TSH stimulates thyrocyte metabolism, glucose transport, and glycolysis. 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) is a glucose analog used in positron emission tomography (PET) to detect occult well-differentiated thyroid carcinoma. The objective of this study was to examine the effects of recombinant human TSH (rTSH) on FDG PET uptake in patients with residual or recurrent disease. Seven patients with well-differentiated thyroid carcinoma, negative 131-I scintigraphy, and biochemical evidence of residual disease were randomized and prospectively studied with FDG PET both on thyroid hormone suppression and rTSH stimulation within 1 wk. All lesions seen on the TSH suppression scans were seen on the rTSH stimulation studies. rTSH stimulation studies identified four additional lesions not seen on TSH suppression. One patient was positive on rTSH stimulation alone. The mean (2.54 ± 0.72 vs. 1.79 ± 0.88) and maximum (2.49 ± 0.95 vs. 1.74 ± 0.81) lesion to background ratios were significantly higher with rTSH stimulation, compared with TSH suppression (P = 0.02 for both). rTSH stimulation improves the detectability of occult thyroid metastases with FDG PET, compared with scans performed on TSH suppression.