ESPE Abstracts (2019) 92 PL7


Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium

Pituitary gigantism is a rare disorder caused by excess of GH/IGF-1 due to GH-secreting lesions, that occurs before epiphyseal closure leading to increased linear growth. These cases have more aggressive features of pituitary disease than sporadic acromegaly, including a younger age at disease onset and larger tumor size, and they can be challenging to treat. Over the past two decades several molecular defects that cause GH-secreting pituitary adenomas have been identified, including multiple endocrine neoplasia syndromes type 1 and 4, Carney complex, McCune-Albright syndrome, familial isolated pituitary adenoma (FIPA) and AIP mutations, pituitary adenoma with paraganglioma/pheochromocytoma, and the recently identified X-linked acrogigantism syndrome (X-LAG). About half of pituitary gigantism cases have genetic predisposition, and AIP mutations represent the most frequent genetic cause of pituitary gigantism (29%). X-LAG is a novel pediatric syndrome due to chromosome Xq26.3 microduplications involving GPR101. X-LAG can be caused by variable degrees of somatic mosaicism for GPR101 duplication in sporadic males. X-LAG accounts for 10% of pituitary gigantism cases and 80% of early-onset pediatric gigantism. Hypothalamic GHRH hypersecretion can accompany the pituitary abnormalities seen in X-LAG, and in vitro studies showed that GHRH receptor antagonist can significantly reduce GH release. Besides sporadic cases, X-LAG represents a new genetic cause of non-AIP FIPA, transmission from affected mother to affected son was reported in 3 FIPA families. X-LAG is more frequent in females, and associated with early-onset pituitary disease (in most cases during the 1 year of life, and always before age of 5) and extremely accelerated linear growth. X-LAG is usually associated with markedly elevated GH and prolactin secretion by mixed pituitary adenomas/hyperplasia. Response to somatostatin analogs is poor and multimodal treatment is frequently required, including neurosurgery, GH receptor antagonist and radiotherapy, which however increase the risk of hypopituitarism.

Volume 92

58th Annual ESPE

Vienna, Austria
19 Sep 2019 - 21 Sep 2019

European Society for Paediatric Endocrinology 

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