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Recent Advances in the Pathogenesis and Therapeutic Strategies of Pituitary Tumors

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 15592

Special Issue Editors

Prof. Dr. Andrea Lania

E-Mail Website
Guest Editor
1. Department of Biomedical Sciences, Humanitas University, Rozzano (MI), Italy
2. Endocrine Unit, Humanitas Clinical and Research Center, Rozzano, MI, Italy
Interests: pituitary adenomas pathogenesis; neuroendocrine tumors pathogenesis and treatment
Dr. Giampaolo Trivellin

E-Mail Website
Guest Editor
1. Department of Biomedical Sciences, Humanitas University, Rozzano, MI, Italy
2. Endocrine Unit, Humanitas Clinical and Research Center, Rozzano, MI, Italy
Interests: genetics and epigenetics of pituitary tumors; pituitary gigantism and acromegaly

Special Issue Information

Dear colleagues,

Pituitary tumors, the third most common intracranial neoplasia, are mostly benign and well-differentiated; however, a sizable proportion of them (up to 45%) may show an invasive behaviour, resistance to conventional treatments, and a predisposition to progression/recurrence and malignancy. About 10% of invasive adenomas are "clinically aggressive", but only in exceptional cases (0.2%) do they metastasize, fulfilling the criteria for "carcinoma."

Although the term “pituitary adenomas” (PAs) remains consecrated by use, the WHO, in 2017, provided a detailed histopathological assessment to categorise PAs into different subtypes and to identify features that should be considered as a marker of aggressiveness.

Pinpointing the biomarkers of invasiveness and, perhaps, of malignancy, molecular biology can support the clinicopathological diagnosis into opening new strategies for early recognition and adequate post-operative management of potentially aggressive forms. Understanding the pathogenesis of pituitary adenomas will enable clinicians to correlate the pathologic and genetic features with clinical data, helping make decisions on the best management of these tumours.

In this Special Issue, we will publish reviews and original research that provide new insights into signalling pathways and biomarkers driving pituitary tumorigenesis, diagnosis, and therapeutic perspectives. Articles about aggressive pituitary tumours will be particularly welcome.

Prof. Dr. Lania Andrea Gerardo Antonio
Dr. Giampaolo Trivellin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pituitary adenoma
  • morphofunctional classification
  • pituitary tumorigenesis
  • pituitary tumours biomarkers
  • pituitary neurosurgery
  • pituitary radiosurgery

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Published Papers (4 papers)

