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Thyroid cancer is a tumour with a steadily increasing incidence. It accounts for 7% to 15% of focal lesions detected by ultrasound, depending on age, gender and other factors affecting its occurrence. Fine-needle aspiration biopsy is an essential method to establish the diagnosis but, in view of its limitations, sonoelastography is seen as a non-invasive technique useful in differentiating the nature of lesions and monitoring them after fine-needle aspiration biopsy. This paper presents a literature review on the role of both sonoelastographic techniques (relative strain sonoelastography, shear wave sonoelastography) to assess the deformability of focal thyroid lesions. Ultrasound examination is a relatively subjective method of thyroid imaging, depending on the skills of the examiner, the experience of the centre, and the quality of equipment used. As a consequence, there are inconsistencies between the results obtained by different examiners (inter-observer variability) and by the same examiner (intra-observer variability). In this paper, the authors present a review of the literature on inter-observer and intra-observer variability in the assessment of individual features of ultrasound imaging of focal lesions in the thyroid. In addition, the authors report on an analysis of cut-off thresholds for the size of lesions constituting the basis for fine-needle aspiration biopsy eligibility assessment. The need to diagnose carcinomas up to 10 mm in diameter is highlighted, however a more liberal approach is recommended in terms of indications for biopsy in lesions associated with a low risk of malignancy, where, based on consultations with patients, active ultrasound surveillance might even be considered.

Numerous scientific societies around the world have published their TIRADS (Thyroid Imaging Reporting and Data System) classifications that evaluate the risk of malignancy of focal thyroid lesions, presenting different ultrasound features for each category and lesion size thresholds to determine eligibility for biopsy. The use of such risk estimation systems in focal thyroid lesions facilitates the reporting of thyroid ultrasound findings and improves the qualification of focal lesions for fine-needle aspiration biopsy (FNAB). In this publication, the three most popular TIRADS classifications, European – EU-TIRADS, Korean – K-TIRADS, and developed by the American Society of Radiology – ACR-TIRADS, are presented and discussed based on a literature review. The results of available head-to-head statistical analyses comparing the classifications are also presented. The advantage of the EU-TIRADS and K-TIRADS systems is that they include only the most important ultrasound features, so their application is not time-consuming, and the scores are easy to incorporate into clinical practice. ACR-TIRADS, unlike other scales, is based on a unique classification system and represents the most comprehensive classification. Each of the five categories of ultrasound features – morphology, echogenicity, shape, margins, microcalcifications – are evaluated and assigned a score from 0 to 3, with a higher score being associated with a higher risk of cancer. Based on the available data, the greatest benefit has been demonstrated for the ACR-TIRADS classification, which also has implications for minimising the number of unnecessary FNABs. However, limitations related to the heterogeneity of the groups analysed in the study, including differences in the populations studied, inclusion criteria, proportions of patients of either sexes, and the number of malignant lesions analysed, should also be taken into account.

Adrenal tumors, such as adrenocortical carcinoma (ACC), adrenocortical adenoma (ACA), and pheochromocytoma (PCC) are complex diseases with unclear causes and treatments. Mitochondria and mitochondrial-derived peptides (MDPs) are crucial for cancer cell survival. The primary aim of this study was to analyze samples from different adrenal diseases, adrenocortical carcinoma, adrenocortical adenoma, and pheochromocytoma, and compare them with normal adrenal tissue to determine whether the expression levels of the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) gene and protein vary between different types of adrenal tumors compared to healthy controls using qPCR, ELISA, and IHC methods. Results showed decreased MOTS-c mRNA expression in all adrenal tumors compared to controls, while serum MOTS-c protein levels increased in ACA and PCC but not in ACC. The local distribution of MOTS-c protein in adrenal tissue was reduced in all tumors. Notably, MOTS-c protein expression declined with ACC progression (stages III and IV) but was unrelated to patient age or sex. Tumor size and testosterone levels positively correlated with MOTS-c mRNA but negatively with serum MOTS-c protein. Additionally, serum MOTS-c protein correlated positively with glucose, total cholesterol, HDL, LDL, and SHGB levels. These findings suggest disrupted expression of MOTS-c in the spectrum of adrenal diseases, which might be caused by mechanisms involving increased mitochondrial dysfunction and structural changes in the tissue associated with disease progression. This study provides a detailed examination of MOTS-c mRNA and protein in adrenal tumors, indicating the potential role of MDPs in tumor biology and progression. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. In a single-center study, 96 patients (19 with adrenal cortical carcinoma and 77 with benign tumors) underwent an adrenalectomy. A total of 14 unaffected adrenal gland tissues from kidney donors were used as controls. Fasting blood samples were collected for laboratory tests, and mRNA expressions of leptin receptor isoforms were assessed by RT-qPCR. The study analyzed correlations between mRNA expressions and clinical data and measured NCI-H295R cell proliferation via a real-time cell analyzer. All adrenal lesions expressed leptin receptor isoforms. Significantly lower LepR1 expression was observed in carcinoma tissues than in adenomas and controls (p = 0.016). Expressions of LepR3&LepR6 were correlated with overall survival (p = 0.036), while LepR2&LepR4 and LepR5 expressions were inversely related to morning serum cortisol levels (p = 0.041). Leptin reduced NCI-H295R cell proliferation (p < 0.0001). The study highlights the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. Specifically, LepR1 may serve as a diagnostic marker for carcinomas, while LepR3&LepR6 have potential use as prognostic markers. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) leads as a primary cause of cancer-related premature mortality in Western populations. This study leverages cutting-edge gene-expression-profiling technologies to perform an in-depth molecular characterization of NSCLC specimens, with the objective of uncovering tumor-specific genomic alterations. By employing DNA microarray analysis, our research aims to refine the classification of NSCLC for early detection, guide molecular-targeted treatment approaches, enhance prognostication, and broaden the scientific understanding of the disease's biology. We identified widespread genomic abnormalities in our samples, including the recurrent loss of chromosomal regions 3p, 5q, 13q, and 21q and the gain of 12p. Furthermore, utilizing Metascape for bioinformatic analysis revealed critical biological pathways disrupted in NSCLC, offering promising leads for novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Primary hyperparathyroidism is a common endocrine disorder characterised by excessive parathormone secretion that results in hypercalcemia, primarily caused by parathyroid adenoma. Accurate localisation of hyperfunctioning tissue is essential for curative surgical treatment. Although conventional imaging modalities like ultrasonography and 99mTc-MIBI scintigraphy (SPECT) along with 18F-fluorocholine PET/CT are commonly employed, there are cases with false-negative imaging results. Case presentation: This case report presents a patient with primary hyperparathyroidism and a parathyroid adenoma detected solely through 68Ga-PSMA-11 PET/CT, typically used for prostate cancer diagnosis. The lesion observed in the PET/CT was confirmed as a parathyroid adenoma through laboratory evaluation, while other imaging techniques failed to detect it. Conclusions: This finding suggests that the PSMA ligands' particular affinity for neovascularisation in focal changes may facilitate the visualisation of parathyroid adenomas. The utilisation of 68Ga-PSMA-11 PET/CT in primary hyperparathyroidism could potentially improve the preoperative localization of parathyroid adenomas when conventional imaging methods are inconclusive. [ABSTRACT FROM AUTHOR]

Introduction: Normosmic isolated hypogonadotropic hypogonadism (nIHH) is a clinically and genetically heterogeneous disorder. Deleterious variants in over 50 genes have been implicated in the etiology of IHH, which also indicates a possible role of digenicity and oligogenicity. Both classes of genes controlling GnRH neuron migration/development and hypothalamic/pituitary signaling and development are strongly implicated in nIHH pathogenesis. The study aimed to investigate the genetic background of nIHH and further expand the genotype-phenotype correlation. Methods: A total of 67 patients with nIHH were enrolled in the study. NGS technology and a 38-gene panel were applied. Results: Causative defects regarded as at least one pathogenic/likely pathogenic (P/LP) variant were found in 23 patients (34%). For another 30 individuals, variants of unknown significance (VUS) or benign (B) were evidenced (45%). The most frequently mutated genes presenting P/LP alterations were GNRHR (n = 5), TACR3 (n = 3), and