Growth hormone plays a central role in the growth of muscles, bones and tissues. It also has metabolic effects and stimulates cell regeneration and proliferation.
Growth Hormone Axis
Growth hormone is controlled by two structures in the brain called the hypothalamus and the pituitary gland, specifically the anterior part of the pituitary.
The hypothalamus produces growth hormone-releasing hormone (GHRH). GHRH stimulates the anterior pituitary to release growth hormone (GH). Growth hormone acts directly on growth hormone receptors in the tissues.
Growth hormone also stimulates the release of insulin-like growth factor 1 (IGF-1), mostly from the liver (but also from various other tissues). IGF-1 travels to the tissues, acting on IGF-1 receptors. It also travels back to the brain and suppresses the hypothalamus and pituitary, suppressing the release of GHRH and growth hormone. The suppressing effect of IGF-1 is called negative feedback and helps to keep growth hormone and IGF-1 levels within normal limits.
Growth hormone is released in pulses, notably at night during deep sleep (slow-wave sleep). There is a peak in growth hormone around age 15-16 years (slightly earlier in girls than boys). Growth hormone levels gradually fall with increasing age.
Growth Hormone Effects
Growth hormone and IGF-1 affect almost all cells and have many functions, most notably:
- Short-term metabolic effects (increasing protein synthesis, increasing lipid oxidation and increasing blood glucose)
- Stimulating cell regeneration and proliferation
- Stimulating muscle growth
- Increasing bone density
- Stimulating growth of the internal organs
Growth hormone and IGF-1 have short-term metabolic effects, with:
- Increased protein synthesis (protein production by the cells)
- Increased lipolysis (breakdown of fat from adipose tissue into free fatty acids to be used as fuel)
- Increased lipid oxidation (the body uses fat for fuel)
- Increased gluconeogenesis (conversion of glycogen to glucose in the liver, increasing the blood glucose level)
- Reduced insulin sensitivity (reduced uptake and use of glucose from the blood)
- Reduced glucose oxidation (less glucose is used for energy)
Factors Controlling Growth Hormone Release
The factors that stimulate the hypothalamus and pituitary to release more GHRH and growth hormone include:
- Ghrelin (produced by the stomach to signal hunger when the stomach is empty and calorie intake is reduced)
- Sleep (particularly slow-wave sleep)
- Hypoglycaemia (low blood sugar)
- Acute stress
- Oestrogen
Ghrelin is described as the hunger hormone. It is released by the stomach when a meal is due, and fewer calories and nutrients are available. Ghrelin levels fall after a meal when the stomach is full and plenty of nutrients are available. Ghrelin stimulates the release of GHRH and growth hormone.
The factors that suppress GHRH and growth hormone release by the hypothalamus and pituitary include:
- Somatostatin secreted by the hypothalamus
- Insulin-like growth factor-1 (IGF-1)
- Insulin
- Visceral adipose tissue (fat tissue around the organs in the abdomen)
- Free fatty acids in the blood
Somatostatin
Somatostatin, also known as growth hormone-inhibiting hormone, is secreted by the:
- Hypothalamus
- Delta cells of the pancreas
- D cells of the stomach and duodenum
Raised IGF-1 stimulates the release of somatostatin by the hypothalamus. Somatostatin acts on the anterior pituitary to suppress the release of:
- Growth hormone
- Thyroid-stimulating hormone
Within the digestive system, somatostatin provides negative feedback around various hormones and processes. If something gets too high (e.g., stomach acidity), somatostatin is released to bring that thing back down (e.g., by suppressing gastrin release and gastric acid secretion).
|
Factors That Stimulate Somatostatin Release |
Factors That Somatostatin Inhibits |
|
High blood sugar, glucagon and insulin |
Glucagon and insulin release (pancreas) |
|
Cholecystokinin (CCK) |
Cholecystokinin release |
|
Vasoactive intestinal peptide |
Vasoactive intestinal peptide release |
|
Increased acidity in the stomach |
Gastrin release and gastric acid secretion |
Growth Hormone Deficiency
Congenital growth hormone deficiency results from a disruption to the growth hormone axis at the hypothalamus or pituitary gland. It can be due to a known genetic mutation affecting the GH1 (growth hormone 1) or GHRHR (growth hormone releasing hormone receptor) genes or to another condition, such as empty sella syndrome, where the pituitary gland is underdeveloped or damaged.
