Growth hormone deficiency

Growth hormone deficiency: description

There is a deficiency of the hormone somatotropin (STH) in case of growth hormone deficiency. It not only acts as a growth hormone, but has many more responsibilities. So it also affects bones, muscles, fat, sugar balance and cognitive functions.

About one in every 4,000 to 10,000 children is affected by isolated growth hormone deficiency. Isolated means that there are no more hormone failures. This is the case for most patients with growth hormone deficiency.

somatotropin

Somatotropin is produced in the body by the hypophysis, the pituitary gland, and distributed in bursts, especially during sleep. This release is regulated by a hormone (GHRH) from a superordinate 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 releases somatomedine, especially insulin like growth factor-1 (IGF-1). IGF-1 is the real growth factor. Through its distribution increase the protein production, cell proliferation and maturation. The fat and carbohydrate metabolism is also affected. The fat dissolution in the fat cells is driven forward and the effect of the hypoglycemic hormone insulin on the target cells is weakened. This increases the blood sugar level. If a sufficiently high level of IGF-1 is present in the blood, this reduces the secretion of somatotropin.

In the case of a growth hormone deficiency, there may be a disturbance at all levels of the somatotropin balance control circuit. In addition to production disorders of the individual factors and hormones and signal pathways, such as receptors for IGF-1, may be disturbed.

Artificial growth hormone

The treatment of growth hormone deficiency has been possible since 1957 – by replacing the missing hormone. The growth hormone used was then obtained from the pituitary gland (pituitary) deceased. Since 1985, the growth hormone can be produced artificially in the laboratory.

Growth hormone deficiency: symptoms

The symptoms that cause growth hormone deficiency are manifold because the hormone performs a variety of functions. In addition, the symptoms are dependent on the age at onset of disease. The main symptom is a growth disorder in minors. In adults with growth hormone deficiency, the growth is usually already completed, which is why other symptoms come to the fore.

Growth hormone deficiency in children

The central but unspecific symptom in children with growth hormone deficiency is decreased length growth. A congenital growth hormone deficiency usually manifests itself between the sixth and twelfth month of life. However, growth can be normal until the second year. The growth disorder in a growth hormone deficiency affects mostly all body parts alike (proportioned short stature).

With a low growth hormone deficiency, affected children are slim. In contrast, a pronounced deficiency leads to the formation of a relatively thick layer of fat under the skin.

Tooth development is affected by the growth delay.

Another important symptom, especially in babies, is a very significantly reduced blood sugar level (hypoglycaemia). In contrast to other diseases that are associated with low blood sugar levels, in congenital growth hormone deficiency, however, the weight and height of the child at birth are usually still inconspicuous.

Especially in newborns, persistent low blood sugar levels may be the only indication of growth hormone deficiency. It may also be added to hyperbilirubinemia. This is an increased amount of bilirubin in the blood. Bilirubin is a breakdown product of hemoglobin (red blood pigment).

In children, a growth hormone deficiency can affect the general condition so that food and drink are denied.

Growth hormone deficiency in adults

In adults with growth hormone deficiency the moderate general well-being and bad mood stand in the foreground. Performance and quality of life can be reduced. In addition, a redistribution of fat to the abdomen and body trunk falls on. Muscle mass and bone density decrease. Blood lipid levels and susceptibility to cardiovascular disease may be elevated. However, growth hormone deficiency in adults may also be largely symptomless.

Other hormonal 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 the sexual organs), ACTH (important for adrenal function), ADH (important for kidney function) and TSH (important for thyroid function). If the growth hormone deficiency is due to a pituitary disease, the formation of these other hormones may also be impaired – with corresponding symptoms.

Symptoms indicate the cause of the disease

There are a number of symptoms that are already indicative of what causes growth hormone deficiency. These include, for example, the so-called pendulum nystagmus (involuntary back and forth of the eye) and a particularly small penis (micropenis). These two symptoms suggest so-called septo-optic dysplasia – a complex neurological disorder that affects the pituitary gland and ocular nerve.

Growth hormone deficiency: causes and risk factors

A growth hormone deficiency is in most cases idiopathic, that is, the cause is unknown. He may also be innate or acquired. Possible causes in such cases, for example hereditary predisposition, inflammation (such as autoimmune hypophysitis), vascular damage, injuries, tumors or consequences of radiation exposure (such as chemotherapy). Even surgical interventions in the sensitive area of ​​the pituitary gland can trigger a growth hormone deficiency.

Even severe mental stress can influence the sensitive process of growth and development.

In most cases, the growth hormone deficiency occurs in isolation, that is, there are no other hormone disorders.

Growth hormone deficiency: examinations and diagnosis

In the child, growth delays often occur during a check-up at the doctor. During regular examinations, the doctor measures the weight and height of the child. These values ​​are entered in the so-called growth curve (percentile curve). From this one can read whether the growth corresponds to the norm or how far it deviates from this.

The causes of diminished growth, however, are very diverse – growth hormone deficiency is only one possible reason. Specialists in growth hormone deficiency are mainly endocrinologists. The field of endocrinology deals with the (hormone) glands of the body.

History Talk

A central role in the diagnosis of growth hormone deficiency is the collection of medical history (medical history). For this purpose, the doctor talks in detail with the parents of the affected child or with the adult patient itself. It is about learning the individual, family and social background of the person concerned. The doctor will ask questions such as:

• What symptoms did you notice?
• Is the mood, performance or eating and drinking behavior noticeably changed?
• Are pre-existing diseases known?
• How did other family members evolve?
• Are there psychological problems?

