Long-term disease-free survival is uncommon in MTC, but the study data indicate that the majority of patients with MTC live for prolonged periods, despite biochemical evidence of persistent disease. Adverse pathological features such as extrathyroidal extension and vascular and perineural invasion were predictors of disease recurrence. The use of serum markers in the follow-up of patients with MTC must be interpreted within the clinical context.

Measurement of serum TSH-stimulated thyroglobulin (Tg) is recognized as a sensitive method for detecting residual/recurrent well-differentiated thyroid carcinoma (WDTC) in patients previously treated by surgery and radioactive iodine (RAI) ablation therapy. WDTC patients who have an undetectable serum Tg on thyroid hormone therapy (THT) in the absence of Tg-antibody interference are considered to be at low risk for residual/recurrent disease. Traditional management has been to withdraw T4 for 4-6 weeks or T3 for 2 weeks to stimulate endogenous TSH. However, this prolonged THT withdrawal induces hypothyroidism and its concomitant morbidity. In the present study, we assess the efficacy of shortening the time of T4 withdrawal to only 3 weeks for detecting residual/recurrent WDTC as a sufficient serum TSH stimulus for obtaining a positive serum Tg result without a routine diagnostic whole body scan (WBS). Additionally, we have evaluated the impact of such a T4 withdrawal interval on quality of life and loss of employment time. A total of 181 patients with WDTC selected for study had previously been treated with a bilateral surgical thyroidectomy followed by RAI ablation therapy (average post-surgery to follow-up interval of 10.8 yr). All of the cohort had an undetectable (< 1 microg/l) serum Tg on THT without Tg-antibody interference. Serum TSH and Tg were measured before and after cessation of T4 therapy for 3 weeks. A serum Tg > or = 2 microg/l was considered positive for residual/recurrent disease. A quality of life questionnaire [Short-Form 36 (SF-36)] was administered before withdrawal, at peak TSH and after resumption of therapy. From the completed SF-36 questionnaires, the overall degree of functional impairment was not severe and did not result in loss of employment time. Moreover, this protocol identified three possible responses to the 3-week T4 withdrawal interval as follows: a) serum Tg undetectable with TSH > or = 25 mIU/l (approximately 75% of total cohort); b) serum Tg > or = 2 microg/l (approximately 10% of total cohort) which will require further investigation and treatment for residual/recurrent disease; c) undetectable serum Tg with inadequate TSH rise (approximately 15% of total cohort), which will require TSH stimulation by either longer T4 withdrawal or recombinant human TSH to exclude residual disease. We conclude that a stimulated serum Tg test performed 3 weeks after T4 withdrawal is a simple and cost-effective first-line screening test with minimal morbidity which is sufficient to evaluate low-risk WDTC patients for recurrent/residual carcinoma.