A Woman with Bilateral Pheochromocytoma and Tuberous Sclerosis Complex.

Background/Objective: Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors. Here, we report an unusual case of synchronous PPGL in an asymptomatic patient with tuberous sclerosis complex (TSC). Case Report: A 49-year-old woman with a history of TSC and end-stage renal disease was referred for evaluation of bilateral adrenal and retroperitoneal masses. She denied chest pain, palpitations, headaches, or previous hypertensive crisis. The laboratory test results showed a plasma normetanephrine level of 20.20 nmol/L (normal range, 0.00-0.89 nmol/L) and plasma chromogranin A level Chromogranin A (CgA) levels of 1518 ng/mL (normal range, 0-103 ng/mL). The plasma metanephrine level was normal. After α-blockade, the patient underwent bilateral adrenalectomy and retroperitoneal mass excision. Pathology confirmed these lesions to be pheochromocytoma and composite paraganglioma/ganglioneuroma, respectively. Her plasma normetanephrine level normalized postoperatively, and the chromogranin A levels improved to 431 ng/mL. Discussion: Routine imaging has increased the incidental diagnosis of PPGL. Diagnostic workup includes measurement of the urinary and/or plasma metanephrine and catecholamine levels followed by tumor localization. Patients with young age, syndromic lesions, bilateral PPGL, or unilateral disease with a positive family history should have genetic testing. Definitive treatment is surgical after α-blockade. Conclusion: This case highlights a rare presentation of bilateral PPGL in a patient with TSC.

Efficacy of radiofrequency ablation for treatment of toxic thyroid nodules-a narrative review.

Background and Objective: Radiofrequency ablation (RFA) has been used in the treatment of benign thyroid nodules for the past 20 years. The adaptation of RFA to benign autonomously functioning thyroid nodules (AFTNs) has been introduced into clinical practice with variable efficacy and outcomes published in the literature. To better understand international practices, we performed a literature search to better elucidate the efficacy and outcomes in the treatment of AFTNs with RFA. Methods: Comprehensive literature searches were independently conducted by two investigators on PubMed, EMBASE, and Scopus in October of 2022 to identify articles reporting AFTN treated by RFA using the terms "RFA", "radiofrequency ablation", "thyroid nodule", "toxic nodules", and "autonomous functioning thyroid nodule". Papers were selected by relevance of the title or abstract, and the date of publication. Key Content and Findings: In patients with toxic nodules, studies have shown 50% remission rate one year after single session of RFA, up to 71% after second dose. Adverse events are generally limited to postoperative pain lasting less than one day, however there are reports of self-limited voice changes, and self-limited hypothyroidism. RFA has been shown to be safe with no reported instances of post-procedure hypothyroidism or hypocalcemia when compared to radioactive iodine (RAI) and surgery. Conclusions: RFA is an acceptable alternative to surgical resection for the treatment of AFTNs in selective patients, however more studies on long-term hyperthyroidism remission rates and nodule regrowth are necessary for further applications.

A retrospective analysis of molecular testing in cytologically indeterminate thyroid nodules with histologic correlation: Experience at a heterogenous multihospital system.

INTRODUCTION: Thyroid malignancy is one of the most common types of cancer in developed nations. Currently, fine-needle aspiration cytology (FNAC) is the most practical screening test for thyroid nodules. However, cytologically indeterminate samples comprise approximately 15%-30% of cases. These include cases classified as atypia of undetermined significance (AUS), follicular neoplasm (FN), and suspicious for malignancy (SFM). Indeterminate cases can be sent for molecular testing for more definitive classification to help guide management and prevent overtreatment of benign thyroid nodules. We conducted a retrospective review on molecular testing of indeterminate thyroid FNAC and reviewed subsequent histologic diagnoses in resection specimens to assess how molecular testing supported a diagnosis and its effect on clinical management of patients at our institution. METHODS: A retrospective chart review was performed on all thyroid FNAC specimens, corresponding molecular testing, and subsequent surgical resection specimens over a 6-year period. RESULTS: A total of 10,253 thyroid FNAC were performed in our hospital system during our study period, of which 10% (n = 1102/10,253) had indeterminate FNAC results. Molecular testing was performed in 16% (n = 178/1102) of indeterminate cytology cases. Genetic alterations were identified in 39% (n = 69/178) of the cases sent for molecular testing. The majority of cytologically indeterminate cases sent for molecular testing were follicular-patterned lesions and their corresponding resection specimens revealed mostly low grade follicular derived neoplasms (i.e., follicular adenoma, non-invasive follicular thyroid neoplasm with papillary-like nuclear features, and follicular variant of papillary thyroid carcinoma). Of the cases with identified genetic alterations, 75% (n = 52/69) were treated surgically. In cases with no genetic alterations identified, only 18% (n = 20/109) were treated surgically. DISCUSSION/CONCLUSION: Molecular testing on cytologically indeterminate thyroid nodules can help provide a more accurate risk of malignancy assessment in patients with lesions that are difficult to diagnosis based solely on FNAC morphology. The types of genetic alterations identified in the resected thyroid lesions were consistent with what has been previously described in the literature. Additionally, we found that in the patients with indeterminate thyroid FNAC with adjunct molecular testing, more than half did not undergo surgical resection. This finding emphasizes the value of adding molecular testing in patients, particularly when attempting to reduce unnecessary surgical intervention.

Impact of surgery versus medical management on cardiovascular manifestations in Graves disease.

