Commentary: Is Stimulation of Thyroglobulin (Tg) Useful in Low-Risk Patients With Thyroid Carcinoma and Undetectable Tg on Thyroxin and Negative Neck Ultrasound?

Martin Schlumberger


Clin Endocrinol. 2005;62(2):119-120. 

The follow-up protocol of thyroid cancer patients after initial treatment with total thyroidectomy and radioiodine ablation has changed over the years. It was based first on the repeated use of X-rays and whole body scanning (WBS) with 131I and, since the end of the 1970s, on the combination of serum thyroglobulin (Tg) determination and of WBS obtained following withdrawal of thyroid hormone treatment. Recently, in low-risk patients, two consensus reports advocated during the first year of follow-up the combination of neck ultrasonography and of serum Tg determination obtained following injections of recombinant human TSH (rhTSH), without performing 131I WBS.[1,2] In routine practice, the high cost of rhTSH is largely balanced by the absence of hypothyroidism, the improvement of the quality of life and by the absence of impairment in the socio-professional life. In this issue of the Journal, Rosario and colleagues[3] advocated only a serum Tg determination during thyroid hormone treatment and a neck ultrasonography for the first control after initial treatment, but this simplification deserves discussion.

Current protocols of follow-up are being established according to risk group. Initially, patients at low risk of recurrent disease are those who have undergone a complete surgical excision of tumour foci, and who had a small tumour (T1 < 2 cm), without tumour extension beyond the thyroid capsule, without lymph node involvement and without distant metastases, and with a well-differentiated tumour histotype. In these patients, the risk of recurrence is 5% or even less, and follow-up should have a high negative predictive value to exclude from the risk the large majority of such patients.

Several studies have reported that low-risk patients with both undetectable serum Tg following TSH stimulation and negative neck ultrasonography have a risk of recurrence of less than 0·5% during the subsequent 10 years. In these studies, most patients were treated with replacement dosage of thyroxine.4-7 Furthermore, complete ablation of thyroid remnants was demonstrated in almost all patients, and is currently defined as an undetectable serum Tg following rhTSH with an absence of abnormality in the thyroid bed on ultrasonography. This finding has several consequences: first, it allows to completely reassure more than 85% of low-risk patients, who can resume a normal life and indeed this will produce substantial psychological benefits; second, the thyroxine dosage can be decreased to obtain a TSH level within the normal range, thus avoiding any side-effect of prolonged over-treatment on the heart and bones; third, the subsequent follow-up of these patients can be limited to yearly serum TSH and Tg determinations on thyroid hormone treatment, thus decreasing both the inconvenience for patients and its financial cost. The utility of any other testing (including another TSH stimulation test) in the absence of abnormalities is not demonstrated and indeed requires further studies. These findings were the basis for the two consensus reports cited above.[1,2]

The rationale for the proposal of Rosario and colleagues[3] is based on the fact that, in low-risk patients, recurrences are rare and mostly occur in neck lymph nodes and can be evidenced by neck ultrasonography. Furthermore, the infrequent distant metastases are usually announced by a detectable serum Tg level on thyroid hormone treatment. Indeed, the combination of serum Tg during thyroid hormone treatment and of neck ultrasonography has a low cost and can be easily performed in all centres, but has several drawbacks, because false negative results cannot be totally excluded. In fact, 10-15% of patients who had an undetectable serum Tg during thyroid hormone treatment, had a detectable serum Tg after TSH stimulation, obtained either following thyroid hormone withdrawal or with injections of rhTSH.3-7 In about 2/3 of them and in the absence of any further treatment, subsequent serum Tg obtained following TSH stimulation became undetectable, and these patients could then be considered at low risk. However, in the other patients it remained high or increased, and a recurrence occurred in the majority of these latter patients.[8,9] Thus, a detectable serum Tg at the first control obtained following TSH stimulation permits the individualization of the few patients who are at a higher risk of recurrence and who should be carefully followed with repeated TSH stimulation testings and with any useful tests until serum Tg negativates spontaneously or until a recurrence is evidenced. Indeed, this may take years to occur.

Because such patients do exist in all series, including in the series under discussion, patients cannot be totally reassured if serum Tg is obtained only during thyroid hormone treatment. This may lead to a delay in the diagnosis of recurrent disease that may decrease the chances of being cured, and in the other patients to prolonged treatment with suppressive doses of thyroxine and to repeated examinations for years, including neck ultrasonography. This is indeed useless in the majority of patients and may induce high cost, side-effects and anxiety. In particular, the repeated use of neck ultrasound in routine may lead to false positive findings that may indicate other expensive tests and have disastrous psychological effects.

Thus, at the present time, and until the long-term outcome of such patients followed up with this simplified protocol is determined, including the number of false negative patients, and until a socioeconomic study is produced, it may be both safer for these patients and more cost-effective for the medical system in general to continue to obtain a TSH stimulation during the first year of follow-up to ensure the cure in the majority of patients. To do this, the use of rhTSH is appropriate.

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