FOXE1 polymorphism rs965513 predisposes to thyroid cancer in a European cohort.

Objective: FOXE1 is an intronless gene on chromosome 9 which plays a significant role in thyroid morphogenesis. Mutations in FOXE1 are associated with thyroid phenotypes including congenital hypothyroidism, thyroid dysgenesis and thyroid cancer. This study aims to investigate the frequency and impact of a SNP (rs965513, G>A) at 9q22.23 in a Western European cohort of patients with differentiated thyroid cancer(DTC), compared to controls. Design: This is a candidate gene case control study. Methods: 277 patients with histologically confirmed DTC were recruited from tertiary referral centres in Ireland and France. 309 cancer-free controls were recruited from the community. DNA was extracted from buccal swabs or whole blood of control subjects and patients with DTC. Allelic and genotypic frequencies among patients were compared with controls, to assess the risk for disease conferred by homozygous and heterozygous carriers compared to WT genotypes. Genotyping was performed using Taqman-based PCR. Results: 277 patients with confirmed DTC and 309 non-cancer controls were genotyped for the variant (rs965513). The frequency of the minor allele among cases was 0.45 compared to 0.34 among controls. The genotypic odds ratio for heterozygotes was 1.66 (CI 1.16-2.39, P =0.00555), increasing to 2.93 (CI 1.70-5.05, P =0.00007) for rare homozygotes. All subjects were in Hardy-Weinberg equilibrium (±χ2, P =0.09, P =0.07 respectively). Conclusions: This FOXE1 polymorphism is a low penetrance variant associated with DTC susceptibility in this cohort. The minor allele was identified among patients with thyroid cancer significantly more frequently than controls. An allele dosage effect was observed, with rare homozygous genotypes conferring greater risk than heterozygotes.

11 C-Metomidate PET/CT is a useful adjunct for lateralization of primary aldosteronism in routine clinical practice.

OBJECTIVE: To describe clinical practice experience of 11 C-Metomidate PET/CT as an adjunct to adrenal vein sampling (AVS) in the lateralization of aldosterone-producing adenomas (APA) in primary aldosteronism (PA). CONTEXT: Accurate lateralization of APA in the setting of PA offers the potential for surgical cure and improved long-term cardiovascular outcomes. Challenges associated with AVS, the current gold standard lateralization modality, mean that only a small proportion of potentially eligible patients currently make it through to surgery. This has prompted consideration of alternative strategies for lateralization, including the application of novel molecular PET tracers such as 11 C-Metomidate. DESIGN: Clinical Service Evaluation/Retrospective audit. PATIENTS: Fifteen individuals with a confirmed diagnosis of PA, undergoing lateralization with 11 C-Metomidate PET/CT prior to final clinical decision on surgical vs medical management. MEASUREMENTS: All patients underwent screening aldosterone renin ratio (ARR), followed by confirmatory testing with the seated saline infusion test, according to Endocrine Society Clinical Practice Guidelines. Adrenal glands were imaged using dedicated adrenal CT. 11 C-Metomidate PET/CT was undertaken due to equivocal or failed AVS. Management outcomes were assessed by longitudinal measurement of blood pressure, ARR, number of hypertensive medications following adrenalectomy or institution of medical therapy. RESULTS: We describe the individual lateralization and clinical outcomes for 15 patients with PA. CONCLUSION: 11 C-Metomidate PET/CT in conjunction with adrenal CT and AVS provided useful information which aided clinical decision-making for PA within a multidisciplinary hypertension clinic.

Differentiated Thyroid Cancer: How Do Current Practice Guidelines Affect Management?

BACKGROUND: International best-practice guidelines recommend completion thyroidectomy and radioiodine remnant ablation (RRA) for patients with differentiated thyroid cancer (DTC) > 4 cm or with specific risk factors. Patients with DTC < 1 cm without risk factors are recommended for lobectomy alone. Indications for aggressive surgery and RRA are less clearly defined for tumours measuring 1-4 cm. A personalised approach to decision-making is recommended. OBJECTIVES: This study assesses therapeutic approaches to DTC as compared to the current British Thyroid Association (BTA) clinical practice guidelines. We ascertained the effect of equivocal guidance in the 1-4 cm tumour cohort on contemporary practice patterns. METHODS: Data were obtained from a prospectively maintained thyroid cancer database of patients treated for DTC in a tertiary referral centre at the University Hospital Galway. Consecutive patients attending a dedicated thyroid cancer clinic between August 2014 and August 2017 were included. Clinicopathological characteristics and management strategies were assessed. RESULTS: Ninety-four percent (n = 168/178) of patients were surgically managed in adherence with guidelines. A minority (n = 10) received surgery not aligned with guidelines. Ninety-seven percent (n = 172/178) of RRA treatment decisions were in accordance with guidelines. The BTA guidelines recommended a personalised decision-making approach for 18.0% (n = 32) and 44.9% (n = 80) of surgery and RRA treatment decisions, respectively. The more aggressive, treatment-driven approach was typically favoured by the multidisciplinary team, with 97% (n = 31/32) undergoing completion thyroidectomy and 100% (n = 80) proceeding to RRA. CONCLUSIONS: Management of DTC at our institution closely adheres to contemporary clinical practice guidelines. The finding of more aggressive management in those requiring a personalised decision-making approach highlights the requirement for improved risk stratification in this cohort to ratio-nalise management strategies.

FNAC and frozen section correlations with definitive histology in thyroid diseases.

The ability to diagnose thyroid cancers pre-op or intra-operatively by fine needle aspiration cytology (FNAC) or frozen section (FS) leads to the delivery of appropriate one-stage surgical management. We aim to study the concordance and discordance of FNAC and FS with final histology in thyroid pathologies. All thyroid procedures from 2007 to 2011(n = 423), involving FNAC and or frozen section in their management pathway were included. FNAC (n = 159) were classified in a five-tier system (Nondiagnostic, Benign, Atypical, Suspicious or Malignant). FS (n = 128) were classified as inconclusive, benign, suspicious or malignant. FNAC and FS were correlated with final histopathology. 159 out of 423 patients had FNAC (PPV 85.1 %), 26 inadequate specimens noted, benign cytology 57, atypical (n = 23), follicular neoplasm (n = 27), suspicious for malignancy (n = 16) and malignant 11. 13 out of 27 follicular neoplasm and 6 of atypical FNAC cases showed malignancy in their final histopathology. Frozen sections; total of 126 patients had intra-operative frozen section biopsies performed. Overall 105 out of 126 FS biopsies were benign; 21 malignancies detected intraoperatively. Three FS were inconclusive and reported benign in final histopathology. Overall, FNAC demonstrated a PPV of 66.6 % and NPV of 84.6 %. FS demonstrated PPV and NPV of 76.1 and 85.7%, respectively. In conclusion, FNAC is considered as the best modality to triage the thyroid nodule pre-operatively. Atypical and follicular neoplasm cytology categories warrant further clinical assessment and close follow-ups when appear benign. The intra-operative frozen sections are helpful to perform a one-stage operation for suspicious thyroid lesion. This study also highlights the recognised limitation of intra-operative frozen section analysis of thyroid neoplasia.