Genetics of gigantism and acromegaly

Abstract

Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The early diagnosis of these conditions helps guide early intervention, screening, and genetic counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the genetics of gigantism and acromegaly.

Pituitary gigantism: a case series from Hospital de San José (Bogotá, Colombia)

“…G igantism is a rare pediatric disease, with an incidence of 8 to 11 cases per million individuals per year. This disease is characterized by increased production of growth hormone (GH) when the epiphyses are still open, and in most cases is secondary to a pituitary adenoma (1). Gigantism can occur sporadically or have a hereditary component (2); in a case series by Rostomyan and cols.…”

“…McCune-Albright syndrome (5%), Carney complex (1%), and multiple endocrine neoplasia type 1 (1%) are less common causes of gigantism (3). The main symptom of the disease is abnormal accelerated growth affecting the musculoskeletal system associated with some other comorbidities (1). The first-choice treatment for gigantism is transsphenoidal surgery (TSS) (4).…”

Gigantism in a McCune-Albright’s syndrome with calcified GH-releasing pituitary adenoma: Case report and literature review

“…Recently, some molecular and genetic etiologies of pituitary gigantism have been revealed to produce several genetic diseases like Multiple Endocrine Neoplasia (MEN) type 1 and 4, MAS, Carney complex, familial isolated PA or in association to defects in the familial succinate dehydrogenase-genes and the recently identified X-linked acrogigantism (X-LAG) syndrome [ 2 , 17 ].…”

Functioning pituitary tumours: Hints from the skin

“…MEN1 caused by inactivating mutations of menin gene includes neuroendo-crine tumours, prolactinomas, and primary hyperparathyroidism (33,34). MEN4 underlines CDKN1B gene inactivation and it includes somatotropinomas, primary pigmented nodular adrenocortical disease and myxomas at different levels as well as lentigines (meaning spotty skin pigmentation) (31,35).…”