Endocrinology application of molecular imaging: current role of PET/CT.

BACKGROUND: In recent years, nuclear medicine imaging methods have proven to be of paramount importance in a wide variety of diseases, particularly in oncology, where they are crucial for assessing the extent of disease when conventional methods fall short. Moreover, nuclear imaging modalities are able to better characterize lesions using target agents related to specific pathways (e.g. glucose metabolism, cellular proliferation, amino acid transport, lipid metabolism, specific receptor ligands). The clinical presentation of endocrine diseases encompasses a broad spectrum of sign and symptoms. Moreover, endocrine tumors show varying degrees of aggressiveness from well differentiated and indolent to highly aggressive cancers, respectively. RATIONALE: With the application of new medicinal radio-compounds and increasingly advanced tomographic imaging technology, the utility of Positron Emission Tomography/Computed Tomography (PET/CT) in the field of endocrine diseases is expanding. AIM: This review aims to analyze and summarize the primary indications of PET/CT, providing a practical approach for clinicians. A comprehensive literature search on PubMed was conducted to provide an updated overview of the available evidence regarding the use of PET/CT in endocrinology. Within this review, we will discuss the applications of PET/CT, compare different radiopharmaceuticals and highlight the uptake mechanism, excluding neuroendocrine carcinomas from discussion. CONCLUSIONS: PET/CT is a valuable tool in diagnosing and managing endocrine disorders due to its capacity to furnish both functional and anatomical information, facilitate early lesion detection, guide treatment decisions, and monitor treatment response. Its non-invasive nature and precision make it an integral component of modern endocrine healthcare. This review aims to provide physicians with a clear perspective on the role of PET/CT imaging, discussing its emerging opportunities and appropriateness of use in endocrinological diseases.

Variations in radioiodine ablation: decision-making after total thyroidectomy.

BACKGROUND: The role of radioiodine treatment following total thyroidectomy for differentiated thyroid cancer is changing. The last major revision of the American Thyroid Association (ATA) Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer in 2015 changed treatment recommendations dramatically in comparison with the European Association of Nuclear Medicine (EANM) 2008 guidelines. We hypothesised that there is marked variability between the different treatment regimens used today. METHODS: We analysed decision-making in all Swiss hospitals offering radioiodine treatment to map current practice within the community and identify consensus and discrepancies. RESULTS AND CONCLUSION: We demonstrated that for low-risk DTC patients after thyroidectomy, some institutions offered only follow-up, while RIT with significant activities is recommended in others. For intermediate- and high-risk patients, radioiodine treatment is generally recommended. Dosing and treatment preparation (recombinant human thyroid stimulation hormone (rhTSH) vs. thyroid hormone withdrawal (THW)) vary significantly among centres.

FNA indication according to ACR-TIRADS, EU-TIRADS and K-TIRADS in thyroid incidentalomas at 18F-FDG PET/CT.

OBJECTIVE: Focal thyroid incidentaloma (TI) occurs in a 2% of 18F-FDG PET/CT and about one-third of TIs is cancer. Due to the lack of evidence on the optimal management of TI, current guidelines suggest performing fine-needle aspiration cytology (FNA). The study aim was to evaluate the reliability of ACR-TIRADS, EU-TIRADS, and K-TIRADS in indicating FNA in TIs. DESIGN: We retrospectively reviewed 18F-FDG PET/CT TIs recorded during the period 2016-2019. Enrolled were TIs with histologic outcome and autonomous nodules. Cases with uncertain matching between 18F-FDG PET/CT, US/scintiscan and histology were excluded. RESULTS: Eighty TIs at 18F-FDG PET/CT (median size 17 mm, median SUVmax 7.85) were included; a 26.2% was cancer. The percentage of nodules classified as high risk according to ACR-TIRADS, EU-TIRADS, and K-TIRADS was 20%, 30%, and 29.8%, respectively. The cancer prevalence in high-risk class was 56.2%, 66.7%, and 65.2% in ACR-TIRADS, EU-TIRADS, and K-TIRADS, respectively. ACR-TIRADS had the lowest number of cases with FNA indication (48%) and the K-TIRADS, the highest one (75%). Evaluating the reliability of the three systems in indicating FNA, we found a 100% sensitivity and NPV for EU-TIRADS and K-TIRADS; while all the three systems showed poor specificity and PPV. CONCLUSION: All TIRADSs were reliable to stratify the risk of cancer in focal TI. Comparing their reliability in indicating FNA, we found a good performance of EU-TIRADS and K-TIRADS. Considering the high cancer percentage expected in this setting of patients, those TIRADS with higher propensity to indicate FNA should be preferred.

