The right drug for the right patient at the right time with the right test in differentiated thyroid cancer (DTC).

Thanks to the identification of crucial molecular pathways, the therapeutic landscape for advanced differentiated thyroid tumors (DTCs) has significantly improved during the last ten years. The therapeutic scenario has been greatly impacted by the discovery of mutually exclusive gene changes in the MAPK and PI3K/AKT pathways, such as or fusions and pathogenic mutations of the and genes. Indeed, multi-kinase inhibitors and selective inhibitors have demonstrated outstanding efficacy for radioactive iodine-refractory (RAI-R) drug treatment, with overall response rates reaching up to 86%.

Long-term surgical outcome and impact on daily life activities of strabismus surgery in thyroid-associated ophthalmopathy with and without previous orbital decompression.

Backgrounds: To report the long-term surgical outcomes and the impact on daily life activities of strabismus surgery in patients with Thyroid Associated Orbitopathy (TAO) with and without previous orbital decompression.

Methods: Patients who underwent strabismus surgery for TAO were retrospectively reviewed. The primary outcome was to evaluate the influence of orbital decompression on the outcomes of TAO related strabismus surgery.

Novel prognostic nomogram for predicting recurrence-free survival in medullary thyroid carcinoma.

Aims: Recently, there have been attempts to improve prognostication and therefore better guide treatment for patients with medullary thyroid carcinoma (MTC). In 2022, the International MTC Grading System (IMTCGS) was developed and validated using a multi-institutional cohort of 327 patients. The aim of the current study was to build upon the findings of the IMTCGS to develop and validate a prognostic nomogram to predict recurrence-free survival (RFS) in MTC.

Molecular pathology of endocrine gland tumors: genetic alterations and clinicopathologic relevance.

Tumors of the endocrine glands are common. Knowledge of their molecular pathology has greatly advanced in the recent past. This review covers the main molecular alterations of tumors of the anterior pituitary, thyroid and parathyroid glands, adrenal cortex, and adrenal medulla and paraganglia.

Association of the Genomic Profile of Medullary Thyroid Carcinoma with Tumor Characteristics and Clinical Outcomes in an International Multicenter Study.

The prognostic importance of and mutations and their relationship to clinicopathologic parameters and outcomes in medullary thyroid carcinoma (MTC) need to be clarified. A multicenter retrospective cohort study was performed utilizing data from 290 patients with MTC. The molecular profile was determined and associations were examined with clinicopathologic data and outcomes.

Expanding the Spectrum of Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre.

The BRAF p.V600E mutation represents the most specific marker for papillary thyroid carcinoma and is potentially related to aggressive behavior and persistent disease. alterations other than the p.

Case report: Dramatic response to pralsetinib in an elderly patient with advanced RET-fusion positive papillary thyroid carcinoma.

We are recently faced with a progressive evolution of the therapeutic paradigm for radioiodine refractory differentiated thyroid cancer (RAI-R DTC), since the advent of tissue agnostic inhibitors. Thus, tumor genotype assessment is always more relevant and is playing a crucial role into clinical practice. We report the case of an elderly patient with advanced papillary thyroid carcinoma (PTC) harboring fusion with four co-occurring mutations involving , , and mutations, treated with pralsetinib under a compassionate use program.

Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System.

: We described clinical features of adrenal insufficiency (AI) reported with tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) in the Food and Drug Administration Adverse Event Reporting System (FAERS). : Reports of AI recorded in FAERS (January 2004-March 2022) were identified through the high-level term "adrenal cortical hypofunctions". Demographic and clinical features were inspected, and disproportionality signals were detected through the Reporting Odds Ratio (ROR) and Information Component (IC) with relevant 95% confidence/credibility interval (CI), using different comparators and adjusting the ROR for co-reported corticosteroids and immune checkpoint inhibitors (ICIs).

The Changing Face of Drug-induced Adrenal Insufficiency in the Food and Drug Administration Adverse Event Reporting System.

Context: Adrenal insufficiency (AI) is a life-threatening condition complicating heterogeneous disorders across various disciplines, with challenging diagnosis and a notable drug-induced component.

Objective: This work aimed to describe the spectrum of drug-induced AI through adverse drug event reports received by the US Food and Drug Administration (FDA).

Methods: A retrospective disproportionality analysis reporting trends of drug-induced AI was conducted on the FDA Adverse Event Reporting System (FAERS) (> 15 000 000 reports since 2004).

The Diagnostic Value of Contrast Enhanced Ultrasound for Localization of Parathyroid Lesions in Primary Hyperparathyroidism: Comparison With Color Doppler Ultrasound: Comparison With Color Doppler Ultrasound.

Objectives: Preoperative localization of pathological parathyroid glands with imaging is essential for focused unilateral neck exploration and minimally invasive techniques. Recently published studies suggested that contrast-enhanced ultrasonography (CEUS) had high accuracy in the localization of hyperfunctioning parathyroid glands, with a general increase in the sensitivity as compared to conventional sonography. The purpose of this study was to determine the usefulness of CEUS in the localization of parathyroid lesions relating to surgical and histopathological data, in comparison to color Doppler ultrasound (CDUS), in the same series of patients.

Novel Glial Cells Missing-2 (GCM2) variants in parathyroid disorders.

Objective: The aim of this study was to analyze variants of the gene glial cells missing-2 (GCM2), encoding a parathyroid cell-specific transcription factor, in familial hypoparathyroidism and in familial isolated hyperparathyroidism (FIHP) without and with parathyroid carcinoma.

