Marius N. Stan

The Accuracy of Thyroid Nodule Ultrasound to Predict Thyroid Cancer: Systematic Review and Meta-Analysis

CONTEXT Significant uncertainty remains surrounding the diagnostic accuracy of sonographic features used to predict the malignant potential of thyroid nodules. OBJECTIVE The objective of the study was to summarize the available literature related to the accuracy of thyroid nodule ultrasound (US) in the prediction of thyroid cancer. METHODS We searched multiple databases and reference lists for cohort studies that enrolled adults with thyroid nodules with reported diagnostic measures of sonography. A total of 14 relevant US features were analyzed. RESULTS We included 31 studies between 1985 and 2012 (number of nodules studied 18,288; average size 15 mm). The frequency of thyroid cancer was 20%. The most common type of cancer was papillary thyroid cancer (84%). The US nodule features with the highest diagnostic odds ratio for malignancy was being taller than wider [11.14 (95% confidence interval 6.6-18.9)]. Conversely, the US nodule features with the highest diagnostic odds ratio for benign nodules was spongiform appearance [12 (95% confidence interval 0.61-234.3)]. Heterogeneity across studies was substantial. Estimates of accuracy depended on the experience of the physician interpreting the US, the type of cancer and nodule (indeterminate), and type of reference standard. In a threshold model, spongiform appearance and cystic nodules were the only two features that, if present, could have avoided the use of fine-needle aspiration biopsy. CONCLUSIONS Low- to moderate-quality evidence suggests that individual ultrasound features are not accurate predictors of thyroid cancer. Two features, cystic content and spongiform appearance, however, might predict benign nodules, but this has limited applicability to clinical practice due to their infrequent occurrence.

The evaluation and treatment of graves ophthalmopathy.

Optimum care of the patient with Graves ophthalmopathy (GO) is achieved through teamwork between the endocrinologist and ophthalmologist, with input from ancillary specialists as needed. Clinical evaluation should include determination of both the severity and the activity of the disease. It is important to assess early in the evaluation the impact of the disease on the patients quality of life and their priorities and expectations regarding management. Once this information has been gathered, careful discussion between patient and physicians can define the management plan. This article reviews the pathophysiology, epidemiology, evaluation, and management of GO.

Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment

Objective To estimate the effectiveness and safety of thyroid hormone treatment among pregnant women with subclinical hypothyroidism. Design Retrospective cohort study. Setting Large US administrative database between 1 January 2010 and 31 December 2014. Participants 5405 pregnant women with subclinical hypothyroidism, defined as untreated thyroid stimulating hormone (TSH) concentration 2.5-10 mIU/L. Exposure Thyroid hormone therapy. Main outcome measure Pregnancy loss and other pre-specified maternal and fetal pregnancy related adverse outcomes. Results Among 5405 pregnant women with subclinical hypothyroidism, 843 with a mean pre-treatment TSH concentration of 4.8 (SD 1.7) mIU/L were treated with thyroid hormone and 4562 with a mean baseline TSH concentration of 3.3 (SD 0.9) mIU/L were not treated (P<0.01). Pregnancy loss was significantly less common among treated women (n=89; 10.6%) than among untreated women (n=614; 13.5%) (P<0.01). Compared with the untreated group, treated women had lower adjusted odds of pregnancy loss (odds ratio 0.62, 95% confidence interval 0.48 to 0.82) but higher odds of preterm delivery (1.60, 1.14 to 2.24), gestational diabetes (1.37, 1.05 to 1.79), and pre-eclampsia (1.61, 1.10 to 2.37); other pregnancy related adverse outcomes were similar between the two groups. The adjusted odds of pregnancy loss were lower in treated women than in untreated women if their pre-treatment TSH concentration was 4.1-10 mIU/L (odds ratio 0.45, 0.30 to 0.65) but not if it was 2.5-4.0 mIU/L (0.91, 0.65 to 1.23) (P<0.01). Conclusion Thyroid hormone treatment was associated with decreased risk of pregnancy loss among women with subclinical hypothyroidism, especially those with pre-treatment TSH concentrations of 4.1-10 mIU/L. However, the increased risk of other pregnancy related adverse outcomes calls for additional studies evaluating the safety of thyroid hormone treatment in this patient population.