Alemtuzumab-induced thyroid events in multiple sclerosis: a systematic review and meta-analysis.

PURPOSE: Autoimmune thyroid events (ATEs) are common side effects after alemtuzumab (ALZ) therapy in patients with multiple sclerosis (MS). Our purpose was to reach more robust evidence on prevalence and outcome of the spectrum of alemtuzumab-induced autoimmune thyroid events in patients with multiple sclerosis. METHODS: PubMed and Scopus were systematically searched through July 2019. Studies dealing with patients without personal history of thyroid dysfunctions and affected by MS treated with ALZ and reporting ATEs were selected. Data on prevalence and outcome of ATEs were extracted. A proportion of meta-analysis with random-effects model was performed. RESULTS: Considering the overall pooled number of 1362 MS patients treated with ALZ (seven included studies), a 33% prevalence of newly diagnosed ATEs was recorded. Among all ATEs, Graves' disease (GD) was the most represented [63% of cases, 95% confidence interval (CI) 52-74%], followed by Hashimoto thyroiditis (15%, 95% CI 10-22%). Interestingly, GD showed a fluctuating course in 15% of cases (95% CI 8-25%). Of all GD, 12% (95% CI 2-42%) likely had spontaneous remission, 56% (95% CI 34-76%) required only antithyroid drugs, 22% (95% CI 13-32%) needed additional RAI, and 11% (95% CI 0.9-29%) underwent definitive surgery. CONCLUSION: Among different categories of ATEs, Graves' hyperthyroidism was the most common thyroid dysfunction, occurring in more than half of cases. Antithyroid drugs should represent the first-line treatment for ALZ-induced GD patients. However, alemtuzumab-induced GD could not be considered as having a more favourable outcome than conventional GD, given the substantial chance to encounter a fluctuating and unpredictable course.

Additional value of integrated 18F-choline PET/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile.

PURPOSE: The localization of hyperfunctioning parathyroid gland(s) (HPTG) in patients with primary hyperparathyroidism (PHPT) with negative or inconclusive first-line imaging is a significant challenge. This study aimed to evaluate the role of integrated 18F-choline PET/4D contrast-enhanced computed tomography (4DCeCT) in these patients, compare its detection rate and sensitivity with those of 18F-choline PET/CT and (4DCeCT), and analyse the association between choline metabolism and morphological, biochemical and molecular parameters of HPTG. METHODS: We prospectively enrolled 44 PHPT patients with negative or inconclusive first-line imaging. 18F-Choline PET/CT and 4DCeCT were performed at the same time, and integrated 18F-choline PET/4DCeCT images were obtained after coregistration. Experienced physicians examined the images. The SUVratio and degree of contrast enhancement were recorded for each positive finding. Histopathology, laboratory and multidisciplinary follow-up were used as the standard of reference. Both the detection rates and sensitivities of the three imaging modalities were calculated retrospectively. Immunohistochemistry was performed to evaluate the molecular profile of HPTGs. RESULTS: 18F-Choline PET/4DCeCT was positive in 32 of 44 patients with PHPT (detection rate 72.7%), and 31 of 31 surgically treated patients (sensitivity 100%). These results were significantly (p < 0.05) better than those of 18F-choline PET/CT (56.8% and 80%, respectively) and those of 4DCeCT (54.5 and 74%, respectively). A significant correlation between SUV and calcium level was found. In a multivariate analysis, only calcium level was significantly associated with 18F-choline PET/4DCeCT findings. SUVratio and Ki67 expression were significantly correlated. CONCLUSION: Integrated 18F-choline PET/4DCeCT should be considered as an effective tool to detect PHPT in patients with negative or inconclusive first-line imaging. Choline metabolism is correlated with both calcium level and Ki67 expression in HPTG.

Endocrine and metabolic adverse effects of immune checkpoint inhibitors: an overview (what endocrinologists should know).

