AUTHOR=Caruso Manuela , Mazzatenta Diego , Asioli Sofia , Costanza Giuseppe , Trivellin Giampaolo , Franke Martin , Abboud Dayana , Hanson Julien , Raverot Véronique , Pétrossians Patrick , Beckers Albert , Cappa Marco , Daly Adrian F. 

TITLE=Case report: Management of pediatric gigantism caused by the TADopathy, X-linked acrogigantism

JOURNAL=Frontiers in Endocrinology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1345363

DOI=10.3389/fendo.2024.1345363

ISSN=1664-2392

ABSTRACT=<p>X-linked acrogigantism (X-LAG) is a rare form of pituitary gigantism that is associated with growth hormone (GH) and prolactin-secreting pituitary adenomas/pituitary neuroendocrine tumors (PitNETs) that develop in infancy. It is caused by a duplication on chromosome Xq26.3 that leads to the misexpression of the gene <italic>GPR101</italic>, a constitutively active stimulator of pituitary GH and prolactin secretion. <italic>GPR101</italic> normally exists within its own topologically associating domain (TAD) and is insulated from surrounding regulatory elements. X-LAG is a TADopathy in which the duplication disrupts a conserved TAD border, leading to a neo-TAD in which ectopic enhancers drive <italic>GPR101</italic> over-expression, thus causing gigantism. Here we trace the full diagnostic and therapeutic pathway of a female patient with X-LAG from 4C-seq studies demonstrating the neo-TAD through medical and surgical interventions and detailed tumor histopathology. The complex nature of treating young children with X-LAG is illustrated, including the achievement of hormonal control using a combination of neurosurgery and adult doses of first-generation somatostatin analogs.</p>