Risks and benefits of parathyroid fine-needle aspiration with parathyroid hormone washout.

OBJECTIVE To describe the experience with parathyroid fine-needle aspiration (FNA) and parathyroid hormone (PTH) washout at Mayo Clinic Rochester, Rochester, Minnesota. METHODS We retrospectively reviewed all parathyroid FNA procedures performed at Mayo Clinic Rochester between January 2000 and December 2007. Clinical, biochemical, and imaging information, parathyroid FNA procedure, and cytology, surgical, and pathology reports were reviewed, and descriptive statistics, sensitivity, specificity, and positive predictive values are presented. RESULTS During the study period, 75 parathyroid FNAs were performed on 74 patients. Cytology results were available for 74 of 75 procedures, with only 31% interpreted as parathyroid cells. PTH washout was performed in 67 patients (91%). Parathyroid FNA with PTH washout had a sensitivity of 84%, specificity of 100%, positive predictive value of 100%, and accuracy of 84%. At the time of surgical treatment, 2 patients were noted to have an inflammatory response from the parathyroid FNA biopsy, 1 had a parathyroid abscess, and 2 had a hematoma. In 3 of these 5 patients, the necessary conversion of a minimally invasive surgical procedure to the standard surgical approach prolonged the surgical time. CONCLUSION Parathyroid FNA with PTH washout had a superior performance in comparison with parathyroid scanning or ultrasonography alone. The main limitations of parathyroid FNA with PTH washout are (1) the need for initial identification of a potential parathyroid adenoma by ultrasonography and (2) the number of false-negative results. Parathyroid FNA resulted in complications affecting the surgical procedure in 3 patients.

Body mass index and the development of amiodarone-induced thyrotoxicosis in adults with congenital heart disease—A cohort study

INTRODUCTION Amiodarone-induced thyrotoxicosis (AIT) is a recognized complication of amiodarone treatment with limited management options. Its predisposing factors are incompletely defined yet a higher prevalence was reported in adults with congenital heart disease (CHD). Therefore we sought to determine the incidence and risk factors for AIT in adults with CHD. METHODS At a tertiary care center we followed a historical cohort of amiodarone-treated CHD patients for the period 1987-2009. Follow-up concluded at AIT diagnosis or with last thyroid assessment on amiodarone. Cumulative incidence of AIT was calculated. AIT association with nutritional status was hypothesized a priori. RESULTS AIT developed in 23/169 patients or 13.6%. The AIT incidence peaked in the 3rd year at 7.7%. AIT patients had a lower body mass index (BMI) at AMIO initiation compared with the rest of the cohort (mean ± standard deviation: 21.9 ± 2.9 vs. 25.1 ± 5.0; p<0.001). Patients with BMI<21 were more likely to develop thyrotoxicosis (RR=6.1) compared to those with BMI>25 (p<0.001). Presence of goiter was strongly associated with AIT (RR 3.6, p=0.002). Affected patients had a trend for higher cyanotic heart disease prevalence (34.8% vs. 17.8%, p=0.059). On multivariate analysis body mass index and goiter remained independent predictors of outcome. CONCLUSIONS BMI<21 at initiation of amiodarone therapy and presence of goiter are strong predictors of AIT in this population. Its incidence is time dependent. These predictors can be used clinically in assessing overall impact of amiodarone therapy in congenital heart disease patients.

A risk prediction index for amiodarone-induced thyrotoxicosis in adults with congenital heart disease

Amiodarone therapy in adults with congenital heart disease (CHD) is associated with a significant risk of amiodarone-induced thyrotoxicosis (AIT). We developed a risk index to identify those patients being considered for amiodarone treatment who are at high risk for AIT. We reviewed the health records of adults with CHD and assessed the association between potential clinical predictors and AIT. Significant predictors were included in multivariate analyses. The parameter estimates from multivariate analysis were subsequently used to develop a risk index. 169 adults met eligibility criteria and 23 developed AIT. The final model included age, cyanotic heart disease and BMI. The risk index developed identified 3 categories of risk. Their AIT likelihood ratios were: 0.37 for low risk (95% CI 0.15–0.92); 1.12 for medium risk (95% CI 0.65–1.91); and 3.47 for high risk (95% CI 1.7–7.11). The AIT predicted risk in our population was 5% for the low risk group, 15% for the medium risk group and 47% for the high risk group. Conclusions. We derived the first model to quantify the risk for developing AIT among adults with CHD. Before using it clinically to help selecting among alternative antiarrhythmic options, it needs validation in an independent population.

