Growth hormone deficiency
Growth Hormone deficiency is a rare disease, which can lead mainly to physical developmental disorders. The main symptom in children is reduced length growth. In adults with growth hormone deficiency, other symptoms come to the fore. Patients receive artificial growth hormone injected under the skin.
There is a deficiency of the hormone somatotropin (STH) in a growth hormone deficiency. It does not only act as as a growth hormone but also has many other tasks. It also affects bones, muscles, fat, sugar balance and cognitive functions.
About one in 4,000 to 10,000 children is affected by an isolated growth hormone deficiency. Isolated means that there are no further hormonal failures. This is the case for most patients with growth hormone deficiency.
Somatotropin is produced in the body by the pituitary gland and is mainly distributed during sleep. This distribution is regulated by a hormone (GHRH) from a higher-level brain region, the hypothalamus.
The release of somatotropin into the blood leads to a variety of reactions in the body. Among other things, the liver Somatomedine releases, especially the insulin like growth factor-1 (IGF-1). IGF-1 is the real growth factor. Through its distribution, protein production, cell proliferation and maturation increase.
The change in fat and carbohydrate is also affected. The fat dissolution in the fetal cells is pre-driven and the effect of the blood-sucking hormone insulin on the target cells is weakened. This increases the blood glucose level. If a sufficiently high level of IGF-1 is present in the blood, this reduces the release of somatotropin.
In the case of a growth hormone deficiency, there may be a disorder at all levels of the control circuit of the somatotropin. In addition to production disturbances of the individual factors and hormones, signaling pathways such as receptors for IGF-1 can also be disturbed.
Growth hormone deficiency symptoms
The symptoms that cause a growth hormone deficiency are numerous because the hormone performs a wide variety of functions. In addition, the symptoms are dependent on the age at the onset of disease. In adults with growth hormone deficiency, the growth is usually already complete which is why other symptoms come to the fore.
Growth hormone deficiency in children
A central but non-specific symptom in children with growth hormone deficiency is reduced length growth. An innate growth hormone deficiency is usually noticeable between the sixth and twelfth months of life. However, growth can also be normal by the second year. The growth disorder in a growth hormone deficiency usually affects all parts of the body equally (proportioned dwarfism).
Affected children are slim when growth hormone deficiency is at low stage. Tooth development is also affected by the growth delay. Another important symptom is especially in babies, a very markedly low blood glucose level (hypoglycemia).
In contrast to other diseases, which are associated with low blood glucose levels, the weight and size of the child at birth are usually still inconspicuous with congenital growth hormone deficiency.
Especially in newborns, the persistent low blood glucose level may be the only indication of a growth hormone deficiency. Hyperbilirubinemia may also ocur. These include an increased amount of bilirubin in the blood.
In children, a growth hormone deficiency can affect the general condition so that food and drink are denied.
Growth hormone deficiency in adults
Performance and quality of life can be reduced. In addition, a redistribution of the fat to the abdomen and body stem occurs. Muscle mass and bone density decrease. The blood fat levels and susceptibility to cardiovascular disease may be increased. However, growth hormone deficiency in adults can also be largely symptomless.
Other hormone disorders
The growth hormone is produced in the pituitary gland. This also produces other hormones. Examples are LH and FSH (important for the function of sexual organs), ACTH (important for adrenal function), ADH (important for renal function) and TSH (important for thyroid function). If the growth hormone deficiency is due to a pituitary disorder, the formation of these other hormones can also be affected.
Growth hormone deficiency causes and risk factors
A growth hormone deficiency is in most cases idiopathic, which means the cause is unknown. It can also be innate or acquired. Possible causes are, for example, hereditary predisposition, inflammation (such as autoimmune hypophysitis), vascular damage, injuries, tumors or consequences of radiation exposure (e.g. by chemotherapy).
Surgical interventions in the sensitive area of the pituitary gland can also cause a growth hormone deficiency. Severe psychological stress can also affect the sensitive process of growth and development. In most cases, the growth hormone deficiency occurs in isolation, that is, there are no further hormonal disorders.
Growth hormone deficiency diagnosis
In the child, growth delays often occur during a precautionary check with the doctor. In regular examinations, the physician measures the weight and size of the child. These values are entered into the so-called growth curve (percentile curve). From this it can be seen whether the growth corresponds to the standard or how far it differs from it.
However, the causes for reduced growth are very diverse – growth hormone deficiency is only one possible reason. Specialists in growth hormone deficiency are primarily endocrinologists. The field of endocrinology deals with the (hormonal) glands of the body.
