Advances in the diagnosis, treatment and molecular genetics of pituitary tumors in childhood

Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2-6% of surgically treated pituitary tumors occur in children, with some variation attributed to a lack of consensus for a pediatric age range and whether age at surgery or age at onset of symptoms was used. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Pituitary adenomas produce a variety of hormonal conditions such as hyperprolactinemia, acromegaly or gigantism, or Cushing disease. Sporadic lesions comprise the majority of pituitary tumors in children and there is sparse information about genetic causes. However, in children more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as Carney complex, McCune-Albright syndrome, multiple endocrine neoplasia type 1 (MEN 1), and familial isolated pituitary adenoma (FIPA). The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments. Molecular understanding of pituitary adenoma formation is essential for the development of medical therapies and the treatment of post-operative recurrences. In general, mutations in genes involved in genetic syndromes associated with pituitary tumors are not a common finding in sporadic lesions. In contrast MEN1 and AIP mutations may be more frequent among specific subgroups of patients, such as in children and young adults with growth hormone-producing adenomas. In this presentation, we review the most recent data on clinical diagnosis and outcomes, as well as in the molecular pathogenesis of pituitary adenomas and discuss some of the most recent findings from our laboratory. Guidelines for genetic screening and clinical counseling of patients with pituitary tumors are provided.