Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.

BACKGROUND: The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS: In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS: A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. CONCLUSIONS: In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048.).

Annual financial impact of well-differentiated thyroid cancer care in the United States.

BACKGROUND: Well-differentiated thyroid cancer (WDTC) is a prevalent disease, which is increasing in incidence faster than any other cancer. Substantial direct medical care costs are related to the diagnosis and treatment of newly diagnosed patients as well as the ongoing surveillance of patients who have a long life expectancy. Prior analyses of the aggregate health care costs attributable to WDTC in the United States have not been reported. METHODS: A stacked cohort cost analysis was performed on the US population from 1985 to 2013 to estimate the number of WDTC survivors in 2013. Incidence rates, and cancer-specific and overall survival were based on Surveillance, Epidemiology, and End Results (SEER) data. Current and projected direct medical care costs attributable to the care of patients with WDTC were then estimated. Health care-related costs and event probabilities were based on Medicare reimbursement schedules and the literature. RESULTS: Estimated overall societal cost of WDTC care in 2013 for all US patients diagnosed after 1985 is $1.6 billion. Diagnosis, surgery, and adjuvant therapy for newly diagnosed patients (41%) constitutes the greatest proportion of costs, followed by surveillance of survivors (37%), and nonoperative death costs attributable to thyroid cancer care (22%). Projected 2030 costs (in 2013 US dollars) based on current incidence trends exceed $3.5 billion. CONCLUSIONS: Health care costs of WDTC are substantial. Unlike other cancers, the majority of the cost is incurred in the initial and continuing phases of care. With the projected increasing incidence, population, and survival trends, costs will continue to escalate.

Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial.

BACKGROUND: Diabetes is a multisystem disorder associated with a nearly twofold excess risk for a broad range of adverse cardiovascular outcomes including coronary heart disease, stroke, and cardiovascular death. Liraglutide is a human glucagon-like peptide receptor analog approved for use in patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: To formally assess the cardiovascular safety of liraglutide, the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial was commenced in 2010. LEADER is a phase 3B, multicenter, international, randomized, double-blind, placebo-controlled clinical trial with long-term follow-up. Patients with T2DM at high risk for cardiovascular disease (CVD) who were either drug naive or treated with oral antihyperglycemic agents or selected insulin regimens (human NPH, long-acting analog, or premixed) alone or in combination with oral antihyperglycemics were eligible for inclusion. Randomized patients are being followed for up to 5 years. The primary end point is the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. CONCLUSIONS: LEADER commenced in September 2010, and enrollment concluded in April 2012. There were 9,340 patients enrolled at 410 sites in 32 countries. The mean age of patients was 64.3 ± 7.2 years, 64.3% were men, and mean body mass index was 32.5 ± 6.3 kg/m2. There were 7,592 (81.3%) patients with prior CVD and 1,748 (18.7%) who were high risk but without prior CVD. It is expected that LEADER will provide conclusive data regarding the cardiovascular safety of liraglutide relative to the current standard of usual care for a global population of patients with T2DM.

Management of thyroid nodules with atypical cytology on fine-needle aspiration biopsy.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) of the thyroid categorized as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is a newly defined category according to the recent Bethesda guidelines. We sought to assess the characteristics and treatment of patients with an AUS/FLUS FNAB at our institution. Additionally, we evaluated the utility of the recommended 3-month timing of repeat FNAB. METHODS: A retrospective study of all patients with an FNAB categorized as AUS/FLUS at an academic tertiary-care center. Clinical, cytological, and ultrasound variables were compared among management groups. Differences in patients receiving repeat FNAB before or after a 3-month interval were compared. RESULTS: A total of 203 patients of the 5,391 FNABs performed at our institution met the Bethesda criteria for AUS/FLUS; 62% were sent directly to surgery, 25% had a repeat FNAB, and 13% were observed. Younger (p=0.006) and male patients (p=0.04) were more likely to go directly to surgery. Microcalcifications, irregular margins, and marked hypoechogenicity on ultrasound did not appear to influence the decision to repeat the FNAB, observe the patient, or refer the patient for surgery. Timing of repeat FNAB (<3 months or ≥3 months) did not alter the diagnostic results of the second FNAB (p=0.73). The overall rate of malignancy in patients undergoing surgery was 15.7%. CONCLUSIONS: Gender and age, not ultrasound characteristics, appear to influence the decision for surgery in AUS/FLUS patients. Timing of repeat biopsy did not alter management, repeat FNAB diagnosis, or rate of malignancy in our cohort.

How to interpret thyroid fine-needle aspiration biopsy reports: a guide for the busy radiologist in the era of the Bethesda Classification System.

