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Pituitary Tumors: Diagnosis and Treatment

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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 (31 May 2023) | Viewed by 20027

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Special Issue Editor

Prof. Dr. Ting Lei

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Guest Editor

Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Interests: pituitary; acromegaly; signaling pathway; transsphenoidal surgery

Special Issue Information

Dear Colleagues,

Pituitary tumors are one of the common diseases affecting approximately 1 in 1000 in the general population. The endocrinologists, neurosurgeons, otolaryngologists, neurologists, ophthalmologists, and neuro-oncologists are frequently dealing with the problem in daily practice. Pituitary adenomas are mostly benign, and some associated with specific syndromes (e.g., acromegaly, Cushing’s syndrome, hyperprolactinemia) due to inappropriate hormonal secretion. However, thorough diagnosis and multidiscipline management of pituitary adenoma remain continuous challenges. The aim of this Special Issue is to provide current advances in diagnosis and treatment of pituitary tumors, with particular interest in the classification of various pituitary adenomas, prospective clinical studies, and innovative therapeutic modalities. Therefore, researchers and physicians are encouraged to submit their findings in this area as original articles or reviews to this Special Issue.

Prof. Dr. Ting Lei
Guest Editor

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Keywords

pituitary tumors
cushing’s disease
acromegaly
prolactinomas
non-functioning pituitary adenomas
somatotropinomas
adrenocorticotropinomas
thyrotroph cell adenomas
surgery
aggressive pituitary tumors

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Published Papers (9 papers)

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Research

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9 pages, 1040 KiB

Open AccessArticle

Gamma Knife Radiosurgery for Cushing’s Disease: Evaluation of Biological Effective Dose from a Single-Center Experience

by Yuan Gao, Mengqi Wang, Yang Wu, Hao Deng, Yangyang Xu, Yan Ren, Chun Wang and Wei Wang

J. Clin. Med. 2023, 12(4), 1288; https://doi.org/10.3390/jcm12041288 - 6 Feb 2023

Cited by 1 | Viewed by 1526

Abstract

Objective: Gamma knife radiosurgery (GKRS) has served as an adjunctive treatment in Cushing’s disease (CD) for decades and has become a vital part of therapy in the management of CD. Biological effective dose (BED) is a radiobiological parameter with time correction, considering the cellular deoxyribonucleic acid repairment. We aimed to investigate the safety and efficacy of GKRS for CD and evaluate the association of BED and treatment outcome. Methods: A cohort study of 31 patients with CD received GKRS in West China Hospital between June 2010 and December 2021. Endocrine remission was defined as normalization of 24 h urinary free cortisol (UFC) or serum cortisol ≤ 50 nmol/L after a 1 mg dexamethasone suppression test. Result: The mean age was 38.6 years old, and females accounted for 77.4%. GKRS was the initial treatment for 21 patients (67.7%), and 32.3% of patients underwent GKRS after surgery due to residual disease and recurrence. The mean endocrine follow-up duration was 22 months. The median marginal dose was 28.0 Gy, and the median BED was 221.5 Gy_2.47. Fourteen patients (45.1%) experienced control of hypercortisolism in the absence of pharmacological treatment, and the median duration to remission was 20.0 months. The cumulative rates of endocrine remission at 1, 2, and 3 years after GKRS were 18.9%, 55.3%, and 72.21%, respectively. The total complication rate was 25.8%, and the mean duration from GKRS to hypopituitary was 17.5 months. The new hypopituitary rate at 1, 2, and 3 years were 7.1%, 30.3%, and 48.4%, respectively. A high BED level (BED > 205 Gy_2.47) was associated with better endocrine remission than a low BED level (BED ≤ 205 Gy_2.47), while no significant differences were found between the BED level and hypopituitarism. Conclusions: GKRS was a second-line therapeutic option for CD with satisfactory safety and efficacy. BED should be considered during GKRS treatment planning, and optimization of BED is a potentially impactful avenue toward improving the efficacy of GKRS. Full article

(This article belongs to the Special Issue Pituitary Tumors: Diagnosis and Treatment)

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11 pages, 639 KiB

Open AccessArticle

The Potential of Self-Assessment and Associated Factors for Delayed Symptomatic Hyponatremia Following Transsphenoidal Surgery: A Single Center Experience

by Pia Roser, Klaus Christian Mende, Georgios K. Dimitriadis, Marius Marc-Daniel Mader, Jens Aberle, Jörg Flitsch and Roman Rotermund