Physical examination

The conversation is followed by a physical examination. In children, this includes above all the measurement of height. This measurement must be as accurate as possible. In addition to the absolute values, it is also possible to calculate the growth trend which is important for the assessment of the growth retardation. However, a reliable statement about the growth rate can only be made for longer observations of at least six to twelve months.

By definition, growth is considered abnormal if the values ​​are below the so-called third length percentile. This means that 70 percent of the same age children are larger. In addition, one can distinguish proportional from disproportional growth disorders. In case of a growth hormone deficiency, the growth disorder is usually proportioned, that is: All body parts are affected by the delayed growth.

In the case of older children, the doctor also pays attention to signs of puberty such as chest training and pubic hair as part of the physical examination.

X-ray

To detect growth hormone deficiency, a left hand X-ray is taken. With the help of this picture the “bone age” can be determined. Normally it corresponds to the age. This can be used to distinguish whether there is a developmental delay or growth hormone deficiency. Without evidence of delayed bone growth, growth hormone deficiency is unlikely.

blood test

Based on 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, such as growth hormone produced by the pituitary gland (especially ACTH and TSH) and the substances released by them, such as cortisone, are also measured. When the cause of growth hormone deficiency is the pituitary gland, several hormones are often affected. The measurement of the control hormone from the hypothalamus, which leads to the release of growth hormone (GHRH), is unreliable.

GH stimulation test

If the blood levels of IGF-1 and IGFB-3 are decreased and no other cause can be found, growth hormone deficiency may be present. To investigate this suspicion, an STH stimulation test can be performed. For this purpose, the substance is injected into the fasted patient, which stimulates the pituitary gland to release somatotropin (for example, glucagon, insulin, arginine, clonidine). Subsequently, a blood sample is taken at intervals several times and analyzed to see if and how much growth hormone was shed.

The value that must be measured to rule out growth hormone deficiency is discussed. Mostly a threshold between 8 and 10 nanograms per milliliter (ng / ml) of blood is given. A value below 7 ng / ml indicates a growth hormone deficiency. If a sufficiently high concentration of somatotropin is measured, there is no shortcoming.

Two abnormal stimulation tests are needed to detect growth hormone deficiency. However, one has to take into account that the test result can be influenced by many factors (for example sex hormones and obesity). As a result, the comparability between two tests can not always be given.

In children, partial stimulation tests should not be performed due to side effects. No stimulation should be done in neonates and infants.

Magnetic Resonance Imaging (MRI)

Magnetic Resonance Imaging (MRI) is only used in cases of suspected growth hormone deficiency in specific cases – when the cause for growth hormone deficiency in the brain is suspected.

Genetic studies

Genetic studies may be necessary in suspected genetic damage as a reason for the growth hormone deficiency. However, the specific mutations discovered so far can only be found in a few cases. However, genetic testing can detect a range of disease syndromes.

Growth hormone deficiency: treatment

In order to plan the treatment of patients with growth hormone deficiency, an inpatient stay is usually necessary. In a specialized specialist clinic, the therapy can be adjusted individually.

Growth hormone deficiency is treated with the administration of artificial growth hormone (somatotropin analogues). This therapy is usually started as soon as possible. The hormone must be injected under the skin (subcutaneously). Since the quantity always has to be exact, the patient and possibly also the parents for the medication are specially trained.

In children, the therapy is usually stopped when the growth in length is complete or there is no growth hormone deficiency. In severe cases, it may be necessary to inject the growth hormone for life.

In adults, permanent treatment may also be necessary. In addition, the effect of the artificial growth hormone can be very different. Reasons include genetic differences of the growth hormone receptor (so-called polymorphisms).

Side effects are possible but rare

Treatment with somatotropin analogues may allow children with growth hormone deficiency to achieve normal body size. In adult patients, the therapy may improve symptoms such as increased fat accumulation on the abdomen, decreased performance and reduced bone density.

In some cases, the hormone treatment may have other, sometimes unwanted effects. First, local reactions at the injection site such as tingling and redness may occur. Other potential side effects include urinary tract, throat, gastrointestinal or ear infections, headache, seizures, generalized pain and bronchial asthma. Rarely, the pressure in the brain can rise. In cancer patients, growth hormone therapy can cause another tumor.

Growth hormone also plays a key role in sugar metabolism and thus the ability of the organism to keep its sugar level constant. If the therapy with artificial growth hormone is poorly adjusted, the sugar balance may be disturbed or not normalizing. This can contribute to the development of diabetes mellitus.

Somatotropin therapy increases bone density. As a result, an existing scoliosis (laterally bent spine) may deteriorate and develop a so-called femoral head epiphysiolysis (a damage to the head of the femur).

Overall, significant side effects are rare with artificial growth hormone therapy. Nevertheless, 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 to be properly adjusted if this concentration is within the intended range. If the treatment has not had sufficient effect after one year, treatment discontinuation may be considered.

surgery

In some cases of growth hormone deficiency surgery may be necessary. This is especially true when brain tumors are responsible for the growth hormone deficiency. The specialists for these procedures are neurosurgeons.

Growth hormone deficiency: disease course and prognosis

An untreated growth hormone deficiency leads to a child remaining smaller than his peers. In addition, other organ functions may be impaired. Possible complications include cardiovascular disease, osteoporosis, insulin resistance and cognitive and mental disorders. It is believed that life expectancy without therapy is also reduced.

If a growth hormone deficiency in children is treated in time, a normal body size is possible and the majority of disease complications is prevented.

In adults with growth hormone deficiency, therapy can, in most cases, significantly improve the quality of life of those affected.

The majority of patients with growth hormone deficiency and an inconspicuous MRI scan later develop normal growth hormone secretion. Because of this, the diagnosis should be “Growth hormone deficiency“And thus the therapy can be checked regularly.