Incidence and implications of negative serum thyroglobulin but positive I-131 whole-body scans in patients with well-differentiated thyroid cancer prepared with rhTSH or thyroid hormone withdrawal


Martin Cherk, Department of Nuclear Medicine, The Alfred Hospital, Commercial Road, Melbourne, Vic. 3004, Australia. Tel.: +61 3 90762432; Fax: +61 3 90762599; E-mail:


Aims  To evaluate the incidence and clinical implications of a positive whole-body I-131 scan but negative stimulated serum Tg/TgAb level following an ablative or diagnostic I-131 dose in patients with well-differentiated thyroid cancer and whether there is a difference in incidence if prepared with thyroid hormone withdrawal compared with rhTSH stimulation.

Methods  I-131 scan findings, serum Tg/TgAb levels, TNM stage and method of thyroid tissue stimulation in 193 consecutive patients (138F, 55M) with well-differentiated thyroid cancer undergoing postoperative ablative I-131 therapy and 121 consecutive (94F, 27M) patients undergoing diagnostic I-131 surveillance scans were retrospectively reviewed. Comparisons of proportions were performed using Chi-square tests. Clinical, biochemical and I-131 scan follow-up data were obtained for each patient cohort.

Results  39/193 (20·2%) postablative I-131 and 10/121 (8·3%) diagnostic I-131 patients had negative stimulated serum Tg/TgAb levels but positive I-131 scans for residual thyroid tissue. Nine (4·7%) of the postablative patients had I-131 uptake in the lateral neck suspicious for loco-regional metastatic disease. In the postablative I-131 group, 38/169 (22·5%) prepared with rhTSH compared to 1/24 (4·2%) prepared with thyroid hormone withdrawal were Tg/TgAb negative but I-131 scan positive (P = 0·04). Follow-up of 21/39 postablative I-131 patients with negative Tg/TgAb but positive I-131 scans confirmed a significant proportion of patients (4/21) (19·1%), remained Tg/TgAb negative/I-131 scan positive, some of whom had higher-risk disease at original diagnosis (2/4) (50%).

Conclusions  Our study confirms that in the setting of I-131 ablation therapy or diagnostic I-131 scanning, a significant proportion of patients (20·2% and 8·3%, respectively) have residual benign or malignant thyroid tissue on whole-body scanning despite a negative stimulated serum Tg level. Whether such patients who would otherwise be missed as having residual thyroid tissue on serum Tg testing alone have a worse clinical outcome remains uncertain. Our findings do however suggest performing both stimulated serum Tg/TgAb levels and I-131 scans for the follow-up of patients with higher-risk thyroid cancer may be important. There may also be a slightly higher incidence of this phenomenon in patients prepared with rhTSH rather than by thyroxine withdrawal.