J. Clin. Med. 2023, 12(1), 306; https://doi.org/10.3390/jcm12010306 - 30 Dec 2022

Cited by 3 | Viewed by 1473

Abstract

(1) Background: We identified screening parameters and associated factors for delayed, symptomatic hyponatremia (DSH) following inpatient discharge after transsphenoidal surgery (TSS). (2) Methods: In this prospective, monocentric study, 108 patients who underwent TSS for pituitary pathologies were included, provided with a questionnaire and instructed to document urine specific gravity, fluid intake/urine output, body weight and clinical symptoms for every of five days following discharge from hospital. (3) Results: The overall incidence of DSH within 14 days following discharge from the hospital was 14.8% (n = 9). Symptomatic patients presented on average 8.6 days after surgery. Mild DSH was present in 3.3% of the patients, moderate in 1.6% and severe hyponatremia in 9.8% of patients. Female sex (p = 0.02) and lower BMI (p = 0.02), as well as nausea (66.7%; p < 0.01) and emesis (33.3%; p < 0.05), were associated with DSH. A significant weight delta between morning and afternoon weight two days before the event of DSH between both groups (1.26 kg (n = 5) vs. 0.79 kg (n = 52), p < 0.05) was detected. (4) Conclusions: Handing out a symptom questionnaire at discharge seems to be an easy and feasible tool for the detection of DSH after hospital discharge. Full article

(This article belongs to the Special Issue Pituitary Tumors: Diagnosis and Treatment)

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16 pages, 2438 KiB

Open AccessArticle

Preoperative Risk Stratification of Increased MIB-1 Labeling Index in Pituitary Adenoma: A Newly Proposed Prognostic Scoring System

by Ivan Maiseyeu, Ági Güresir, Hartmut Vatter, Ulrich Herrlinger, Albert Becker, Johannes Wach and Erdem Güresir

J. Clin. Med. 2022, 11(23), 7151; https://doi.org/10.3390/jcm11237151 - 1 Dec 2022

Viewed by 1750

Abstract

The MIB-1 index is an important risk factor for progression-free survival (PFS) in pituitary adenoma (PA). Preoperatively, the MIB-1 index is not available in the decision-making process. A preoperative method regarding MIB-1 index estimation in PA has not been evaluated so far. Between 2011 and 2021, 109 patients with tumor morphology data, MIB-1 index data, and inflammatory and pituitary hormone laboratory values underwent surgery for PA. An MIB-1 index cutoff point (≥4/<4%) determines the probability of PFS in completely resected PA. An elevated MIB-1 index (≥4%) was present in 32 cases (29.4%) and was significantly associated with increased IGF-1, age ≤ 60, increased ACTH, and increased fibrinogen levels in the multivariable analysis. A scoring system (“FATE”) using preoperative IGF-1, age, ACTH, and plasma fibrinogen level enables the estimation of the MIB-1 index (sensitivity 72%, specificity 68%). The FATE score is also significantly associated with the time to PA progression after the complete resection of the PA. We propose the FATE score to preoperatively estimate the risk of an elevated MIB-1 index (≥4%), which might enable tailoring to medical decision-making, and follow-up interval scheduling, as well as inform future studies analyzing proliferative activities. Full article

(This article belongs to the Special Issue Pituitary Tumors: Diagnosis and Treatment)

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13 pages, 2198 KiB

Open AccessArticle

Reoperation for Recurrent and Persistent Cushing’s Disease without Visible MRI Findings

by Baofeng Wang, Shuying Zheng, Jie Ren, Zhihong Zhong, Hong Jiang, Qingfang Sun, Tingwei Su, Weiqing Wang, Yuhao Sun and Liuguan Bian

J. Clin. Med. 2022, 11(22), 6848; https://doi.org/10.3390/jcm11226848 - 20 Nov 2022

Cited by 4 | Viewed by 1893

Abstract

Purpose: Transsphenoidal surgery is the first-line treatment for Cushing’s disease (CD), even with negative preoperative magnetic resonance imaging (MRI) results. Some patients with persistent or recurring hypercortisolism have negative MRI findings after the initial surgery. We aimed to analyze the efficacy of repeat surgery in two groups of patients and determine if there is an association between positive MRI findings and early remission. Patients and Methods: Clinical, imaging, and biochemical information of 42 patients who underwent repeat surgery by a single neurosurgeon between 2002 and 2021 was retrospectively analyzed. We compared the endocrinological, histopathological, and surgical outcomes before and after repeat surgery among 14 CD patients with negative MRI findings and 28 patients with positive MRI findings. Results: Immediate remission was achieved in 29 patients (69.0%) who underwent repeat surgery. Among all patients, 28 (66.7%) had MRI findings consistent with solid lesions. There was no significant difference in remission rates between the recurrence and persistence groups (77.8% vs. 57.1%, odds ratio = 2.625, 95% confidence interval = 0.651 to 10.586). Patients in remission after repeat surgery were not associated with positive MRI findings (odds ratio = 3.667, 95% confidence interval = 0.920 to 14.622). Conclusions: In terms of recurrence, repeat surgery in patients with either positive or negative MRI findings showed reasonable remission rates. For persistent disease with positive MRI findings, repeat surgery is still an option; however, more solid evidence is needed to determine if negative MRI findings are predictors for failed reoperations for persistent hypercortisolism. Full article

