Clinical Biology of the Pituitary Adenoma

Author:

Melmed Shlomo1ORCID,Kaiser Ursula B2,Lopes M Beatriz3ORCID,Bertherat Jerome4,Syro Luis V5,Raverot Gerald6ORCID,Reincke Martin7ORCID,Johannsson Gudmundur8ORCID,Beckers Albert9,Fleseriu Maria10,Giustina Andrea11ORCID,Wass John A H12,Ho Ken K Y13

Affiliation:

1. Cedars-Sinai Medical Center , Los Angeles, CA , USA

2. Brigham & Women’s Hospital and Harvard Medical School , Boston, MA , USA

3. University of Virginia School of Medicine , Charlottesville, VA , USA

4. Université de Paris, Assistance Publique–Hôpitaux de Paris , Paris , France

5. Hospital Pablo Tobon Uribe and Clinica Medellin – Grupo Quirónsalud , Medellin , Colombia

6. Hospices Civils de Lyon and Lyon 1 University , Lyon , France

7. University Hospital of LMU, Ludwig-Maximilians-Universität , Munich , Germany

8. Sahlgrenska University Hospital & Institute of Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden

9. University of Liège , Liège , Belgium

10. Oregon Health & Science University , Portland, OR , USA

11. San Raffaele Vita-Salute University and IRCCS Hospital , Milan , Italy

12. University of Oxford , Oxford , UK

13. The Garvan Institute of Medical Research and St. Vincents Hospital , Sydney , Australia

Abstract

Abstract All endocrine glands are susceptible to neoplastic growth, yet the health consequences of these neoplasms differ between endocrine tissues. Pituitary neoplasms are highly prevalent and overwhelmingly benign, exhibiting a spectrum of diverse behaviors and impact on health. To understand the clinical biology of these common yet often innocuous neoplasms, we review pituitary physiology and adenoma epidemiology, pathophysiology, behavior, and clinical consequences. The anterior pituitary develops in response to a range of complex brain signals integrating with intrinsic ectodermal cell transcriptional events that together determine gland growth, cell type differentiation, and hormonal production, in turn maintaining optimal endocrine health. Pituitary adenomas occur in 10% of the population; however, the overwhelming majority remain harmless during life. Triggered by somatic or germline mutations, disease-causing adenomas manifest pathogenic mechanisms that disrupt intrapituitary signaling to promote benign cell proliferation associated with chromosomal instability. Cellular senescence acts as a mechanistic buffer protecting against malignant transformation, an extremely rare event. It is estimated that fewer than one-thousandth of all pituitary adenomas cause clinically significant disease. Adenomas variably and adversely affect morbidity and mortality depending on cell type, hormone secretory activity, and growth behavior. For most clinically apparent adenomas, multimodal therapy controlling hormone secretion and adenoma growth lead to improved quality of life and normalized mortality. The clinical biology of pituitary adenomas, and particularly their benign nature, stands in marked contrast to other tumors of the endocrine system, such as thyroid and neuroendocrine tumors.

Publisher

The Endocrine Society

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism

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