OBJECTIVE: Fine-needle aspiration biopsy (FNAB) is the current primary test to risk stratify thyroid nodules. However, in up to one third of biopsies, cytology is indeterminate. The Bethesda System for Reporting Thyroid Cytopathology categorizes thyroid cytology findings into six groups, with each group assigned a putative malignancy risk. This article reviews the Bethesda System, emphasizing the key facts necessary to understand thyroid biopsy results and effectively manage patients after FNAB. CONCLUSION: It is important to diagnose and stratify the risk of malignancy in thyroid nodules. A working knowledge of the Bethesda System permits accurate, evidence-based risk stratification of patients with thyroid nodules and thereby facilitates their management. Because it is a uniform diagnostic approach, the Bethesda System allows comparisons of different management strategies across different institutions.

Imaging behavior of the normal adrenal on ferumoxytol-enhanced MRI: preliminary findings.

OBJECTIVE: Ultrasmall superparamagnetic iron oxide nanoparticles, such as ferumoxytol, produce decreased MR signal on susceptibility-inducing T2*-weighted sequences in tissues of the reticuloendothelial system. However, acute iron deposition in the adrenals has not been reported. The purpose of this article is to report our initial observations of the imaging behavior of the normal adrenals on ferumoxytol-enhanced T2*-weighted magnetic resonance imaging. SUBJECTS AND METHODS: Quantitative T2* imaging was performed at 3 T using a breath-hold monopolar multiecho gradient echo sequence with six equally spaced in-phase echoes in nine patients. Changes in signal-to-noise ratio (SNR) were analyzed prior to and 48 hours after ferumoxytol administration in the adrenals, liver and spleen (positive controls), and pancreas and skeletal muscle (negative controls). RESULTS: In comparison with unenhanced images, there was an average SNR decrease of 67.4% in the right adrenal, 77.6% in the left adrenal, 68.4% in the liver, 89.1% in the spleen, 15.0% in the pancreas, and 9.5% in skeletal muscle on T2*-weighted images obtained 48 hours after ferumoxytol administration. The decrease in SNR observed in the adrenals was significantly greater than that seen in the pancreas and skeletal muscle (left adrenal, p < 0.0001; right adrenal, p = 0.0002) and similar to that seen in the liver and spleen. CONCLUSION: The normal adrenal loses signal on ferumoxytol-enhanced T2*-weighted MRI. Acute iron deposition within the adrenals has not been previously described. The mechanism of ferumoxytol uptake in the adrenal and potential clinical applications warrant further investigation.

Radioactive Iodine: A Living History.

Background: Before the development of antithyroid drugs in the 1940s, treatment of Graves' hyperthyroidism was primarily surgical. Surgical mortality was quite variable, but a significant minority of patients died during or after surgery. Summary: In 1936, Karl Compton, President of the Massachusetts Institute of Technology, in a lecture attended by Massachusetts General Hospital physicians, suggested that artificially radioactive isotopes might be useful for studying metabolism. By 1942, Hertz and Roberts reported on the successful use of radioactive iodine (RAI) to treat Graves' hyperthyroidism. RAI uptake was subsequently demonstrated in well-differentiated thyroid cancer metastases. In 1948, Seidlin demonstrated stimulation of uptake in thyroid cancer metastases by thyrotropin (TSH). By 1990, 69% of endocrinologists in North America recommended RAI for Graves' hyperthyroidism. Currently RAI is less frequently used for Graves' hyperthyroidism, related to concerns about exacerbation of thyroid eye disease, about radiation exposure, and about potential adverse consequences of permanent hypothyroidism. Similarly, RAI was administered to the majority of patients with thyroid cancer for decades, but its use is now more selective. Conclusions: RAI is a remarkable example of interinstitutional cooperation between physicians and scientists to transition from bench to bedside in only three years. It is the model for a theranostic approach to disease (the simultaneous use of a radioactive drug for diagnosis and therapy). The future of RAI is less certain; inhibition of TSH receptor stimulating antibodies in Graves' disease and more precise targeting of genes that drive thyroid oncogenesis may diminish the use of RAI. Alternatively, redifferentiation techniques may improve the efficacy of RAI in RAI-refractory thyroid cancer.

Effectors Enabling Adaptation to Mitochondrial Complex I Loss in Hürthle Cell Carcinoma.

Oncocytic (Hürthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here, we utilize RNA sequencing and metabolomics to identify candidate molecular effectors activated by these genetic drivers. We find glutathione biosynthesis, amino acid metabolism, mitochondrial unfolded protein response, and lipid peroxide scavenging to be increased in HCC. A CRISPR-Cas9 knockout screen in a new HCC model reveals which pathways are key for fitness, and highlights loss of GPX4, a defense against lipid peroxides and ferroptosis, as a strong liability. Rescuing complex I redox activity with the yeast NADH dehydrogenase (NDI1) in HCC cells diminishes ferroptosis sensitivity, while inhibiting complex I in normal thyroid cells augments ferroptosis induction. Our work demonstrates unmitigated lipid peroxide stress to be an HCC vulnerability that is mechanistically coupled to the genetic loss of mitochondrial complex I activity. SIGNIFICANCE: HCC harbors abundant mitochondria, mitochondrial DNA mutations, and chromosomal losses. Using a CRISPR-Cas9 screen inspired by transcriptomic and metabolomic profiling, we identify molecular effectors essential for cell fitness. We uncover lipid peroxide stress as a vulnerability coupled to mitochondrial complex I loss in HCC. See related article by Frank et al., p. 1884. This article is highlighted in the In This Issue feature, p. 1749.

Autoimmune thyroid disease.

PURPOSE OF REVIEW: Autoimmune thyroid disorders (AITDs) are the most common organ-specific autoimmune disorders. The genetics as well as clinical and laboratory manifestations of AITDs are reviewed. RECENT FINDINGS: We discuss the association between specific rheumatologic disorders and AITDs and manifestations of AITDs that mimic rheumatologic disorders. The recently discovered common molecular pathways involved in these processes are discussed. SUMMARY: AITDs and rheumatologic disorders have significant commonalities both clinically and etiologically. This information is important for rheumatologists and primary care physicians who care for patients with these disorders.

Brown fat at PET/CT: correlation with patient characteristics.

PURPOSES: To assess the prevalence of brown fat in patients with cancer, compare demographic characteristics of those with and those without brown fat, and correlate these characteristics with the mean and maximum standardized uptake values of brown fat. MATERIALS AND METHODS: This case-control study was institutional review board approved and HIPAA compliant. Informed consent was waived. Reports of 12 195 consecutive positron emission tomography/computed tomography examinations performed in 6867 patients between January 2004 and November 2008 were reviewed for documented fluorodeoxyglucose (FDG) uptake in brown fat (n = 298). Control patients (n = 298) without brown fat were chosen and matched for age, sex, and month and year of examination. Age, sex, weight, body mass index, ethnicity, and examination stage (initial vs restaging) were compared between groups. Paired Student t test, χ(2) test, Pearson correlation coefficient, and analysis of variance were used for statistical analysis. RESULTS: Uptake of FDG in brown fat was demonstrated in 298 of 6867 (4.33%) patients. Prevalence of brown fat was significantly higher in female (5.9% [211 of 3587]) than in male patients (2.65% [87 of 3280]; P < .001). Those with brown fat had significantly lower body weight (147.5 lb ± 3.8 vs 168.61 lb ± 5.0; P < .001) and body mass index (24.3 ± 0.54 vs 27.6 ± 0.77; P < .001) than control patients. There was no significant difference in the prevalence of brown fat among ethnic groups. The maximum standardized uptake value of brown fat had a significant inverse correlation with age (r = -0.3, P < .001). CONCLUSION: Patients with brown fat were more likely to be female and thinner than those without brown fat. Younger patients were more likely to have higher maximum standardized uptake values of brown fat.

Painful Subacute Thyroiditis is Commonly Misdiagnosed as Suspicious Thyroid Nodular Disease.

OBJECTIVE: To investigate and characterize the clinical and radiologic features of 10 patients with painful subacute thyroiditis with ultrasound findings considered suspicious for malignancy or for whom biopsy of a suspicious area was recommended by an attending radiologist. PATIENTS AND METHODS: Ten patients with painful subacute thyroiditis were seen from June 1, 2016, through January 1, 2019. All 10 patients presented to an endocrine or thyroid clinic with a neck ultrasound report stating findings suspicious for malignancy or nodular disease. Clinical, laboratory, radiographic, and pathologic data were (retrospectively collected and) reviewed. RESULTS: The mean ± SD patient age was 49.0±15.0 years at diagnosis; 8 patients were female. All the patients presented with a low or undetectable serum thyrotropin level. Six of 7 patients with available inflammatory markers had elevated levels. Thyrotropin receptor antibodies were absent in all 6 patients tested. On follow-up imaging, 8 patients had complete resolution or improvement of described findings, 1 was lost to follow-up, and 1 had an incidental nodule that was biopsied after the episode of thyroiditis and found to be papillary thyroid carcinoma. CONCLUSION: Painful subacute thyroiditis demonstrates specific sonographic patterns that may be misdiagnosed as suspicious thyroid nodular disease. Recognition of the innocent and transient nature of these findings is important for the proper management and monitoring of these patients.

Imaging "Thyroiditis": A Primer for Radiologists.

A variety of inflammatory disorders, generically classified as "thyroiditis," can affect the thyroid gland diffusely, generating distinctive radiographic patterns. While a precise diagnosis can seldom be made based on sonographic appearance alone, interpreting these patterns in the correct clinical and biochemical context will help support the most appropriate diagnosis. We believe that the generic term "thyroiditis" is often not helpful and often may be incorrect. Therefore, it is important for radiologists to understand the sonographic and functional correlations to provide the most appropriate differential diagnosis in their reports. This brief review is designed to provide information and guidance for radiologists when dealing with various thyroid disorders which cause diffuse changes in the thyroid and underline the pitfalls most often encountered in clinical practice.

Progress in Treating Advanced Thyroid Cancers in the Era of Targeted Therapy.

Background: Thyroid cancer is a common malignancy whose detection has increased significantly in past decades. Most of the increased incidence is due to detection of early well-differentiated thyroid cancer, but the incidence of more advanced thyroid cancers has increased as well. Recent methodological advancements have allowed for a deep understanding of the molecular underpinnings of the various types of thyroid cancer. Summary: Thyroid cancers harbor a high frequency of potential druggable molecular alterations, including the highest frequency of oncogenic driver kinase fusions seen across all solid tumors. Analyses of poorly differentiated and anaplastic thyroid carcinoma confirmed that these tumors develop from more well-differentiated follicular-derived thyroid cancers through acquired additional mutations. The recognition of driver genomic alterations in thyroid cancers not only predicts tumor phenotype but also now can inform treatment approaches. Conclusions: Major progress in understanding the oncogenic molecular underpinnings across the array of thyroid cancers has led to considerable gains in gene-specific systemic therapies for many cancers. This article focuses on the molecular characteristics of aggressive follicular-derived thyroid cancers and medullary thyroid cancer and highlights advancements in treating thyroid cancer in the era of targeted therapy.

Controversies, Consensus, and Collaboration in the Use of 131I Therapy in Differentiated Thyroid Cancer: A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association.

BACKGROUND: Publication of the 2015 American Thyroid Association (ATA) management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer was met with disagreement by the extended nuclear medicine community with regard to some of the recommendations related to the diagnostic and therapeutic use of radioiodine (131I). Because of these concerns, the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging declined to endorse the ATA guidelines. As a result of these differences in opinion, patients and clinicians risk receiving conflicting advice with regard to several key thyroid cancer management issues. SUMMARY: To address some of the differences in opinion and controversies associated with the therapeutic uses of 131I in differentiated thyroid cancer constructively, the ATA, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association each sent senior leadership and subject-matter experts to a two-day interactive meeting. The goals of this first meeting were to (i) formalize the dialogue and activities between the four societies; (ii) discuss indications for 131I adjuvant treatment; (iii) define the optimal prescribed activity of 131I for adjuvant treatment; and (iv) clarify the definition and classification of 131I-refractory thyroid cancer. CONCLUSION: By fostering an open, productive, and evidence-based discussion, the Martinique meeting restored trust, confidence, and a sense of collegiality between individuals and organizations that are committed to optimal thyroid disease management. The result of this first meeting is a set of nine principles (The Martinique Principles) that (i) describe a commitment to proactive, purposeful, and inclusive interdisciplinary cooperation; (ii) define the goals of 131I therapy as remnant ablation, adjuvant treatment, or treatment of known disease; (iii) describe the importance of evaluating postoperative disease status and multiple other factors beyond clinicopathologic staging in 131I therapy decision making; (iv) recognize that the optimal administered activity of 131I adjuvant treatment cannot be definitely determined from the published literature; and (v) acknowledge that current definitions of 131I-refractory disease are suboptimal and do not represent definitive criteria to mandate whether 131I therapy should be recommended.

A phase II study of gefitinib in patients with advanced thyroid cancer.

OBJECTIVE: To determine the efficacy of gefitinib in patients with advanced thyroid cancer. DESIGN: In this open-label phase II trial, 27 patients with radioiodine-refractory, locally advanced, or metastatic thyroid cancer were treated with 250 mg of daily gefitinib. Histologic subtypes included papillary (41%), follicular (22%), anaplastic (19%), medullary (15%), and Hürthle cell carcinomas (4%). The primary endpoint was overall response rate. Secondary endpoints were toxicity, progression-free survival (PFS), and overall survival (OS). MAIN OUTCOMES: There were no objective responses among the 25 patients evaluated. After 3, 6, and 12 months of treatment, 48%, 24%, and 12% of patients had stable disease (SD), respectively. Median PFS and OS were 3.7 and 17.5 months, respectively. Five patients with SD had a decrease in thyroglobulin (Tg) to <90% of baseline that was maintained for at least 3 months. CONCLUSIONS: Although gefitinib therapy did not result in any tumor responses, 32% of patients had reductions in tumor volume that did not meet criteria for partial response rate. Along with falling Tg levels and prolonged SD in a subset of patients, this may indicate biologic activity.

No Evidence of Increase in Calcitonin Concentrations or Development of C-Cell Malignancy in Response to Liraglutide for Up to 5 Years in the LEADER Trial.

OBJECTIVE: To describe the changes in serum levels of calcitonin in liraglutide- and placebo-treated patients in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation (LEADER) trial over a 3.5-5-year period. RESEARCH DESIGN AND METHODS: Patients (n = 9,340) with type 2 diabetes and high risk for cardiovascular events were randomized 1:1 to liraglutide or placebo. We analyzed calcitonin levels, thyroid and C-cell adverse events, and neoplasms. RESULTS: At 36 months, patients randomized to liraglutide versus placebo showed no evidence of increase in calcitonin concentrations in male (estimated treatment ratio [ETR] 1.03 [95% CI 1.00, 1.06]; P = 0.068) and female (ETR 1.00 [95% CI 0.97, 1.02]; P = 0.671) subgroups. There were no episodes of C-cell hyperplasia or medullary thyroid carcinoma in liraglutide-treated patients. CONCLUSIONS: There was no evidence of a difference in calcitonin concentrations between the liraglutide and placebo groups, and no C-cell malignancies occurred in the liraglutide group.

Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma.

Hürthle cell carcinoma of the thyroid (HCC) is a form of thyroid cancer recalcitrant to radioiodine therapy that exhibits an accumulation of mitochondria. We performed whole-exome sequencing on a cohort of primary, recurrent, and metastatic tumors, and identified recurrent mutations in DAXX, TP53, NRAS, NF1, CDKN1A, ARHGAP35, and the TERT promoter. Parallel analysis of mtDNA revealed recurrent homoplasmic mutations in subunits of complex I of the electron transport chain. Analysis of DNA copy-number alterations uncovered widespread loss of chromosomes culminating in near-haploid chromosomal content in a large fraction of HCC, which was maintained during metastatic spread. This work uncovers a distinct molecular origin of HCC compared with other thyroid malignancies.

Prevalence of thyroid cancer in familial adenomatous polyposis syndrome and the role of screening ultrasound examinations.

BACKGROUND & AIMS: Thyroid carcinoma is an extraintestinal manifestation of familial adenomatous polyposis (FAP) syndrome, but the precise risk is unknown. The optimal approach for thyroid cancer screening has not been established. We sought to define the prevalence of thyroid cancer and the role of screening ultrasound in FAP patients. METHODS: We performed a retrospective chart review of 51 patients with a proven diagnosis of FAP at a single tertiary institution. Clinical records, genetic test results, ultrasound examinations, and histopathology were reviewed. RESULTS: Papillary thyroid cancer was diagnosed in 6 female patients (12%). The mean age of thyroid cancer diagnosis was 33 years, and mean tumor size was 12 mm. However, all patients had additional malignant foci that were small (1-9 mm), and none had suspicious features of malignancy on ultrasound. Of 28 patients who had at least one screening ultrasound, 22 (79%) had thyroid nodules, and 2 (7%) had papillary thyroid carcinoma. Of those with nodules, 68% had multinodular disease. A follow-up ultrasound in 12 patients after a mean of 15 months revealed no changes in either the number or size of nodules. CONCLUSIONS: The 12% prevalence of thyroid cancer in this series of FAP patients is significantly higher than in previous reports. Among patients undergoing screening ultrasound, 7% had thyroid cancer. Nodular thyroid disease is very common in FAP. Because small nodules (<9 mm) might also be malignant, close follow-up with ultrasound and fine-needle aspiration might be warranted.

Sunitinib (sutent)-induced thyrotoxicosis due to destructive thyroiditis: a case report.

Numerous drugs have been associated with destructive thyroiditis (subacute thyroiditis). Sunitinib, a tyrosine kinase inhibitor employed in renal cell carcinoma and gastrointestinal stromal tumors, has recently been linked to destructive thyroiditis with resultant hypothyroidism. We report a patient with transient overt thyrotoxicosis followed by hypothyroidism, apparently related to sunitinib therapy.