Clinical Endocrinology (1991). 35,519-520

Serum thyroglobulin measurements in thyroid cancer: evaluation of 'false' positive results E. G. Black and M. C. Sheppard Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK (Recelved3 June 1991; returned for revision 18 July 1991; finally revised 2 August 1991; accepted 20 August 1991)

Summary OBJECTIVE Serum thyroglobulin (Tg) should be undetectable in patients successfully treated for thyroid carcinoma. We have examined the course of disease in 19 patients with raised serum Tg ( > 5 pgll) on lnltlal measurement but no other evidence of residual, recurrent or metastatlc cancer. DESIGN 416 patients from several centres were followed for periods between 1 and 9 years. Serum Tg was measured at 6-12-month intervals. PATIENTS All had differentiated thyroid cancer, treated by partial or total thyroidectomyandlor '*'Iablatlon, and were receiving suppressive thyroxine therapy. MEASUREMENT Serum Tg was measured and clinical, Xray and scan assessment made of presenceor absence of residual, recurrent or metastatic cancer. RESULTS Of 416 patients initially assessed, only 19 had Tg>5 pgll but no clinical or radiological evidence of disease. At follow-up, 11 patients had developed overt with a signs of malignancy; one had been treated with lsrl subsequent fall In Tg; five had Tg between 5 and 20 pgll with Incompletely suppressed TSH levels; two subjects remainedwith slightly elevated Tg and undetectable TSH. CONCLUSION Patients with elevated Tg require careful follow-up even In the apparent absence of disease. Moderate elevation of serum Tg may be due to Inadequate thyroxine suppression therapy, assessed by detectable TSH values measured in a sensitive assay.

Thyroid malignancy is a rare condition (less than 0 5 % of new malignancies and less than 0.5% of cancer deaths in the UK) and the majority of patients have an excellent prognosis. It is important therefore to monitor treated patients in the most cost-effective way with least disruption of their activities. The only tumour marker of any value in patients with follicular or papillary thyroid cancer is the circulating Correspondence: Professor M. C. Sheppard, Department of Medicine, Queen Elizabeth Hospital, Birmingham B15 2TH, UK.

concentration of thyroglobulin (Tg); Tg synthesis in, and release from, normal thyroid tissue is under the control of thyroid stimulating hormone (TSH). The measurement of serum Tg is now widely accepted as a sensitive and specific alternative to radioiodine scans in the detection of residual, recurrent, or metastatic disease in patients with differentiated thyroid carcinoma, following apparent definitive therapy with thyroidectomy and/or ablative doses of radioiodine. A raised serum Tg concentration in the apparent absence of carcinoma may indicate small foci of disease which are undetectable by standard screening and X-ray techniques, inadequate suppression of Tg from residual normal thyroid tissue by thyroid hormone administration, or a misleading false positive result. We have evaluated the results of our long-term follow-up study of patients in whom we have measured serum Tg, to attempt to assign patients initially considered to have false positive results to one of these categories. Subjects and methods

We have published previously our analysis of the use of serum Tg in 416 patients with treated differentiated thyroid carcinoma followed for 6 months to 7 years (Black et al., 1987). Samples were analysed from a number of different centres and therefore investigation and clinical management varied considerably. At follow-up, presence of cancer was diagnosed by radioiodine scans, X-ray or clinical examination. All patients were assessed whilst taking thyroid hormone (usually thyroxine). Serum Tg was measured by a double-antibody radioimmunoassay (Black et af., 1981) regardless of the presence of endogenous anti-Tg antibodies, which we have shown to have no significant effect in the assay (Black & Hoffenberg, 1983). Serum Tg measurements were analysed according to the apparent absence or presence of residual, recurrent or metastatic cancer and divided into groups with Tg concentration less than or greater than 5 pg/L Overall correlation between serum Tg values and presence or absence of cancer was 96.5%. At initial assessment there were 19patients with serum Tg > 5 pg/l who were apparently free of thyroid cancer. Of these patients, 13 were female and six male, nine had papillary, eight follicular, and two mixed papillary and follicular cancers; 12 had undergone partial and seven total thyroidectomy, and 15 had received one or more ablative doses of I3II. They were followed for periods of 1-9 years. 519

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Clinical Endocrinology (1991) 35

Results

These 19 subjects can be divided into four groups: Group A, 11 patients in whom raised serum Tg values preceded diagnosis of tumour recurrence by 8 months to 3.5 years. Details of one such patient have been reported previously (Black et al., 1987). Group B, one patient who was treated with radioiodine on the basis of an elevated serum Tg value alone, which then fell, suggesting the presence of undetectable disease. Group C, five patients with serum Tg between 5 and 20 pg/l, but in whom serum TSH, as measured by assays with high sensitivity (lower limit of detection 0.1 mU/1), was not suppressed completely by thyroxine treatment. Increasing the thyroxine dose in one subject studied serially over 5years (Table 1) showed that once the TSH value had become suppressed, the serum Tg level fell below 5 pg/l. Group D, two patients in whom serum TSH was undetectable but with serum Tg ranging between 5 and 35 pg/l. Discussion

These results show the importance of careful follow-up of patients with elevated serum Tg concentrations but no

Table 1 Serum thyroglobulin, TSH and thyroid hormone

concentrations measured during a serial increase in thyroxine dosage, Group C, patient DW (36-year-old female)

Date 10 June 82 9 Dec 82 26 Jan 84 22 Jan 85 21 Jan 86 20 Jan 87

Thyroglobulin (/%/I)

TSH (mU/l)

6.1 6.3 5.6

1.o 1.5 1.6 1.6

Serum thyroglobulin measurements in thyroid cancer: evaluation of 'false' positive results.

Serum thyroglobulin (Tg) should be undetectable in patients successfully treated for thyroid carcinoma. We have examined the course of disease in 19 p...
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