The standard approach to differentiated thyroid cancer (ie, papillary and follicular) is to perform a total thyroidectomy and then treat the patient with radioactive iodine (131-I). Periodic monitoring is performed by use of history and physical examination in conjunction with serum thyroglobulin levels and occasional radioisotope scans and, perhaps, neck sonograms. The most important laboratory test to follow is the serum thyroglobulin level. Of course, following surgery and 131-I therapy, there should be very little, if any, residual thyroid tissue and, as a result, the thyroglobulin level should be less than 1 ng/mL. However, the recent availability of recombinant human TSH (rhTSH) has allowed the possibility of detecting very small amounts of residual thyroid tissue. In practice, following rhTSH injection, residual thyroid tissue (benign or malignant) is stimulated to produce thyroglobulin.
Powell and colleagues studied this issue in patients with differentiated thyroid cancer. They identified 31 patients who had undetectable basal thyroglobulin levels (< 0.5 ng/mL) while taking levothyroxine suppression. Only 5 of these 31 patients had a serum thyroglobulin level that rose to greater than 2 ng/mL following stimulation with rhTSH. Only 1 patient was found to have both an elevated rhTSH stimulated thyroglobulin level and neck uptake on a radioisotope scan. After a mean follow-up period of 21 months, none of these 31 patients have had definite radiologic evidence of recurrent disease. These authors concluded that in this clinical context, the utility of rhTSH-stimulated thyroglobulin level was of questionable clinical utility.
This study is of interest, but the conclusion is somewhat controversial. It does appear that these 31 patients had a relatively good course with no apparent evidence of disease recurrence. In particular, the 5 patients with elevated rhTSH-stimulated thyroglobulin levels have not yet shown evidence of recurrent or persistent disease. The problem is, of course, that perhaps the rhTSH-stimulated thyroglobulin levels are more sensitive than other detection techniques such as sonograms and radioisotope scans. In any case, it can be argued that even if rhTSH-stimulated thyroglobulin levels were actually detecting residual disease, in this study, it does appear that it was predicting significant clinical disease.
Robbins and colleagues came to a different conclusion. They tested the hypothesis that the serum thyroglobulin level following rhTSH stimulation was a more sensitive indicator of residual thyroid disease than is a thyroglobulin level drawn during levothyroxine suppression. They analyzed 364 patients with differentiated thyroid cancer. Residual thyroid cancer was identified in 18% of subjects with a serum thyroglobulin less than 0.6 ng/mL when drawn while taking levothyroxine. Eighty-eight percent of patients who had a thyroglobulin level (drawn on levothyroxine suppression) between 3 and 8 ng/mL had thyroid cancer, and 100% of patients with a serum thyroglobulin level greater than 7 ng/mL had thyroid cancer. By contrast, only 6% of subjects with an rhTSH-stimulated thyroglobulin less than 0.6 ng/mL had residual thyroid cancer. All patients with an rhTSH-stimulated thyroglobulin level greater than 10 ng/mL had residual disease. Statistical analysis showed that the stimulated thyroglobulin was significantly more accurate than the thyroglobulin taken while on suppression, especially for thyroglobulin concentrations below 2 ng/mL. These authors concluded that it is preferable to perform an rhTSH-stimulated thyroglobulin rather than simply measuring thyroglobulin while taking levothyroxine.
These studies by Powell and Robbins and their colleagues arrived at different conclusions. The Powell study indicated that rhTSH-stimulated thyroglobulin levels are not that clinically useful in detecting residual thyroid cancer compared with thyroglobulin levels drawn while taking levothyroxine. The Robbins study suggests that rhTSH thyroglobulin levels are more accurate and sensitive. Further studies in this area are needed, and it would be important to evaluate the complete articles when they appear to better examine precisely how each group identified residual thyroid cancer other than by the changes in thyroglobulin levels.
RhTSH, as noted above, can be utilized to assess for residual thyroid disease in selected patients who have previously had a thyroidectomy and radioiodine therapy. The precise clinical usefulness of rhTSH is being examined with regard to sensitivity and specificity compared with a standard levothyroxine withdrawal scan and thyroglobulin measurement. RhTSH is thought to be a very safe and well-tolerated agent. Biondi and colleagues performed 24-hour Holter EKG monitoring and Doppler echocardiography before and after rhTSH administration in 11 patients on chronic levothyroxine suppression. They found no significant changes in average heart rate or prevalence of atrial and/or ventricular premature beats. There were also no significant changes in left ventricular morphology and systolic or diastolic function. Arterial blood pressure was slightly reduced with rhTSH administration (systolic arterial pressure 125 vs 120, P = .077; diastolic arterial pressure 83 vs 78, P = .053). However, these mild changes were not associated with clinical symptoms. The authors concluded that rhTSH is safe and well tolerated from a vascular standpoint. Previous studies, as well as large-scale clinical experience, have confirmed that rhTSH is very well tolerated, with only a small percentage of patients noting transient dizziness or malaise.
Medscape Diabetes. 2003;5(1) © 2003 Medscape
Cite this: Kenneth D Burman. Highlights of the 74th Annual Meeting of the American Thyroid Association - Medscape - Feb 06, 2003.