Advances in the Diagnosis, Treatment and Molecular Genetics of Pituitary Adenomas in Childhood

F Keil Margaret, Constantine A Stratakis
European Endocrinology, 2008;4(2):81-5

Abstract

The pituitary gland has an essential role in the maintenance of homeostasis, normal growth and reproductive function. Although pituitary tumours are rare in childhood and adolescence and are typically histologically benign, significant morbidity may result due to their location, mass effect and/or interference with normal pituitary hormone functions.1 The early identification of pituitary tumours in children is necessary to avoid serious adverse effects on both physiological and cognitive outcomes as a result of pituitary hormone dysregulation during the critical periods of growth in childhood and adolescence. In this report, we review recent findings on the diagnosis, evaluation, treatment and molecular genetics of pituitary adenomas presenting in childhood.

Citation European Endocrinology, 2008;4(2):81-5
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Pituitary Adenomas
Due to the rarity of pituitary tumours in children and adolescents, accurate information regarding the prevalence and incidence of these tumours is lacking. Data from autopsy studies (primarily concerned with adults) show that pituitary adenomas develop in approximately 17–25% of the population.1,2 In addition, studies using radiological imaging report a similar incidence of pituitary gland lesions in the general population (up to 20%) with no gender predilection.3 Approximately 3.5–8.5% of all pituitary tumours are diagnosed before 20 years of age and they account for approximately 3% of all diagnosed intracranial tumoirs in childhood.4–8

The majority of pituitary tumoirs are sporadic; however, in children more commonly than in adults they can be part of a genetic condition predisposing the sufferer to pituitary and other tumours. Even sporadic tumours may harbour significant genetic abnormalities. Most pituitary tumours are monoclonal lesions and modifications in expression of various oncogenes or tumour suppressor genes, including GNAS, pituitary tumour transforming gene (PTTG), HMGA2 and FGFR-4, have been identified.9,10 Pituitary tumour development and cell growth are probably influenced by both pituitary and hypothalamic factors.1,11,12 Other factors and genetic events seem to be implicated in pituitary cell clonal expansion, and oncogene activation is necessary to propagate tumour growth.9,13 An example of this secondary phenomenon is the widespread presence of GNAS-activating mutations in sporadic growth hormone (GH)-secreting pituitary tumours (in up to 40% of all such lesions).14

Adrenal corticotrophic hormone (ACTH)-producing adenomas are the most common functional pituitary tumours in early childhood, although they are still considerably rare. No genetic defects have been consistently associated with childhood corticotropinomas, which only rarely occur in the familial setting, and even then occur most commonly in the context of multiple endocrine neoplasia type 1 (MEN1).15–17

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