Immune checkpoint inhibitors (ICIs) are novel anticancer agents, recently introduced with the aim of boosting the immune response against tumors. ICIs are monoclonal autoantibodies that specifically target inhibitory receptors on T cells: cytotoxic T lymphocyte antigen 4 (CTLA4), programmed death 1 (PD-1) and its ligand (PD-1L). ICIs also generate peculiar dysimmune toxicities, called immune-related adverse events (irAEs), that can potentially affect any tissue, and some may be life-threatening if not promptly recognized. The endocrine and metabolic side effects of ICIs are reviewed here, with a particular focus on their clinical presentation and management. They are among the most frequent toxicities (around 10%) and include hypophysitis, thyroid disorders, adrenalitis, and diabetes mellitus. Treatment is based on the replacement of specific hormone deficits, accompanied by immunosuppression (with corticosteroids or other drugs), depending on irAEs grade, often without the need of ICI withdrawal, except in more severe forms. Prompt recognition of endocrine and metabolic irAEs and adequate treatment allow the patients to continue a therapy they are benefiting from. Endocrinologists, as an integral part of the multidisciplinary oncologic team, need to be familiar with the unique toxicity profile of these anticancer agents. Practical recommendations for their management are proposed.

Multicentre clinical evaluation of the new highly sensitive Elecsys® thyroglobulin II assay in patients with differentiated thyroid carcinoma.

OBJECTIVE: A highly sensitive thyroglobulin assay (Elecsys® Tg II, Roche Diagnostics, Penzberg, Germany) has become available for monitoring patients with differentiated thyroid cancer (DTC). Here, we evaluated the clinical performance of Elecsys® Tg II assay in a multicentre patients series and compare it with the established Access® Tg assay (Beckman Coulter, Brea, CA, USA). DESIGN: Retrospective analysis on prospectively selected patients in four thyroid cancer referral centres with uniform DTC management. PARTICIPANTS: All DTC cases diagnosed, treated and followed up in four tertiary referral centres for thyroid cancer since January 2005 (n = 1456) were retrieved, and predefined selection criteria were applied to prevent relevant enrolment biases. A series of 204 patients was finally selected for this study. MEASUREMENTS: Samples had been stored at -80°C. Tg was measured by fully automated immunometric Elecsys® Tg II and Access® Tg assays in a centralized laboratory. RESULTS: Two hundred and four DTC were finally included. Of these, 10.8% had structural recurrence (sREC), and 81.4% showed no evidence of disease (NED) at the end of follow-up. There was a significant analytical bias between methods that cannot be used interchangeably. Using ROC curve analysis, the best basal and rhTSH-stimulated Tg cut-offs to detect sREC were 0.41 µg/L and 1.82 µg/L for Elecsys® and 0.36 µg/L and 1.62 µg/L for Access® assay, respectively. Using Cox proportional hazard regression, Tg was the only independent predictor of cancer relapse. CONCLUSIONS: Using appropriate assay-specific cut-offs, the clinical performance of the Elecsys® Tg II assay was comparable to that provided by the well-established Access® Tg assay.

Molecular imaging with (99m)Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison.

PURPOSE: To compare mutation analysis of cytology specimens and (99m)Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm. METHODS: Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and (99m)Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of (99m)Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method. RESULTS: In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. (99m)Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative (99m)Tc-MIBI scan reliably excluded malignancy. CONCLUSION: In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of (99m)Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material.

Preoperative measurement of serum thyroglobulin to predict malignancy in thyroid nodules: a systematic review.

Several articles have assessed the role of preoperative serum thyroglobulin (Tg) as predictor of malignancy of thyroid nodules, with particular focus on nodules with indeterminate cytology. However, the role of serum Tg as diagnostic marker remains unclear. The aim of the study was to perform a systematic review to add more evidence-based data on this topic. A comprehensive literature search was conducted to find relevant published articles on this topic. MeSH terms were: "thyroglobulin" and "predict*". In order to include only recent serum Tg assay methods, we analyzed the timeframe between 2001 and July 31(st), 2014. To expand our search, references of the retrieved articles were also screened. Thirteen studies, including 3,580 patients, were analyzed. Nine out of these studies reported data on thyroid nodules with prior indeterminate cytology. Preoperative serum Tg levels demonstrated suboptimal accuracy in discriminating malignant from benign nodules due to a significant overlap of values between these groups. However, most articles demonstrated a statistically significant difference in mean or median serum Tg between patients with cancer and benign lesions correlated to final histology. Furthermore, most studies reported Tg as independent predictor of malignancy. According to the most recent literature, the preoperative measurement of Tg alone fails to discriminate thyroid cancers from benign lesions. However, our data show that Tg is an independent predictor of malignancy; as a consequence, the presurgical determination of Tg should be considered in patients with thyroid nodules, especially when cytology is indeterminate.

