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Medicina
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New Therapeutic Horizons for Pituitary Tumors
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New Therapeutic Horizons for Pituitary Tumors

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 16781

Special Issue Editors

Dr. Georgia Ntali

E-Mail Website
Guest Editor
Department of Endocrinology and Diabetes, General Hospital Evangelismos, Athens, Greece
Interests: neuroendocrinology; reproductive endocrinology
Dr. Cristina Capatina

E-Mail Website
Guest Editor
1. Department of Endocrinology, University of Medicine and Pharmacy 'Carol Davila', Bucharest, Romania
2. Department of Pituitary and Neuroendocrine Pathology, C.I. Parhon National Institute of Endocrinology, Bucharest, Romania
Interests: neuroendocrinology

Special Issue Information

Dear Colleagues,

Pituitary tumors are a heterogenous group characterized by diverse presentation, pathogenesis, and outcomes. Ongoing progress in our understanding of tumor biology is likely to show the way to improved prognostication and precision medicine.

A subset of these tumors have an aggressive behavior, showing resistance to treatment and/or multiple recurrences in spite of the optimal use of standard therapies (surgery, conventional medical treatments, and radiotherapy). Temozolomide (TMZ) has been the most used therapeutic option, but only one third of patients actually show a partial or complete radiological response. Emerging therapies consist of peptide receptor radionuclide therapy, vascular endothelial growth factor receptor-targeted therapy, tyrosine kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and more recently, immune checkpoint inhibitors. The development of new prognostic markers and potential therapeutic targets will allow a better understanding and use of therapies, but also improvement and development of novel ones. In the era of personalized medicine, the selection of appropriate treatment based on the biological identity of the tumor will hopefully result in better outcomes for patients bearing aggressive PitNETs.

The aim of this Special Issue is to present and discuss novel treatments and the upcoming landscape in the field of treatment of pituitary tumors. Manuscripts of different types concerning this topic will be considered—case reports, clinical studies, trials, systematic reviews, and prospective studies regarding the treatment of pituitary tumors.

Dr. Georgia Ntali
Dr. Cristina Capatina
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. Medicina is an international peer-reviewed open access monthly 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 1800 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

  • aggressive pituitary tumors
  • immunotherapy
  • peptide receptor radionuclide
  • temozolomide
  • targeted therapy

Published Papers (5 papers)

