Гигантизм: причины, симптомы и генетические факторы

Human growth disorder

Gigantism (γίγας, gígas, "giant", plural γίγαντες, gígantes), also known as giantism, is a condition characterized by excessive growth and height significantly above average. In humans, this condition is caused by over production of growth hormone in childhood. It is a rare disorder resulting from increased levels of growth hormone before the fusion of the growth plate which usually occurs at some point soon after puberty. This increase is most often due to abnormal tumor growths on the pituitary gland. Gigantism should not be confused with acromegaly, the adult form of the disorder, characterized by somatic enlargement specifically in the extremities and face.

Gigantism is characterized by an excess of growth hormone (GH). The excess of growth hormone that brings about gigantism is virtually always caused by pituitary growths (adenomas). As a result of the excessive amounts of growth hormone, children achieve heights that are well above normal ranges. The specific age of onset for gigantism varies between patients and gender, but the common age that excessive growth symptoms start to appear has been found to be around 13 years.

Growth hormone (GH) and insulin like growth factor I (IGF I) are two substances that have been identified as influencing growth plate formation and bone growth and, therefore, gigantism. Their specific mechanisms are still not well understood. More broadly, GH and IGF have both been identified to be involved in most stages of growth: embryonic, prenatal, and postnatal. Moreover, the receptor gene for IGF has been shown to be particularly influential throughout various stages of development, especially prenatally. This is the same for GH receptor genes which have been known to drive overall growth throughout various pathways. Growth hormone is a precursor (upstream) of IGF I, but each has its independent role in hormonal pathways. Yet both seem to ultimately come together to have a joint effect on growth. Insulin like growth factor 1 (IGF 1) is an excellent test for evaluation of GH hyper secretion. It does not undergo diurnal variation and will thus be consistently elevated in GH hyper secretion and therefore patients with gigantism. A single normal IGF 1 value will reliably exclude GH hypersecretion. Additionally, DNA mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are common in gigantism patients. They have been found to be present in about 29 percent of patients with gigantism. Mutations in AIP sequencing can have deleterious effects by inducing the development of pituitary adenomas which in turn can cause gigantism. This is typical in gigantism. Additionally, a large variety of other known genetic disorders have been found to influence the development of gigantism such as multiple endocrine neoplasia type 1 and 4, McCune Albright syndrome, Carney complex, familial isolated pituitary adenoma, X linked acrogigantism (X LAG). Although various gene mutations have been associated with gigantism, over 50 percent of cases cannot be linked to genetic causes, showing the complex nature of the disorder.

Pegvisomant is one pharmaceutical drug which has received attention for being a possible treatment route for gigantism. Reduction of the levels of IGF I as a result of pegvisomant administration can be incredibly beneficial for the pediatric gigantism patients. Finding the optimal level of pegvisomant is important so normal body growth is not negatively affected. In order to do this, titration of the medication can be used as a way to find the proper administration level. In some cases the condition can be passed on genetically through a mutated gene. Other names somewhat obsolete for this pathology are hypersoma (Greek: hyper over the normal level; soma body) and somatomegaly (Greek; soma body, genitive somatos of the body; megas, gen. megalou great). In the past, while many of them were social outcasts because of their height, some (usually unintentionally) found employment in Friedrich Wilhelm I's famous Potsdam Giants regiment. Many of those who have been identified with gigantism have had multiple health problems involving the circulatory or skeletal system, as the strain of maintaining a large, heavy body places abnormal demands on both the bones and the heart.