitory hormone. The pituitary releases growth hormone, which acts on the liver to produce insulin-like growth factor 1 (IGF-1, somatomedin C).  IGF-1 is responsible for the growth promoting effects of growth hormone. GH also has metabolic effects such as stimulation of lipolysis and inhibition of carbohydrate metabolism.  Growth hormone secretion is episodic and pulsatile and is stimulated by sleep, exercise, stress, hypoglycemia, dopamine, certain amino acids, GHRH, beta-blockers, and glucagon.

The second most common tumor of the pituitary gland is a GH cell adenoma. If excess GH secretion occurs prior to epiphyseal closure a child develops gigantism. Excess GH secretion in adults results in acromegaly. The major clinical manifestations of growth hormone excess include:

• Skin & subcutaneous tissue overgrowth
• Skeletal overgrowth (sinuses, prognathism, kyphosis)
• Excessive sweating
• Goitre
• Hypertension
• Diabetes mellitus
• Cardiomyopathy
• Gynecomastia
• Galactorrhea
• Menstrual disturbances
• Peripheral neuropathy
• Macroglossia
• Acanthosis nigricans
• Osteoarthritis
• Carpal tunnel syndrome
• Myopathy
• Hirsutism
• Visual field defects
• Headaches

 Acral enlargement (skin, subcutaneous tissue and skeletal overgrowth) is seen in all patients. This is usually recognized by increases in ring, glove, or shoe sizes. Also, since this is a tumor of the pituitary gland, a patient can experience visual defects and hypopituitarism.

The most useful tests for the diagnosis of acromegaly are the GH response to an oral glucose load and measurement of IGF1.  Although elevated GH measurements in the fasting state  (>5 ng/mL) are consistent with the diagnosis of acromegaly, they are not diagnostic because nonspecific effects such as stress can also elevate GH levels. However, failure to suppress GH below 2 ng/mL following a 100g oral glucose tolerance test confirms the diagnosis of acromegaly especially if it is coupled with an elevated level of IGF-1. Pituitary imaging studies are useful in localizing the tumor.

Growth hormone deficiency in adults is present when one of the following conditions are met:

• 1 abnormal definitive GH test plus evidence of at least 1 other pituitary hormone deficiency
• 1 abnormal definitive GH test plus a previous diagnosis of GH deficiency in childhood
• 2 abnormal definitive GH tests when there are no other pituitary hormone deficiencies & there is no previous diagnosis of GH deficiency in childhood

When GH deficiency is diagnosed, a CT or MRI search for a CNS lesion must be pursued.  Thyroid status should also be determined, because hypothyroidism can induce reversible GH deficiency.  Random measurements of GH are usually uninformative because basal GH levels are normally low and do not differentiate patients who are deficient from those who are not.   Therefore, to diagnose GH deficiency, stimulated GH measurements must be assessed.  Stimulated GH tests are obtained first by using physiologic stimulants such as exercise or sleep or pharmacologic stimulants such as clonidine.  When using exercise, GH is measured immediately upon completion of 20 minutes of exercise and again at 40 minutes.  When using sleep, GH is measured 60 minutes after the patient falls asleep.  When using clonidine, 5 ug/kg is given orally and GH is measured 90 minutes later.  

Another approach to screening for GH deficiency is to measure insulin-like growth factor-1.  In GH deficiency, IGF-1 should be suppressed because GH stimulates its synthesis. Because IGF-1 does not have diurnal variation, it can be measured on a random sample.  

GH is measured with an automated chemiluminescent  immunoassay. Reference range is 0-5.0 ng/mL in males and 0-10 ng/mL in females. 

Specimen requirement is one tube of blood drawn in a red top tube, with or without gel, after an overnight fast.  

References

Ayuk J, Sheppard MC. Growth hormone and its disorders. Postgrad Med J. 2006;82(963):24-30.

Hartman ML, Veldhuis JD, Thorner MO. Normal control of growth hormone secretion. Horm Res. 1993;40(1-3):37-47