Why do HGH levels drop with age

Growth hormone deficiency

Growth hormone deficiency: description

If there is a growth hormone deficiency, there is a deficiency in the hormone somatotropin (STH). In addition to acting as a growth hormone, it has many other roles as well. It also influences bones, muscles, fat, sugar balance and cognitive functions.

Isolated growth hormone deficiency affects around one in 4,000 to 10,000 children. Isolated means that there are no further hormonal failures. This is the case for most growth hormone deficient patients.

Somatotropin

Somatotropin is produced in the body by the pituitary gland, and is released in bursts, especially during sleep. This release is regulated by a hormone (GHRH) from a higher-level brain region, the hypothalamus.

The release of somatotropin into the blood leads to a wide variety of reactions in the body. Among other things, the liver releases somatomedins, especially insulin-like growth factor-1 (IGF-1). IGF-1 is the real growth factor. Its release increases protein production, cell reproduction and maturation. The metabolism of fat and carbohydrates is also influenced. The fat dissolution in the fat cells is promoted and the effect of the blood sugar lowering hormone insulin on the target cells is weakened. This causes the blood sugar level to rise. If there is a sufficiently high level of IGF-1 in the blood, this reduces the release of somatotropin.

If there is a growth hormone deficiency, there can be a disorder at all levels of the control circuit of the somatotropin balance. In addition to production disorders of the individual factors and hormones, signaling pathways, such as receptors for IGF-1, can also be disrupted.

Artificial growth hormone

Treatment of growth hormone deficiency has been possible since 1957 - by replacing the missing hormone. The growth hormone used at that time was obtained from the pituitary gland (pituitary gland) of the deceased. Since 1985 the growth hormone can be produced artificially in the laboratory.

Growth hormone deficiency: symptoms

The symptoms that a growth hormone deficiency triggers are diverse, as the hormone fulfills a wide variety of functions. In addition, the symptoms depend on the age at the onset of the disease. The main symptom in minors is stunted growth. In adults with growth hormone deficiency, growth has usually already been 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 reduced growth in length. A congenital growth hormone deficiency is usually noticeable between the ages of six and twelve months. However, growth can also be normal until the second year. The growth disorder caused by a growth hormone deficiency usually affects all parts of the body equally (proportioned short stature).

If the growth hormone deficiency is only slight, affected children are slim. A pronounced deficiency, on the other hand, leads to the formation of a relatively thick layer of fat under the skin.

Tooth development is also affected by the growth retardation.

Another important symptom, especially in babies, is a markedly low blood sugar level (hypoglycaemia). In contrast to other diseases that are associated with low blood sugar levels, if the child is born with growth hormone deficiency, the weight and height of the child are usually normal at birth.

Persistent low blood sugar levels, especially in newborns, can be the only indication of a growth hormone deficiency. However, hyperbilirubinemia can also occur. This means 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 well-being to such an extent that eating and drinking are refused.

Growth hormone deficiency in adults

In adults with growth hormone deficiency, the moderate general well-being and bad mood are in the foreground. This can reduce performance and quality of life. In addition, a redistribution of fat to the stomach and trunk is noticeable. Muscle mass and bone density decrease. Blood lipid levels and susceptibility to cardiovascular diseases can be increased. However, growth hormone deficiency in adults can also be largely asymptomatic.

More hormonal imbalances

The growth hormone is produced in the pituitary gland. This also makes other hormones. Examples are LH and FSH (important for the function of the sexual organs), ACTH (important for the function of the adrenal gland), ADH (important for the kidney function) and TSH (important for the thyroid function). If the growth hormone deficiency is due to a disease of the pituitary gland, the production of these other hormones can also be impaired - with corresponding symptoms.

Symptoms indicate the cause of the disease

There are a number of symptoms that already give an indication of what is causing the growth hormone deficiency. These include, for example, the so-called pendulum nystagmus (involuntary swinging of the eye) and a particularly small penis (micropenis). These two symptoms suggest what is known as septo-optic dysplasia - a complex neurological disorder that affects the pituitary gland and the ocular nerve.

Growth Hormone Deficiency: Causes and Risk Factors

In most cases, growth hormone deficiency is idiopathic, meaning the cause is unknown. But it can also be congenital or acquired. Possible causes in such cases are, for example, hereditary predisposition, inflammation (such as autoimmune hypophysitis), vascular damage, injuries, tumors or the consequences of radiation exposure (e.g. from chemotherapy). Surgical interventions in the sensitive area of ​​the pituitary gland can also trigger a growth hormone deficiency.

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

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

Growth hormone deficiency: examinations and diagnosis

In children, growth retardations are often noticed during a medical check-up. During the regular examinations, the doctor measures the child's weight and height. These values ​​are entered in the so-called growth curve (percentile curve). From this it can be seen whether the growth corresponds to the norm or how far it deviates from it.

However, the causes of decreased growth are very diverse - growth hormone deficiency is only one possible reason. Especially endocrinologists are specialists in growth hormone deficiency. The field of endocrinology deals with the (hormone) glands of the body.

