Brief overview
- Treatment: Injections with genetically engineered artificial growth hormone until growth is complete, possibly also in adulthood
- Symptoms: In children, mainly impaired growth, possibly impaired tooth development; in adults, poor general condition, fat distribution disorder, susceptibility to cardiovascular diseases
- Causes and risk factors: A specific cause can only be found in a quarter of cases; congenital or acquired, for example due to heredity, pituitary tumor, as a result of radiation, inflammation, injury
- Diagnosis: Medical history, body measurements, blood tests for specific hormones, hand X-ray to determine growth, magnetic resonance imaging if necessary
- Prognosis: Untreated, usually reduced growth, complications possible, with treatment normal growth is possible, in adults with treatment improvement in quality of life
What is growth hormone deficiency?
Growth hormone deficiency is a deficiency of the hormone somatotropin (STH). It not only acts as a growth hormone, but also has many other functions. For example, it influences bones, muscles, fat, sugar balance and cognitive functions.
Growth hormone deficiency occurs both congenitally and as an acquired disease.
Somatotropin
Somatotropin is produced in the body by the pituitary gland and is released intermittently, 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 variety of reactions in the body. Among other things, the liver releases somatomedins, in particular insulin-like growth factor 1 (IGF-1).
IGF-1 is the actual growth factor. Its release increases protein production, cell proliferation and maturation. IGF-1 also influences fat and carbohydrate metabolism, driving fat breakdown in the fat cells and weakening the effect of the blood sugar-lowering hormone insulin on the target cells. 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.
In the case of a growth hormone deficiency, a disruption is possible at all levels of the control circuit of the somatotropin balance. In addition to production disorders of the individual factors and hormones, disturbed signaling pathways are possible, such as receptors for IGF-1.
The treatment of growth hormone deficiency has been possible since 1957 – by replacing the missing hormone. At that time, the growth hormone used was extracted from the pituitary gland of deceased people.
Today (since 1985), genetically engineered, artificial somatotropin is used, which doctors administer by injection.
What can be done about growth hormone deficiency?
In order to plan the treatment of patients with growth hormone deficiency, an inpatient stay is usually necessary. In a specialized clinic, the doctors adjust the therapy individually.
Doctors treat growth hormone deficiency with the regular administration of artificial growth hormone (somatotropin analogs). This therapy is usually started as soon as possible after diagnosis. The hormone must be injected under the skin (subcutaneously). As the amount must always be exact, the patient and, if necessary, the parents are given special training on how to administer the medication.
In children, the practitioners often stop the therapy when the growth in length is complete or there is no longer a growth hormone deficiency. In severe cases, it is necessary to inject the growth hormone for the rest of the patient’s life.
In adults, long-term treatment is also necessary in some cases.
Doctors are now continuing treatment with artificial somatotropin even after growth has been completed, as the hormone has an effect on many metabolic processes. A positive effect of treatment in adult patients on many physical processes has now been proven.
Side effects are possible, but rare
In many cases, treatment with somatotropin analogs enables children with growth hormone deficiency to reach a normal height. In adult patients, the therapy improves symptoms such as increased fat accumulation on the abdomen, reduced performance and reduced bone density.
In some cases, hormone treatment has other, sometimes undesirable, effects. For example, local reactions such as tingling and redness sometimes occur at the injection site. Other possible side effects include urinary tract, throat, gastrointestinal or ear infections, headaches, seizures, general pain and bronchial asthma. Rarely, there is an increase in pressure in the brain. In cancer patients, it is possible that growth hormone therapy may cause another tumor to develop.
Somatotropin therapy increases bone density. This may worsen an existing scoliosis (laterally curved spine) and so-called femoral head epiphysiolysis (damage to the head of the femur) may develop.
Overall, significant side effects are rare during treatment with artificial growth hormone. Nevertheless, the doctor should monitor the treatment closely at least every other month. An important parameter is the IGF-1 concentration in the blood. The therapy is considered to be correctly adjusted if this concentration is within the intended range. Only if the treatment does not have a sufficient effect after one year should treatment be discontinued.
Surgery
In some cases of growth hormone deficiency, surgery in the area of the pituitary gland is necessary. This is particularly the case if brain tumors are responsible for the growth hormone deficiency. Specialists for these operations are neurosurgeons.
Symptoms
Growth hormone deficiency in children
The central but non-specific symptom in children with growth hormone deficiency is reduced growth in length. A congenital growth hormone deficiency usually becomes noticeable between the sixth and twelfth month of life. Until the second year, however, growth is often still normal. The growth disorder caused by a growth hormone deficiency usually affects all parts of the body equally (proportionate short stature).
If 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 growth retardation.
Another important symptom, especially in babies, is a very significantly reduced blood sugar level (hypoglycemia). In contrast to other diseases that are associated with low blood sugar levels, the weight and height of the child are usually still normal at birth in the case of congenital growth hormone deficiency.
In children, a growth hormone deficiency often affects their general condition to such an extent that they refuse to eat or drink.
