Growth hormone deficiency is a medical condition where pituitary hormone located at the base of the brain does not produce enough growth hormone. The growth hormone (GH) is not the only hormone that the pituitary gland produces. It produces other hormones as well that are also related to growth, the most notable being IGF-I, or insulin-like growth factor I, which is closely related to insulin. IGF-I helps promote normal bone and tissue growth and development, including the tissues of liver, kidney, lungs, and nerves. Although normal IGF-I levels does not mean that you don't have GHD, a low level of IGF-I without conditions such as poorly controlled diabetes, liver disease, and oral oestrogen therapy is a strong evidence that you have GHD. [1]
How is the growth hormone secreted?
The growth hormone is released into your bloodstream in stable low levels interrupted by bursts of secretion. These pulses are most evident during your slow-wave sleep, that is, when you are in a state of deep, usually dreamless sleep (non-REM sleep). Secretion of growth hormone increases highly when you reach puberty. Maximum concentrations is reached during early puberty in girls and late puberty in boys. [2]
Types of adult growth hormone deficiency There are two distinct subdivisions of the condition in adults:
Children with growth hormone deficiency transitioning to adulthood or congenital GHD
Growth hormone deficiency acquired during adulthood,which is again of two types
Acquired
Idiopathic
Congenital growth hormone deficiency is one where the deficiency is present from birth and is a result of genetic mutation, or structural defects in the pituitary gland, or multiple hormones deficits because of embryonic injury /trauma.
Acquired growth hormone deficiency is which you acquire later in life as a result of trauma, infection, radiation therapy, pituitary gland disease, or tumour growth within the brain.
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Idiopathic growth hormone deficiency is a rare condition which has no known or diagnosable cause.
Signs and symptoms
A person with GHD is usually of normal size at birth. Sometimes, the infant may show symptoms of low blood sugar. If the infant is a boy, he may have a small penis.
As GHD is a disorder of growth, the child will start developing the following symptoms
Facial bones would develop late; long bones in the body will take longer to lengthen
Slow tooth eruption
Poor nail growth; growth of fine hair
Truncal obesity
Voice would be high pitched
However, if you acquire GHD later in life, your symptoms will be more generalized and may seem unconnected to the GD hormone. The signs and symptoms may vary from changes in memory, changes in processing speed and attention, to depression and anxiety and fatigue, to a general lack of well-being or lack of strength.
Other symptoms include
Neuromuscular dysfunction
Abdominal fat
High cholesterol
Decreased muscle mass and bone density
Decreased insulin sensitivity
Impaired cardiac function
Increased rate of plaque formation in the arterial walls
Decreased sweating
The degree of the deficiency in growth hormone depends directly on your increase in cholesterol levels, especially, low-density lipoprotein-C (LDL), waist hip ratio, and risk of high blood pressure. Incidentally, all of these are responsible for the increased risk of cardiovascular mortality.
Causes of growth hormone deficiency Benign tumour of the pituitary gland (pituitary adenoma and craniopharyngioma) is the most important cause of adult growth hormone deficiency accounting for 65 percent of the total cases. [1]
Other causes of adult growth hormone deficiency include
Perinatal or postnatal trauma
Central nervous system infection
Rathke's cleft cyst
Metastatic tumours of pituitary gland
Diseases like Langerhans cell (type of white blood cells that fight infection) histiocytosis, sarcoidosis, and tuberculosis of parts of brain associated with growth hormone
Radiation therapy
Surgery of the pituitary or hypothalamus
Sheehan's syndrome
In idiopathic GHD, no known cause is found.
Diagnosis
Most cases of growth hormone deficiency in adults comprise diagnosis of GHD in childhood.According to a study published in the International Journal of Endocrinology, adult onset growth hormone deficiency is not a common disorder, and its symptoms are difficult to diagnose, because it does not show any characteristic or indicative sign or symptom. [3]
There are a number of tests to diagnose adult growth hormone deficiency, but experts worldwide believe the insulin tolerance test and the growth-hormone releasing hormone (GHRH) + arginine test (combined test) to be the best available test of GHD in adults.
Insulin tolerance test (ITT):
In this test, insulin injections are given to induce extreme hypoglycaemia (below 2.2 mmol/litre). This causes the release of growth hormone. GH levels are measured for two hours in intervals of 15 to 30 minutes.
