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Biomedicines
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Neuroendocrine Neoplasia and Endocrine Tumors: Pathogenic Features, Prognostic Markers and...
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Neuroendocrine Neoplasia and Endocrine Tumors: Pathogenic Features, Prognostic Markers and New Therapeutic Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 3028

Special Issue Editor

Dr. Mara Carsote

E-Mail Website
Guest Editor
1. Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
2. Department of Endocrinology, C.I. Parhon National Institute of Endocrinology, 011863 Bucharest, Romania
Interests: thyroid; adrenal; pituitary; osteoporosis; neuroendocrine tumors; bone; fracture; gynecological endocrinology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The complex domain of neuroendocrine neoplasia, including endocrine tumors with neuroendocrine components, represents one of the most dynamic multidisciplinary topics that are studied today. Great progress has recently been made with new prognostic markers and therapies that are proving their utility in different applications, from clinical presentation to personalized therapeutic approaches. A stratified perspective includes a large panel of conditions underlying neuroendocrine traits that vary from very rare entities to more frequent pathologies, such as gastro-pancreatic-intestinal neuroendocrine neoplasms, depending on the tumors’ sites and profiles in both pediatric and adult populations. In addition, early prognostic markers might be useful for prompt diagnoses in subjects with hereditary conditions or patients harboring pathogenic variants of different genes.

Dr. Mara Carsote
Guest Editor

Manuscript Submission Information

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Keywords

  • neuroendocrine tumors
  • endocrine tumors
  • somatostatin analogues
  • carcinoid syndrome
  • PRRT
  • mTOR inhibitor
  • lymph node
  • neuroendocrine marker
  • hormone
  • ki67

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Related Special Issue

Published Papers (3 papers)

