Molecular basis of pituitary gigantism

Pituitary gigantism is a very rare condition that develops before the end of the pubertal period, due to an excess of growth hormone usually secreted by a pituitary adenoma. This disease is accompanied by a significant reduction in life expectancy. Until very recently, little scientific research had been specifically dedicated to patients with gigantism, probably because of the rarity of the condition and the consequent difficulty of assembling large series. Following works on FIPA and AIP gene mutations, it became evident that patients with these mutations have more aggressive pituitary adenomas preferentially secreting growth hormone, and develop the disease much earlier in life (frequently before the end of puberty), thereby permitting the development of gigantism. These works have stimulated scientific, and particu-larly genetic, studies on patients with gigantism. Several genetic etiologies are now known. The most frequent cause is a mutation of the AIP gene (about 30 %). In 10 % the cause is a duplica-tion involving the GPR101 gene, which is responsible for X-Linked AcroGigantism (X-LAG). This syndrome, discovered very recently, includes the most extreme forms of human gigantism (with heights greater than 2m50), such as Julius Koch, alias the giant Constantin (2m59), who died at the age of 30 in 1902. A careful study of his DNA allowed the diagnosis to be considered. This work on X-LAG has advanced our understanding of the physiology of growth and the pathological hypothalamic-pituitary mechanisms that govern the formation of somatotropic adenonomas.(c) 2022 Published by Elsevier Masson SAS on behalf of l'Academie nationale de medecine.

Automated summary

Pituitary gigantism is a rare condition caused by excessive secretion of growth hormone from a pituitary adenoma. Recent genetic studies have identified various gene mutations associated with this condition, such as X-Linked AcroGigantism. Understanding the physiology and pathology of growth in these cases has been advanced through these studies.