SERUM THYROGLOBULIN IN THE FOLLOW-UP OF PATIENTS WITH TREATED DIFFERENTIATED THYROID-CANCER

To determine the significance of serum the yroglobulin (Tg) level in terms of presence or absence of thyroid cancer, we evaluated available serum Tg data on and off T-4 therapy in 180 patients with differentiated thyroid cancer who have now been followed up to 18 yr. The presence of cancer was established by radioiodine scans, x-rays, and clinical examination, Thirty-two patients with detectable serum Tg autoantibodies were excluded from this analysis. Tg was measured by RIA with a sensitivity of 1 ng/mL. Patients who had all stages of cancer, but who had no evidence of active disease after treatment, were grouped according to operative and I-131 ablative therapy. In patients with a partial thyroidectomy with or without ablation, the presence of Tg did not indicate the presence of cancer since levels were often above either a 5 ng/mL or a 10 ng/mL cutoff. The presence of residual normal thyroid tissue decreases the diagnostic value of serum Tg assay. In patients who underwent near total (NTT) or total thyroidectomy (TT) and I-131 ablation, 3 of 55 (5.5%) patients had Tg greater than 5 ng/mL and 1 of 55 (1.8%) patients had Tg greater than 10 ng/mL during therapy, whereas off therapy 13 of 57 (22.8%) patients had Tg greater than 5 ng/mL and 6 of 57 (10.5%,) patients had Tg levels greater than 10 ng/mL. In this group of patients, a Tg level less than 10 ng/mL during suppressive therapy indicated the absence of apparent tumor in 54 of 55 (98.2%) of patients. Whereas sensitivity of the assay was increased by withdrawal of hormone, ''false positives'' increased especially at lower (3-6 ng/mL) cut-off levels. No cut-off value properly categorized all patients. These data suggest, that even in patients who underwent I-131 ablation and total thyroidectomy and were thought to be cured, small foci of thyroid tissue which are undetectable by standard 2 mCi I-131 scans may exist and produce some Tg. However, these residual cells do not appear to cause an adverse prognosis in most patients. In patients with recurrent or continued disease, during T-4 treatment, Tg levels ranged between 2-21,000 ng/mL and 5 of 11 patients had a Tg less than 5 ng/mL. Off treatment, Tg levels ranged between 6-10,700 ng/mL and 3 of 13 patients had a Tg less than 10 ng/mL. In 4 patients Tg levels were less than 10 ng/mL on treatment but greater than 10 ng/mL off therapy. In this group a Tg level greater than 10 ng/mL when off T-4 therapy indicated the presence of active disease in 10 of 23 (76.9%) patients, although similar values occurred in some patients apparently free of disease. In the NTT and TT+ I-131 ablation group Tg levels were uniformly lower when patients were on TI therapy, but TSH levels below the normal range were not associated with lower Tg values. In this group there also was no correlation of Tg values and the amount of I-131 used for ablation. In the NTT and TT+ I-131 ablation group, Tg levels while on replacement decreased to undetectable levels in 23 of 55 patients over time after treatment. We concluded that after I-131 therapy and during T-4 treatment there may be gradual atrophy or death of residual Tg-producing cells.