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Management of Pituitary Tumors: Current and Future Treatment Options

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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 2023) | Viewed by 16682

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Prof. Dr. Ilan Shimon

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Guest Editor

1. Institute of Endocrinology, Beilinson Campus, Rabin Medical Center, Petach-Tikva, Israel
2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Interests: pituitary; acromegaly; cushing; prolactinoma; pituitary adenoma

Prof. Dr. Amit Akirov

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Guest Editor

Special Issue Information

Dear Colleagues,

Pituitary disorders may be associated with significant morbidity and may require the use of multiple treatment modalities. As in other disciplines of medicine, the field of pituitary disorders has undergone rapid advances and these have transformed our understanding of important principles underlying normal and abnormal pituitary function, as well as our approach to the management of pituitary disorder. This Special Issue will focus on current and future medical treatment options for patients with various pituitary disorders, including functional and non-functional pituitary adenomas. Experts in the field of medical treatment of pitutiary disorders will provide updates on the management and outcomes of the available and new and emerging therapies.

Prof. Dr. Ilan Shimon
Prof. Dr. Amit Akirov
Guest Editors

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Keywords

pituitary
cushing syndrome
acromegaly
prolactinoma
non-functioning pituitary adenoma
hypopituitarism
hypophysitis

Published Papers (5 papers)

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Research

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14 pages, 1874 KiB

Open AccessArticle

Use of Neuronavigation and Augmented Reality in Transsphenoidal Pituitary Adenoma Surgery

by Miriam H. A. Bopp, Benjamin Saß, Mirza Pojskić, Felix Corr, Dustin Grimm, André Kemmling and Christopher Nimsky

J. Clin. Med. 2022, 11(19), 5590; https://doi.org/10.3390/jcm11195590 - 23 Sep 2022

Cited by 11 | Viewed by 2716

Abstract

The aim of this study was to report on the clinical experience with microscope-based augmented reality (AR) in transsphenoidal surgery compared to the classical microscope-based approach. AR support was established using the head-up displays of the operating microscope, with navigation based on fiducial-/surface- or automatic intraoperative computed tomography (iCT)-based registration. In a consecutive single surgeon series of 165 transsphenoidal procedures, 81 patients underwent surgery without AR support and 84 patients underwent surgery with AR support. AR was integrated straightforwardly within the workflow. ICT-based registration increased AR accuracy significantly (target registration error, TRE, 0.76 ± 0.33 mm) compared to the landmark-based approach (TRE 1.85 ± 1.02 mm). The application of low-dose iCT protocols led to a significant reduction in applied effective dosage being comparable to a single chest radiograph. No major vascular or neurological complications occurred. No difference in surgical time was seen, time to set-up patient registration prolonged intraoperative preparation time on average by twelve minutes (32.33 ± 13.35 vs. 44.13 ± 13.67 min), but seems justifiable by the fact that AR greatly and reliably facilitated surgical orientation and increased surgeon comfort and patient safety, not only in patients who had previous transsphenoidal surgery but also in cases with anatomical variants. Automatic intraoperative imaging-based registration is recommended. Full article

(This article belongs to the Special Issue Management of Pituitary Tumors: Current and Future Treatment Options)

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14 pages, 1760 KiB

Open AccessArticle

Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?

by Amit Akirov, Ilan Shimon, Maria Fleseriu, Idit Dotan, Yossi Manisterski, Nirit Aviran-Barak, Varda Nadler, Sandra Alboim, Tzipora Shochat, Gloria Tsvetov and Dania Hirsch

J. Clin. Med. 2022, 11(6), 1558; https://doi.org/10.3390/jcm11061558 - 11 Mar 2022

Cited by 5 | Viewed by 2293

Abstract

Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing’s disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Methods: Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to 31 November 2021. Results: The cohort included 105 patients (82 women, 78%; mean age, 41.5 ± 14.5 years), including 80 microadenomas (mean size, 5.2 ± 2.2 mm) and 25 macroadenomas (mean size, 18.0 ± 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, p = NS) and Cushingoid features (27.5% vs. 20.0%, p = NS). Mean 24 h urinary free cortisol (5.2 ± 5.4 × ULN vs. 7.8 ± 8.7 × ULN) and serum cortisol following low-dose dexamethasone (372.0 ± 324.5 vs. 487.6 ± 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 ± 1.2 × ULN vs. 1.3 ± 0.8 × ULN, respectively, p = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. Conclusions: While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study. Full article

(This article belongs to the Special Issue Management of Pituitary Tumors: Current and Future Treatment Options)

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13 pages, 606 KiB

Open AccessArticle

Quality of Life and Sleep in Patients with Pituitary Adenoma in Relation to Tumor Type and Compression of the Optic Chiasm

by Karol Piotr Sagan, Elżbieta Andrysiak-Mamos, Ernest Tyburski, Leszek Michał Sagan and Anhelli Syrenicz