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Research

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11 pages, 258 KiB  
Article
Echocardiographic Findings in Cardiomyopathy Due to Acromegaly
by Oscar Orihuela Rodríguez, Leobardo Valle Nava, Aldo Ferreira-Hermosillo, Héctor A. Carmona-Ruiz, Ariana Acevedo Meléndez, Andrés Jacobo Ruvalcaba and Ernesto Sosa-Eroza
Biomedicines 2025, 13(3), 605; https://doi.org/10.3390/biomedicines13030605 - 1 Mar 2025
Viewed by 202
Abstract
Background: Cardiomyopathy is the leading cause of morbidity and mortality in patients with acromegaly. Pharmacological and surgical treatment of the disease has been associated with morphological and functional benefits for the heart, but other studies have shown that the condition and its [...] Read more.
Background: Cardiomyopathy is the leading cause of morbidity and mortality in patients with acromegaly. Pharmacological and surgical treatment of the disease has been associated with morphological and functional benefits for the heart, but other studies have shown that the condition and its effects may be irreversible. This study aims to uncover the most frequent echocardiographic changes in patients with cardiomyopathy due to acromegaly. Methods: An observational, descriptive, cross-sectional study was performed. Patients were referred from the Endocrinology department to the Cardiology department. This study was conducted from November 2020 to November 2022. Patients with the following criteria were included: over 18 years of age, of both genders, and with a complete clinical record and complete laboratory studies. Results: A total of 89 men (38%) and 148 women (62%) were included, with a mean age of 48 ± 12 years in the men and 49 ± 13 years in the women (p = 0.223). The most frequent cardiac findings were concentric hypertrophy (CHT) in 116 patients (49%), concentric remodeling (CR) in 52 patients (22%), and eccentric hypertrophy (EH) in 18 patients (8%). The left ventricular ejection fraction (LVEF) was preserved in the entire population. Left atrial enlargement (LAE) was observed in 88 patients (37%), diastolic dysfunction in 61 patients (26%), right ventricular dilatation in 47 patients (20%), right atrial enlargement in 120 patients (51), and pulmonary hypertension in 28 patients (12%). Valvular insufficiencies (VIs) were observed: tricuspid VIs in 73%, mitral VIs in 49%, and aortic VIs in 24% of the population. Conclusions: The frequency of changes in the four chambers is elevated in cardiomyopathy due to acromegaly. Full article
(This article belongs to the Special Issue Neuroendocrine Neoplasia and Endocrine Tumors: Pathogenic Features, Prognostic Markers and New Therapeutic Approaches)
14 pages, 2401 KiB  
Article
Treatments and Outcomes in Neuroendocrine Patients Treated with Long-Acting Somatostatin Analogues: An Italian Real-World Propensity Score-Matched Cohort Study
by Nicoletta Ranallo, Andrea Roncadori, Nicola Gentili, William Balzi, Mattia Altini, Virginia Ghini, Roberta Maltoni, Alice Andalò, Martina Cavallucci, Maddalena Sansovini, Valentina Fausti, Maria Teresa Montella, Ilaria Massa and Valentina Danesi
Biomedicines 2025, 13(2), 515; https://doi.org/10.3390/biomedicines13020515 - 19 Feb 2025
Viewed by 387
Abstract
Objectives: The aim of this study was to investigate the treatment patterns and outcomes in two propensity score-matched cohorts of patients with neuroendocrine tumours (NETs) treated with first-line somatostatin analogue (SSA). Methods: Metastatic NET patients treated with first-line SSA (2009–2022) were [...] Read more.
Objectives: The aim of this study was to investigate the treatment patterns and outcomes in two propensity score-matched cohorts of patients with neuroendocrine tumours (NETs) treated with first-line somatostatin analogue (SSA). Methods: Metastatic NET patients treated with first-line SSA (2009–2022) were retrospectively examined. First-line lanreotide vs. octreotide cohorts were matched 1:1 by propensity scores for demographics, tumour characteristics, and diagnosis year. Progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan–Meier analysis and the Cox proportional hazards model. Results: Among 441 patients, 310 were matched (155 in both the octreotide and lanreotide groups). First-line SSA was monotherapy (63.5%) or combination with other medications (36.5%). A total of 77% of second-line patients (188/244) maintained their initial SSA medication in combination with other therapies. Radioligand therapy with lanreotide (N = 72; 29.5%) or octreotide (N = 70; 28.7%) was the most common second-line treatment. First-line lanreotide and octreotide cohorts had similar median PFS (15.5; 95% CI: 13.6–19.1 vs. 14.0; 95% CI: 12.0–15.8 months), despite octreotide having a 36% higher likelihood of moving to the second line than lanreotide (95% CI: 1.05–1.76, p = 0.018). Multiple metastases (HR = 1.45; p = 0.004, 95% CI: 1.13–1.87) and Ki-67 > 20% (HR = 2.34; p < 0.001, 95% CI: 1.43–3.83) were significantly associated with the worst PFS. First-line lanreotide patients had a median OS of 10.4 years (95% CI: 7.5-NA) and octreotide 9.2 years (95% CI: 7.3-NA) (p = 0.537). Bone metastases increased death risk by 91% (p = 0.014; 95% CI: 1.14–3.20). Conclusions: SSA monotherapy is the main first-line treatment and most subsequent treatments include SSA with additional medications. Cohorts had similar PFS/OS, but octreotide demonstrated a 36% significantly higher likelihood of moving to the second-line treatment. Full article
(This article belongs to the Special Issue Neuroendocrine Neoplasia and Endocrine Tumors: Pathogenic Features, Prognostic Markers and New Therapeutic Approaches)
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Figure 1

Figure 1
<p>The flowchart of the process of case selection.</p> Full article ">Figure 2
<p>Sankey diagram showing the treatment patterns and sequences of the post-matching cohort (N = 310) from the first line (L1) up to the seventh line (L7) of treatment. Chemotherapy treatment (Chemo) includes the following agents: capecitabine, oxaliplatin, etoposide, temozolomide, carboplatin, streptozotocin, fluorouracil, doxorubicin, dacarbazine, epirubicin, and irinotecan. Abbreviations: PSM, propensity score matching; Octreo, octreotide; Lanreo, lanreotide; Chemo, chemotherapy; PRRT, peptide receptor radionuclide therapy.</p> Full article ">Figure 3
<p>First line time to next treatment (TTNT): (<b>a</b>) KM estimates of first-line treatment persistence. KM curves are drawn separately for first-line SSA treatment. Censored observations are represented with a vertical line in the curves at the time of censoring; (<b>b</b>) Multivariable Cox PH regression model for estimating the effect of baseline characteristics on first-line time to subsequent treatment.</p> Full article ">Figure 4
<p>Progression-free survival (PFS): (<b>a</b>) KM estimates of PFS curves associated with first line grouped by SSA treatment. Censored observations are represented with a vertical line in the curves at the time of censoring; (<b>b</b>) multivariable Cox PH regression model for estimating the effect of baseline characteristics on PFS.</p> Full article ">Figure 5
<p>Overall survival (OS): (<b>a</b>) KM estimates of OS according to first-line SSA treatment. Censored observations are represented with a vertical line in the curves at the time of censoring; (<b>b</b>) multivariable Cox PH regression model for estimating the effect of baseline characteristics on OS.</p> Full article ">