CHD7, FGFR1, NSMF, BMP4, and NROB1 (n = 2 each). Monogenic variants with solid clinical significance (P/LP) were observed in 15% of subjects, whereas oligogenic defects were detected in 19% of patients. Regarding recurrence, 17 novel pathogenic variants affecting 10 genes were identified for 17 patients. The most recurrent pathogenic change was GNRHR: p.Arg139His, detected in four unrelated subjects. Another interesting observation is that P/LP defects were found more often in genes related to hypothalamic-pituitary pathways than those related to GnRH. Conclusions: The growing importance of the neuroendocrine pathway and related genes is drawing increasing attention to nIHH. However, the underestimated potential of VUS variants in IHH etiology, particularly those presenting recurrence, should be further elucidated. [ABSTRACT FROM AUTHOR]

Breast cancer, known for its diverse subtypes, ranks as one of the leading causes of cancer-related deaths. Prostate-specific membrane antigen (PSMA), primarily associated with prostate cancer, has also been identified in breast cancer, though its role remains unclear. This study aimed to evaluate PSMA expression across different subtypes of early-stage breast cancer and investigate its correlation with clinicopathological factors. This retrospective study included 98 breast cancer cases. PSMA expression was examined in both tumor cells and tumor-associated blood vessels. The analysis revealed PSMA expression in tumor-associated blood vessels in 88 cases and in tumor cells in 75 cases. Ki67 expression correlated positively with PSMA expression in blood vessels (p < 0.0001, RSpearman 0.42) and tumor cells (p = 0.010, RSpearman 0.26). The estrogen and progesterone receptor expression correlated negatively with PSMA levels in blood vessels (p = 0.0053, R Spearman −0.26 and p = 0.00026, R Spearman −0.347, respectively). Human epidermal growth factor receptor 2 (HER2) status did not significantly impact PSMA expression. We did not detect any statistically significant differences between breast cancer subtypes. These findings provide evidence for a heterogenous PSMA expression in breast cancer tissue and suggest its correlation with tumor aggressiveness. Despite the limited sample size, the study provides valuable insights into the potential of PSMA as a prognostic, diagnostic, and therapeutic target in the management of breast cancer. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis (HT) is the leading cause of hypothyroidism, affecting mainly the female population. Many patients with HT have metabolic disorders and nutritional deficiencies. The aim of this study was to evaluate vitamin D, A, E, B2, and B6 concentrations, thyroid function, metabolic profile, and anthropometric parameters of patients with Hashimoto's thyroiditis. In 81 female patients with HT (study group), vitamin A and B2 concentrations were significantly lower than in 34 healthy women (control group). No differences were noted in vitamin D, E, and B6 concentrations between groups. Moreover, HT patients had similar anthropometric parameters, lipid profiles, and glucose and insulin concentrations compared to controls. This study showed some relationships between vitamin concentrations and anthropometric or biochemical profiles in HT patients. Among others, in the HT group, the concentration of vitamin D was positively correlated with the level of HDL and negatively correlated with BMI, total fat mass, and insulin level, which influence cardiovascular risk. The results indicate that patients with HT should be routinely tested for vitamin concentrations to prevent nutritional deficiencies. Further studies are also needed on the role of vitamins in the development and progression of HT and the presence of metabolic complications in this population. [ABSTRACT FROM AUTHOR]

Simple Summary: The lack of biomarkers in neuroendocrine tumors (NETs) represents a critical unmet need. Conventional single analytes lack the required diagnostic accuracy. Multianalyte assays (e.g., NETest) offer improved performance but remain costly and largely unavailable. In our study, serum beta-human chorionic gonadotropin (β-hCG) shows promise as a biomarker in metastatic pancreatic NETs. β-hCG concentrations strongly correlate with established indicators of aggressive tumor behavior, including progressive disease, per RECIST; greater liver tumor burden; and higher WHO tumor grade. Throughout the study period, β-hCG levels increased consistently, with sharper rises noted in more aggressive tumors. As a widely available and inexpensive assay, serum β-hCG emerges as a useful tool for the evaluation of treatment response and disease monitoring in pancreatic NETs, especially in the transitional period until multianalyte assays become a mainstay in scientific guidelines. Despite recent advances, neuroendocrine tumors (NETs) remain a challenging topic, due