Clinical Presentation and Diagnostic Challenges of Thyroid Lymphoma: A Cohort Study.

BACKGROUND Thyroid lymphoma is a relatively rare disease often posing a diagnostic challenge. Reaching the final diagnosis can be delayed if insufficient biopsy material is obtained for immunohistochemistry analysis. The aim of this study was to evaluate the clinical, biochemical, and radiological features of thyroid lymphoma. METHODS A retrospective analysis was conducted of all Mayo Clinic patients evaluated between 2000 and 2014 who had a tissue biopsy positive for thyroid lymphoma. RESULTS Seventy-five subjects had biopsy-proven thyroid lymphoma, and 62.7% were primary thyroid lymphomas. The median age at diagnosis was 67 years (range 20-90 years). A total of 50.7% were male, and 54.7% had a history of Hashimotos thyroiditis. Presenting symptoms included neck mass (88%), dysphagia (45.3%), and hoarseness (37.3%). The typical ultrasound appearance consisted of a solid, hypoechoic mass with increased vascularity and variable edge characteristics. Fine-needle aspiration (FNA) biopsies were abnormal in 70.7% of cases, and 42% indicated a specific lymphoma subtype. The diagnosis was confirmed in 53.3% by core biopsy, in 21.3% by thyroidectomy (partial or total), in 12% through incisional biopsy, and in 12% by lymph node biopsy. Core biopsy had a higher sensitivity compared with FNA (93% vs. 71%, p = 0.006). CONCLUSION A rapidly enlarging neck mass in the setting of Hashimotos thyroiditis should raise suspicion for thyroid lymphoma. Radiologically, this usually presents as a large, unilateral, thyroid-centered mass, hypoechoic by ultrasound, and expanding into adjacent soft tissues. Core-needle biopsy should be the first diagnostic test to expedite reaching the final diagnosis and decrease patient burden of additional tests and interventions.

Teriparatide Therapy and Reduced Postoperative Hospitalization for Postsurgical Hypoparathyroidism

IMPORTANCE Up to 20% of patients undergoing thyroidectomy develop hypocalcemia after surgery. Although usually transient, severe symptomatic hypocalcemia may occur. Teriparatide acetate (recombinant human parathyroid hormone 1-34) therapy can rapidly raise calcium levels. OBJECTIVE To test the hypothesis that teriparatide therapy in patients with postthyroidectomy hypoparathyroidism would expedite relief of symptomatic hypocalcemia and reduce the duration of hospitalization compared with standard treatment. DESIGN, SETTING, AND PARTICIPANTS Case series of all hospitalized patients 18 years or older treated with teriparatide for symptomatic postthyroidectomy hypocalcemia occurring immediately after thyroidectomy at Mayo Clinic, Rochester, Minnesota, between January 1, 2008, and June 30, 2014. A secondary analysis was performed with matched control and cohort groups having postthyroidectomy hypocalcemia of similar degree who received standard treatment only. Participants included 8 hospitalized patients who received teriparatide therapy after 24 hours of standard treatment (cases) and eight control patients selected from a cohort of 1193 thyroidectomies were matched for age, sex, body mass index, and nadir calcium levels. INTERVENTION Teriparatide acetate therapy (20 µg twice daily) subcutaneously for 1 week, with the option of continuing at 20 µg/d for up to 3 weeks. MAIN OUTCOMES AND MEASURES Safety, symptom resolution, calcium supplementation, and duration of hospitalization. RESULTS Among the 16 case and control patients the median nadir calcium level was 7.1 mg/dL in both groups. Most patients underwent thyroidectomy for thyroid cancer. Teriparatide therapy was safe, with no adverse events noted, and completely eliminated symptomatic hypocalcemia in all treated patients within 24 hours of initiation. Hospital discharge occurred at a median of 1.0 day (interquartile range, 1.0-1.0 day) after teriparatide therapy initiation among cases vs 2.5 days (interquartile range, 1.8-3.0 days) after the equivalent clinical point was reached in controls (P = .01). This value was 2.0 days in the source cohort (P = .02). On hospital discharge, patients had similar calcium levels. Six months after surgery, all patients treated with teriparatide showed partial or complete parathyroid recovery. Calcium supplementation and calcium levels were comparable between the groups. CONCLUSIONS AND RELEVANCE In this pilot study, teriparatide therapy in patients with postthyroidectomy hypoparathyroidism was safe, rapidly eliminated hypocalcemic symptoms, and likely reduced the duration of hospitalization. Given the limitations of this small study, a large-scale randomized trial is needed to verify these results and to assess the long-term effect of teriparatide therapy on clinical outcomes.

