J Clin Endocrinol Metab, Sep 2006, 91(9):

Introduction Population studies - 3-8% of asymptomatic adults have thyroid nodules - More thyroid nodules being detected with development of imaging studies - Nodules have a 5-15% prevalence of malignancy  Recommendation of FNA of solitary nodules (10-15 mm) On ultrasound examination - Many patients thought to have a solitary nodule by physical exam ; Found to have additional nodules larger than 10 mm in diameter

Recommended diagnostic approach for multiple nodules - Based on variable studies - Some advocate routine FNA of all nodules ( > 10 mm) - Others recommend FNA of only the largest nodule - Still others advocate follow- up alone ; Based on that cancer is rare when multiple nodules are present  Absence of studies investigating the prevalence and location of thyroid cancer in pts. with multiple thyroid nodules !! Introduction

Introduction Sonographic characteristics as predictors of thyroid cancer - Nodule size - Presence of microcalcifications - Hypoechogenicity, solid composition, and irregular margins  Based on small patients population and none of studies has systemically compared multiple nodules in the same gland.

In this study - Performance of a large number of US guided FNAs - FNA for all nodules (> 10 mm) regardless of the sonographic appearance  Provides a large, unbiased sample to assess the risk of cancer in patients with multiple thyroid nodules - Retrospectively review for the records of all pts. with one or more thyroid nodules (> 10 mm) The goal of this study - To compare the risk of thyroid cancer in pts. with solitary nodules to that in pts. with multiple nodules - To determine usefulness of sonographic features in predicting the risk of malignancy

Patients and Methods Patients without prior thyroid surgery - Referred to the multidisciplinary Thyroid Nodule Clinic at the Brigham and Women’s Hospital (Boston), 1995 – 2003 Thyroid Ultrasonography US guided – FNA Sonographic features were recorded. ; Size, composition, echogenicity margin appearance, calcifications 3 to 4 aspirates were performed per Nodule using a 25-gauge needle.

Results 295 (14.9%) cases

* As the number of nodules increased, the frequency of cancer in the largest nodule decreased (P = 0.03), thus reducing the predictive value of FNA of the largest nodule.

* A strategy of biopsying the largest nodule would have detected only 86% of patients with two nodules who had cancer and approximately 50% of patients with three or more nodules who had cancer.

NS

* For any set of sonographic features, the likelihood of a nodule being malignant is approximately TWICE as high in solitary compared with nonsolitary nodule and more than 1.5 TIMES as high in a man compared with a woman.

Discussion This analysis of 1985 pts. with one or more thyroid nodule (> 10mm) Demonstrates… - The likelihood of thyroid cancer is independent of the number of nodules - Sonographic characteristics  Unable to accurately distinguish benign from malignant disease - No other investigations have provided a complete malignancy assessment of all thyroid nodules larger than 10 mm.

Numerous studies about relationship between sonographic features of thyroid cancer and malignancy - NOT sufficiently high or low to prelude the necessity of FNA - Have been based on small patient population - In this study ; Large sample size ; Avoiding ascertainment bias by performing FNA on all nodules Discussion

Variable published guidelines for appropriate evaluation of patients with more than one thyroid nodule - “ FNA of all thyroid nodules when possibility of malignancy is appreciable” - “ FNA of most nodules greater than mm, particularly those with worrisome sonographic charactersitics ” - Desirable to be able to identify nodules with high risk of malignancy to permit prioritization for FNA  This study demonstrates that a number of features correlate with the chance a nodule is cancer

The results of this study - Support recommendation about… ; How to select which nodules to biopsy * Among pts. with two nodules, about 15% of cancers would have been missed if only the largest nodule had been aspirated.

In some cases with multiple nodules - The results of multivariate analysis can provide guidance about which nodules should be sampled. ; Nodule with highest sonographic risk  Would be one chosen to undergo biopsy

Conclusion In patient with one or more thyroid nodules (>10 mm) - The likelihood of thyroid cancer per patient is independent of number of nodules. - The likelihood per nodule decreases as the number of nodules increases. For exclusion of cancer in multiple nodule - Up to four nodules should be considered for FNA. Sonographic characteristics - Can be used to prioritize nodules for FNA based on their individual risk of cancer.