Successful management of a multiple endocrine neoplasia type 1-associated thymic neuroendocrine neoplasms with acute chest pain as initial symptom: A rare case report.

Key Clinical Message: Acute chest pain can be the first manifestation of multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN). Comprehensive treatment may be an effective strategy for MEN1-associated NEN. Abstract: Multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN) is caused by the mutation of tumor suppressor MEN1 gene. Patients with MEN1-associated NEN initially presenting with acute chest pain are very rare. In the manuscript, we reported a case of a 45-year-old man who developed MEN1-associated NEN with acute chest pain as initial symptom. Thoracoscopic thymotomy was performed and thymic NEN was successfully removed. Genetic test showed a germline mutation of MEN1 gene in this patient. Immunohistochemical staining exhibited Syn(+), CgA(+), INSM1(+), CD56(+) and Ki67-positive cells (2%) in MEN1-associated NEN. Further evaluation unveiled MEN1-associated benign tumors including digestive NEN and pituitary gland adenoma. The 99mTc-HYNIC-TOC scintigraphy showed that focally increased radioactivity in the mid-upper abdomen. This patient was administered with 50Gy/25F of radiation dose to treat the postoperative lesions. Subsequently, sandostatin LAR (30 mg per week) was used as systemic therapy. He had no recurrence or metastasis for 6-month follow-up. Thus, acute chest pain can be the first manifestation of MEN1-associated NEN, and comprehensive treatment including surgery, radiation and systemic treatment may be an effective strategy for MEN1-associated NEN.

Diversities of Mechanism in Patients with VHL Syndrome and diabetes: A Report of Two Cases and Literature Review.

Background: Von Hippel-Lindau (VHL) syndrome is characterized by tumorous lesions affecting multiple organs. Pancreatic involvement in VHL syndrome can present as endocrine tumors and pancreatic cysts, which can interfere with both exocrine and endocrine functions of the pancreas. Diabetes is an uncommon complication of VHL syndrome. Purpose: This study aims to summarize the various mechanisms of diabetes in VHL syndrome by reporting two cases and conducting a literature review. Methods: We analyzed the clinical and imaging data of two patients with VHL syndrome and diabetes. Additionally, we reviewed the existing literature to explore the clinical diversities and management strategies for VHL syndrome complicated with diabetes. Results: The first patient presented with liver metastasis of pancreatic neuroendocrine tumor and multiple pheochromocytoma. After surgery, the patient's diabetic control improved, as evidenced by a significant reduction in insulin dosage. This indicates a potential insulin resistance due to elevated metanephrine levels prior to surgery and partial insulin deficiency caused by distal pancreatectomy. The second patient had multiple hemangioblastomas, as well as multiple pancreatic cysts and positive pancreatic islet autoantibodies. Diabetes in this case may be attributed to pancreatic lesions and the coexistence of autoimmune insulitis. A literature review of other patients with VHL combined with diabetes revealed multiple mechanisms, including increased catecholamine levels, pancreatic lesions, surgical removal of pancreatic tissue, endocrine treatment, and possibly the coexistence of autoimmune insulitis. Conclusion: VHL syndrome complicated with diabetes involves diverse mechanisms.

Pituitary stalk interruption syndrome and liver cirrhosis associated with diabetes and an inactivating KCNJ11 gene mutation: a case report and literature review.

Background: Pituitary stalk interruption syndrome (PSIS) is a congenital disease commonly found in patients with combined pituitary hormone deficiency (CPHD). Most PSIS patients manifest growth retardation and delayed puberty. We report a rare case of PSIS with tall stature, liver cirrhosis and diabetes, possibly caused by an inactivating KCNJ11 gene mutation. Case presentation: A 37-year-old female patient initially presented with liver cirrhosis and diabetes, without any secondary sexual characteristics. Endocrine investigation indicated CPHD. Small anterior pituitary, invisible pituitary stalk and no eutopic posterior lobe hypersignal in the sella turcica viewed in magnetic resonance imaging (MRI) confirmed the diagnosis of PSIS. Despite receiving no growth hormone or sex hormone therapy, she reached a final height of 186 cm. Liver histopathology revealed nonalcoholic fatty cirrhosis. Genetic testing identified a heterozygous p.Arg301Cys mutation in the KCNJ11 gene. Conclusion: This is a rare case of PSIS with liver cirrhosis and diabetes associated with an inactivating KCNJ11 gene mutation. It's supposed that early hyperinsulinism caused by the KCNJ11 gene mutation, as well as delayed epiphyseal closure due to estrogen deficiency, contributed to the patient's exceptionally tall stature. Untreated growth hormone deficiency (GHD) resulted in increased visceral fat, leading to nonalcoholic fatty liver disease (NAFLD) and cirrhosis. The decline in ß cell function with age, combined with NAFLD, may have played a role in the development of diabetes.