Review

Jump to: Research

36 pages, 752 KiB  
Review
Diabetes Mellitus in Non-Functioning Adrenal Incidentalomas: Analysis of the Mild Autonomous Cortisol Secretion (MACS) Impact on Glucose Profile
by Alexandra-Ioana Trandafir, Adina Ghemigian, Mihai-Lucian Ciobica, Claudiu Nistor, Maria-Magdalena Gurzun, Tiberiu Vasile Ioan Nistor, Eugenia Petrova and Mara Carsote
Biomedicines 2024, 12(7), 1606; https://doi.org/10.3390/biomedicines12071606 - 18 Jul 2024
Viewed by 1687
Abstract
Non-functioning adrenal incidentalomas (NFAIs) have been placed in relationship with a higher risk of glucose profile anomalies, while the full-blown typical picture of Cushing’s syndrome (CS) and associated secondary (glucocorticoid-induced) diabetes mellitus is not explicitly confirmed in this instance. Our objective was to [...] Read more.
Non-functioning adrenal incidentalomas (NFAIs) have been placed in relationship with a higher risk of glucose profile anomalies, while the full-blown typical picture of Cushing’s syndrome (CS) and associated secondary (glucocorticoid-induced) diabetes mellitus is not explicitly confirmed in this instance. Our objective was to highlight the most recent data concerning the glucose profile, particularly, type 2 diabetes mellitus (T2DM) in NFAIs with/without mild autonomous cortisol secretion (MACS). This was a comprehensive review of the literature; the search was conducted according to various combinations of key terms. We included English-published, original studies across a 5-year window of publication time (from January 2020 until 1 April 2024) on PubMed. We excluded case reports, reviews, studies on T1DM or secondary diabetes, and experimental data. We identified 37 studies of various designs (14 retrospective studies as well 13 cross-sectional, 4 cohorts, 3 prospective, and 2 case–control studies) that analysed 17,391 individuals, with a female-to-male ratio of 1.47 (aged between 14 and 96 years). T2DM prevalence in MACS (affecting 10 to 30% of NFAIs) ranged from 12% to 44%. The highest T2DM prevalence in NFAI was 45.2% in one study. MACS versus (non-MACS) NFAIs (n = 16) showed an increased risk of T2DM and even of prediabetes or higher fasting plasma glucose or HbA1c (no unanimous results). T2DM prevalence was analysed in NFAI (N = 1243, female-to-male ratio of 1.11, mean age of 60.42) versus (non-tumour) controls (N = 1548, female-to-male ratio of 0.91, average age of 60.22) amid four studies, and two of them were confirmatory with respect to a higher rate in NFAIs. Four studies included a sub-group of CS compared to NFAI/MACS, and two of them did not confirm an increased rate of glucose profile anomalies in CS versus NFAIs/ACS. The longest period of follow-up with concern to the glycaemic profile was 10.5 years, and one cohort showed a significant increase in the T2DM rate at 17.9% compared to the baseline value of 0.03%. Additionally, inconsistent data from six studies enrolling 1039 individuals that underwent adrenalectomy (N = 674) and conservative management (N = 365) pinpointed the impact of the surgery in NFAIs. The regulation of the glucose metabolism after adrenalectomy versus baseline versus conservative management (n = 3) was improved. To our knowledge, this comprehensive review included one of the largest recent analyses in the field of glucose profile amid the confirmation of MACS/NFAI. In light of the rising incidence of NFAI/AIs due to easier access to imagery scans and endocrine evaluation across the spectrum of modern medicine, it is critical to assess if these patients have an increased frequency of cardio-metabolic disorders that worsen their overall comorbidity and mortality profile, including via the confirmation of T2DM. Full article
(This article belongs to the Special Issue Neuroendocrine Neoplasia and Endocrine Tumors: Pathogenic Features, Prognostic Markers and New Therapeutic Approaches)
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<p>Flow chart diagram of search and main sections of results according to our methods.</p> Full article ">
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