Medical History Interview
A central role in the diagnosis of growth hormone deficiency is the elevation of the patient’s history (anamnesis). For this purpose, the doctor is in close contact with the parents of the affected child or with the adult patient himself. The aim is to find out the individual, family and social background of the person concerned. The doctor will ask the following questions, among other things:
- What symptoms do you notice?
- Is the mood, performance or eating and drinking behavior noticeably changed?
- Are previous medical conditions known?
- How did other family members develop?
- Do psychological stresses exist?
In order to determine a growth hormone deficiency, an X-ray image of the left hand is made. With this image, the “bone age” can be determined. In the normal case it corresponds to the age of life. This makes it possible to distinguish whether there is a developmental delay or a growth hormone deficiency. Without evidence of delayed bone growth, a growth hormone deficiency is unlikely.
Using a blood test, the physician measures routine parameters as well as the concentration of growth hormone somatotropin (STH), IGF-binding protein-3 (IGFBP-3) and IGF-I. However, the blood levels of other hormones produced by the pituitary gland (especially ACTH and TSH) are also measured, as are the hormones produced by them, such as cortisone. If the cause of growth hormone deficiency is in the pituitary gland, several hormones are often affected.
GH stimulation test
If the blood levels of IGF-1 and IGFB-3 are lowered and no other cause can be found, there may be a growth hormone deficiency. An STH stimulation test can be performed to investigate this suspicion.
For this purpose, the patient is injected a substance that stimulates the pituitary gland for the distribution of somatotropin (e.g. glucagon, insulin, arginine, clonidine). Subsequently, a blood sample is taken and analyzed several times to see if and how much growth hormone has been distributed.
Magnetic resonance tomography (MRI)
Magnetic resonance tomography (MRI) is only carried out in special cases, if the cause of the growth hormone deficiency is suspected in the brain.
Genetic investigations can be necessary in case of suspicion of genetic defects as a reason for the growth hormone deficiency. However, specific mutations has been discovered in a few cases.
Growth hormone deficiency treatment
The growth hormone deficiency is treated with the administration of artificial growth hormone (somatotropin analogs). This therapy is usually started as soon as possible. The hormone must be injected under the skin (subcutaneously).
In children, the therapy is usually terminated when the length growth is completed or there is no longer a growth hormone deficiency. In severe cases, it may be necessary to inject the growth hormone throughout life.
Permanent treatment may also be necessary in adults. Moreover, the effect of the artificial growth hormone can be very different.
Side effects are possible, but rarely
Treatment with somatotropin analogs may allow children with growth hormone deficiency to reach a normal body size. In adult patients, the therapy can improve symptoms such as increased fat accumulation on the abdomen, reduced performance and reduced bone density.
In some cases, the hormonal treatment may have other undesirable effects. First, local reactions may occur at the puncture site, such as tingling and redness. Other possible side effects are urinary tract, throat, gastrointestinal or ear infections, headaches, spasm attacks, general pain and bronchial asthma. Rarely, the pressure in the brain may increase. In cancer patients, growth hormone therapy can lead to a further tumor.
The growth hormone also has a crucial significance for the sugar metabolism and thus the ability of the organism to keep the sugar level constant. If therapy with artificial growth hormone is poorly adjusted, the sugar balance may be disturbed or not normalized. This can contribute to the development of diabetes mellitus.
Somatotropin therapy increases bone density. As a result, an existing scoliosis (lateral vertebral spine) can deteriorate and develop a so-called femoral head epiphysiolysis (a damage to the head of the femur).
Overall, significant side effects are rare under therapy with artificial growth hormone. However, treatment should be closely monitored at least every other month. An important parameter is the IGF-1 concentration in the blood. The therapy is considered correct if this concentration is in the intended range. If the treatment has not shown a sufficient effect after one year, treatment discontinuation may be considered.
In some cases of growth hormone deficiency, surgery may be necessary. This is especially true if brain tumors are responsible for the growth hormone deficiency. The specialists for these interventions are the neurosurgeons.
Growth hormone deficiency disease course and prognosis
An untreated growth hormone deficiency causes a child to remain smaller than its peers. In addition, other organ functions may be affected. Possible complications include cardiovascular diseases, osteoporosis, insulin resistance and cognitive as well as mental disorders. It is believed that life expectancy without therapy is also diminished.
If a growth hormone deficiency in children is treated in a timely manner, a normal body size is possible and the majority of the complications of the disease are prevented.
In adults with growth hormone deficiency, therapy can significantly improve the quality of life of those affected.