Decreased programmed cell death ligand 2-positive monocytic myeloid-derived suppressor cells and programmed cell death protein 1-positive T-regulatory cells in patients with type 2 diabetes: implications for immunopathogenesis.

Objectives: The activation of immune cells plays a significant role in the progression of type 2 diabetes. This study aimed to investigate the potential role of myeloid-derived suppressor cells (MDSCs) and T-regulatory cells (Tregs) in type 2 diabetes. Methods: A total of 61 patients diagnosed with type 2 diabetes were recruited. Clinical characteristics were reviewed and peripheral blood samples were collected. We calculated the percentage of different cells. Frequencies of MDSC subsets refered to the percentage of G-MDSCs (CD15+CD33+CD11b+CD14-HLA-DR-/low) in CD45 positive cells and the percentage of M-MDSCs (CD14+CD15-CD11b+CD33+HLA-DR-/low) in lymphocytes plus monocytes. Results: Frequencies of programmed cell death ligand 1-positive granulocytic MDSCs (PD-L1+ G-MDSCs), programmed cell death ligand 2-positive monocytic MDSCs (PD-L2+ M-MDSCs), PD-L2+ G-MDSC, and programmed cell death protein 1-positive Tregs (PD-1+Tregs) were decreased in patients with type 2 diabetes. The frequency of PD-1+ Tregs was positively related to PD-L2+ M-MDSCs (r= 0.357, P = 0.009) and negatively related to HbA1c (r = -0.265, P = 0.042), fasting insulin level (r = -0.260, P = 0.047), and waist circumference (r = -0.373, P = 0.005). Conclusions: Decreased PD-L2+ M-MDSCs and PD-1+ Tregs may promote effector T cell activation, leading to chronic low-grade inflammation in type 2 diabetes. These findings highlight the contribution of MDSCs and Tregs to the immunopathogenesis of type 2 diabetes and suggest their potential as targets for new therapeutic approaches.

The concordance and discordance of diabetic kidney disease and retinopathy in patients with type 2 diabetes mellitus: A cross-sectional study of 26,809 patients from 5 primary hospitals in China.

Introduction: Diabetic kidney disease (DKD) and diabetic retinopathy (DR) share similar pathophysiological mechanisms. However, signs of DKD may be present at diagnosis of diabetes without retinopathy. Risk factors for the development of DKD and DR may not be identical. Methods: This study aimed to evaluate the concordance and discordance between DKD and DR by investigating the distribution of DKD and DR in patients with type 2 diabetes mellitus from 5 Chinese cities. A total of 26,809 patients were involved in this study. The clinical characteristics were compared among patients based on the presence of DKD and DR. Logistic regression models were used to analyze the independent risk factors of DKD and DR. Results: The prevalence of DKD and DR was 32.3% and 34.6%, respectively. Among eligible patients, 1,752 patients without DR had an increased urinary albumin-to-creatinine ratio (ACR) or reduced estimated glomerular filtration rate (eGFR), and 1,483 patients with DR had no DKD. The positive predictive value of DR for DKD was 47.4% and negative predictive value was 67.1%. Elder age, male gender, a longer duration of disease, higher values of waist circumference and HbA1c were associated with both DR and DKD. A lower educational level was associated with DR. Higher BP and TG would predict increased prevalence of DKD. Conclusions: DKD and DR shared many risk factors, but a significant discordance was present in patients with type 2 diabetes mellitus. DKD was more strongly associated with blood pressure and triglycerides than DR.

The feasibility and efficacy of a community-based multifactorial intervention to improve the cardiovascular risk factor control among patients with type 2 diabetes: A 2-year cluster randomized trial.

TRIAL DESIGN: Our study is to investigate the feasibility and effectiveness of multiple cardiovascular factors intervention (MFI) in type 2 diabetes patients in China's primary care setting. METHODS: We performed a cluster randomized trial to compare the proportion of patients achieved the targets between usual care group (control, 9 sites, n = 868) and MFI group (8 sites, n = 739) among patients with type 2 diabetes in primary care setting. Logistic regression model with random effects was used to estimate the association of the effect of intervention and the proportion achieved the targets. RESULTS: At baseline, the end of 1 year, and 2 years follow-up, the proportion of patients achieved all 3 target goals (HbA1c < 7.0%, blood pressure < 130/80 mm Hg and low-density lipoprotein cholesterol < 2.6 mmol/L) were 5.7%, 5.9%, 5.7% in the control group and 5.9%, 10.6%, 12.3% in the MFI group. After adjusting sex, age, diabetes duration, body mass index, HbA1c, blood pressure, and low-density lipoprotein cholesterol at baseline, there was no difference between the 2 groups (OR (95% CI): 1.27 (0.38-4.27) and 1.86 (0.79-4.38) for the first year and second year, respectively). When stratified by payment method, the patients with medical insurance or public expenses had a higher proportion achieved target goals (6.9% vs 16.4%, OR (95% CI): 2.30 (1.04-5.08)) in the second year. CONCLUSIONS: The controlling of cardiovascular risk factor targets remains suboptimal among patients with type 2 diabetes in primary care setting. MFI in type 2 diabetes improved cardiovascular disease risk profile, especially in the patients with medical insurance.