Laser capture microdissection is a valuable tool in the preoperative molecular screening of follicular lesions of the thyroid: an institutional experience.

OBJECTIVES: The application of molecular tests to thyroid fine needle aspiration (FNA) has been shown to be a valuable tool to better refine the pre-operative malignant risk of patients with indeterminate cytology results. In this study, we investigated the feasibility of using the laser capture microdissection (LCM) technique to obtain DNA and RNA for molecular tests in routine thyroid FNA smears. METHODS: Nine coupled FNA and histological retrospective cases and 31 prospective FNA cases with a follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) diagnosis were included in this study. Both cytological and histological specimens were investigated by direct sequencing and reverse transcription-polymerase chain reaction (RT-PCR) for BRAF and RAS mutations and for PAX8/PPARG and RET/PTC rearrangements, respectively. RESULTS: LCM yielded good DNA and RNA quality in all cases (100%) in both series, irrespective of the staining used (Giemsa, Papanicolaou, immunostain for thyroglobulin) and the cytology technique (conventional or liquid-based preparations). Total mutations found in the FNA and in the corresponding histological specimen in both series were: one PAX8/PPARG rearrangement in a follicular carcinoma (FC), four NRAS mutations [in two FCs, one papillary carcinoma and one follicular adenoma (FA)] and one HRAS mutation in one FA. The sensitivity was 67% and the specificity was 91%. CONCLUSIONS: LCM is a valuable tool to obtain good quality DNA and RNA for molecular tests in cytological material from thyroid FNA, and can be a useful option in the management of patients with an FN/SFN FNA diagnosis.

Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers.

BRAF(V600E) is the most frequent genetic mutation in papillary thyroid cancer (PTC) and has been reported as an independent predictor of poor prognosis of these patients. Current guidelines do not recommend the use of BRAF(V600E) mutational analysis on cytologic specimens from fine needle aspiration due to several reasons. Recently, immunohistochemistry using VE1, a mouse anti-human BRAF(V600E) antibody, has been reported as a highly reliable technique in detecting BRAF-mutated thyroid and nonthyroid cancers. The aim of this study was to test the reliability of VE1 immunohistochemistry on microhistologic samples from core needle biopsy (CNB) in identifying BRAF-mutated PTC. A series of 30 nodules (size ranging from 7 to 22 mm) from 30 patients who underwent surgery following CNB were included in the study. All these lesions had had inconclusive cytology. In all cases, both VE1 and BRAF(V600E) genotypes were evaluated. After surgery, final histology demonstrated 21 cancers and 9 benign lesions. CNB correctly diagnosed 20/20 PTC and 5/5 adenomatous nodules. One follicular thyroid cancer and 4 benign lesions were assessed at CNB as uncertain follicular neoplasm. VE1 immunohistochemistry revealed 8 mutated PTC and 22 negative cases. A 100% agreement was found when positive and negative VE1 results were compared with BRAF mutational status. These data are the first demonstration that VE1 immunohistochemistry performed on thyroid CNB samples perfectly matches with genetic analysis of BRAF status. Thus, VE1 antibody can be used on thyroid microhistologic specimens to detect BRAF(V600E)-mutated PTC before surgery.

Relationship between antithyroglobulin autoantibodies and thyroglobulin recovery rates using different thyroglobulin concentrations in the recovery buffer.

The aim of the work was to examine the relationship between thyroglobulin autoantibody (TgAb) levels and the Tg recovery rate (TgRR) using different concentrations of Tg (50, 10, 5, and 1 µg/l) in the recovery buffer. A total number of 225 serum samples from individual patients were analyzed. Samples were selected for their TgAb in 6 groups: TgAb1 000 IU/ml (n=28). TgAb were measured with 2 different assays (VARELISA and BRAHMS Anti-Tgn RIA). TgAb levels and the TgRR determined using the 50, 10, 5, and 1 µg/l buffers showed strong significant correlations with a Spearmans' rho of - 0.720, - 0.688, - 0.686, and - 0.356, respectively, for the VARELISA assay and - 0.670, -0.617, - 0.570, and - 0.274, respectively, for the Anti-Tgn assay (all p<0.001). TgRRs were a median of 94.8% (30.5-113.0%), 90.8% (40.6-127.6%), 90.0% (8.2-119.3%), and 89.4% (range - 43.6-121.6%) for the TgRR determined using recovery buffers with concentrations of 50, 10, 5, and 1 µg/l respectively. With decreasing Tg concentration in the recovery buffer the percentage of abnormal results increased, although the extreme increase we found in the 1 µg/l group is largely caused by a lack of analytical precision in the 73 sera with Tg levels exceeding 5 µg/l. Our results give cause for further investigation into reviving the concept of Tg-recovery measurement using 5 µg/l Tg in the recovery buffer instead of the traditional 50 µg/l.