BACKGROUND: Graves disease is well known to have multiple adverse effects on the cardiovascular system. We compared the cardiovascular outcomes after surgical intervention versus medical treatment in patients with Graves disease. METHODS: We performed a retrospective study of all Graves disease patients with a cardiovascular comorbidity who underwent either surgical or medical management (N = 151). Perioperative biochemical and cardiovascular outcomes from the surgical versus the medical groups were analyzed. RESULTS: Of 151 patients, 69 (45.6%) patients underwent total thyroidectomy and 82 (54.3%) patients received medical treatment. Hypertension resolved in 44.7% of the patients from the surgical group vs 18% in the medical group (P = .03). Tachyarrhythmias, including atrial fibrillation and tachycardia, improved in 85.9% of patients in the surgical group vs 66% in the medical group (P = .01). All cardiovascular manifestations examined, hypertension, tachyarrhythmias, and heart failure, improved in 69% of patients in the surgical group and 42.6% of patients in the medical group during the follow-up period (P < .01). CONCLUSION: Surgical treatment offers a significant and rapid clinical improvement of cardiovascular manifestations in Graves disease patients, such as hypertension, tachyarrhythmias, and heart failure. Surgery should be considered and recommended in Graves disease patients with known cardiovascular manifestations.

Impact of psychiatric comorbidities on outcomes related to thyroid and parathyroid operations.

BACKGROUND: We examined the effect of psychiatric comorbidities on perioperative surgical outcomes and the leading causes of readmissions in patients who underwent thyroid and parathyroid operations. METHOD: Patient information was retrieved from the Nationwide Readmission Database (2010-2017). Multivariate analysis was used to identify predictors for hospital readmissions. RESULTS: A total of 181,007 and 53,808 patients underwent thyroid and parathyroid operations, respectively. Of those, 8,468 (4.7%) and 6,112 (11.4%) patients were readmitted within 30 days. Psychiatric comorbidities were more frequent in readmitted cohorts after thyroidectomies (14.9% vs 10.4%; P < .001) and parathyroidectomies (16.8% vs 11.5%; P < .001), with anxiety being the most frequent cause (thyroid: 7.87%, parathyroid: 6.8%). Psychiatric comorbidities were associated with greater risk of in-hospital mortality (thyroid: odds ratio = 2.07, 95% confidence interval = 1.13-3.53; P = .015 and parathyroid: odds ratio = 1.67, 95% confidence interval = 1.04-2.70; P = .005), postoperative complications (thyroid: odds ratio = 1.528, 95% confidence interval = 1.473-1.585; P < .001 and parathyroid: odds ratio = 3.26, 95% confidence interval = 2.84-3.73; P < .001), prolonged duration of stay (thyroid: beta coefficient = 1.142, 95% confidence interval = 1.076-1.207; P < .001 and parathyroid: beta coefficient = 2.15, 95% confidence interval = 1.976-2.32; P < .001), and 30-day readmissions (thyroid: hazard ratio = 1.18, 95% confidence interval = 1.03-1.18; P = .047 and parathyroid: hazard ratio = 1.23, 95% confidence interval = 1.11-1.36; P < .001). Psychosis had the greatest risk of readmission (thyroid: hazard ratio = 1.51 and parathyroid: hazard ratio = 1.42), and dementia (odds ratio = 2.58) had the greatest risk of postoperative complications. CONCLUSION: Concomitant psychiatric conditions after thyroid and parathyroid operations were associated with increased risk of postoperative complications, prolonged hospital stays, and greater rates of readmissions.

MEF2B is a member of the BCL6 gene transcriptional complex and induces its expression in diffuse large B-cell lymphoma of the germinal center B-cell-like type.

Myocyte enhancer-binding factor 2B (MEF2B) has been implicated as a transcriptional regulator for BCL6. However, details about the interaction between MEF2B and BCL6 during expression, as well as the relationship of MEF2B to the expression of other germinal center (GC) markers, have not yet been fully explained. Using germinal center B-cell-like diffuse large B-cell lymphoma (GC-DLBCL) and activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell lines, we analyzed the expression of MEF2B and its associations with BCL6, CD10, and ERK. Furthermore, small interfering RNA (siRNA) was used to study the possible effects of MEF2B knockdown on these proteins and cell growth. Analysis of the BCL6 transcriptional complex was performed using electrophoretic mobility shift assay. The correlation between MEF2B expression and the genetic type of DLBCL was assessed using immunohistochemistry on 111 patient samples, and via in silico analysis of publicly available microarray (Gene Expression Omnibus (GEO)) datasets. Our results indicate that the expression of MEF2B protein is important for the growth of GC-DLBCL cells, as evidenced by MEF2B knockdown inhibition of cell growth and the subsequent suppression of BCL6, CD10, and ERK phosphorylation. Analysis of BCL6 transcription factors in nuclear extracts of MEF2-expressing DLBCL cells showed involvement of MEF2B with AP-2α and BCL6 proteins in the formation of the BCL6 gene transcriptional complex. Indeed, differential expression of MEF2B in the GC-DLBCL is statistically significant compared to the ABC-DLBCL in the GEO datasets, as well as in tissue microarray, as indicated via immunohistochemistry (Visco-Young algorithm). Our findings indicate that MEF2B is an essential component of the BCL6 gene transcriptional complex for the regulation of DLBCL growth via the promotion of BCL6 expression. Beyond its regulatory role in DLBCL growth, MEF2B expression correlated positively with BCL6 and CD10 expression, and was preferentially expressed in the GBC-DLBCL group.