Mercedes Falciglia

Molecular Testing for Mutations in Improving the Fine-Needle Aspiration Diagnosis of Thyroid Nodules

CONTEXT Thyroid nodules are common in adults, but only a small fraction of them are malignant. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for cancer diagnosis in thyroid nodules. However, 10-40% of nodules are diagnosed as indeterminate by cytology, making it difficult to optimally manage these patients. OBJECTIVE The aim of this study was to establish the feasibility and role of testing for tumor-specific mutations in improving the FNA diagnosis of thyroid nodules. DESIGN The prospective study included 470 FNA samples of thyroid nodules from 328 patients. At the time of aspiration, a small portion of the material was collected and tested for BRAF, RAS, RET/PTC, and PAX8/PPARgamma mutations. The mutational status was correlated with cytology and either surgical pathology diagnosis or follow-up (mean, 34 months). RESULTS A sufficient amount of nucleic acids were isolated in 98% of samples. Thirty-two mutations were found, including 18 BRAF, eight RAS, five RET/PTC, and one PAX8/PPARgamma. The presence of any mutation was a strong indicator of cancer because 31 (97%) of mutation-positive nodules had a malignant diagnosis after surgery. A combination of cytology and molecular testing showed significant improvement in the diagnostic accuracy and allowed better prediction of malignancy in the nodules with indeterminate cytology. CONCLUSIONS These results indicate that molecular testing of thyroid nodules for a panel of mutations can be effectively performed in a clinical setting. It enhances the accuracy of FNA cytology and is of particular value for thyroid nodules with indeterminate cytology.

Hyperglycemia–related mortality in critically ill patients varies with admission diagnosis*

Objectives: Hyperglycemia during critical illness is common and is associated with increased mortality. Intensive insulin therapy has improved outcomes in some, but not all, intervention trials. It is unclear whether the benefits of treatment differ among specific patient populations. The purpose of the study was to determine the association between hyperglycemia and risk– adjusted mortality in critically ill patients and in separate groups stratified by admission diagnosis. A secondary purpose was to determine whether mortality risk from hyperglycemia varies with intensive care unit type, length of stay, or diagnosed diabetes. Design: Retrospective cohort study. Setting: One hundred seventy-three U.S. medical, surgical, and cardiac intensive care units. Patients: Two hundred fifty-nine thousand and forty admissions from October 2002 to September 2005; unadjusted mortality rate, 11.2%. Interventions: None. Measurements and Main Results: A two–level logistic regression model determined the relationship between glycemia and mortality. Age, diagnosis, comorbidities, and laboratory variables were used to calculate a predicted mortality rate, which was then analyzed with mean glucose to determine the association of hyperglycemia with hospital mortality. Hyperglycemia was associated with increased mortality independent of illness severity. Compared with normoglycemic individuals (70–110 mg/dL), adjusted odds of mortality (odds ratio, [95% confidence interval]) for mean glucose 111–145, 146–199, 200–300, and >300 mg/dL was 1.31 (1.26–1.36), 1.82 (1.74–1.90), 2.13 (2.03–2.25), and 2.85 (2.58–3.14), respectively. Furthermore, the adjusted odds of mortality related to hyperglycemia varied with admission diagnosis, demonstrating a clear association in some patients (acute myocardial infarction, arrhythmia, unstable angina, pulmonary embolism) and little or no association in others. Hyperglycemia was associated with increased mortality independent of intensive care unit type, length of stay, and diabetes. Conclusions: The association between hyperglycemia and mortality implicates hyperglycemia as a potentially harmful and correctable abnormality in critically ill patients. The finding that hyperglycemia–related risk varied with admission diagnosis suggests differences in the interaction between specific medical conditions and injury from hyperglycemia. The design and interpretation of future trials should consider the primary disease states of patients and the balance of medical conditions in the intensive care unit studied.

