Three-week thyroxine withdrawal thyroglobulin stimulation screening test to detect low-risk residual/recurrent well-differentiated thyroid carcinoma

Abstract

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.

Influence of age and primary tumor size on the risk for residual/recurrent well‐differentiated thyroid carcinoma

“…This is justified by the fact that stimulated thyroglobulin measurements have been shown to be highly sensitive and specific in detecting disease among patients who have undergone total or near-total thyroidectomy and radioactive remnant ablation. 25,[38][39][40] Though early stimulated thyroglobulin measurements may become undetectable with longer follow-up in the absence of therapy, 41,42 we believe that a steady-state titer was attained considering 85% of patients had a stimulated test greater than 1 year after surgery and that the mean time to the stimulated test was 5.8 years after radioactive remnant ablation.…”

“…Patients with undetectable thyroglobulin measurements while on thyroxine suppression therapy (<1 lg/L) underwent periodic follow-up measurements of stimulated thyroglobulin (after a 21 or 22 day period of withdrawal from L-thyroxine). 25 A positive stimulated thyroglobulin at follow-up was defined by a value !2 lg/L, in the absence of anti-thyroglobulin antibodies. For those patients who had detectable thyroglobulin measurements while on thyroxine suppression therapy, follow-up stimulated thyroglobulin measurements were obtained prior to repeat radioactive iodine therapy (after a minimum two weeks of tri-iodothyronine withdrawal).…”

Recommendations of the Latin American Thyroid Society on diagnosis and management of differentiated thyroid cancer

“…High TSH levels can be achieved after three to four weeks of thyroid hormone withdrawal. A TSH level higher than 30 mUI/mL is usually required (50,51). Another option is the administration of rhTSH (0.9 mg intramuscularly) for two consecutive days, followed by 131 I on the third day.…”

Five-year longitudinal evaluation of quality of life in a cohort of patients with differentiated thyroid carcinoma

“…Cancer rehabilitation involves improving psychological symptoms and the perception of restored well-being after or during treatment (Crevenna et al, 2003). QoL has been extensively evaluated in DTC subjects independently of the cognitive and jobrelated disturbances brought about by changes in circulating thyroid hormone levels for diagnostic and therapeutic purposes (Dow et al, 1997;BotellaCarretero et al, 2003;Golger et al, 2003). More recently, the clinical benefits of the use of recombinant human thyroid-stimulating hormone (TSH), versus thyroid hormone withdrawal, on the preservation of QoL have been demonstrated (Schroeder et al, 2006;Taïeb et al, 2009;Lee et al, 2010).…”