Shufang Yang

Background: Pheochromocytoma is a rare catecholamine-secreting tumor that can present with severe hypertensive episodes and other symptoms due to excessive catecholamine release. Approximately 30% of pheochromocytomas are associated with hereditary syndromes, including multiple endocrine neoplasia type 2A (MEN2A), an autosomal dominant disorder caused by mutations in the RET proto-oncogene. MEN2A is characterized by the presence of medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism. Case Presentation: We report the case of a 19-year-old female who presented with pheochromocytoma without experiencing a crisis, despite having a significant adrenal mass and undergoing high-dose glucocorticoid treatment. Genetic testing revealed a heterozygous missense mutation in the RET gene (c.1900T > C: p. Cys634Arg), associated with MEN2A. Further endocrine evaluation identified a thyroid nodule with mildly elevated calcitonin levels, but normal electrolyte and parathyroid hormone levels. Over a 15-month postoperative follow-up, the patient exhibited persistently mild hypercalcitoninemia with stable thyroid nodule size, while PTH and serum calcium levels showed a progressive increase. Further parathyroid scintigraphy using 99mTc-MIBI was performed, yielding a negative result for parathyroid adenoma. Conclusion: Patients with MEN2A require comprehensive, long-term follow-up to monitor for recurrence of pheochromocytoma and the development of additional endocrine neoplasms. This case highlights the role of genetic testing in guiding the management of hereditary pheochromocytoma and supports the importance of personalized monitoring strategies in patients with MEN2A.

Background: The current preoperative malignancy risk evaluation for thyroid nodules involves stepwise diagnostic modalities including ultrasonography, thyroid function serology and fine-needle aspiration (FNA) cytopathology, respectively. We aimed to substantiate the stepwise contributions of each diagnostic step and additionally investigate the diagnostic significance of quantitative chromogenic imprinted gene in-situ hybridization (QCIGISH)—an adjunctive molecular test based on epigenetic imprinting alterations. Methods: A total of 114 cytopathologically-diagnosed and histopathologically-confirmed thyroid nodules with complete ultrasonographic and serological examination records were evaluated using QCIGISH in the study. Logistic regression models for thyroid malignancy prediction were developed with the stepwise addition of each diagnostic modality and the contribution of each step evaluated in terms of discrimination performance and goodness-of-fit. Results: From the baseline model using ultrasonography [area under the receiver operating characteristics curve (AUROC): 0.79; 95% confidence interval (CI): 0.71–0.86], significant improvements in thyroid malignancy discrimination were observed with the stepwise addition of thyroid function serology (AUROC: 0.82; 95% CI: 0.74–0.90; P=0.23) and FNA cytopathology (AUROC: 0.88; 95% CI: 0.81–0.94; P=0.02), respectively. The inclusion of QCIGISH as an adjunctive molecular test further advanced the preceding model’s diagnostic performance (AUROC: 0.95; 95% CI: 0.91–1.00, P=0.007). Conclusions: Our study demonstrated the significant stepwise diagnostic contributions of standard clinical assessments in the malignancy risk stratification of thyroid nodules. However, the addition of molecular imprinting detection further enabled a more accurate and definitive preoperative evaluation especially for morphologically indeterminate thyroid nodules and cases with potentially discordant results among standard modalities.

