A Prospective Comparative Study of Parathyroid Dual-Phase Scintigraphy, Dual-Isotope Subtraction Scintigraphy, 4D-CT, and Ultrasonography in Primary Hyperparathyroidism.

PURPOSE: Preoperative localization of the diseased parathyroid gland(s) in primary hyperparathyroidism allows for minimally invasive surgery. This study was designed to establish the optimal first-line preoperative imaging modality. PATIENTS AND METHODS: Ninety-one patients were studied consecutively in a prospective head-to-head comparison of dual isotope (Tc-MIBI vs I) subtraction parathyroid scintigraphy (PS), dual-phase PS, 4-dimensional (4D) CT, and ultrasonography (US). Surgery, histological confirmation, and postoperative normalization of Ca and parathyroid hormone were the reference standard. RESULTS: Ninety-seven hyperfunctioning parathyroid glands (HPGs) were identified by the reference standard. Sensitivity and specificity for subtraction PS, dual-phase PS, 4D-CT, and US were 93%, 65%, 58%, and 57% as well as 99%, 99.6%, 86%, and 95%, respectively. Interrater agreement was excellent for subtraction PS (κ = 0.96) while only fair for 4D-CT (κ = 0.34). Pinhole imaging and subtraction of delayed images (the latter especially in case of a nodular thyroid gland) increased the sensitivity of subtraction PS. SPECT/low-dose CT did not increase sensitivity but aided in the exact localization of the HPGs. Of 7 negative subtraction PS studies, 4D-CT and US were able to locate 3 and 1 additional HPGs, respectively. CONCLUSIONS: Dual isotope pinhole subtraction PS has higher diagnostic accuracy compared with dual-phase PS, 4D-CT, and US as a first-line imaging study in primary hyperparathyroidism. In case of a negative scintigraphy or suspicion of multiglandular disease, 4D-CT and/or US is recommended as a second-line modality. However, diagnostic algorithms should be adapted in accordance with local availability and expertise.

A simple procedure for routine RNA extraction and miRNA array analyses from a single thyroid in vivo fine needle aspirate.

CONTEXT: microRNA (miRNA) expression profiling and classification of tissue obtained from fine-needle aspirates (FNA) could be a major improvement of the preoperative diagnosis of thyroid nodules. OBJECTIVE: Before this can be clinically implemented, a robust and non-toxic method for obtaining sufficient quantity and quality of RNA from single in vivo FNA has to be established. RNAlater is a non-toxic RNA-stabilizing agent. However, due to the high density of RNAlater, pelleting of the tissue samples is difficult, and results in low recovery of RNA that is insufficient for subsequent miRNA array expression analysis. We therefore developed a simple centrifugation method for capturing tissue stored in RNAlater on a 0.45-µm filter. DESIGN: FNA from 24 patients with a solitary cold thyroid nodule was stored in Trizol, liquid nitrogen, or RNAlater. The tissue stored in RNAlater was either pelleted by centrifugation or captured on the 0.45-µm filters. RNA was extracted using the Trizol method. To validate results, FNA from additional 30 patients were analyzed based on the modified RNAlater protocol. MAIN OUTCOME: Capturing FNA tissue samples on the filters increased the RNA yield 10 fold and maintained RNA purity, permitting miRNA array expression profiling and allowing comparable levels of known miRNA-clusters regardless of preservation technique. Results were confirmed in an additional 30 patients. CONCLUSION: The modified RNAlater protocol is well suited for isolating RNA from single thyroid in vivo FNA in a clinical setting. Furthermore this permits shipping of FNA samples at room temperature from peripheral centers to a centralized array core facility.