Screening cardiovascular risk factors of diabetes patients in the primary diabetes clinics.

ABSTRACT: To evaluate the atherosclerotic cardiovascular diseases (ASCVD) risk factors in type 2 diabetes patients from the primary diabetes clinics for further comprehensive intervention in China.A cross-sectional study was conducted in 5 primary diabetes chain hospitals in Beijing, Lanzhou, Harbin, Chengdu, and Taiyuan in continuous patients with type 2 diabetes from March 2016 to December 2019. The data collected at the first visit were analyzed, and proportions of patients reached the targets (glycosylated hemoglobin [HbA1c] < 7%, blood pressure < 130/80 mm Hg, and low-density lipoprotein cholesterol [LDL-C] < 2.6mmol/l) were calculated. The clinical characteristics and the associated factors with achievement in HbA1c, blood pressure, and LDL-C targets were analyzed.A total of 20,412 participants, including 11,353 men (55.6%), with an average age of (59.4 ±â€Š10.4) years were enrolled. Nearly 95% diabetes had one or more ASCVD risk factors other than hyperglycemia. The control rates of HbA1c, blood pressure, and LDL-C were 26.5%, 27.8%, and 42.6%, respectively. Only 4.1% patients achieved all 3 targets. Nearly 95% patients had one or more ASCVD risk factors other than hyperglyciemia. Diabetes duration, family history, and overweight/obesity were associated with the number of aggregated ASCVD risk factors. The patients with older age, no overweight/obesity, not smoking, less ASCVD risk factors, and having special diabetes care insurance (Chengdu) were associated with a higher control rates.To deal with poor control status, global management of ASCVD risk factors, weight loss, and smoking cessation must be emphasized in the primary diabetes care settings. Special diabetes care insurance should be advocated.Current ClinicalTrial.gov protocol ID NCT03707379. Date of Registration: October 16, 2018. https://clinicaltrials.gov.

Patient Discomfort in Relation to Thyroid Nodule Fine-Needle Aspiration (FNA) Performed with or without Parenteral and/or Topical Anesthetic.

OBJECTIVE: There is much reported variation in the impact of local anesthesia on thyroid fine-needle aspiration (FNA) related discomfort. We compare patients undergoing thyroid FNA with subcutaneous injection or topical anesthetic to no anesthetic. METHODS: We conducted a retrospective review of 585 sequential ultrasound guided thyroid FNA procedures in Mayo Clinic. Group 1 (n = 200), no anesthetic; Group 2 (n = 185), subcutaneous injection anesthetic; and Group 3 (n = 200), topical anesthetic. Patient demographics, number of FNA passes, needle gauge, and cytopathology were recorded plus a discomfort score (0 to 10) before and immediately post procedure in all 3 groups and peak discomfort during the FNA in Groups 1 and 2. RESULTS: There were no differences among the 3 groups in age, sex, FNA sufficiency rate, cytopathology, and FNA passes number. There was no significant difference between Groups 1 and 2 in peak discomfort score during the FNA: 0 (45%, 42.2%), 1 to 2 (19%, 24.9%), 3 to 5 (23.5%, 20.5%), 6 to 8 (9.5%, 10.8%), 9 to 10 (3%, 1.6%), respectively. Discomfort score post procedure: 0 (78.5%, 77.8%, 53.5%), 1 to 2 (13%, 13%, 36.5%), 3 to 5 (7%, 7%, 9%), 6 to 8 (1.5%, 2.2%, 1%), 9 to 10 (0%, 0%, 0%) for groups 1, 2, and 3, respectively. There were no significant differences among the 3 groups for a discomfort score ≥3. CONCLUSION: FNA associated patient discomfort was comparable during and after the procedure regardless of the use of anesthetic or the type utilized. Approximately 90% of patients experienced mild to moderate discomfort during the procedure. And 90% reported no more than a level 2 discomfort post procedure. ABBREVIATIONS: End = endocrinology; FNA = fine-needle aspiration; MCF = Mayo Clinic Florida; MCR = Mayo Clinic Rochester.