J. Endocrinol. Invest. 18.'165-166,1995 Post-surgical follow-up of differentiated thyroid cancer F. Pacini, R. Elisei, L. Fugazzola, F. Cetani, C. Romei, F. Mancusi, and A. Pinchera Istituto di Endocrinologia, University of Pisa, Italy INTRODUCTION Another methodological problem to consider, is the effect of iodine contamination as source of falsely negative WBS. Many iodine containing foods and drugs may be inadvertently assumed by the patient before performing WBS. Since in our experience such possibility is not rare, it is important to inform the patient and the family doctor to avoid iodine containing food or medications before WBS. If possible, we also recommend routine measurements of urinary iodine excretion to rule out iodine contamination. After surgery, the presence of 131 uptake in the thyroid bed when performing the first WBS, is the rule. Depending on its extent, it may prevent 131 1 uptake of metastatic tissue elsewhere in the body. It is our policy, and of many other authors, to ablate any thyroid residue with therapeutic doses of 131 1 (30-50 mCi). Metastases of well differentiated thyroid cancer (DTC) retain some differentiation function of the normal follicular cells, mainly iodine uptake and thyroglobulin (Tg) synthesis and secretion. These properties have been used to develop diagnostic tools - whole body scan (WBS) with 131 1 and serum Tg measurement for monitoring patients with DTC after thyroidectomy. This article will review the methodological and clinical problems associated with the follow-up of these patients. 1 WHOLE BODY SCAN Iodine uptake in metastatic thyroid cancer requires high stimulation of the cells by endogenous TSH to be visualized by scanning devices. Thus, patients must be rendered hypothyroid before performing WBS. The usual time required to induce sufficiently high levels of TSH is 45 days withdrawal for L-thyroxine (L-T4) and 15 days for L-triiodothyronine. Some authors have used administration of exogenous bovine TSH to promote 131 1 uptake from metastatic tissue, but this procedure has been abandoned because it may be associated with allergic reaction, neutralizing anti-TSH antibodies and because the efficiency with respect to endogenous TSH is much lower. Initial trials using recombinant TSH seem promising in inducing efficient levels of uptake in the tumor avoiding the unpleasant effect of hypothyroidism to the patient. The choice of the amount of 131 1 to be given as tracer dose for WBS has been a matter of controversy. Tracer doses as low as 0.2-0.5 mCi have been associated with too much falsely negative WBS. On the other hand, larger diagnostic doses of 131 1 activity may produce a sublethal radiation effect on the metastases which is enough to prevent subsequent uptake of the therapeutic 131 1 administration, but not enough to kill the cell. Based on these considerations, the optimal scanning dose of 131 1 is comprised between 2 and 5 mCi. SERUM TG MEASUREMENT The introduction of serum Tg measurement. some 20 years ago (1), has greatly enhanced the management of patients with DTC. After thyroidectomy there is a very good correlation between serum Tg concentrations and presence of persistent or recurrent disease. Residual thyroid tissue is associated with low-moderate levels of circulating Tg, while high Tg levels are almost invariably present in patients with well differentiated metastases from DTC. The higher Tg elevations are found in patients with lung or bone metastases, but also lymph node metastases express significant amount of serum Tg (2, 3). Tg secretion is under TSH control. SuppreSSion of endogenous TSH by L-T4 therapy decreases the levels of serum Tg with respect to off L-T4 values. However, even on L-T4, serum Tg levels remain detectable in the case of distant metastases, while may become undetectable in the case of node metastases. Thus, serum Tg results must be considered with caution in patients studied on L-T4 (4). CORRELATION BETWEEN SERUM TG AND WBS Usually, a good correlation is found between the results of serum Tg and those of WBS (5). Patients with positive WBS have almost invariably detectable Key-words.' Thyroid cancer, follow-up, thyroglohulin, whole body scan. Correspondence: Dr. F. Pacini, Istituto di Endocrinologia, Viale del Tirreno 64, 56018 Tirrenia, Pisa. Italy 165 Thyroid cancer follow-up levels of serum Tg, while negative WBS are often associated with undetectable serum Tg levels. However, the process of iodine uptake and that of TD secretion follow two different biological pathways, thus it is not rare to find metastases which have lost the ability to take up radioiodine without loosing the ability of secreting Tg (6). In a large study comparing the results of WBS with those of serum Tg we have found that negative WBS with detectable serum Tg is found in about 20% of the cases. These patients have thyroid residues or metastases with a low iodine avidity which are not detected by WBS performed with tracer doses of 131 1, but can be suspected on the basis of detectable serum Tg measurement. The repetition of WBS after the administration of therapeutic doses of 131 1 is able to localize the site of metastatic involvement in these patients (7). obtained every 6 months on L-T4 suppressive therapy. REFERENCES 1. Van Herle A.J., Uller R.P., Matthews N.L., Brown J. Radioimmunoassay for measurement of thyroglobulin in human serum. J. Clin. Invest. 521320,1973. 2. Pacini F., Pinchera A., Giani C, Grasso L., Doveri F., Baschieri L. Serum thyroglobulin in thyroid carcinoma and other thyroid disorders. J. Endocrinol. Invest. 3: 283, 1980. 3. Barsano C.P., Skosey C., de Groot L.J., et al. Serum thyroglobulin in the management of patients with thyroid cancer. Arch. Intern. Med. 142: 763,1982. 4. Pacini F, Lari R., Mazzeo S., Grasso L., Taddei D, Pinchera A. Diagnostic value of a single serum thyroglobulin determination on and off thyroid suppressive therapy in the follow-up of patients with differentiated thyroid cancer. Clin. Endocrinol. 23: 405,1985. CONCLUSION In summary, the protocol we recommend for monitoring patients with thyroid cancer is the following: WBS with 131 1 is performed 45 days after surgery (with 1 mCi as tracer dose), followed by radioiodine therapy (30-100 mCi) for ablation of thyroid residues. Further treatment consists of L-T4 therapy with a dose able to suppress endogenous TSH secretion. After 12 months, a second WBS using 5 mCi as tracer dose and measurement of serum Tg levels off L-T4 therapy is performed. Treatment with ;:::: 100 mCi is administered in case of positive WBS in the thyroid bed and/or metastases, regardless of the serum Tg values. In case of negative WBS and elevated Tg levels, therapy with 131 1 is administered and a post-therapeutic WBS is performed, usually 5-7 days after. In patients apparently free of disease (i.e. patients with negative WBS and undetectable serum Tg levels), further WBSs are repeated every 3-5 years, while positive patients are studied yearly. Serum Tg determinations are also 5. Ashcraft MW., Van Herle A.J. The comparative value of serum thyroglobulin measurements and iodine-131 total body scans in the follow up studies of patients with treated differentiated thyroid cancer. Am. J. Med. 71. 806, 1981. 6. Pacini F., Pinchera A., Giani C., Grasso L., Baschieri L. Serum thyroglobulin concentrations and 131-1 whole body scan in the diagnosis of metastases from differentiated thyroid carcinoma (after thyroidectomy). Clin. Endocrinol. (Oxf.) 13: 107,1980. 7. Pacini F., Lippi F., Formica N., Elisei R., Anelli S., Ceccarelli C., Pinchera A. Therapeutic doses of iodine 131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels. J. Nucl. Med. 28.'188,1987. 166