High sensitive thyroglobulin assay on thyroxine therapy: can it avoid stimulation test in low and high risk differentiated thyroid carcinoma patients?

Thyroglobulin (Tg) is a key marker in the follow-up of differentiated thyroid cancer (DTC). Diagnostic accuracy of serum Tg is higher after TSH stimulation than during thyroxine treatment. However, some studies suggest that TSH stimulation could be not necessary in a large part of patients, if Tg is measured by high sensitive assay under replacement therapy. The aim of this study was to evaluate the need of Tg stimulation test in DTC followed-up by sensitive Tg assay. In a prospective multicenter explorative study, 68 low or high risk patients underwent Tg measurement on thyroxine (ON-LT4-Tg) and after LT4 withdrawal (OFF-LT4-Tg). Undetectable ON-LT4-Tg and OFF-LT4-Tg values (i. e.,<0.15 ng/ml) were found in 56/68 patients, all with negative imaging workup. Twelve subjects had skewed OFF-LT4-Tg: 8 cases had increased ON-LT4-Tg and local recurrence (n=6), distant metastasis (n=1), or benign thyroglossal duct (n=1); the remaining 4 patients had undetectable ON-T4-Tg but detectable OFF-LT4-Tg and neck metastasis was recorded in one of these. By ROC analysis, the most accurate cutoff for ON-LT4-Tg and OFF-LT4-Tg were set at 0.23 ng/ml and 0.70 ng/ml, respectively. A positive ON-LT4-Tg value accurately predicts a positive stimulation test and confers an Odds Ratio of 464 (95% CI from 26.3 to 8 173.2, p<0.0001) to have persistent/recurrent disease. This study shows that DTC patients with ON-LT4-Tg below 0.23 ng/ml by our high sensitive assay should be considered disease free and they can avoid Tg stimulation test. High sensitive Tg assays should be used to better manage DTC patients.

Evaluation of the BRAHMS KRYPTOR thyroglobulin "mini-recovery" test in thyroid healthy subjects.

The aim of the work was to compare the automated thyroglobulin (Tg) assay on the automated BRAHMS KRYPTOR platform (hTG KRYPTOR) to the established BRAHMS Tg Plus immunoradiometric assay for the measurement of Tg levels and regular Tg recovery rates and to assess a recovery test using a low Tg concentration of 10 µg/l ("mini-recovery") in samples with a native Tg level of <10 µg/l. Tg levels and recovery rates, as well as the mini-recovery, were determined in 208 serum samples from thyroid-healthy patients using both assays. The reference ranges for the Tg-Plus assay are 2.0-51.0 µg/l for Tg levels and 81.5-108% for recovery rates at 100 µg/l. The reference ranges for hTG KRYPTOR are 2.4-47.8 µg/l for Tg, 83.3-110.4% for a conventional recovery with 80 µg/l in Tg levels ≥ 10.0 µg/l (n=121) and 94.4-122.9% for the mini-recovery with Tg <10.0 µg/l (n=87). The correlation between the Tg-Plus and hTG KRYPTOR is excellent for Tg (r2=0.95; p<0.001), but not significant for recovery rates. Tg levels determined using the KRYPTOR Tg assay are clinically comparable to the conventional Tg-Plus assay. New features of the KRYPTOR assay such as the ability to perform a "mini-recovery" still require further study before clinical use.

Thyroglobulin and thyroglobulin autoantibodies measurement using the automated KRYPTOR® platform in patients with differentiated thyroid carcinoma.