Background: Early-onset diabetes appears to be an aggressive phenotype of type 2 diabetes (T2D). The impact of the age of onset of T2D on albuminuria, especially high urinary albumin excretion, remains to be investigated. Objective: To determine whether adults diagnosed with T2D between the ages of 18 and 45 more aggressively develop albuminuria. Methods: Conducted at Taizhou People’s Hospital from November 2018 to August 2020, this cross-sectional study enrolled T2D patients. Anthropometric measures, metabolic profiles, and urinary albumin creatinine ratio were examined. Patients were categorized into early-onset (≤ 45 years) and late-onset (> 45 years) groups. Univariate and multivariate analyses were performed to identify albuminuria risk factors. Subgroups were formed based on age at diabetes diagnosis and gender. Multivariate ordinal logistic regression analysis was then conducted to identify distinct risk factors within each subgroup. Results: Analyzing 1900 T2D patients, it was found significantly higher albuminuria prevalence in early-onset patients (35.08% vs 29.92%, P = 0.022). The risk of albuminuria in early-onset patients was 1.509 times higher than that in late-onset patients, especially among male patients, where the risk increased to 1.980. For late-onset patients, disease duration and glycated hemoglobin (HbA1c) were identified as risk factors, whereas for early-onset patients, body-mass index (BMI) and systolic blood pressure were associated with increased risk. Among male patients, age at diagnosis of diabetes, blood pressure, and BMI were identified as risk factors, while for female patients, disease duration and HbA1c played a significant role. Additionally, high-density lipoprotein cholesterol was found to be a protective factor against albuminuria. Conclusion: Individuals diagnosed with T2D before 45 face heightened albuminuria risk, especially males. Risk factors vary by gender and onset age, highlighting the need for tailored management strategies.

Adrenocortical carcinoma (ACC) is a rare malignancy with dismal prognosis. Hypoxia is one of characteristics of cancer leading to tumor progression. For ACC, however, no reliable prognostic signature on the basis of hypoxia genes has been built. Our study aimed to develop a hypoxia-associated gene signature in ACC. Data of ACC patients were obtained from TCGA and GEO databases. The genes included in hypoxia risk signature were identified using the Cox regression analysis as well as LASSO regression analysis. GSEA was applied to discover the enriched gene sets. To detect a possible connection between the gene signature and immune cells, the CIBERSORT technique was applied. In ACC, the hypoxia signature including three genes (CCNA2, COL5A1, and EFNA3) was built to predict prognosis and reflect the immune microenvironment. Patients with high-risk scores tended to have a poor prognosis. According to the multivariate regression analysis, the hypoxia signature could be served as an independent indicator in ACC patients. GSEA demonstrated that gene sets linked to cancer proliferation and cell cycle were differentially enriched in high-risk classes. Additionally, we found that PDL1 and CTLA4 expression were significantly lower in the high-risk group than in the low-risk group, and resting NK cells displayed a significant increase in the high-risk group. In summary, the hypoxia risk signature created in our study might predict prognosis and evaluate the tumor immune microenvironment for ACC.

Adrenocortical carcinoma (ACC) is a rare malignant tumor with poor prognosis. Ferroptosis, a new form of cell death, differs from other forms of cell death and plays a vital role in tumor progress. Our study aimed to establish a ferroptosis-related signature with prognostic value in ACC. RNA-seq data and corresponding clinical characteristics for ACC were downloaded from TCGA and GEO databases. Genes included in ferroptosis risk signature were assessed by univariable and multivariable Cox regression analysis as well as lasso regression analysis. The prognostic value of the ferroptosis risk signature was assessed using K-M and ROC curves. Furthermore, we performed GSEA to discover the enriched gene sets in high-risk group. Additionally, TIMER website was applied to detect a possible connection between the signature and immune cells infiltration. ssGSEA was performed to evaluate scores of immune cells and immune-related pathways in two groups. A ferroptosis signature comprised of six genes (SLC7A11, TP53, HELLS, ACSL4, PCBP2, and HMGB1) was constructed to predict prognosis and reflect the immune infiltration in ACC. Patients in high-risk group were inclined to have worse prognosis. The ferroptosis model performed well in predicting prognosis and could be served as an independent indicator in ACC. GSEA revealed that gene sets correlated with biological processes including cell cycle, DNA replication, base excision repair, and P53 signaling pathway were highly enriched in high-risk group. In addition, we discovered that the expressional levels of hub genes were linked to six immune cells’ infiltration in ACC tumor. ssGSEA revealed that contents of most immune cells significantly decreased in the high-risk group. In conclusion, the novel ferroptosis risk signature could be useful in predicting prognosis and reflecting immune infiltration in ACC. It also brings us new insights into the possible value of targeting ferroptosis during the therapy of ACC.