Design: We characterized 2 families with hypoparathyroidism and 19 with FIHP in which we examined the mechanism of action of GCM2 variants.

Methods: Leukocyte DNA of hypoparathyroid individuals was Sanger sequenced for CASR, PTH, GNA11 and GCM2 mutations.

Unexpected Widespread Bone Metastases from a BRAF K601N Mutated Follicular Thyroid Carcinoma within a Previously Resected Multinodular Goiter.

Follicular thyroid carcinoma (FTC) represents the second most common malignant thyroid neoplasm after papillary carcinoma (PTC). FTC is characterized by the tendency to metastasize to distant sites such as bone and lung. In the last 20 years, the understanding of the molecular pathology of thyroid tumors has greatly improved.

Pathogenic Mitochondrial DNA Mutation Load Inversely Correlates with Malignant Features in Familial Oncocytic Parathyroid Tumors Associated with Hyperparathyroidism-Jaw Tumor Syndrome.

While somatic disruptive mitochondrial DNA (mtDNA) mutations that severely affect the respiratory chain are counter-selected in most human neoplasms, they are the genetic hallmark of indolent oncocytomas, where they appear to contribute to reduce tumorigenic potential. A correlation between mtDNA mutation type and load, and the clinical outcome of a tumor, corroborated by functional studies, is currently lacking. Recurrent familial oncocytomas are extremely rare entities, and they offer the chance to investigate the determinants of oncocytic transformation and the role of both germline and somatic mtDNA mutations in cancer.

International Medullary Thyroid Carcinoma Grading System: A Validated Grading System for Medullary Thyroid Carcinoma.

Purpose: Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely accepted pathologic grading scheme. In 2020, two groups separately developed slightly different schemes (the Memorial Sloan Kettering Cancer Center and Sydney grade) on the basis of proliferative activity (mitotic index and/or Ki67 proliferative index) and tumor necrosis.

Basal and Calcium-Stimulated Procalcitonin for the Diagnosis of Medullary Thyroid Cancers: Lights and Shadows.

Background: Procalcitonin (proCt) was recently proposed as an alternative or in addition to calcitonin (Ct) in medullary thyroid cancer (MTC) diagnostics.

Methods: Serum basal Ct (bCt) and proCt (bproCt) levels were measured before surgery from a consecutive series of patients with (n=43) and without (n=75) MTC, retrospectively collected in Padua. Serum bproCt, bCt and stimulated proCt and Ct (sproCt and sCt) were measured in another consecutive series of 33 patients seen at three tertiary-level institutions undergoing a calcium stimulation test prior to surgery, 20 of them with a final diagnosis of MTC, and 13 with non-MTC nodular disease.

Minimal Extrathyroidal Extension in Predicting 1-Year Outcomes: A Longitudinal Multicenter Study of Low-to-Intermediate-Risk Papillary Thyroid Carcinoma (ITCO#4).

The role of minimal extrathyroidal extension (mETE) as a risk factor for persistent papillary thyroid carcinoma (PTC) is still debated. The aims of this study were to assess the clinical impact of mETE as a predictor of worse initial treatment response in PTC patients and to verify the impact of radioiodine therapy after surgery in patients with mETE. We reviewed all records in the Italian Thyroid Cancer Observatory database and selected 2237 consecutive patients with PTC who satisfied the inclusion criteria (PTC with no lymph node metastases and at least 1 year of follow-up).

Impact of 18F-FDG PET/CT on Clinical Management of Suspected Radio-Iodine Refractory Differentiated Thyroid Cancer (RAI-R-DTC).

Background: As reported in the literature, [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) provides useful qualitative and semi-quantitative data for the prognosis of advanced differentiated thyroid cancer. Instead, there is a lack of data about the real clinical impact of 18F-FDG PET/CT on the choice of the more effective therapeutic approach for advanced differentiated thyroid cancer (DTC) that starts to lose iodine avidity. The primary aim of this retrospective study was to assess how 18F-FDG PET/CT can guide the choice of the best therapeutic approach to RAI-refractory DTC (RAI-R-DTC) in patients with a doubtful iodine uptake/negative 18F-FDG PET/CT I whole-body scan after several radioactive iodine therapies (RAIT).

Gene expression profile in metastatic and non-metastatic parathyroid carcinoma.

Parathyroid carcinoma (PC) is one of the rarest and aggressive malignancies of the endocrine system. In some instances, the histological diagnosis remains uncertain unless there is evidence of gross local invasion or secondary spread. The identification of molecular markers could improve the diagnostic accuracy of these lesions.

Results and Clinical Interpretation of Germline Analysis in a Series of Patients with Medullary Thyroid Carcinoma: The Challenge of the Variants of Uncertain Significance.

Germline variants are responsible for approximately 25% of medullary thyroid carcinoma (MTC) cases. Identification of variant carriers allows for the adoption of preventative measures which are dependent on the risk associated with the specific alteration. From 2002 to 2020, at our cancer genetics clinic, genetic testing was performed in 163 subjects (102 complete gene analyses and 61 targeted analyses), 72 of whom presented with MTC.

Pre-operative imaging workup for surgical intervention in primary hyperparathyroidism: A tertiary referral center experience.

Purpose: Preoperative imaging in patients with primary hyperparathyroidism provides important localization information, allowing the surgeon to perform a focused surgery. However there are no evidence-based guidelines suggesting which preoperative imaging should be used, resulting in a risk of excessive prescription of exams and waste of economic resources. The main purpose of this study was to describe our experience on the performance of various imaging techniques for the preoperative localization of abnormal parathyroid gland/s, with a focus on the sensitivity and specificity of each technique.