Acquired growth hormone deficiency is often idiopathic (without a clear cause) but can be secondary to infection, trauma or surgery.
Growth hormone deficiency can occur in isolation or with other pituitary hormone deficiencies. When the pituitary gland does not produce several pituitary hormones, this is called hypopituitarism or multiple pituitary hormone deficiency. Hypopituitarism can cause:
- Hypothyroidism (inadequate TSH resulting in low thyroid hormones)
- Adrenal insufficiency (inadequate ACTH resulting in low cortisol)
- Hypogonadism (inadequate LH and FSH leading to low sex hormones)
Growth hormone deficiency in children may present with:
- Poor growth (severe slowing from 2 – 3 years onwards)
- Short stature
- Delayed development of movement and strength
- Delayed puberty
Acromegaly
Acromegaly is the result of excessive growth hormone. The most common cause of excessive growth hormone secretion is a pituitary adenoma (a hormone-secreting pituitary gland tumour). Pituitary adenomas can be classified based on their size:
- Microadenomas are smaller than 10mm
- Macroadenomas are bigger than 10mm
Macroadenomas can be large enough to compress local structures. The optic chiasm sits just above the pituitary gland. The optic chiasm is where the optic nerves from the eyes cross over to the opposite side of the head before travelling to the visual cortex in the occipital lobe. A pituitary tumour of sufficient size can press on the optic chiasm, disrupting the signal from the medial half of the retina, which senses the outer half of the vision. Loss of the outer vision in both eyes is called bitemporal hemianopia. The inner half of the vision is unaffected, as the fibres that carry this information do not cross at the optic chiasm and stay on the same side of the head.
Excess growth hormone causes tissue growth, leading to:
- Prominent forehead and brow (frontal bossing)
- Coarse, sweaty skin
- Large nose
- Large tongue (macroglossia)
- Large hands and feet
- Large protruding jaw (prognathism)
Additional features of acromegaly include:
- Hypertension (high blood pressure)
- Cardiac hypertrophy (heart muscle growth)
- Type 2 diabetes
- Carpal tunnel syndrome
- Arthritis
- Colorectal cancer
Testing
Testing growth hormone in a blood sample does not provide useful information. Growth hormone levels can fluctuate massively in someone without growth hormone pathology, making a single sample meaningless.
Insulin-like growth factor-1 (IGF-1) can be tested on a blood sample. IGF-1 levels are more stable than growth hormone levels. IGF-1 may be used as a screening test for growth hormone deficiency and acromegaly. However, dynamic tests are required to make a diagnosis. Dynamic tests involve giving a stimulus and measuring the response.
Growth hormone stimulation tests are used to diagnose growth hormone deficiency. These involve measuring the response to a stimulus that should increase growth hormone release. Growth hormone levels are monitored before and after the stimulus. Failure of the growth hormone level to rise indicates growth hormone deficiency. The insulin tolerance test is one option, which involves giving short-acting insulin to induce hypoglycaemia (low blood sugar), which should stimulate growth hormone release. Other options include giving glucagon or arginine.
The growth hormone suppression test is used to diagnose acromegaly. It involves a period of fasting, followed by consuming a 75g glucose drink. Drinking a glucose drink leads to a spike in blood glucose and the release of insulin, which should suppress growth hormone release. Growth hormone levels are monitored before and after administering the drink. Failure to suppress the growth hormone level indicates acromegaly.
Medications
Somatropin is synthetic growth hormone used to treat growth hormone deficiency. It is given by subcutaneous injection. IGF-1 levels are used to monitor the treatment.
Somatostatin analogues (e.g., octreotide) work by mimicking the effects of somatostatin. They are used to treat acromegaly, as they inhibit growth hormone release by the pituitary.
Pegvisomant is a growth hormone receptor antagonist that blocks growth hormone receptors. It is an option for treating acromegaly, given by subcutaneous injection.
Last updated July 2024
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