What is it and what is its purpose?

Growth hormone (GH), also called somatotropin, is a hormone produced by the pituitary gland located at the base of the brain. This hormone plays a crucial role in the development of the body, influencing bone growth and the metabolism. 
The effects of growth hormone are manifold. Among the most important, GH: promotes the growth of bones and tissues during childhood and adolescence; regulates the metabolism of fats, proteins and carbohydrates and helps in the repair and regeneration of tissues. It also increases blood glucose levels and causes the liver to produce glucose again. Some conditions stimulate the release of GH by the pituitary gland, for example, physical activity (especially weight training and high-intensity training), sleep and a balanced diet rich in protein and low in refined sugars. In contrast, it has been shown that chronic stress can inhibit the production of this hormone.

Growth hormone deficiency in childhood and adulthood, causes and symptoms

Growth hormone deficiency is an isolated pituitary deficiency, i.e. without other hormonal changes, which is most common in children but can also occur in adulthood. It can be congenital or acquired. A congenital deficiency may be due to genetic mutations that result in abnormalities of the GHRH receptor, the hypothalamic hormone that stimulates the pituitary to produce GH, or of the GH1 gene, which codes for the GH hormone. These abnormalities cause either impaired and, therefore, hypofunctional GH production or a lack of production of the hormone. An acquired deficiency occurs, for example, as a result of head trauma, pituitary or hypothalamic tumours, radiation therapy of the skull, inflammation or infection in the brain.
In children, GH deficiency can lead to slowed or stunted growth, with lower than average height for age and gender. Children may also have delays in bone maturation and tooth development and may experience hypoglycaemia (reduced blood glucose levels).
If early intervention is not forthcoming, the child will, in later years, assume the typical appearance of pituitary short stature, also known as harmonic dwarfism, in which the child is short in stature but the normal proportions between upper and lower limbs are maintained. This characteristic makes it possible to distinguish short stature due to GH deficiency from disharmonic dwarfism (e.g. due to thyroid disorders), in which the proportions between body segments are not maintained.
In adults, a GH deficiency can cause a reduction in muscle mass and bone density, an increase in fat mass, and alterations in metabolism with an associated increased risk of cardiovascular disease.

How is the diagnosis made, and what tests should be carried out?

The diagnostic suspicion of GH hormone deficiency is raised on the basis of clinical evaluations and statural and weight growth measurements routinely performed by the pediatrician. The physician refers the patient for laboratory analyses to assess the various causes of reduced growth, such as hypothyroidism, coeliac disease, malnutrition and inflammatory states. The basal measurement of GH is not conclusive because GH levels are pulsatile, i.e. they show significant variations during the day and are therefore difficult to interpret. The levels of IGF1 , a growth factor induced by GH, and the levels of the protein that binds it, IGFBP-3, which will be lower than the average values related to the patient’s age, are then measured. If the diagnostic suspicion persists, GH stimulation tests are performed, where the response of the secretion of this hormone is evaluated following specific stimuli such as, for example, administering arginine or insulin, which should cause an increase in the levels of the hormone in the blood. In patients with short stature and suspected GH deficiency, the diagnosis is made when GH concentrations do not reach a threshold value after two specific stimuli performed on different days. Imaging studies, such as wrist radiography, may also be indicated to determine bone age (which in these patients does not correspond to their actual age) and a brain MRI, to exclude underlying brain diseases.

Genetic analysis, when should it be done and which genes should be tested?

In some cases, GH deficiency may have a genetic basis. It is then possible to perform a genetic analysis aimed at identifying mutations in specific genes involved in the production or function of GH. Gene research can be carried out if there is a suspicion of a genetic cause, especially in the presence of a family history of GH deficiency. 
Some of the best studied genes include:

• GH1: a gene that codes for growth hormone;
• GHRHR: a gene that codes for the GHRH receptor, the hypothalamic hormone that stimulates the release of GH in the pituitary gland;
• SHOX: a gene involved in bone development. Mutations in SHOX can cause short stature and other abnormalities in the absence of a GH deficiency. The search for this mutation can be indicated when more common causes of short stature have been excluded.

Therapy and side effects

Once the diagnosis of growth hormone deficiency has been made, the doctor (pediatrician and/or endocrinologist) must determine the continuation of treatment depending on the clinical presentation and the underlying causes. The main therapy for GH deficiency is the administration of recombinant GH (rhGH) by daily subcutaneous injections at the dosage prescribed by the doctor, depending on the patient’s age and response to therapy. In children, the treatment lasts until the final height is reached. In adults, therapy can be continuous or cyclical depending on the clinical presentation and response to treatment.
Side effects may include fluid retention with the formation of oedema, hyperglycaemia, joint and muscle pain, and metabolic changes. Therefore, regular monitoring of the therapy is indicated.

Bibliography
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