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Review

38 pages, 1653 KiB  
Review
Pituitary Tumorigenesis—Implications for Management
by Rodanthi Vamvoukaki, Maria Chrysoulaki, Grigoria Betsi and Paraskevi Xekouki
Medicina 2023, 59(4), 812; https://doi.org/10.3390/medicina59040812 - 21 Apr 2023
Viewed by 3176
Abstract
Pituitary neuroendocrine tumors (PitNETs), the third most common intracranial tumor, are mostly benign. However, some of them may display a more aggressive behavior, invading into the surrounding structures. While they may rarely metastasize, they may resist different treatment modalities. Several major advances in [...] Read more.
Pituitary neuroendocrine tumors (PitNETs), the third most common intracranial tumor, are mostly benign. However, some of them may display a more aggressive behavior, invading into the surrounding structures. While they may rarely metastasize, they may resist different treatment modalities. Several major advances in molecular biology in the past few years led to the discovery of the possible mechanisms involved in pituitary tumorigenesis with a possible therapeutic implication. The mutations in the different proteins involved in the Gsa/protein kinase A/c AMP signaling pathway are well-known and are responsible for many PitNETS, such as somatotropinomas and, in the context of syndromes, as the McCune–Albright syndrome, Carney complex, familiar isolated pituitary adenoma (FIPA), and X-linked acrogigantism (XLAG). The other pathways involved are the MAPK/ERK, PI3K/Akt, Wnt, and the most recently studied HIPPO pathways. Moreover, the mutations in several other tumor suppressor genes, such as menin and CDKN1B, are responsible for the MEN1 and MEN4 syndromes and succinate dehydrogenase (SDHx) in the context of the 3PAs syndrome. Furthermore, the pituitary stem cells and miRNAs hold an essential role in pituitary tumorigenesis and may represent new molecular targets for their diagnosis and treatment. This review aims to summarize the different cell signaling pathways and genes involved in pituitary tumorigenesis in an attempt to clarify their implications for diagnosis and management. Full article
(This article belongs to the Special Issue New Therapeutic Horizons for Pituitary Tumors)
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10 pages, 332 KiB  
Review
Management of Nelson’s Syndrome
by Athanasios Fountas and Niki Karavitaki
Medicina 2022, 58(11), 1580; https://doi.org/10.3390/medicina58111580 - 2 Nov 2022
Viewed by 1850
Abstract
Nelson’s syndrome is a potentially severe condition that may develop in patients with Cushing’s disease treated with bilateral adrenalectomy. Its management can be challenging. Pituitary surgery followed or not by radiotherapy offers the most optimal tumour control, whilst pituitary irradiation alone needs to [...] Read more.
Nelson’s syndrome is a potentially severe condition that may develop in patients with Cushing’s disease treated with bilateral adrenalectomy. Its management can be challenging. Pituitary surgery followed or not by radiotherapy offers the most optimal tumour control, whilst pituitary irradiation alone needs to be considered in cases requiring intervention and are poor surgical candidates. Observation is an option for patients with small lesions, not causing mass effects to vital adjacent structures but close follow-up is required for a timely detection of corticotroph tumour progression and for further treatment if required. To date, no medical therapy has been consistently proven to be effective in Nelson’s syndrome. Pharmacotherapy, however, should be considered when other management approaches have failed. A subset of patients with Nelson’s syndrome may develop further tumour growth after primary treatment, and, in some cases, a truly aggressive tumour behaviour can be demonstrated. In the absence of evidence-based guidance, the management of these cases is individualized and tailored to previously offered treatments. Temozolomide has been used in patients with aggressive Nelson’s with no consistent results. Development of tumour-targeted therapeutic agents are an unmet need for the management of aggressive cases of Nelson’s syndrome. Full article
(This article belongs to the Special Issue New Therapeutic Horizons for Pituitary Tumors)
17 pages, 388 KiB  
Review
Treatment of Prolactinoma
by Warrick J. Inder and Christina Jang
Medicina 2022, 58(8), 1095; https://doi.org/10.3390/medicina58081095 - 13 Aug 2022
Cited by 12 | Viewed by 5246
Abstract
Prolactinomas are the commonest form of pituitary neuroendocrine tumor (PitNET), representing approximately half of such tumors. Dopamine agonists (DAs) have traditionally been the primary treatment for the majority of prolactinomas, with surgery considered the second line. The aim of this review is to [...] Read more.