(This article belongs to the Special Issue Pituitary Tumors: Diagnosis and Treatment)

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15 pages, 1120 KiB

Open AccessArticle

Extra-Pseudocapsular Transsphenoidal Surgery for Microprolactinoma in Women

by Juan Chen, Xiang Guo, Zhuangzhuang Miao, Zhuo Zhang, Shengwen Liu, Xueyan Wan, Kai Shu, Yan Yang and Ting Lei

J. Clin. Med. 2022, 11(13), 3920; https://doi.org/10.3390/jcm11133920 - 5 Jul 2022

Cited by 4 | Viewed by 1877

Abstract

A recall for histological pseudocapsule (PS) and reappraisal of transsphenoidal surgery (TSS) as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas are getting vibrant. We hope to investigate the effectiveness and risks of extra-pseudocapsular transsphenoidal surgery (EPTSS) for young women with microprolactinoma, and to look into the factors that influenced remission and recurrence, and thus to figure out the possible indication shift for primary TSS. We proposed a new classification method of microprolactinoma based on the relationship between tumor and pituitary position, which can be divided into hypo-pituitary, para-pituitary and supra-pituitary groups. We retrospectively analyzed 133 patients of women (<50 yr) with microprolactinoma (≤10 mm) who underwent EPTSS in a tertiary center. PS were identified in 113 (84.96%) microadenomas intraoperatively. The long-term surgical cure rate was 88.2%, and the comprehensive remission rate was 95.8% in total. There was no severe or permanent complication, and the surgical morbidity rate was 4.5%. The recurrence rate with over 5 years of follow-up was 9.2%, and a lot lower for the tumors in the complete PS group (0) and hypo-pituitary group (2.1%). Use of the extra-pseudocapsule dissection in microprolactinoma resulted in a good chance of increasing the surgical remission without increasing the risk of CSF leakage or endocrine deficits. First-line EPTSS may offer a greater opportunity of long-term cure for young female patients with microprolactinoma of hypo-pituitary located and Knosp grade 0-II. Full article

(This article belongs to the Special Issue Pituitary Tumors: Diagnosis and Treatment)

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Review

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14 pages, 549 KiB

Open AccessReview

Progress and Challenges of Immune Checkpoint Inhibitor-Induced Hypophysitis

by Piaohong Chen, Jianwei Li and Huiwen Tan

J. Clin. Med. 2023, 12(10), 3468; https://doi.org/10.3390/jcm12103468 - 15 May 2023

Cited by 4 | Viewed by 2527

Abstract

Immune checkpoint inhibitors (ICIs) are a new type of antitumor drug which can achieve antitumor goals by blocking the binding of immune checkpoints to their ligands, thereby enhancing the activity of T cells. Meanwhile, ICIs block the binding of immune checkpoints to their ligands, disrupting the immune tolerance of T cells to self-antigens, which may lead to a series of immune-related adverse events (irAEs). Immune checkpoint inhibitor-induced hypophysitis (IH) is a relatively rare irAE. Due to the lack of specificity in clinical manifestations, it is difficult to accurately diagnose IH in a timely manner in clinical practice. However, the risk of adverse events, especially IH, for patients receiving ICIs has not been adequately investigated. Missed or delayed diagnosis may lead to poor prognosis or even adverse clinical outcomes. In this article, we summarize the epidemiology, pathogenesis, clinical manifestations, diagnosis and treatment of IH. Full article

(This article belongs to the Special Issue Pituitary Tumors: Diagnosis and Treatment)