RhAbDOmyOlysIs AfTER WIThDRAWAl Of ThyROID hORmONE IN A PATIENT WITh PAPIllARy ThyROID CANCER

OBJECTIVE To report a case of rhabdomyolysis presenting with severe hyperkalemia after withdrawal of thyroid hormone in a patient with differentiated thyroid cancer. METHODS We describe the clinical and laboratory findings of the study patient and review the relevant literature. RESULTS A 54-year-old man with progressive generalized weakness and myalgias presented with acute renal failure and hyperkalemia. He had undergone total thyroidectomy for papillary thyroid cancer 6 weeks earlier and had discontinued thyroid hormone 2 weeks before his current presentation in preparation for thyroid remnant ablation. He had a history of multiple colon and small-bowel resections for familial adenomatous polyposis and desmoid tumor. He was severely dehydrated on examination. Laboratory tests results included the following values: creatine phosphokinase, 5265 U/L (reference range, 52-336 U/L); creatinine, 2.1 mg/dL; potassium, >8.0 mEq/L; and thyrotropin, 92.2 mIU/L. His condition was diagnosed as rhabdomyolysis, and his fluid deficit and hyperkalemia were treated aggressively. Cardiac status remained stable, and both acute renal failure and hyperkalemia improved. He then received remnant ablation, and thyroid hormone was restarted. His muscle complaints resolved over the following 3 months. CONCLUSIONS Hypothyroidism-induced rhabdomyolysis can occur during thyroid hormone withdrawal and can present with life-threatening hyperkalemia. Patients under-going thyroid hormone withdrawal should be assessed for risk of rhabdomyolysis, and preventive strategies should be implemented, including prevention of dehydration. The use of recombinant thyrotropin, rather than thyroid hormone withdrawal, should be considered in those who are at high risk for such complications.

Amiodarone-induced thyrotoxicosis in adults with congenital heart disease--clinical presentation and response to therapy.

OBJECTIVE The development of amiodarone-induced thyrotoxicosis (AIT) can threaten the hemodynamic stability of adult patients with congenital heart disease (CHD). Here, we describe the natural history and treatment response of AIT in this at-risk population. METHODS We studied retrospectively all cases of AIT that occurred in CHD patients at our institution after a minimum of 3 months on amiodarone. Subjects were identified from the cohort of adults with CHD who were treated at the Mayo Clinic Adult CHD clinic between 1987 and 2009. RESULTS We identified 23 cases of AIT: 7 were type 1, 13 were type 2, and 3 were undefined due to insufficient data. Most patients were symptomatic (17 of 23, 74%), with arrhythmia and weight loss as the most common symptoms. The majority (12 of 23, 52%) were initially observed; 10 patients (43%) were treated medically and 1 patient (5%) underwent thyroidectomy. Four patients from the observation group eventually required active treatment and 3 patients from the medical group required surgery. Asymptomatic patients tended to resolve under observation (5 of 7, 71.4%) rather than progress to active treatment (0 of 4) (P = .06). Discontinuation of amiodarone, AIT type, or use of perchlorate did not impact AIT duration. CONCLUSION AIT in CHD patients exhibits a wide range of severity and sensitivity to medical therapy. Asymptomatic patients display a trend toward AIT resolution with observation alone. Amiodarone continuation does not appear to impact management outcome or disease duration. Additional studies in this high-risk population could identify elements of pathophysiology that would point toward better disease prevention and treatment.