The aim of the present study is 1) to compare our established manual thyroglobulin (Tg) and Tg autoantibody (TgAb) immunoassays to the automated KRYPTOR® platform from the same manufacturer, in a large group of DTC patients and 2) to evaluate whether a change in assay methods could be made without disrupting the serial monitoring pattern. Sera from 160 patients with histologically proven DTC were obtained and Tg and TgAb measured by manual immunoassays and a fully automated platform. We found an excellent agreement between the 2 methods for Tg measurement (R=0.9888, p<0.00001) with a 90% overall concordance rate. At the same time, a weak relationship was found between the two methods for TgAb measurement (R=0.4438, p<0.03). However, 151 patients had concordant results with a 94% overall concordance rate. In conclusion, the excellent correlation we found between the Tg assays make the fully automated KRYPTOR® Tg assay interchangeable with the established Dyno-test® Tg-plus in patients with DTC. A very high qualitative concordance rate was found between Dyno-test® TgAbn and KRYPTOR® TgAb assays, making these methods interchangeable to screen sera for the presence of TgAb. However, since quantitative discordances still occurred in some patients a re-baseline of TgAb positive patients is strongly supported before changing the TgAb assay method.

Heterophile antibodies rarely influence the measurement of thyroglobulin and thyroglobulin antibodies in differentiated thyroid cancer patients.

The aim of the study was to determine the impact of heterophile antibodies on the measurement of serum thyroglobulin (Tg), thyroglobulin recovery, and thyroglobulin antibody levels in differentiated thyroid carcinoma patients. We studied serum samples of 201 individual patients that were followed in our hospital for differentiated thyroid carcinoma and 52 control samples. Samples were split; half were treated by incubating the sample for 1 h in HAB-blocking tubes, the remainder was left untreated. Subsequently thyroglobulin and thyroglobulin antibody levels were measured in both the blocked and untreated samples. A difference between the two samples was considered significant if the blocked sample deviated from the untreated one by more than 2.77 times the standard deviation for the method. In the measurement of Tg, 2 patients showed a moderate, but significant lowering of Tg levels after blocking treatment, but not so great as to affect clinical management. None of the 52 controls showed heterophile antibody interference in thyroglobulin measurement. Neither in DTC patients, nor in controls was any possible heterophile antibody interference encountered. And in all thyroid carcinoma patients, and in all but one controls, no interference was found in the thyroglobulin antibody measurement. All in all a possible heterophile antibody interference was found in 3/759 tests (0.4%). We can assume that heterophile antibody interference is not a factor to be reckoned with in the daily practice of Tg measurement in the treatment and follow-up of differentiated thyroid carcinoma patients.

18F-FDG-PET/CT Imaging in Advanced Glottic Cancer: A Tool for Clinical Decision in Comparison with Conventional Imaging.

This study assessed the role of 18F-FDG PET-CT (PET/CT) to detect the cartilage and paraglottic infiltration in advanced glottic cancer comparing the results with those of conventional imaging (CI) (contrast-enhanced computed tomography and/or magnetic resonance). In addition, we assessed the prognostic value of quantitative parameters, measured on baseline PET/CT, in terms of event-free survival (EFS) and overall survival (OS). We retrospectively analyzed 27 patients with glottic squamous cell carcinoma stage III and IVA, treated in our institute between 2010 and 2016, comparing PET/CT, performed for staging and radiotherapy planning, and CI findings. Cohen's K was used to compare concordance between PET/CT and CI. Imaging findings were correlated with endoscopic evaluation and histological reports (gold standard (GS)). All lesions shown by CI were also detected by PET/CT imaging, and in 5 cases, a better definition of local infiltration was achieved with PET/CT than CI (5 CT). Sensitivity, specificity, and accuracy of PET/CT and CT were 95%, 86%, and 93% and 70%, 86%, and 74% for, respectively. MRI showed sensitivity and specificity of 100%. One false-negative (FN) cases and 1 false-positive (FP) case were observed with PET/CT with no difference compared to MRI (10 cases). Six FN cases and 1 FP case were observed with CT. Cohen's K was 0.60 (PET vs. CI) and 0.80 (PET vs. GS). Patients were followed-up for at least 24 months to calculate EFS and OS. 13 local recurrence and 7 deaths were recorded. Among quantitative PET parameters, baseline MTV was the most powerful predictor of outcome. Our data suggest a reliable sensitivity and accuracy of PET/CT in the evaluation of local extension, proving a useful method for initial local staging in addition to the well-established role in lymph-node and distant sites assessment. Furthermore, pretreatment MTV provides better prognostic information than other PET/CT parameters.