J. Clin. Med. 2021, 10(9), 1879; https://doi.org/10.3390/jcm10091879 - 26 Apr 2021

Cited by 8 | Viewed by 3142

Abstract

Objective: To determine the effect of transsphenoidal surgery on quality of life and sleep in patients with pituitary adenomas depending on tumor type and compression of the optic chiasm. Methods: In this prospective study, patients with pituitary adenomas who were scheduled for transsphenoidal surgery completed the Short Form 36 Questionnaire, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale preoperatively and 7.5 (±1.5) months after surgery. Patients were analyzed based on tumor type and compression of the optic chiasm. Results: Significant improvements with large effect sizes were seen for patients with Cushing’s disease in general health (Z = −2.37; p = 0.018), vitality (Z = −2.05; p = 0.041), and mental health (Z = −2.06; p = 0.040). A significant deterioration with large effect size occurred in physical functioning (Z = −2.02; p = 0.043) in patients with acromegaly. A significant improvement with medium effect size was seen in subjective sleep quality, (Z = −2.24; p = 0.025), sleep duration (Z = −2.11; p = 0.035), and habitual sleep efficiency (Z = −2.26; p = 0.024) after decompression of the optic chiasm. Multiple significant correlations were observed between sleep parameters and Short Form 36 subscales before and after treatment. Conclusions: Changes in quality of life during the follow-up period depend on tumor type. Circadian rhythm disturbances may resolve promptly after decompression of the optic chiasm. Quality of life in pituitary adenoma patients is associated with quality of sleep in many dimensions, thus implying that developing strategies to improve sleep quality could increase overall well-being and everyday functioning in pituitary adenoma patients. Full article

(This article belongs to the Special Issue Management of Pituitary Tumors: Current and Future Treatment Options)

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Review

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38 pages, 15560 KiB

Open AccessReview

Continuing Challenges in the Definitive Diagnosis of Cushing’s Disease: A Structured Review Focusing on Molecular Imaging and a Proposal for Diagnostic Work-Up

by Tessa N. A. Slagboom, Dirk Jan Stenvers, Elsmarieke van de Giessen, Stefan D. Roosendaal, Maartje M. L. de Win, Joseph C. J. Bot, Eleonora Aronica, René Post, Jantien Hoogmoed, Madeleine L. Drent and Alberto M. Pereira

J. Clin. Med. 2023, 12(8), 2919; https://doi.org/10.3390/jcm12082919 - 17 Apr 2023

Cited by 2 | Viewed by 1619

Abstract

The definitive diagnosis of Cushing’s disease (CD) in the presence of pituitary microadenoma remains a continuous challenge. Novel available pituitary imaging techniques are emerging. This study aimed to provide a structured analysis of the diagnostic accuracy as well as the clinical use of molecular imaging in patients with ACTH-dependent Cushing’s syndrome (CS). We also discuss the role of multidisciplinary counseling in decision making. Additionally, we propose a complementary diagnostic algorithm for both de novo and recurrent or persistent CD. A structured literature search was conducted and two illustrative CD cases discussed at our Pituitary Center are presented. A total of 14 CD (n = 201) and 30 ectopic CS (n = 301) articles were included. MRI was negative or inconclusive in a quarter of CD patients. ¹¹C-Met showed higher pituitary adenoma detection than ¹⁸F-FDG PET–CT (87% versus 49%). Up to 100% detection rates were found for ¹⁸F-FET, ⁶⁸Ga-DOTA-TATE, and ⁶⁸Ga-DOTA-CRH, but were based on single studies. The use of molecular imaging modalities in the detection of pituitary microadenoma in ACTH-dependent CS is of added and complementary value, serving as one of the available tools in the diagnostic work-up. In selected CD cases, it seems justified to even refrain from IPSS. Full article

(This article belongs to the Special Issue Management of Pituitary Tumors: Current and Future Treatment Options)

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16 pages, 1142 KiB

Open AccessReview

Targeting Aggressive Pituitary Adenomas at the Molecular Level—A Review

by Benjamin Voellger, Zhuo Zhang, Julia Benzel, Junwen Wang, Ting Lei, Christopher Nimsky and Jörg-Walter Bartsch

J. Clin. Med. 2022, 11(1), 124; https://doi.org/10.3390/jcm11010124 - 27 Dec 2021

Cited by 9 | Viewed by 5298

Abstract

Pituitary adenomas (PAs) are mostly benign endocrine tumors that can be treated by resection or medication. However, up to 10% of PAs show an aggressive behavior with invasion of adjacent tissue, rapid proliferation, or recurrence. Here, we provide an overview of target structures in aggressive PAs and summarize current clinical trials including, but not limited to, PAs. Mainly, drug targets in PAs are based on general features of tumor cells such as immune checkpoints, so that programmed cell death 1 (ligand 1) (PD-1/PD-L1) targeting may bear potential to cure aggressive PAs. In addition, epidermal growth factor receptor (EGFR), mammalian target of rapamycin (mTOR), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and their downstream pathways are triggered in PAs, thereby modulating tumor cell proliferation, migration and/or tumor angiogenesis. Temozolomide (TMZ) can be an effective treatment of aggressive PAs. Combination of TMZ with 5-Fluorouracil (5-FU) or with radiotherapy could strengthen the therapeutic effects as compared to TMZ alone. Dopamine agonists (DAs) are the first line treatment for prolactinomas. Dopamine receptors are also expressed in other subtypes of PAs which renders Das potentially suitable to treat other subtypes of PAs. Furthermore, targeting the invasive behavior of PAs could improve therapy. In this regard, human matrix metalloproteinase (MMP) family members and estrogens receptors (ERs) are highly expressed in aggressive PAs, and numerous studies demonstrated the role of these proteins to modulate invasiveness of PAs. This leaves a number of treatment options for aggressive PAs as reviewed here. Full article

(This article belongs to the Special Issue Management of Pituitary Tumors: Current and Future Treatment Options)

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