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12 pages, 1047 KiB

Open AccessReview

Cognitive Dysfunction, an Increasingly Valued Long-Term Impairment in Acromegaly

by Juan Chen, Zhigao Xiang, Zhuo Zhang, Yan Yang, Kai Shu and Ting Lei

J. Clin. Med. 2023, 12(6), 2283; https://doi.org/10.3390/jcm12062283 - 15 Mar 2023

Cited by 4 | Viewed by 2657

Abstract

Acromegaly is a chronic disease caused by the overproduction of growth hormone (GH) and accompanying insulin-like growth factor-1 (IGF-1), which is often caused by GH-secreting pituitary adenomas. In addition to its somatic burden, a growing number of studies have found that patients suffering from acromegaly exhibit psychosocial and personality changes. Over the past 70 years, there has been increasing interest in the cognitive impairment and neuropsychological issues of patients with acromegaly, and a variety of neuropsychological and neurophysiological tests have been used to measure cognitive changes in patients. The impact of disease progression status, treatment modalities, and various comorbidities on cognitive function and the mechanisms of cognitive impairment in patients with acromegaly are therefore outlined in this review. Multidisciplinary assessment has important implications for the management of acromegaly, particularly in relation to cognitive function. Here, we summarize the relevant literature concerning cognitive-behavioral research on acromegaly to demonstrate the impact of long-term impairment caused by GH and IGF-1 on the cognitive behavior of patients. Full article

(This article belongs to the Special Issue Pituitary Tumors: Diagnosis and Treatment)

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Other

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11 pages, 828 KiB

Open AccessSystematic Review

The Role of Aromatase Inhibitors in Male Prolactinoma

by Amit Akirov and Yaron Rudman

J. Clin. Med. 2023, 12(4), 1437; https://doi.org/10.3390/jcm12041437 - 10 Feb 2023

Cited by 4 | Viewed by 3572

Abstract

Background: dopamine agonists are the recommended treatment for male prolactinomas, but some patients may develop dopamine-agonist-resistant hyperprolactinemia, leading to persistent hypogonadism that requires treatment with testosterone. However, testosterone replacement therapy may be associated with a decrease in the efficacy of dopamine agonists due to the aromatization of testosterone to estradiol, which can stimulate the proliferation and hyperplasia of lactotroph cells in the pituitary, inducing resistance to dopamine agonists. Objective: this paper systematically reviewed the role of aromatase inhibitors for men with prolactinoma and dopamine-agonist-resistant or persistent hypogonadism following treatment. Method: we performed a systematic review of all studies (according to PRISMA guidelines), assessing the role of aromatase inhibitors, including anastrozole and letrozole, for male prolactinoma. An English-language search for relevant studies was conducted on PubMed from its inception to 1 December 2022. The reference lists of the relevant studies were also reviewed. Results: our systematic review identified six articles (nine patients), including five case reports and a single case series, on the use of aromatase inhibitors for male prolactinomas. Reducing estrogen levels with an aromatase inhibitor improved sensitivity to dopamine agonists, as the addition of anastrozole or letrozole improves the control of prolactin levels and may lead to the shrinkage of tumors. Conclusion: aromatase inhibitors are of potential value to patients with dopamine-agonist-resistant prolactinoma, or when hypogonadism persists while using high-dose dopamine agonists. Full article

(This article belongs to the Special Issue Pituitary Tumors: Diagnosis and Treatment)

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14 pages, 3006 KiB

Open AccessCase Report

Pituicytoma Associated with Suspected Cushing’s Disease: Two Case Reports and a Literature Review

by Tongxin Xiao, Lian Duan, Shi Chen, Lin Lu, Yong Yao, Xinxin Mao, Huijuan Zhu and Hui Pan

J. Clin. Med. 2022, 11(16), 4805; https://doi.org/10.3390/jcm11164805 - 17 Aug 2022

Cited by 1 | Viewed by 1901

Abstract

(1) Background: Pituicytomas are rare gliomas located in the neurohypophysis or infundibulum. A misdiagnosis of pituicytoma as pituitary adenoma is common because of similar location and occasional endocrine disturbances. (2) Case presentation: We present two cases with the comorbidity of pituicytoma and Cushing’s disease (CD). Case 1 is that of a 51-year-old woman, the first reported case of the comorbidity of pituicytoma, CD, and central diabetes insipidus. She received a diagnosis of CD and central diabetes insipidus. After transsphenoidal surgery, histopathology confirmed the diagnosis of pituicytoma and adrenocorticotropin-secreting microadenoma; case 2 is that of a 29-year-old man who received a biochemical diagnosis of CD, but he received a histopathological confirmation of only pituicytoma. Both patients achieved a remission of hypercortisolism without relapse during the follow-up, but they developed hypopituitarism after surgery. We also reviewed all published 18 cases with the comorbidity of pituicytoma and any pituitary adenoma. (3) Conclusions: Pituicytoma might present pituitary hyperfunction disorders such as CD or acromegaly, with or without pathologically confirmed pituitary adenoma. CD is the most common hyperpituitarism occurring concurrently with pituicytomas. The remission rate and hypopituitarism after surgery seem similar or slightly lower in CD than in common pituitary adenomas, but the long-term prognosis is unexplored. Full article

(This article belongs to the Special Issue Pituitary Tumors: Diagnosis and Treatment)

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