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Research

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16 pages, 2877 KiB  
Article
Neurofibromatosis Type 1 Has a Wide Spectrum of Growth Hormone Excess
by Fady Hannah-Shmouni, Giampaolo Trivellin, Pablo Beckers, Lefkothea P. Karaviti, Maya Lodish, Christina Tatsi, Adekunle M. Adesina, Fotini Adamidou, Gesthimani Mintziori, Jami L. Josefson, Martha Quezado and Constantine A. Stratakis
J. Clin. Med. 2022, 11(8), 2168; https://doi.org/10.3390/jcm11082168 - 13 Apr 2022
Cited by 9 | Viewed by 3827
Abstract
Overgrowth due to growth hormone (GH) excess affects approximately 10% of patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). Our aim is to describe the clinical, biochemical, pathological, and genetic features of GH excess in a retrospective case series of [...] Read more.
Overgrowth due to growth hormone (GH) excess affects approximately 10% of patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). Our aim is to describe the clinical, biochemical, pathological, and genetic features of GH excess in a retrospective case series of 10 children and adults with NF1 referred to a tertiary care clinical research center. Six children (median age = 4 years, range of 3–5 years), one 14-year-old adolescent, and three adults (median age = 42 years, range of 29–52 years) were diagnosed with NF1 and GH excess. GH excess was confirmed by the failure to suppress GH (<1 ng/mL) on oral glucose tolerance test (OGTT, n = 9) and frequent overnight sampling of GH levels (n = 6). Genetic testing was ascertained through targeted or whole-exome sequencing (n = 9). Five patients (all children) had an OPG without any pituitary abnormality, three patients (one adolescent and two adults) had a pituitary lesion (two tumors, one suggestive hyperplasia) without an OPG, and two patients (one child and one adult) had a pituitary lesion (a pituitary tumor and suggestive hyperplasia, respectively) with a concomitant OPG. The serial overnight sampling of GH levels in six patients revealed abnormal overnight GH profiling. Two adult patients had a voluminous pituitary gland on pituitary imaging. One pituitary tumor from an adolescent patient who harbored a germline heterozygous p.Gln514Pro NF1 variant stained positive for GH and prolactin. One child who harbored a heterozygous truncating variant in exon 46 of NF1 had an OPG that, when compared to normal optic nerves, stained strongly for GPR101, an orphan G protein-coupled receptor causing GH excess in X-linked acrogigantism. We describe a series of patients with GH excess and NF1. Our findings show the variability in patterns of serial overnight GH secretion, somatotroph tumor or hyperplasia in some cases of NF1 and GH excess. Further studies are required to ascertain the link between NF1, GH excess and GPR101, which may aid in the characterization of the molecular underpinning of GH excess in NF1. Full article
(This article belongs to the Special Issue Recent Advances in the Pathogenesis and Therapeutic Strategies of Pituitary Tumors)
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15 pages, 1747 KiB  
Article
Differential microRNA Expression in USP8-Mutated and Wild-Type Corticotroph Pituitary Tumors Reflect the Difference in Protein Ubiquitination Processes
by Mateusz Bujko, Paulina Kober, Joanna Boresowicz, Natalia Rusetska, Natalia Zeber-Lubecka, Agnieszka Paziewska, Monika Pekul, Grzegorz Zielinski, Andrzej Styk, Jacek Kunicki, Jerzy Ostrowski, Janusz A Siedlecki and Maria Maksymowicz
J. Clin. Med. 2021, 10(3), 375; https://doi.org/10.3390/jcm10030375 - 20 Jan 2021
Cited by 13 | Viewed by 2758
Abstract
Background: USP8 mutations are the most common driver changes in corticotroph pituitary tumors. They have direct effect on cells’ proteome through disturbance of ubiquitination process and also influence gene expression. The aim of this study was to compare microRNA profiles in USP8-mutated [...] Read more.
Background: USP8 mutations are the most common driver changes in corticotroph pituitary tumors. They have direct effect on cells’ proteome through disturbance of ubiquitination process and also influence gene expression. The aim of this study was to compare microRNA profiles in USP8-mutated and wild-type tumors and determine the probable role of differential microRNA expression by integrative microRNA and mRNA analysis. Methods: Patients with Cushing’s disease (n = 28) and silent corticotroph tumors (n = 20) were included. USP8 mutations were identified with Sanger sequencing. MicroRNA and gene expression was determined with next-generation sequencing. Results: USP8-mutated patients with Cushing’s disease showed higher rate of clinical remission and trend towards lower tumor volume than wild-type patients. Comparison of microRNA profiles of USP8-mutated and wild-type tumors revealed 68 differentially expressed microRNAs. Their target genes were determined by in silico prediction and microRNA/mRNA correlation analysis. GeneSet Enrichment analysis of putative targets showed that the most significantly overrepresented genes are involved in protein ubiquitination-related processes. Only few microRNAs influence the expression of genes differentially expressed between USP8-mutated and wild-type tumors. Conclusions: Differences in microRNA expression in corticotropinomas stratified according to USP8 status reflect disturbed ubiquitination processes, but do not correspond to differences in gene expression between these tumors. Full article
(This article belongs to the Special Issue Recent Advances in the Pathogenesis and Therapeutic Strategies of Pituitary Tumors)
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11 pages, 1363 KiB  
Article
Pituitary Disease in AIP Mutation-Positive Familial Isolated Pituitary Adenoma (FIPA): A Kindred-Based Overview
by Ismene Bilbao Garay, Adrian F. Daly, Nerea Egaña Zunzunegi and Albert Beckers
J. Clin. Med. 2020, 9(6), 2003; https://doi.org/10.3390/jcm9062003 - 26 Jun 2020
Cited by 11 | Viewed by 3877
Abstract
Clinically-relevant pituitary adenomas occur in about 1:1000 of the general population, but only about 5% occur in a known genetic or familial setting. Familial isolated pituitary adenomas (FIPA) are one of the most important inherited settings for pituitary adenomas and the most frequent [...] Read more.
Clinically-relevant pituitary adenomas occur in about 1:1000 of the general population, but only about 5% occur in a known genetic or familial setting. Familial isolated pituitary adenomas (FIPA) are one of the most important inherited settings for pituitary adenomas and the most frequent genetic cause is a germline mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene. AIP mutations lead to young-onset macroadenomas that are difficult to treat. Most are growth hormone secreting tumors, but all other secretory types can exist and the clinical profile of affected patients is variable. We present an overview of the current understanding of AIP mutation-related pituitary disease and illustrate various key clinical factors using examples from one of the largest AIP mutation-positive FIPA families identified to date, in which six mutation-affected members with pituitary disease have been diagnosed. We highlight various clinically significant features of FIPA and AIP mutations, including issues related to patients with acromegaly, prolactinoma, apoplexy and non-functioning pituitary adenomas. The challenges faced by these AIP mutation-positive patients due to their disease and the long-term outcomes in older patients are discussed. Similarly, the pitfalls encountered due to incomplete penetrance of pituitary adenomas in AIP-mutated kindreds are discussed. Full article
(This article belongs to the Special Issue Recent Advances in the Pathogenesis and Therapeutic Strategies of Pituitary Tumors)
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Review

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30 pages, 5430 KiB  
Review
Current and Emerging Medical Therapies in Pituitary Tumors
by Nicolas Sahakian, Frédéric Castinetti, Thierry Brue and Thomas Cuny
J. Clin. Med. 2022, 11(4), 955; https://doi.org/10.3390/jcm11040955 - 12 Feb 2022
Cited by 9 | Viewed by 3879
Abstract
Pituitary tumors (PT) represent in, the majority of cases, benign tumors for which surgical treatment still remains, except for prolactin-secreting PT, the first-line therapeutic option. Nonetheless, the role played by medical therapies for the management of such tumors, before or after surgery, has [...] Read more.
Pituitary tumors (PT) represent in, the majority of cases, benign tumors for which surgical treatment still remains, except for prolactin-secreting PT, the first-line therapeutic option. Nonetheless, the role played by medical therapies for the management of such tumors, before or after surgery, has evolved considerably, due in part to the recent development of well-tolerated and highly efficient molecules. In this review, our aim was to present a state-of-the-art of the current medical therapies used in the field of PT and the benefits and caveats for each of them, and further specify their positioning in the therapeutic algorithm of each phenotype. Finally, we discuss the future of PT medical therapies, based on the most recent studies published in this field. Full article
(This article belongs to the Special Issue Recent Advances in the Pathogenesis and Therapeutic Strategies of Pituitary Tumors)
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