Anamnesis interview

A central role in diagnosing growth hormone deficiency is taking a medical history (anamnesis). To this end, the doctor talks in detail with the parents of the child concerned or with the adult patient himself. The aim is to find out about the individual, family and social background of the person concerned. The doctor will ask the following questions, among others:

  • What symptoms did you notice?
  • Have you changed your mood, performance or eating and drinking behavior noticeably?
  • Are you aware of any previous illnesses?
  • How did other family members develop?
  • Are there psychological stresses?

Physical examination

The interview is followed by a physical exam. In the case of children, this includes measuring their height. This measurement must be as accurate as possible. In addition to the absolute values, the growth development can also be calculated, which is important for assessing the growth retardation. A reliable statement about the growth rate can only be made with longer observation over at least six to twelve months.

By definition, growth is classified as abnormal if the values ​​are below the so-called third percentile of length. This means that 70 percent of children of the same age are older. In addition, one can differentiate between proportional and disproportionate growth disorders. In the case of a growth hormone deficiency, the growth disorder is usually proportionate, i.e. all parts of the body are affected by the delayed growth.

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

X-ray examination

An X-ray of the left hand is taken to check for growth hormone deficiency. With the help of this picture, the "bone age" can be determined. Normally it corresponds to the age. This can be used to differentiate whether there is a developmental delay or a growth hormone deficiency. Without evidence of delayed bone growth, growth hormone deficiency is unlikely.

Blood test

Using a blood test, the doctor measures routine parameters as well as the concentration of the growth hormone somatotropin (STH), IGF binding protein-3 (IGFBP-3) and IGF-I. The blood levels of other hormones that are produced by the pituitary gland like growth hormone (especially ACTH and TSH), as well as the substances released by them such as cortisone, are also measured. When the cause of the growth hormone deficiency is in the pituitary gland, multiple hormones are often affected. The measurement of the control hormone from the hypothalamus, which leads to the release of growth hormone (GHRH), is unreliable.

STH stimulation test

If the blood levels of IGF-1 and IGFB-3 are low and no other cause can be found, there may be a growth hormone deficiency. To investigate this suspicion, an STH stimulation test can be performed. For this purpose, the fasting patient is injected with a substance that stimulates the pituitary gland to release somatotropin (e.g. glucagon, insulin, arginine, clonidine). A blood sample is then taken several times at regular intervals and analyzed to see whether and how much growth hormone has been released.

The minimum value that must be measured in order to rule out a growth hormone deficiency is discussed. Usually a limit value 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 deficiency.

Two suspicious stimulation tests are required to detect a growth hormone deficiency. But you have 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 cannot always be given.

Stimulation tests may not be performed in children due to side effects. No stimulation should be given to newborns and infants.

Magnetic resonance imaging (MRI)

Magnetic resonance imaging (MRI) is only performed in special cases if a growth hormone deficiency is suspected - namely if the cause of the growth hormone deficiency in the brain is suspected.

Genetic Studies

Genetic tests may be necessary if genetic damage is suspected as the reason for the growth hormone deficiency. However, the specific mutations discovered so far can only be found in a few cases. However, a number of disease syndromes can be detected with a genetic test.

Read more about the examinations

Find out here which examinations can be useful for this disease:

Growth Hormone Deficiency: Treatment

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

The 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 has to be injected under the skin (subcutaneously). Since the amount must always be exact, the patient and, if necessary, the parents, are specially trained in how to administer the medication.

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

Permanent treatment may also be necessary in adults. In addition, the effect of the artificial growth hormone can be very different. The reasons for this include genetic differences in the growth hormone receptor (so-called polymorphisms).

Side effects are possible, but rare

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

In some cases, the hormone treatment can have other, sometimes undesirable effects. First of all, local reactions such as tingling and reddening may occur at the injection site. Other possible side effects are urinary tract, throat, gastrointestinal or ear infections, headaches, seizures, general pain and bronchial asthma. The pressure in the brain can rarely increase. In cancer patients, growth hormone therapy can cause another tumor.

The growth hormone is also of crucial importance for the sugar metabolism and thus the ability of the organism to keep the sugar level constant. If the therapy with artificial growth hormone is poorly adjusted, the sugar balance may be disturbed or not normalize. This can contribute to the development of diabetes mellitus.

Somatotropin therapy increases bone density. This can worsen an existing scoliosis (laterally bent spine) and develop what is known as femoral head epiphysiolysis (damage to the head of the thigh bone).

Overall, significant side effects are rare with artificial growth hormone therapy. However, the treatment should be checked closely at least every other month. An important parameter is the IGF-1 concentration in the blood. Therapy is considered to be properly adjusted when this concentration is in the intended range. If the treatment has not shown sufficient effect after one year, treatment discontinuation can 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 interventions are the neurosurgeons.

Growth hormone deficiency: disease course and prognosis

Untreated growth hormone deficiency causes a child to stay smaller than their peers. In addition, other organ functions can be impaired. Possible complications include cardiovascular disease, osteoporosis, insulin resistance, and cognitive and mental disorders. It is assumed that life expectancy is also reduced without therapy.

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

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

The majority of patients with growth hormone deficiency and an unremarkable MRI scan later develop normal growth hormone levels. For this reason, the diagnosis "Growth hormone deficiency“And thus the therapy should also be checked regularly.

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