If the level is less than 5 ng/mL (nanogram per millilitre), you may have GHD,but if your highest concentration is less than 3 ng/mL, you may have severe GHD.
Note, however, that if you have a history of seizure or heart disease, this test will not work for you. The test suitable for you would be the glucagon stimulation test (GST). Here, 1 to 1.5 mg of glucagon is administered intramuscularly and the GH level are measured between 90 and 240 minutes.
GHRH + arginine test: GHRH is the growth-hormone releasing hormone. In this test, arginine equivalent to 0.5g per kilo of your body weight, along with GHRH equivalent to 1microgram per kilo of your body weight will be administered to you intravenously.
Serum samples will then be collected every 15 to 30 minutes for two hours. This test is normally safe,but there's just a probability that you may experience flushing. Serious side effects are however rare.
This test is not suitable for patients with chronic kidney failure and in people with hypothalamic damage, for example, in those with radiation induced hypopituitarism.
Treatment of growth hormone deficiency
Growth hormone therapy is the only way you can treat this condition.
The growth hormone used in the treatment of GHD is biosynthetic human growth hormone with a potency of 3 IU/mg (as per World Health Organization's guidelines).
The hormone is given as shots or self-administered a few times in a week or on a daily basis, just like people with diabetes self-administer insulin.
GH dose requirement:
Women require higher doses of GH.
Older people require lower doses of GH, for example, if you are more than 60 years, you may be started on doses of 100 200 g (microgram) per day and increased more slowly.
If you are aged 30 60 years, you may be prescribed a starting dose of 300 g/day that is increased by 100 200 g every 1 2 months or as per your doctor's recommendation. You might see the benefits only after 6 or more months of treatment.
Individuals less than 30 years of ageare generally prescribed higher initial doses of 400 500 g per day. [2]
Side effects of growth hormone therapy
Although optimal dosage of the growth hormone does not usually have any side effects, it can affect the way other hormones work. For example, initiation of GH therapy may lead to partial cortisol deficiency. It may also inhibit normal production of thyroid hormone.
Insulin resistance and type 2 diabetes can occur or worsen in patients with pre-existing diabetes.
Other side effects include fluid retention, high blood pressure, paraesthesia (tingling or pricking sensation caused by damage to peripheral nerves), joint stiffness, peripheral oedema, arthralgia, and myalgia, and carpal tunnel syndrome. Older adults, heavier adults, or women are more prone to these adverse effects.
Benefits of growth hormone therapy
Abdominal obesity has everything to do with metabolic syndrome and insulin resistance. GH therapy can reduce this fat as early as 3 months of treatment. Insulin sensitivity however improves only after a year of GH therapy.
Studies have shown that treatment with GH significantly improved lean body mass, LDL cholesterol, total cholesterol, and diastolic blood pressure with use of GH in GH-deficient adults. [2]
Similarly, GH replacement treatment for 6 12 months can lead to significant improvements in body composition, muscle strength, self-esteem scores, energy levels, and emotional reactions if you are growth hormone deficient.
Another study demonstrated that up to 70 percent of patients with the fibromyalgia syndrome also showed reduced growth hormone production. Treatment with growth hormone resulted in improvement in perceived energy levels, body image, and pain level and cognition. [4]
Researchers have also found that growth hormone therapy increases bone metabolism that ultimately translates to an increase in bone mineral density, albeit after one and a half to two years. [5]
References
1. Molitch ME, et al. Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Guidelines. Journal of Clinical Endocrinology & Metabolism. 96(6):1587 1609.
2. Gupta V. Adult growth hormone deficiency. Indian Journal of Endocrinology and Metabolism. 2011;15(Suppl3):S197-S202. doi:10.4103/2230-8210.84865.
3. Glynn N, Agha A. Diagnosing Growth Hormone Deficiency in Adults. International Journal of Endocrinology. 2012;2012:1-7. doi:10.1155/2012/972617.
4. Romano T. Adult growth hormone deficiency in fibromyalgia. PB89 Pain Practice Issue. 2009 Mar;9(Sup 1):118.
5. Giustina A, Mazziotti G, Canalis E. Growth Hormone, Insulin-Like Growth Factors, and the Skeleton. Endocrine Reviews. 2008;29(5):535-559. doi:10.1210/er.2007-0036.
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