Context: Thyroid nodules and goiter are common and fine needle aspiration biopsy (FNAB) is the first investigation of choice in distinguishing benign from malignant disease.

Objective: To assess if simple clinical and biochemical parameters can predict the likelihood of thyroid malignancy in subjects undergoing FNAB.

Design: Prospective cohort.

Setting: Single Secondary/Tertiary Care Clinic.

Participants: 1500 consecutive patients without overt thyroid dysfunction (1304 females and 196 males, mean age 47.8 yr) presenting with palpable thyroid enlargement between 1984 and 2002 were evaluated by FNAB of the thyroid.

Intervention(s): None

Main Outcome Measures: Goiter type was assessed clinically and classified as diffuse in 183, multinodular in 456 or solitary nodule in 861 cases. Serum TSH concentration at presentation was measured in a sensitive assay in patients presenting after 1988 (n = 1183). The final cytological or histological diagnosis was determined after surgery (n = 553) or a minimum 2 yr clinical follow-up period (mean 9.5 yr, range 2-18 yr).

Results: The overall sensitivity and specificity of FNAB in predicting malignancy were 88% and 84% respectively. The risk of diagnosis of malignancy rose in parallel with the serum TSH at presentation, with significant increases evident in patients with serum TSH>0.9mU/l compared with those with lower TSH. Binary logistic regression analysis revealed significantly increased adjusted odds ratios (AOR) for the diagnosis of malignancy in subjects with serum TSH 1.0-1.7mU/l compared with TSH<0.4mU/l (AOR 2.72, 95%CI 1.02-7.27, P = 0.046), with further increases evident in those with TSH 1.8-5.5mU/l (AOR 3.88, 95%CI 1.48-10.19, P = 0.006, compared with TSH<0.4mU/l) and >5.5mU/l (AOR 11.18, 95%CI 3.23-8.63, P < 0.001, compared with TSH<0.4mU/l). Males (AOR 1.8, 95%CI 1.04-3.1, P = 0.04), younger patients (AOR 1.1, 95%CI 1.01-1.15, P = 0.025) and those with clinically solitary nodules (AOR 2.53, 95%CI 1.5-4.28, P = 0.001) were also at increased risk. Based on these findings, a formula to predict the risk of the diagnosis of thyroid malignancy in individual patients, taking into account their gender, age, goiter type determined clinically and serum TSH was calculated.

Conclusions: The risk of malignancy in a thyroid nodule increases with serum TSH concentrations within the normal range. In addition to patient's gender, age and goiter type, the serum TSH concentration at presentation is an independent predictor of the presence of thyroid malignancy. We propose that these simple clinical and biochemical factors can serve as an adjunct to FNAB in predicting risk of malignancy.