Causes and consequences of hyperglycemia in critical illness

Purpose of reviewThis article reviews recent epidemiologic and intervention studies addressing the impact of hyperglycemia on morbidity and mortality in critically ill patients. It also discusses a growing body of literature examining why elevated blood glucose occurs in hospitalized patients without previously recognized diabetes. Recent findingsHyperglycemia is highly prevalent in the intensive care unit. Numerous observational studies have demonstrated the association between hyperglycemia and adverse outcomes, independent of pre-existing diabetes. Intervention trials of insulin therapy are limited but overall demonstrate that glucose lowering significantly improves outcomes. The ideal target for blood glucose and the population that would benefit most from intervention remain controversial. Less frequently studied than the consequences, the causes of hyperglycemia occurring during critical illness remain unclear. Although glucose abnormalities in hospitalized patients have traditionally been explained by mediators of stress, a growing body of evidence has examined whether underlying defects in glucose metabolism may also be important contributors. SummaryIn general, evidence suggests that hyperglycemia is a potentially correctable abnormality that has deleterious effects in critically ill individuals. Hyperglycemic patients without previously recognized diabetes appear to be particularly vulnerable, and thus further examination of the mechanisms underlying the development of elevated blood glucose is warranted.

Efficacy of Thyroid Hormone Suppression for Benign Thyroid Nodules: Meta-Analysis of Randomized Trials

OBJECTIVE: To determine the efficacy of thyroid hormone suppressive therapy (THST) to decrease benign thyroid nodule volume. DESIGN: Meta-analysis. METHODS: Systematic search using electronic databases (PubMed, Medline, Cochrane Library) through August 2004, paper review, and contacting experts and drug manufacturers. Only randomized controlled studies of THST vs no treatment or placebo, for reduction of benign thyroid nodule volume, were included. Exclusion criteria were: >6-month treatment, lack of ultrasound volume measurement, and region of endemic goiter. Primary outcome was clinically relevant nodule volume reduction (>50%), with a random effects model (RevMan4.2). RESULTS: Nine randomized trials were included (609 subjects). Subjects were 88% more likely to experience >50% nodule volume reduction with THST than placebo or no treatment (relative risk = 1.88; 95% CI = 1.18-3.01; P = 0.008). However, 8 subjects must be subjected to the risk of cardiac and skeletal side effects from THST, for one to benefit from therapy (number needed to treat = 8, risk difference = 0.13; 95% CI = 0.06-0.19; P = 0.0003). Sensitivity analysis reveals that 15 null studies would have to have been missed to reverse statistical significance (fail-safe N = 15). Review of the only study with long-term treatment (5 years) suggests no significant difference in nodule volume reduction between THST and placebo. Further, studies with follow-up after THST withdrawal demonstrate rapid increase in thyroid nodule and goiter volumes. CONCLUSION: THST appears more likely than placebo or no treatment to significantly reduce benign thyroid nodule volume, but long-term treatment may be less effective and regrowth is likely following cessation of therapy. Given the risks of THST, routine use is not recommended for benign nodules.

The role of hyperglycemia in acute illness: Supporting evidence and its limitations

Hyperglycemia is common in acutely ill hospitalized patients and has been linked to poor outcomes, independent of pre-existing diabetes. Correction of hyperglycemia has been shown to decrease morbidity and mortality; however, establishing evidence-based guidelines has been challenging because insulin intervention studies have varied in the questions they have addressed, glucose levels studied, feeding regimen, and quality of methodology. This article reviews the findings and limitations of recent intervention studies that have addressed treatment of inpatient hyperglycemia with intravenous insulin infusion therapy. Discussion of underlying causes of hospital-related hyperglycemia and mechanisms explaining the deleterious effects of hyperglycemia and improved outcomes with insulin intervention are described. Current guidelines from various professional organizations recommend treatment of inpatient hyperglycemia, although exact glycemic targets and identification of which patient subsets will receive greatest benefit from glucose lowering remain an area of ongoing research.

Amiodarone-induced thyrotoxicosis and thyroid cancer: Clinical, immunohistochemical, and molecular genetic studies of a case and review of the literature

Amiodarone-induced thyrotoxicosis (AIT) is a well-known complication of amiodarone treatment found in 3% to 12% of patients. Two types of AIT have been described, each associated with a distinct histologic pattern of thyroid involvement. Type 1, which typically develops in the background of pre-existing thyroid disease, is due to iodine-induced excess thyroid hormone synthesis, whereas type 2 is due to destructive thyroiditis. The prevalence of thyroid cancer in patients with AIT is unknown. We report a case of papillary thyroid carcinoma associated with type 2 AIT.

