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The silent variants of pituitary tumors: demographic, radiological and molecular characteristics

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Abstract

Introduction

Tumors of the anterior pituitary gland (PTs) are mostly benign tumors with a low prevalence, which has nevertheless increased with advances in brain radiology techniques. Nearly half of PTs are not associated with a clinical endocrine syndrome. These tumors have been indistinctly named non-functioning pituitary adenomas (NFPAs) or silent pituitary tumors (SPTs) and the mechanisms of silencing are not fully known.

Aim

To study the frequency and characterize the silent variant of PTs in a large local series, and to assess their pituitary adenohypophyseal gene expression.

Methods

This observational, cross-sectional study was performed in a Pituitary Tumor Center of Excellence and involved 268 PTs. After identifying the different subtypes according to the immunohistochemical (IHC) expression of adenohypophyseal hormones, we studied their gene expression by RT-qPCR.

Results

We found that silent tumors were larger and more invasive, but not more proliferative than their functional counterparts. The RT-qPCR complements the IHC typification of PTs, reducing the proportion of null-cell subtype. Finally, some silent PT subtype variants showed lower specific adenohypophyseal hormone gene expression than their functional counterparts, which may contribute to the absence of endocrine manifestations.

Conclusions

This paper highlights the importance of identifying the silent variant of the PTs subtypes. As expected, silent tumors were larger and more invasive than their functioning counterparts. However, there was no difference in the proliferation activity between them. Finally, the lower specific gene expression in the silent than in the functioning counterparts of some PTs subtypes gives insights into the silencing mechanisms of PTs.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Acknowledgements

We thank J. Abarca (Neurosurgery Department, Hospital General Universitario de Alicante, Alicante, Spain), I. Monjas (Otolaryngology Department, Alicante General University Hospital, Alicante, Spain), P. Riesgo (Neurosurgery Department, University Hospital La Ribera, Valencia, Spain), J.A. Simal (Neurosurgery Department, Polytechnic University Hospital La Fe, Valencia, Spain), and H. Sandoval (Neurosurgery Department, University of Albacete Hospital Complex, Albacete, Spain) for their surgical contributions. We also thank the biobanks of the University of Albacete Hospital Complex, Alicante General University Hospital, and Polytechnic University Hospital La Fe.

Funding

This work is funded by Novartis Oncology through the Spanish Society of Endocrinology and Nutrition (SEEN). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Biochemical Analysis, Alicante General University Hospital-Institute for Health and Biomedical Research (ISABIAL), 03010, Alicante, Spain

    M. E. Torregrosa-Quesada

  2. Research Laboratory, Alicante General University Hospital-Institute for Health and Biomedical Research (ISABIAL). CIBER Rare Diseases, 03010, Alicante, Spain

    A. García-Martínez

  3. Centro de Investigación Operacional (CIO), Miguel Hernández University, 03010, Alicante, Spain

    A. Sánchez-Barbie

  4. Department of Pathology, Alicante General University Hospital-Institute for Health and Biomedical Research (ISABIAL), 03010, Alicante, Spain

    S. Silva-Ortega & I. Aranda

  5. Department of Endocrinology and Nutrition, Polytechnic University Hospital La Fe, 46026, Valencia, Spain

    R. Cámara

  6. Department of Endocrinology and Nutrition, Hospital La Ribera, Alzira, 46600, Valencia, Spain

    C. Fajardo

  7. Department of Endocrinology and Nutrition, Albacete General University Hospital, 02006, Albacete, Spain

    C. Lamas

  8. Department of Endocrinology and Nutrition, Alicante General University Hospital. Institute for Health and Biomedical Research (ISABIAL). University Miguel Hernandez. CIBER Rare Diseases, 03010, Alicante, Spain

    A. Pico

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  1. M. E. Torregrosa-Quesada
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  2. A. García-Martínez
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  3. A. Sánchez-Barbie
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Contributions

Conceptualization, MET, AGM and AP; methodology, MET, AGM, SSO, IA and AP; validation, MET, AGM, SSO, IA and AP; formal analysis, MET, AGM, ASB and AP; investigation, MET, AGM and AP; resources, MET, AGM, SSO, IA, RC, CF, CL and AP; writing—original draft preparation, MET, AGM and AP; writing—review and editing, MET, AGM, ASB, SSO, IA, RC, CF, CL and AP; supervision, AGM and AP; project administration, AGM and AP; funding acquisition, AP All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to A. Pico.

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The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Samples were donated by patients to the Institutional BioBank for research purposes with the corresponding consent for publication.

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Torregrosa-Quesada, M.E., García-Martínez, A., Sánchez-Barbie, A. et al. The silent variants of pituitary tumors: demographic, radiological and molecular characteristics. J Endocrinol Invest 44, 1637–1648 (2021). https://doi.org/10.1007/s40618-020-01468-2

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