What is Growth Hormone Deficiency?

Growth hormone deficiency is a disorder that involves the pituitary gland (a small gland located at the base of the brain). This gland produces growth hormone and other hormones (chemical messengers of the body). When it does not produce enough growth hormone, growth will be slower than normal. If other pituitary hormones are absent or present in inadequate amounts, the condition is called hypopituitarism.

Growth hormone deficiency can occur at any age. Growth hormone is necessary for normal growth and development in children. In adults, growth hormone is needed to maintain the proper amounts of body fat, muscle, and bone. In adults, low or absent growth hormone can also cause emotional symptoms, such as tiredness and lack of motivation.

Symptoms

The most common sign of growth hormone deficiency in children is the slowing of growth to less than two inches per year. A child with growth hormone deficiency may also have the following symptoms:

• Short height for child's age
• Increased fat around the waist and in the face
• Feeling upset about his or her height
• The child may look younger than other children his or her age
• Delayed onset of puberty
• Delayed tooth development

Adults with growth hormone deficiency may have the following symptoms:Low energy

• Decreased strength and exercise tolerance
  
• Decreased muscle mass
  
• Weight gain
  
• Anxiety or depression
  
• Thin and dry skin

Treatment

growth hormone deficiency is treated by replacing GH with daily injections under the skin or into muscle. Until 1985, growth hormone for treatment was obtained by extraction from human pituitary glands collected at autopsy. Since 1985, recombinant human growth hormone (rhGH) is a recombinant form of human GH produced by genetically engineered bacteria, manufactured by recombinant DNA technology. In both children and adults, costs of treatment in terms of money, effort, and the impact on day-to-day life, are substantial.

Treatment in childhood
GH treatment is not recommended for children who are not growing despite having normal levels of growth hormone, and in the UK it is not licensed for this use.[10] Children requiring treatment usually receive daily injections of growth hormone. Most pediatric endocrinologists monitor growth and adjust dose every 3–6 months and many of these visits involve blood tests and x-rays. Treatment is usually extended as long as the child is growing, and lifelong continuation may be recommended for those most severely deficient. Nearly painless insulin syringes, pen injectors, or a needle-free delivery system reduce the discomfort. Injection sites include the biceps, thigh, buttocks, and stomach. Injection sites should be rotated daily to avoid lipoatrophy. Treatment is expensive, costing as much as $US 10,000 to 40,000 a year in the USA.

Treatment in adulthood
GH supplementation is not recommended medically for the physiologic age-related decline in GH/IGF secretion.It may be appropriate in diagnosed adult-onset deficiency, where a weekly dose approximately 25% of that given to children is given. Lower doses again are called for in the elderly to reduce the incidence of side effects and maintain age-dependent normal levels of IGF-I.

In many countries, including the UK, the majority view among endocrinologists is that the failure of treatment to provide any demonstrable, measurable benefits in terms of outcomes means treatment is not recommended for all adults with severe growth hormone deficiency , and national guidelines in the UK as set out by NICE suggest three criteria which all need to be met for treatment to be indicated:

• Severe GH deficiency, defined as a peak GH response of <9mU/litre during an insulin tolerance test
• 
  Perceived impairment of quality of life, as assessed by questionnaire
• 
  They are already treated for other pituitary hormone disorders

Where treatment is indicated, duration is dependent upon indication. Cost of adult treatment in the UK is UKP 3000-4000 annually.

Side-effects

• 
  Headache
• Joint pain and muscle pain
• Fluid retention, and carpal tunnel syndrome
• Mild hypertension
• Visual problems
• Nausea and vomiting
• Paraesthesiae
• Antibody formation
• Reactions at the injection site
• Rarely, benign intracranial hypertension.
  

Causes

Growth hormone deficiency is caused by low or absent secretion of growth hormone from the pituitary gland. This condition may be present at birth, or it may develop after birth due to trauma, infections, radiation to the head, or other conditions (for example, tumors).

Adults with growth hormone deficiency usually have a history of pituitary tumors that may have been treated with surgery or radiation.

In some cases, no cause can be identified.

Tests & Diagnosis

For children, the doctor will ask about the child's medical history. If the child's height and weight have been plotted on a growth chart, the doctor will evaluate if the child's growth appears to be leveling off or departing from the child's established growth curve. Past growth patterns are important in determining if the child has a growth problem; the earlier a problem is detected, the earlier it can be treated (if possible) and the better the chance the child has at reaching his or her full growth potential.

The doctor may perform blood tests to determine if a hormone deficiency or other disease is present. X-rays may also be taken to check how the child's bone size compares to the child's height and chronological age.

In adults, blood tests may be performed to determine if a hormone deficiency is present. Adults with growth hormone deficiency may also have increased levels of total cholesterol, low-density-lipoprotein (LDL) cholesterol, apolipoprotein B, and triglycerides. Other tests that may be performed include CT scan and/or MRI of the brain and/or bones. Images from these tests may reveal tumors or reduced bone density.

Prognosis

In childhood
When treated with GHD, a severely deficient child will begin to grow faster within months. In the first year of treatment, the rate of growth may increase from half as fast as other children are growing to twice as fast (e.g., from 1 inch a year to 4 inches, or 2.5 cm to 10). Growth typically slows in subsequent years, but usually remains above normal so that over several years a child who had fallen far behind in his height may grow into the normal height range. Excess adipose tissue may be reduced.

In adulthood
GHD treatment can confer a number of measurable benefits to severely GHD-deficient adults, such as enhanced energy and strength, and improved bone density. Muscle mass may increase at the expense of adipose tissue. Although adults with hypopituitarism have been shown to have a reduced life expectancy, and a cardiovascular mortality rate more than double controls, treatment has not been shown to improve mortality, although blood lipid levels do improve. Similarly, although measurements of bone density improve with treatment, no rates of fractures have not been shown to improve.

Effects on quality of life are unproven, with a number of studies finding that adults with GHD had near-normal indicators of QoL at baseline (giving little scope for improvement), and many using outdated dosing strategies. However, it may be that those adults with poor QoL at the start of treatment do benefit.