Eagle's syndrome reconsidered as a cervical manifestation of heterotopic ossification: Woman presenting with a neck mass

CASE REPORT A 39-year-old black woman presented to the otolaryngology clinic complaining of difficulty swallowing and an enlarging neck mass. She smoked one-half pack of cigarettes per day, drank alcohol, and intermittently used crack cocaine. Physical examination revealed a 3-cm fixed, firm, nontender left level II neck mass. Examination of the oral cavity revealed a medially displaced left tonsil, and a firm bony mass medial to the mandible was felt on palpation of the floor of the mouth. The remainder of the head and neck physical examination, including fiberoptic endoscopy, was unremarkable. Computed tomography scan of the neck revealed completely calcified stylohyoid ligaments, with the left being thicker than the right (Fig 1). Because of the patient’s increasing symptoms, surgical management was recommended. Resection of the ossified left stylohyoid ligament was performed through a cervical approach. Using a Gigli saw, a 3.5-cm-long segment of the 1-cm thick ossified stylohyoid ligament was excised. The patient tolerated the procedure well and was discharged on the first postoperative day. On follow-up, the patient reported complete resolution of her symptoms. Histopathologic examination of the stylohyoid ligament revealed trabecular bone with normocellular marrow (Fig 2).

Validation of American Thyroid Association Ultrasound Risk Assessment of Thyroid Nodules Selected for Ultrasound Fine-Needle Aspiration

OBJECTIVE The aim of this study was to validate the American Thyroid Association (ATA) sonographic risk assessment of thyroid nodules. METHODS The ATA sonographic risk assessment was prospectively applied to 206 thyroid nodules selected for ultrasound-guided fine-needle aspiration (US-FNA), and analyzed with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), as well as surgical pathology for the subset undergoing surgical excision. RESULTS The analysis included 206 thyroid nodules averaging 2.4 cm (range 1-7 cm; standard error of the mean 0.07). Using the ATA US pattern risk assessment, nodules were classified as high (4%), intermediate (31%), low (38%), and very low (26%) risk of malignancy. Nodule size was inversely correlated with sonographic risk assessment, as lower risk nodules were larger on average (p < 0.0001). Malignancy rates determined by cytology/surgical pathology were high 100%, intermediate 11%, low 8%, and very low 2%, which were closely aligned with ATA malignancy risk estimates (high 70-90%, intermediate 10-20%, low 5-10%, and very low 3%). ATA US pattern risk assessment also appropriately predicted the proportion of nodules classified as malignant or suspicious for malignancy through TBSRTC classification-high (77%), intermediate (6%), low (1%), and very low 0%-as well as benign TBSRTC classification-high (0%), intermediate (47%), low (61%), and very low (70%) (p < 0.0001). Malignancy rates of surgically excised, cytologically indeterminate nodules followed ATA sonographic risk stratification (high 100%, intermediate 21%, low 17%, and very low 12%; p = 0.003). CONCLUSION This prospective study supports the new ATA sonographic pattern risk assessment for selection of thyroid nodules for US-FNA based upon TBSRTC and surgical pathology results. In the setting of indeterminate cytopathology, nodules categorized as atypia of undetermined significance/follicular lesion of undetermined significance with ATA high-risk sonographic patterns have a high likelihood of being malignant.

One Institution's Experience in Implementing Protocols for Glycemic Management

The objective for monitoring blood glucose is to determine the need for intervention. This article describes an institutions comprehensive program of protocols and education initiated to manage inpatient hyperglycemia.

Diabetes Transition Care From an Inpatient to Outpatient Setting in a Veteran Population Quality Improvement Pilot Study

Purpose The purpose of the study was to evaluate a diabetes transition care program in a population of veterans with diabetes by calculating 30-day readmission rates and assessing glycemic control. Methods Hospitalized patients with poorly controlled diabetes were identified to participate in the diabetes transition care program. The program included follow-up through a postdischarge telephone call by the diabetes educator, with an opportunity for a face-to-face clinic visit. A retrospective before-and-after study design was used. Analysis included calculating the readmission rate and the pre- and postintervention A1C rates to evaluate the intervention. Results Of the 40 participants, 100% completed the intervention. All 40 participants received a postdischarge telephone call as follow-up, with 20% presenting for a face-to-face visit. The 30-day readmission rate for the cohort was 10%, in comparison to 14.3% for patients who did not receive the intervention but were otherwise comparable. For those who had repeat A1C measurements conducted 2 to 8 months after time of enrollment in the program (n = 33), average A1C declined −2.2%, from 11.3% (100 mmol/mol) to 9.1% (76 mmol/mol). Conclusions Diabetes-specific transition of care for those with complex psychiatric, medical, and social needs was feasible, with good outcomes in hospital readmission rates and glycemic control, when executed by an adult nurse practitioner who was the inpatient diabetes educator.