The causes and consequences of pituitary gigantism. Issue 12 (December 2018)

• Record Type: Journal Article
• Authors: Beckers, Albert; Petrossians, Patrick; Hanson, Julien; Daly, Adrian
• Is Part Of: Nature reviews. Volume 14:Issue 12(2018)
• Page Start: 705
• Page End: 720
• Publication Date: 2018-12
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1038/s41574-018-0114-1
• Languages: English
• ISSNs: 1759-5029

Abstract

Abstract In the general population, height is determined by a complex interplay between genetic and environmental factors. Pituitary gigantism is a rare but very important subgroup of patients with excessive height, as it has an identifiable and clinically treatable cause. The disease is caused by chronic growth hormone and insulin-like growth factor 1 secretion from a pituitary somatotrope adenoma that forms before the closure of the epiphyses. If not controlled effectively, this hormonal hypersecretion could lead to extremely elevated final adult height. The past 10 years have seen marked advances in the understanding of pituitary gigantism, including the identification of genetic causes in ~50% of cases, such as mutations in theAIP gene or chromosome Xq26.3 duplications in X-linked acrogigantism syndrome. Pituitary gigantism has a male preponderance, and patients usually have large pituitary adenomas. The large tumour size, together with the young age of patients and frequent resistance to medical therapy, makes the management of pituitary gigantism complex. Early diagnosis and rapid referral for effective therapy appear to improve outcomes in patients with pituitary gigantism; therefore, a high level of clinical suspicion and efficient use of diagnostic resources is key to controlling overgrowth and preventing patients from reaching very elevated final adult heights. Pituitary gigantism is a rare growth disorder caused by excessive release of growth hormone and insulin-like growth factor 1. This Review discusses the diagnosis, genetic causes and clinical management of pituitary gigantism. Key points Nearly 50% of patients with pituitary gigantism have a known underlying genetic cause; therefore, these patients should be strongly considered for genetic counselling and screening. Once growth hormone (GH) hypersecretion has been established, efforts should be made to avoid delays in instigating treatment to control levels of GH and insulin-like growth factor 1. A shorter time between diagnosis and the commencement of treatment is associated with a decreased final height in pituitary gigantism. Pituitary gigantism is a disease that predominantly affects males, but males also have a longer delay in time to diagnosis than females, leading to a low proportion of male patients who have disease control by 18 years of age. Somatotropinomas in pituitary gigantism are usually large (macroadenomas) and might be difficult to cure with surgery or medical therapy alone; therefore, multimodal approaches are common in pituitary gigantism. The effect of large tumour size and multiple surgeries and radiotherapy is that patients with pituitary gigantism often have hypopituitarism at long-term follow-up.