Prolactinomas are the commonest form of pituitary neuroendocrine tumor (PitNET), representing approximately half of such tumors. Dopamine agonists (DAs) have traditionally been the primary treatment for the majority of prolactinomas, with surgery considered the second line. The aim of this review is to examine the historical and modern management of prolactinomas, including medical therapy with DAs, transsphenoidal surgery, and multimodality therapy for the treatment of aggressive prolactinomas and metastatic PitNETs, with an emphasis on the efficacy, safety, and future directions of current therapeutic modalities. DAs have been the mainstay of prolactinoma management since the 1970s, initially with bromocriptine and more recently with cabergoline. Cabergoline normalizes prolactin in up to 85% of patients and causes tumor shrinkage in up to 80%. Primary surgical resection of microprolactinomas and enclosed macroprolactinomas performed by experienced pituitary neurosurgeons have similar remission rates to cabergoline. Aggressive prolactinomas and metastatic PitNETS should receive multimodality therapy including high dose cabergoline, surgery, radiation therapy (preferably using stereotactic radiosurgery where suitable), and temozolomide. DAs remain a reliable mode of therapy for most prolactinomas but results from transsphenoidal surgery in expert hands have improved considerably over the last one to two decades. Surgery should be strongly considered as primary therapy, particularly in the setting of microprolactinomas, non-invasive macroprolactinomas, or prior to attempting pregnancy, and has an important role in the management of DA resistant and aggressive prolactinomas. Full article
(This article belongs to the Special Issue New Therapeutic Horizons for Pituitary Tumors)
14 pages, 382 KiB  
Review
Updating the Landscape for Functioning Gonadotroph Tumors
by Georgia Ntali and Cristina Capatina
Medicina 2022, 58(8), 1071; https://doi.org/10.3390/medicina58081071 - 8 Aug 2022
Cited by 6 | Viewed by 2817
Abstract
Functioning gonadotroph adenomas (FGAs) are rare tumors, as the overwhelming majority of gonadotroph tumors are clinically silent. Literature is based on case reports and small case series. Gonadotroph tumors are poorly differentiated and produce and secrete hormones inefficiently, but in exceptional cases, they [...] Read more.
Functioning gonadotroph adenomas (FGAs) are rare tumors, as the overwhelming majority of gonadotroph tumors are clinically silent. Literature is based on case reports and small case series. Gonadotroph tumors are poorly differentiated and produce and secrete hormones inefficiently, but in exceptional cases, they cause clinical syndromes due to hypersecretion of intact gonadotropins. The clinical spectrum of endocrine dysfunction includes an exaggerated response of ovaries characterized as ovarian hyperstimulation syndrome (OHSS) in premenopausal females and adolescent girls, testicular enlargement in males, and isosexual precocious puberty in children. Transsphenoidal surgery and removal of tumor reduces hormonal hypersecretion, improves endocrine dysfunction, and provides tissue for further analysis. Medical therapies (somatostatin analogues, dopamine agonists, GnRH agonists/antagonists) are partially or totally ineffective in many cases, especially with respect to antitumor effect. This review aims to update recent literature on these rare functioning tumors and highlight their therapeutic management. Full article
(This article belongs to the Special Issue New Therapeutic Horizons for Pituitary Tumors)
12 pages, 489 KiB  
Review
Clinical Management of Acromegaly: Therapeutic Frontiers and New Perspectives for Somatostatin Receptor Ligands (SRLs)
by Alessandro Brunetti, Simone Antonini, Andrea Saladino, Elisabetta Lavezzi, Benedetta Zampetti and Renato Cozzi
Medicina 2022, 58(6), 794; https://doi.org/10.3390/medicina58060794 - 13 Jun 2022
Cited by 2 | Viewed by 3195
Abstract
Somatostatin receptor ligands (SRLs) represent a true milestone in the medical therapy for acromegaly. The first-generation SRLs (FG-SRLs), octreotide and lanreotide, have demonstrated good efficacy in disease control and tumor shrinkage, and are still considered first-line medical therapies. The development of long-acting release [...] Read more.
Somatostatin receptor ligands (SRLs) represent a true milestone in the medical therapy for acromegaly. The first-generation SRLs (FG-SRLs), octreotide and lanreotide, have demonstrated good efficacy in disease control and tumor shrinkage, and are still considered first-line medical therapies. The development of long-acting release (LAR) formulations has certainly improved the therapeutic tolerability of these drugs, although many patients still experience therapy-related burden. As such, new formulations have recently been developed to improve adherence and therapeutic efficacy and more solutions are on the way. In the case of FG-SRL-resistant disease, pasireotide, the only second generation SRL currently available, demonstrated superiority in disease control and tumor shrinkage compared to FG-SRLs. However, its use in clinical practice is still limited due to concern for impairment in glucose homeostasis. In this review, we discuss the news about the present and future role of SRLs in acromegaly, exploring the therapeutical frontiers of this drug class. Moreover, we provide practical guidance on the use of pasireotide, based on the data in the literature and our clinical experience. Full article
(This article belongs to the Special Issue New Therapeutic Horizons for Pituitary Tumors)
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