Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Pituitary gland

New pathways in the pathogenesis of pituitary adenomas

Acromegaly is caused by a growth-hormone-secreting pituitary adenoma. Mutations in the AIP gene predispose patients to young-onset pituitary adenomas that are resistant to somatostatin analogue therapy. Chalal et al. describe a potential mechanism by which AIP modulates responsiveness to somatostatin analogues and identify PLAGL1 as a potential modulator of therapeutic activity.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. Giustina, A. et al. A consensus on criteria for cure of acromegaly. J. Clin. Endocrinol. Metab. 95, 3141–3148 (2008).

    Article  Google Scholar 

  2. Sherlock, M. et al. Mortality in patients with pituitary disease. Endocr. Rev. 31, 301–342 (2010).

    Article  Google Scholar 

  3. Chalal, H. S. et al. Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1 pathway. J. Clin. Endocrinol. Metab.

  4. Lyons, J. et al. Two G protein oncogenes in human endocrine tumors. Science 249, 655–659 (1990).

    Article  CAS  Google Scholar 

  5. Vierimaa, O. et al. Pituitary adenoma predisposition caused by germline mutation in the AIP gene. Science 312, 1228–1230 (2006).

    Article  CAS  Google Scholar 

  6. Trivellin, G. & Korbonits, M. AIP and its interacting partners. J. Endocrinol. 210, 137–155 (2011).

    Article  CAS  Google Scholar 

  7. Cazabat, L. et al. Germline AIP mutations in apparently sporadic pituitary adenomas: prevalence in a prospective single-center cohort of 443 patients. J. Clin. Endocrinol. Metab. 97, E663–E670 (2012).

    Article  CAS  Google Scholar 

  8. Varrault, A. et al. Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth. Dev. Cell 11, 711–722 (2006).

    Article  CAS  Google Scholar 

  9. Pagotto, U. et al. The expression of the antiproliferative gene ZAC is lost or highly reduced in nonfunctioning pituitary adenomas. Cancer Res. 60, 6794–6799 (2000).

    CAS  PubMed  Google Scholar 

  10. Theodoropoulou, M., Stalla, G. K. & Spengler, D. ZAC1 target genes and pituitary tumorigenesis. Mol. Cell. Endocrinol. 326, 60–65 (2010).

    Article  CAS  Google Scholar 

Download references


The authors wish to thank the Melvin Burkhardt Chair in Neurosurgical Oncology and the Karen Colina Wilson Research endowment in the Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center at the Cleveland Clinic.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Robert J. Weil.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Marko, N., Weil, R. New pathways in the pathogenesis of pituitary adenomas. Nat Rev Endocrinol 8, 572–573 (2012).

Download citation

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing