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In recent years, 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has emerged as an important tool for the postoperative management of patients with differentiated thyroid cancer (DTC) and it is widely used in selected clinical situations. The most valuable role that FDG-PET/CT plays in clinical practice is that it can be used to obtain prognostic information in patients with increasing thyroglobulin (Tg) levels and negative 131I whole-body scan post-thyroidectomy and radioiodine (RAI) ablation. FDG-PET/CT may also have a potential role in the initial staging and follow-up of high-risk patients with aggressive histological subtypes, in the identification of patients who are at the highest risk of disease-specific mortality, in the management of patients with RAI-refractory disease, in clinical trials of novel targeted therapies in patients with advanced metastatic disease, and in the evaluation of thyroid nodules with indeterminate fineneedle aspiration for cytology. However, several controversies remain to be resolved, namely: the cutoff value of Tg in the selection of DTC patients for FDG-PET/CT, whether FDG-PET/CT scanning should be performed under thyrotropin stimulation or suppression, and the clinical significance of thyroid FDG-PET/CT incidentalomas. The aim of the present article is to provide an overview of the data about the molecular basis for, clinical indications of, and controversies related to the use of FDG-PET/CT in patients with DTC.

OBJECTIVES: To evaluate the diagnostic accuracy of fine-needle aspiration biopsy (FNAB) to preoperatively diagnose medullary thyroid cancer (MTC) among multiple international centers and evaluate how the cytological diagnosis alone could impact patient management. METHODS: We performed a retrospective chart review of sporadic MTC (sMTC) patients from 12 institutions over the last 29 years. FNAB cytology results were compared to final pathologic diagnoses to calculate FNAB sensitivity. To evaluate the impact of cytology sensitivity for MTC according to current practice and to avoid confounding results by local treatment protocols, changes in treatment patterns over time, and the influence of ancillary findings (e.g., serum calcitonin), therapeutic interventions based on FNAB cytology alone were projected into 1 of 4 treatment categories: total thyroidectomy (TT) and central neck dissection (CND), TT without CND, diagnostic hemithyroidectomy, or observation. RESULTS: A total of 313 patients from 4 continents and 7 countries were included, 245 of whom underwent FNAB. FNAB cytology revealed MTC in 43.7% and possible MTC in an additional 2.4%. A total of 113 (46.1%) patients with surgical pathology revealing sMTC had FNAB findings that supported TT with CND, while 37 (15.1%) supported TT alone. In the remaining cases, diagnostic hemithyroidectomy and observation were projected in 32.7% and 6.1%, respectively. CONCLUSION: FNAB is an important diagnostic tool in the evaluation of thyroid nodules, but the low sensitivity of cytological evaluation alone in sMTC limits its ability to command an optimal preoperative evaluation and initial surgery in over half of affected patients.

CONTEXT: Heart failure (HF) is a major cause of morbidity and mortality in Europe and in the United States. The aim of this review article was to assess the results of the prospective studies that evaluated the risk of HF in patients with overt and subclinical thyroid disease and discuss the mechanism of this dysfunction. EVIDENCE ACQUISITION: Reports published with the following search terms were searched:, thyroid, hypothyroidism, hyperthyroidism, subclinical hyperthyroidism, subclinical hypothyroidism, levothyroxine, triiodothyronine, antithyroid drugs, radioiodine, deiodinases, clinical symptoms, heart rate, HF, systolic function, diastolic function, systemic vascular resistance, endothelial function, amiodarone and atrial fibrillation. The investigation was restricted to reports published in English. EVIDENCE SYNTHESIS: The outcome of this analysis suggests that patients with untreated overt thyroid dysfunction are at increased risk of HF. Moreover, persistent subclinical thyroid dysfunction is associated with the development of HF in patients with serum TSH 10 mU/l. CONCLUSIONS: The timely recognition and effective treatment of cardiac symptoms in patients with thyroid dysfunction is mandatory because the prognosis of HF may be improved with the appropriate treatment of thyroid dysfunction

This volume aims to describe subclinical endocrine disorders, which arise essentially from nonfunctioning or functioning lesions.

Subclinical hypothyroidism (SH) is a frequent condition affecting millions of people around the world. Defined by increased thyrotropin-stimulating hormone (TSH) and accompanied by normal thyroid hormone levels, SH reflects a mild tissue hypothyroidism that has been associated with metabolic derangements and-although this issue is still contentious-possibly with increased cardiovascular risk. Depending on the degree of TSH elevation, SH has accordingly been associated with hyperlipidemia, arterial hypertension, and cardiovascular disease (CVD), as well as, increasingly, newly emerging CVD risk factors such as serum C-reactive protein and retinol binding protein 4 levels. There have also been reports of abnormalities in glucose metabolism and of hemostatic parameters, mainly underscored by the increased activity of factor VII. This review discusses the results of the latest studies on the various parameters affected by SH while highlighting the need for timely treatment with levothyroxine

A risk-stratified approach to predict the rate of recurrence and death from thyroid cancer was based on the recently revised American Thyroid Association guidelines. A stratified approach to predict the risk from the adverse effects of L-T4 was devised, taking into account the age of the patient, as well as the presence of preexisting cardiovascular and skeletal risk factors that might predispose to the development of long-term adverse cardiovascular or skeletal outcomes, particularly increased heart rate and left ventricular mass, atrial fibrillation, and osteoporosis. Nine potential patient categories can be defined, with differing TSH targets for both initial and long-term L-T4 therapy.

The association of endogenous subclinical hyperthyroidism (SHyper) with cardiovascular mortality is controversial. This may reflect the different causes of endogenous SHyper in the population studied due to differences in iodine intake, and different selection criteria, e.g. sex, age, and race, the cutoff for serum TSH level, the duration of follow-up, and the presence of co-morbidities. A small sample size of SHyper patients could have caused a low statistical power in some of these studies. In other studies, the results were not adjusted for relevant confounders. Importantly, various meta-analyses have also given conflicting results

The aim of the study was to define the frequency of hereditary forms and the genotype/phenotype correlations in a large cohort of Italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.Germline mutations were detected in 32.1% of cases, but frequencies varied widely depending on the classification criteria and ranged from 100% in patients with associated syndromic lesions to 11.6% in patients with a single tumor and a negative family history. The types and number of pheochromocytomas/paragangliomas as well as age at presentation and malignancy suggest which gene should be screened first. Genomic rearrangements were found in two of 160 patients (1.2%).

Various studies have demonstrated the safety and efficacy of recombinant human thyroid-stimulating hormone (rhTSH) for radioiodine remnant ablation. On this basis, rhTSH was approved in Europe for the radioiodine ablation of low-risk differentiated thyroid cancer (DTC) during thyroid hormone therapy with L-thyroxine (L-T4). Moreover, in December 2007, the US Federal Drug Administration approved the use of rhTSH for adjuvant treatment with radioiodine in patients with DTC without evidence of metastatic thyroid cancer. Quality of life was found to be better with rhTSH preparation than with L-thyroxine withdrawal, thereby resulting in benefits for society as a whole. Furthermore, rhTSH for radioiodine remnant ablation results in a longer effective radioiodine half-life within remnant thyroid tissue and a lower specific absorbed dose in the blood and exposure of bone marrow to X-rays. More studies are required to establish the amount of radioiodine to be administered especially in high-risk patients.

Objective: Intrathyroidal lymphoid infiltrate (TLI) may show qualitative and quantitative differences in Hashimoto thyroiditis (HT); thyroidal functional status (TFS) may differ among HT patients. The aim of this study has been to evaluate TLI in different TFS of HT. Methods: Flow-cytometry (FC) was applied to thyroidal fine-needle cytology samples (FNC) in 23 patients. TLI was analyzed using the following fluoresceinated antibodies: CD3, CD4, CD5, CD8, CD10, CD19, CD25, CD69, CD95 (FAS). TFS was determined by serum TSH, FT3, FT4 immunoassays, in specific clinical settings, to classify the patients as euthyroid (16) and hypothyroid (7). Pearson’s correlation coefficient was used to evaluate possible correlations between CD4/CD8 ratio, CD4+ CD25+ CD69-: regulatory T (Treg) cells proportion, CD95 expression and TFS. Results: B-lymphocytes (CD19+, CD10±, CD5-, CD3-) were present in 18 cases, T-lymphocytes (CD19-, CD10-, CD5+, CD3+) in all the cases. CD4/CD8≥2:1 ratio was observed in 16 euthyroid and 3 hypothyroid; CD4/CD8≤1:1 ratio in none of euthyroid and in 4 hypothyroid. CD4+ CD25+ CD69- Treg cells proportion was lower in hypothyroid than in the euthyroid patients; CD4+, CD25+, CD95(FAS)+ were mainly expressed in hypothyroidism. Statistical analysis did not demonstrate associations among CD4/CD8 ratios, Treg cells proportions and CD95 expression in the two TFS. Conclusions: FNC may be used to assess TLI in HT. Intrathyroidal CD4/CD8 ≤ 1:1 ratio, CD4+, CD25+, CD69- cells reduction and CD95(FAS)+ are expression of Treg cells apoptosis and might be related to intense thyroidal damage and risk of hypothyroidism. Further studies are needed to assess their possible prognostic significance.

OBJECTIVE: The purpose of this study was to correlate the presence and patterns of distribution of B-flow imaging (BFI) twinkling signs within thyroid nodules with the histologic evidence of microcalcifications and the results of the sonographically guided fine-needle aspiration to establish their role in predicting the risk of malignancy. METHODS: Between September 2006 and December 2007, 343 consecutive patients with 479 suspected nodules (maximum diameter > 9 mm) were enrolled in this prospective study. Sonographic and BFI examinations were performed with a commercially available real-time sonography system, and all patients also underwent a cytologic evaluation. Written informed consent was obtained from all patients. Patients with suspicious or malignant cytologic features underwent surgery. RESULTS: On histologic examination, 66 of 479 nodules were malignant (59 papillary thyroid carcinoma, 1 Hürthle cell carcinoma, and 6 follicular carcinoma). All sonographic characteristics, which were potential predictors of thyroid malignancy (microcalcifications, hypoechogenicity, absence of a halo, and a predominantly solid composition), were found in different percentages in both histologically verified malignant and benign nodules. For BFI, pattern 3 (> or = 4 signs and distance > 2 mm) was the most predictive factor for malignancy (specificity, 99.6%; sensitivity, 65.2%), whereas pattern 2 (> or = 4 signs and distance < 2 mm) was a positive factor because it was detected only in benign lesions, with a positive predictive of 0. CONCLUSIONS: Our results indicate that BFI can overcome the limits of the traditional B-mode and color Doppler sonographic features in the diagnosis of thyroid nodules. This technique provides maximum specificity levels both in the case of benign nodules with pattern 2 and in the case of malignant nodules with pattern 3.