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Familial pituitary tumor syndromes

Nature Reviews Endocrinology volume 5, pages 453–461 (2009)Cite this article

Abstract

The vast majority of pituitary tumors are benign and occur sporadically; however, they can still result in significant morbidity and even premature mortality through mass effects and hormone dysfunction. The etiology of sporadic tumors is still poorly understood; by contrast, advances have been made in our understanding of familial pituitary adenoma syndromes in the past decade. Currently, four genes are known to be associated with familial pituitary tumor syndromes: MEN1, CDKN1B, PRKAR1A and AIP. The first three genes are associated with a variety of extrapituitary pathologies, for example, primary hyperparathyroidism with multiple endocrine neoplasia type 1, which might aid identification of these syndromes. By contrast, AIP mutations seem to occur in the setting of isolated familial pituitary adenomas, particularly of the growth-hormone-secreting subtype. Awareness and identification of familial pituitary tumor syndromes is important because of potential associated pathologies and important implications for family members. Here, we review the current knowledge of familial pituitary tumor syndromes.

Key Points

  • Less than 5% of pituitary tumors are familial; the rest are sporadic

  • Identification of inherited pituitary syndromes is important because of the associated pathologies; pituitary tumors might be the presenting feature in these syndromes and important implications exist for family members

  • Four genes have so far been identified as associated with familial pituitary tumor syndromes: MEN1, CDKN1B, PRKAR1A and AIP

  • Up to 20% of patients with clinical features of multiple endocrine neoplasia type 1 do not have a mutation in MEN1; these patients might have mutations in CDKN1B or other genes not yet identified

  • AIP has been identified as a mutated gene in patients with familial isolated pituitary adenomas, particularly those who have adenomas that secrete growth hormone

  • Features that suggest an inherited pituitary tumor syndrome include parathyroid tumors, pancreatic endocrine tumors, atrial myxomas, lentigines, Schwann-cell tumors (Carney complex), family history and young age at onset

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Acknowledgements

M. S. Elston is supported by an National Health and Medical Research Council medical postgraduate research scholarship and New South Wales Cancer Institute Research Scholars Award.

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  1. Cancer Genetics Laboratory, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, St Leonards, NSW, Australia

    Marianne S. Elston, Kerrie L. McDonald, Roderick J. Clifton-Bligh & Bruce G. Robinson

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R. J. Clifton-Bligh declares an association with the following companies: Eli Lilly (speakers bureau), Sanofi-Aventis (speakers bureau), Servier (speakers bureau). B. G. Robinson declares an association with the following company: AstraZeneca (grant/research support). The other authors declare no competing interests.

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Elston, M., McDonald, K., Clifton-Bligh, R. et al. Familial pituitary tumor syndromes. Nat Rev Endocrinol 5, 453–461 (2009). https://doi.org/10.1038/nrendo.2009.126

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