Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study.

OBJECTIVE: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases. DESIGN AND METHODS: An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017. RESULTS: Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4-1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis. CONCLUSIONS: Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.

Thyroid fine-needle aspiration and The Bethesda Classification System.

INTRODUCTION: Fine-needle aspiration (FNA) is a cornerstone in diagnosing thyroid nodules. For decades, Danish FNA has been categorised into the groups: "FNA not performed", "Inadequate", "Cystic", "Inconclusive", "Benign", "Suspicious", "Malignant" and "Information missing". Internationally, The Bethesda Classification System (TBCS) is increasingly accepted, especially owing to a detailed specification of FNA suspicious for malignancy. The Danish "Suspicious" group is very broad and includes atypia, follicular neoplasia and FNA suspicious of other malignancies. The purpose of this study was to apply TBCS to the Danish "Suspicious" FNA group and to estimate the frequency of malignancy in the individual Bethesda groups (BG). METHODS: This descriptive study is based on a prospective cohort from the THYKIR database. It includes 479 patients with a "Suspicious" FNA and surgical treatment in The Region of Southern Denmark from 2001 to 2013. Based on pathology records, FNA was classified according to the TBCS. Malignancy was determined by the histological diagnosis from the THYKIR database. RESULTS: The Danish "Suspicious" group was allocated to the BG I, II, III, IV, V and VI with a malignancy risk of 36.4%, 13.3%, 17.2%, 16.1%, 55.3% and 88.2%, respectively. CONCLUSIONS: The Danish "Suspicious" group contains a broad spectrum of BG with varying malignancy risk. The results indicate a need for standardisation of the Danish FNA classification. A national introduction of the TBCS might secure an international and comparable standard. FUNDING: none. TRIAL REGISTRATION: not relevant.

Risk of malignancy in fine-needle aspiration biopsy in patients with thyroid nodules.

INTRODUCTION: Fine-needle aspiration biopsy (FNAB) is the cornerstone of thyroid nodule evaluation. In most cases, FNAB can discriminate between benign and malignant disease. In other cases, it is only indicative of malignancy and the results are considered "suspicious". In Denmark, thyroid FNAB results are categorised into six groups: "inadequate", "cystic", "inconclusive", "benign", "suspicious" and "malignant". The risk of malignancy in the Danish "suspicious" group is of interest for patients as well as doctors participating in the diagnosis and treatment. The Danish Thyroid Surgery Database (THYKIR) registers preoperative thyroid FNAB and final histology. The aim of this study was to assess the malignancy risk among patients with a suspicious thyroid FNAB according to the Danish criteria and to identify possible predictors of malignant histology. METHODS: A prospective cohort counting 483 patients with a "suspicious" thyroid FNAB who had been treated surgically in The Region of Southern Denmark in the 2001-2013 period was retrieved from the THYKIR database. RESULTS: The risk of malignancy in the Danish thyroid FNAB "suspicious" group is 22%. Serum thyroid-stimulating hormone outside the normal range and vocal cord palsy may be patient-related predictors of malignancy. CONCLUSION: Awaiting the introduction of reliable tools for preoperative evaluation, the current practice with histo-logical clarification of the "suspicious" thyroid FNAB seems justified. FUNDING: none. TRIAL REGISTRATION: not relevant.