Succinate dehydrogenase gene mutations in cardiac paragangliomas.

Pheochromocytomas and paragangliomas are chromaffin cell tumors arising from neuroendocrine cells. At least 1/3 of paragangliomas are related to germline mutations in 1 of 17 genes. Although these tumors can occur throughout the body, cardiac paragangliomas are very rare, accounting for <0.3% of mediastinal tumors. The purpose of this study was to determine the clinical characteristics of patients with cardiac paragangliomas, particularly focusing on their genetic backgrounds. A retrospective chart analysis of 15 patients with cardiac paragangliomas was performed to determine clinical presentation, genetic background, diagnostic workup, and outcomes. The average age at diagnosis was 41.9 years. Typical symptoms of paraganglioma (e.g., hypertension, sweating, palpitations, headache) were reported at initial presentation in 13 patients (86.7%); the remaining 2, as well as 4 symptomatic patients, initially presented with cardiac-specific symptoms (e.g., chest pain, dyspnea). Genetic testing was done in 13 patients (86.7%); 10 (76.9%) were positive for mutations in succinate dehydrogenase (SDHx) subunits B, C, or D. Thirteen patients (86.7%) underwent surgery to remove the paraganglioma with no intraoperative morbidity or mortality; 1 additional patient underwent surgical resection but experienced intraoperative complications after removal of the tumor due to co-morbidities and did not survive. SDHx mutations are known to be associated with mediastinal locations and malignant behavior of paragangliomas. In this report, the investigators extend the locations of predominantly SDHx-related paragangliomas to cardiac tumors. In conclusion, cardiac paragangliomas are frequently associated with underlying SDHx germline mutations, suggesting a need for genetic testing of all patients with this rare tumor.

Validation of the UST thyroid scoring index against ultrasensitive assays for thyroid-stimulating hormone and free thyroxine

BACKGROUND: Clinical manifestations of thyroid dysfunction are variable. The UST Scoring Index for thyroid disorders, formulated in the 1990s to evaluate thyroid functional status, was based on total thyroid hormone levels and thyroidal iodine uptake. However, with the advent of newer and more sensitive tests, the recommendations and practice now dictate the use of thyrotropin (TSH) and free thyroxine (FT4) levels in the confirmation of thyroid dysfunction.OBJECTIVE: To validate the UST Scoring Index for thyroid disorders using TSH and FT4.METHODS/RESULTS: The UST Clinical Scoring Index was administered to 170 patients presenting for thyroid-relatedcomplaints. Thyroid function tests were then requested (TSH and Free T4) and they were classified according to biochemical status. We obtained the following: 43 hyperthyroid, 102 euthyroid and 25 hypothyroid subjects. The mean TSH for the 3 groups were 0.08, 1.28, and 41.50 uIU/mL respectively (NV 0.27-3.75.) Mean FT4 levels were 36.18, 18.33, and 8.43 pM/L respectively (NV 10.3-25.0.) The most frequent findings in the biochemically hyperthyroid group were thyroid enlargement (88%), easy tiredness (74%), palpitations (70%), and nervousness (65%); in the euthyroid group, easy tiredness (62%), thyroid enlargement (54%), palpitations (53%), and irritability (49%); in the hypothyroid group, easy tiredness (64%), exertional dyspnea (52%), weight gain (44%), and constipation (44%.) The UST scoring index for thyroid disorders has a sensitivity of 67%, specificity of 84%, and accuracy rate of 80 %, with AUC of 0.850 on ROC analysis for the detection ofhyperthyroidism. For detecting hypothyroidism, it has a sensitivity of 40%, specificity of 92%, and asccuracy rate of 85%, with AUC 0.7553 on ROC analysis.CONCLUSION: The UST scoring index for thyroid disorders has good sensitivity, specificity and accuracy rate based on ROC when validated using TSH and FT4 for the detection of hyperthyroidism and hypothyroidism.