Eleftheria Karaviti

Background/Objectives: The concurrent occurrence of papillary (PTC) and medullary (MTC) thyroid carcinoma within the same thyroid gland is an exceptionally rare clinical entity. We conducted a systematic review to synthesize available evidence on the clinicopathological features, diagnostic pathways, and therapeutic outcomes of patients presenting with simultaneous PTC and MTC. Methods: This systematic review was conducted in accordance with PRISMA guidelines and was registered in PROSPERO. Comprehensive electronic searches across PubMed, MEDLINE, EMBASE, Scopus, and Web of Science were performed up to January 2025. Original clinical cohorts reporting on synchronous PTC and MTC (sample size ≥ 10) were included, while single-case reports and small series (n < 10) were excluded. Study quality was evaluated using the Newcastle–Ottawa Scale (NOS), and a narrative synthesis was performed. Results: Eight studies comprising 462 patients met the inclusion criteria. Over 70% of patients had preoperative cytological suspicion or biochemical evidence (elevated calcitonin) of MTC, whereas synchronous preoperative identification of both malignancies occurred in only 24% of cases. Among patients with available histological subtype data, 61% (148/243) presented with true collision tumors separated by normal thyroid parenchyma, whereas 39% (95/243) exhibited mixed medullary–follicular thyroid carcinoma (MMFTC) morphology. Primary MTC lesions were generally larger than the concurrent PTCs. Overall lymph node metastasis was reported in 44% of evaluated patients (predominantly MTC-derived), and distant metastasis occurred in 8%. Conclusions: Simultaneous PTC and MTC are predominantly characterized by an incidental PTC microcarcinoma alongside a larger MTC component that dictates disease staging and nodal dissemination. Further prospective studies and basic research are required to fully understand the potential shared pathophysiological mechanisms and the behavior of these coexisting tumors.

Background: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. Soluble receptor for advanced glycation end products (sRAGE) has emerged as a candidate biomarker in metabolic, inflammatory, and malignant diseases, although its prognostic significance in LC remains uncertain. Methods: Serum sRAGE levels were prospectively measured at baseline and prior to the second cycle of treatment in patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Associations of sRAGE with overall survival (OS), progression-free survival (PFS), clinical features, and other biomarkers were analyzed. Results: In total, 42 patients were enrolled in this study. sRAGE was detected in 16 patients (38.1%) at baseline and in 15 patients (37.5%) after the first cycle of treatment. Pre-treatment sRAGE levels were strongly correlated with post-treatment levels (Pearson’s r = 0.78; 95% CI, 0.61–0.88; p = 4.1 × 10⁻⁹) and moderately correlated with PD-L1 tumor proportion score in NSCLC patients (Spearman’s ρ = 0.4, p = 0.049). Pre-treatment sRAGE levels tended to be higher in patients with indeterminate/high risk of liver fibrosis compared to patients with low risk (Wilcoxon rank-sum test, p = 0.041). Post-treatment change in sRAGE levels was correlated with whole blood cell count-derived inflammatory markers. A preliminary association between decreased sRAGE and overall survival in SCLC patients was observed. Conclusions: Serum sRAGE shows potential as a blood-based biomarker reflecting metabolic, immune, and inflammatory status in lung cancer, warranting further investigation to clarify its prognostic and therapeutic relevance.

This review highlights the role of Anti-Müllerian Hormone (AMH) in ovarian insufficiency and as a predictor of menopause. AMH, produced by granulosa cells in growing follicles, is a key marker of ovarian reserve, reflecting the remaining pool of viable follicles. In cases of primary ovarian insufficiency (POI), AMH levels are significantly reduced, aiding in diagnosis and distinguishing POI from other causes of amenorrhea. AMH levels below 8 pmol/L have shown high sensitivity (85%) and specificity (100%) for diagnosing POI in women with secondary oligomenorrhea. Regarding ovarian aging, AMH declines steadily with age, serving as a reliable predictor of menopausal timing. AMH levels are linked to menopausal symptoms, particularly vasomotor symptoms like hot flashes and their severity. However, its reliability for diagnosing menopause is inconsistent, especially in younger populations or when determining the exact onset. AMH levels can predict an earlier onset of menopause with limited sensitivity and specificity, particularly when using age-specific concentrations, as lower age-specific AMH levels are associated with an earlier menopause onset. Tracking AMH over time can improve the prediction of menopause. The accuracy of AMH measurements can be enhanced when considered alongside other hormonal markers or clinical symptoms. In polycystic ovary syndrome (PCOS), elevated AMH levels suggest a delayed onset of menopause, indicating an approximately two-year longer reproductive lifespan compared to women without PCOS (mean menopause age: 51.4 years in PCOS cases vs. 49.7 years in healthy controls). In endometriosis, AMH levels generally decline after surgery; however, they remain stable after chemotherapy, even years later, indicating that the decline in ovarian reserve may not be significantly affected.

Immune Checkpoint Inhibitors (ICIs) have revolutionized cancer treatment, offering hope for patients with various malignancies. However, along with their remarkable anticancer effects, ICIs can also trigger immune-related adverse events (irAEs). One such noteworthy complication is the development of Diabetes Mellitus (DM), which particularly resembles Type 1 Diabetes Mellitus (T1DM). The aim of this review is to provide insights into the epidemiology, pathophysiology, diagnostic issues, and treatment considerations of ICI-induced DM (ICI-DM), emphasizing the importance of early recognition and management to mitigate adverse outcomes. Although still rare, the incidence has increased with the widespread use of ICIs, especially PD-1/PD-L1 blockers (from 0.2% to 1.9%). Factors affecting the development of ICI-DM, such as specific ICIs, patient demographics, and genetic predispositions, are discussed. The complex interplay between immune dysregulation and pancreatic β-cell destruction contributes to diagnostic challenges, with presentations varying from asymptomatic hyperglycemia to diabetic ketoacidosis (DKA). Management strategies prioritize meticulous glycemic and electrolyte regulation along with tailored intravenous insulin therapy in cases of DKA. DM remission is rare, therefore treatment with both long-acting insulin at bedtime and short-acting insulin before meals is needed in longterm. Total daily insulin requirements can be estimated at 0.3–0.4 units/kg/day for most patients as a starting dose.

Immune checkpoint inhibitors (ICIs) are a revolutionary class of drugs that powerfully contribute to cancer therapy by harnessing the immune system to fight malignancies. However, their successful use as anti-cancer drugs is accompanied by a wide spectrum of immune-related adverse effects (irAEs), including endocrinopathies. Among them, thyroid dysfunction stands out as one of the most common endocrinopathies induced by ICI therapy and surfaces as a prominent concern. Destructive thyroiditis is the pathophysiological basis shared by the most common patterns of thyrotoxicosis followed by hypothyroidism and isolated hypothyroidism. Diagnostic approach is guided by clinical manifestation, laboratory evaluation and imaging modalities. Treatment approaches range from the substitution of levothyroxine to the utilization of beta blockers, depending on the extent of thyroid dysfunction’s severity. While the medical community is dealing with the evolution and complexities of immunotherapy, recognizing and effectively managing ICI-induced thyroid dysfunction emerged as crucial for enhancing patient safety and achieving improved outcomes. The aim of this review is to navigate the significance of ICI-induced thyroid dysfunction unraveling the various patterns, underlying mechanisms, diagnostic approaches, and treatment strategies. It, also, highlights the impact of various factors such as cancer subtype, ICI dosage, age, and genetic susceptibility on the risk of experiencing dysfunction.