Growth hormone deficiency in adults
In adults with growth hormone deficiency, the main symptoms are a moderate general state of health and low mood. Performance and quality of life are often reduced as a result. There is also a noticeable redistribution of fat towards the abdomen and trunk. Muscle mass and bone density decrease. Blood lipid levels and susceptibility to cardiovascular disease are often increased. However, growth hormone deficiency in adults may also be largely asymptomatic.
Other hormone disorders
Growth hormone is produced in the pituitary gland. This also produces other hormones. Examples are
- LH (luteinizing hormone) and FSH (follicle-stimulating hormone, important for the function of the sexual organs)
- ACTH (adrenocorticotropic hormone, important for the function of the adrenal gland)
- ADH (antidiuretic hormone, important for kidney function)
- TSH (thyroid-stimulating hormone, important for thyroid function)
If the growth hormone deficiency is due to a general disease of the pituitary gland, the production of these other hormones is usually impaired – with corresponding symptoms.
There are a number of symptoms that in some cases provide an indication of what is causing the growth hormone deficiency. These include, for example, so-called pendular nystagmus (involuntary oscillation of the eye back and forth) and a particularly small penis (micropenis). These two symptoms are indicative of septo-optic dysplasia – a complex neurological disorder that affects the pituitary gland and ocular nerve.
Causes and risk factors
In most cases, growth hormone deficiency is idiopathic, i.e. the cause is unknown. A specific cause can only be determined in around a quarter of cases.
The disease is congenital or acquired later. Possible causes include hereditary predisposition, inflammation (such as autoimmune hypophysitis), vascular damage, injuries, tumors or the effects of radiation exposure (such as chemotherapy). Surgical interventions in the sensitive area of the pituitary gland can also trigger a growth hormone deficiency under certain circumstances.
Severe psychological stress sometimes influences the sensitive process of growth and development.
In most cases, growth hormone deficiency occurs in isolation, i.e. there are no other hormonal disorders.
Examinations and diagnosis
However, the causes of reduced growth are very diverse – growth hormone deficiency is only one possible reason. Specialists in growth hormone deficiency are primarily endocrinologists. The specialist 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 taking of a medical history (anamnesis). To do this, the doctor talks in detail with the parents of the affected child or with the adult patient themselves. The aim is to find out the individual, family and social background of the person affected. The doctor will ask the following questions, among others:
- What symptoms have you noticed?
- Are there any noticeable changes in mood, performance or eating and drinking behavior?
- Are you aware of any previous illnesses?
- How have other family members developed?
- Is there any psychological stress?
Physical examination
By definition, growth is classified as abnormal if the values are below the so-called third length percentile. This means that 70 percent of children of the same age are taller.
Even more specifically, the child’s growth can be set in relation to the height of the parents and thus to an expected target height. For the “target height”, take the average height of both parents. For boys, add 6.5 centimeters, for girls subtract 6.5 centimeters. This height can be used to measure an expected growth curve. The permitted deviation range is assumed to be 8.5 centimeters upwards and downwards.
A distinction can also be made between proportional and disproportional growth disorders. In the case of growth hormone deficiency, the growth disorder is usually proportional, i.e. all parts of the body are affected by the delayed growth.
In older children, the doctor will also look for signs of puberty such as the development of breasts and pubic hair as part of the physical examination.
X-ray examination
Blood test
The doctor uses a blood test to measure routine parameters and the concentration of 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) are also measured, as well as the substances they release, such as cortisone. If the cause of the growth hormone deficiency lies in 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.
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, it is possible to carry out a so-called STH stimulation test. To do this, the doctor injects the fasting patient with a substance that stimulates the pituitary gland to release somatotropin (such as glucagon, insulin, arginine, clonidine). A blood sample is then taken several times at intervals and the doctor analyzes it to see whether and how much growth hormone has been released.
Two conspicuous stimulation tests are required to detect a growth hormone deficiency. However, it must be borne in mind that the test result is influenced by many factors (e.g. sex hormones and obesity). This means that it is not always possible to compare two tests.
In some cases, stimulation tests must not be carried out on children due to side effects. No stimulation may be carried out on newborns and infants.
Magnetic resonance imaging (MRI)
Magnetic resonance imaging (MRI) is only used in special cases of suspected growth hormone deficiency – if the doctor suspects the cause of the growth hormone deficiency in the brain, for example in the form of a tumor.
Genetic tests
Genetic tests may be necessary if genetic damage is suspected as the cause of growth hormone deficiency. However, the specific mutations discovered to date can only be found in a few cases. However, a number of disease syndromes can be identified by genetic testing.
Disease progression and prognosis
If growth hormone deficiency in children is treated in time, normal height is possible and the majority of disease complications can be prevented.
In adults with growth hormone deficiency, treatment significantly improves the quality of life of those affected in most cases.
The majority of patients with growth hormone deficiency and an unremarkable MRI examination later develop normal growth hormone secretion. For this reason, the diagnosis of growth hormone deficiency and therefore also the therapy should be reviewed regularly.