to their diversity and the lack of suitable biomarkers. Multianalyte assays and the shift to an omics-based approach improve on the conventional single-analyte strategy, albeit with their own drawbacks. We explored the potential of serum β-hCG as a biomarker for NETs and discussed its role in disease monitoring. We recruited 40 patients with non-functioning pancreatic NETs, all with liver metastases. Serum β-hCG concentrations were measured at 3-month intervals over 48 months. We performed a comparative and a repeated measures analysis of β-hCG depending on WHO grade (G1, G2), liver tumor burden (LTB; below 10%, 10–25%), and RECIST 1.1. (stable disease, progressive disease). Patients with progressive disease (p < 0.001), 10–25% LTB (p < 0.001) and WHO Grade 2 (p < 0.001) displayed higher β-hCG concentrations. Throughout the study, β-hCG concentrations consistently increased across the entire cohort. Delta β-hCG during the study period was greater in patients with 10–25% LTB (p < 0.001), progressive disease (p < 0.001), and G2 (p = 0.003). Serum β-hCG correlates with established indicators of malignancy and disease progression in metastatic NETs, supporting further studies as a monitoring and prognostic biomarker. Despite promising results from novel biomarkers, there is still a place for single-analyte assays in NETs. [ABSTRACT FROM AUTHOR]

Background: Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. Detecting the primary tumour in TIO is challenging using conventional imaging methods. This study assesses the efficacy of [68Ga]Ga-DOTATATE PET/CT in identifying the primary tumour. Methods: Six patients with suspected TIO underwent [68Ga]Ga-DOTATATE PET/CT. The patients' clinical history and biochemical parameters were analysed. Results: [68Ga]Ga-DOTATATE PET/CT successfully identified primary tumours in four patients (femoral bones for two, iliac bone for one, subcutaneous tissue of pubic region for one). Tumour removal led to clinical and laboratory improvement. In one patient, PET/CT showed rib uptake, but the biopsy was negative. One patient showed no tumour lesions on PET/CT despite clinical evidence. Two patients had focal recurrence at the primary tumour site, detected by follow-up PET/CT. Conclusions: [68Ga]Ga-DOTATATE PET/CT is a valuable tool for detecting primary tumours in TIO, aiding in accurate diagnosis and guiding surgery, leading to improved outcomes. Further research is needed to validate these findings and explore [68Ga]Ga-DOTATATE PET/CT in other paraneoplastic syndromes. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates a promising avenue for improving the diagnosis and treatment of triple-negative breast cancer (TNBC), a highly aggressive form of breast cancer with limited therapeutic options. The researchers focus on the prostate-specific membrane antigen (PSMA), known for its presence in prostate cancer but also identified in breast cancer. Using 18F-PSMA-1007 PET/CT, the study aims to assess PSMA's in vivo expression in TNBC patients and compare it with the standard [18F]FDG PET/CT. The findings suggest that [18F]PSMA-1007 PET/CT may outperform current methods in detecting distant metastases, especially in the brain. This research not only enhances our understanding of PSMA expression in TNBC but also hints at potential advancements in diagnostic imaging and targeted therapies for this challenging cancer type. Background: Triple-negative breast cancer (TNBC) exhibits high aggressiveness and a notably poorer prognosis at advanced stages. Nuclear medicine offers new possibilities, not only for diagnosis but also potentially promising therapeutic strategies. This prospective study explores the potential of prostate-specific membrane antigen (PSMA) as a diagnostic and therapeutic target in TNBC. Methods: the research investigates PSMA expression in vivo among TNBC patients using [18F]PSMA-1007 PET/CT and compares it head-to-head with the standard-of-care [18F]FDG PET/CT. Results: The study involves 10 TNBC patients, revealing comparable uptake of [18F]PSMA-1007 and [18F]FDG in primary and metastatic lesions. Nodal metastases were found in eight patients, showing similar SUVmax values in both modalities. Two patients had uncountable lung metastases positive in both [18F]FDG and [18F]PSMA-1007 scans. PET-positive bone metastases were identified by 18F-PSMA in four patients, while elevated [18F]FDG uptake was found only in three of them. Distant metastases displayed higher SUVmax values in the [18F]PSMA-1007 PET/CT, as compared to [18F]FDG. Additionally, brain metastases were exclusively detected using [18F]PSMA-1007. Conclusions: the findings provide valuable insights into the expression of PSMA in TNBC and underscore the potential clinical significance of [18F]PSMA-1007 PET/CT in enhancing both diagnostic and therapeutic approaches for this aggressive breast cancer subtype. [ABSTRACT FROM AUTHOR]