Article

A heritable predisposition to pituitary tumors

Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Pituitary (Impact Factor: 3.2). 12/2009; 13(2):130-7. DOI: 10.1007/s11102-009-0212-0
Source: PubMed

ABSTRACT

Pituitary tumors are prevalent in the general population, with a frequency of nearly 1 in 5. The cause of most pituitary tumors remains unknown, although a genetic contribution is recognized for some. We analyzed the Utah Population Data Base (UPDB), a resource combining a computerized genealogy of the Utah population with a statewide tumor registry, to investigate familial clustering of pituitary tumors. We analyzed the genetic relationships among 741 individuals diagnosed with benign or malignant pituitary tumors who had Utah genealogy data. To test for evidence of genetic contribution to predisposition, we compared average relatedness between all pairs of individuals with pituitary tumors with the expected relatedness in this population. We also estimated relative risks (RRs) for pituitary tumors in close and distant relatives of cases by comparing observed and expected numbers of cases among relatives. Relative risks for first- and third-degree relatives were significantly elevated (RR = 2.83 and 1.63, respectively), while relative risk for second-degree relatives was not significantly different from 1.0 (RR = 0.83). The average pairwise relatedness of pituitary tumor cases was significantly higher than expected, even when close relationships were ignored. The significantly elevated risks to relatives as well as the significant excess distant relatedness observed in cases provide strong support for a genetic contribution to predisposition to pituitary tumors. Multiple high-risk pedigrees can be identified in the UPDB, and study of such pedigrees might allow identification of the gene(s) responsible for our observations. Recognizing genetic contribution to the disease may also help with counseling family members of affected individuals.

Download full-text

Full-text

Available from: Lisa A Cannon-Albright
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pituitary adenomas usually present sporadically, with a multifactorial pathogenesis including somatic mutational events in cancer-related genes. Genetic predisposition implies the presence of germline DNA alterations with a range of impacts on pituitary cell biology, translating into a variable penetrance of the disease. Genetic causes must be considered in the presence of specific clinical settings, such as familial occurrence of pituitary adenoma, with or without extrapituitary diseases, and may also be suspected in young patients (<30 years of age) with macroadenomas. We review the clinical implications of genetic predisposition, with special attention on multiple endocrine neoplasia type 1, Carney complex and familial isolated pituitary adenoma. Genetic screening in selected patients with an apparently sporadic disease is also discussed.
    Full-text · Article · Feb 2011 · Expert Review of Endocrinology & Metabolism
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pituitary incidentalomas are a common finding with a poorly understood natural history. Over the last few decades, numerous studies have sought to decipher the optimal evaluation and treatment of these lesions. This paper aims to elucidate the current evidence regarding their prevalence, natural history, evaluation, and management. A search of articles on PubMed (National Library of Medicine) and reference lists of all relevant articles was conducted to identify all studies pertaining to the incidence, natural history, workup, treatment, and follow-up of incidental pituitary and sellar lesions, nonfunctioning pituitary adenomas, and incidentalomas. The reported prevalence of pituitary incidentalomas has increased significantly in recent years. A complete history, physical, and endocrinological workup with formal visual field testing in the event of optic apparatus involvement constitutes the basics of the initial evaluation. Although data regarding the natural history of pituitary incidentalomas remain sparse, they seem to suggest that progression to pituitary apoplexy (0.6/100 patient-years), visual field deficits (0.6/100 patient-years), and endocrine dysfunction (0.8/100 patient-years) remains low. In larger lesions, apoplexy risk may be higher. While the majority of pituitary incidentalomas can be managed conservatively, involvement of the optic apparatus, endocrine dysfunction, ophthalmological symptoms, and progressive increase in size represent the main indications for surgery.
    Full-text · Article · Dec 2011 · Neurosurgical FOCUS
  • Source

    Full-text · Chapter · Jan 2012
Show more