Thyroglobulin, calcitonin and CEA in thyroid cancer follow-up

What they measure. Thyroglobulin is the storage protein for thyroid hormone and is made only by thyroid follicular cells, normal or cancerous. After total thyroidectomy and radioactive iodine for papillary or follicular thyroid cancer, it should become undetectable; a measurable or rising level means residual or recurrent disease. Modern high-sensitivity assays make the old practice of stopping thyroid hormone to stimulate thyroglobulin unnecessary for most patients. Anti-thyroglobulin antibodies, present in about a quarter of patients, interfere with the assay and must be measured alongside it; a falling antibody titre is itself reassuring. Medullary thyroid cancer arises from C cells, which make calcitonin and often carcinoembryonic antigen (CEA); both are measured before surgery, at three to six months after, and then according to the result.

What changes. The American Thyroid Association guidelines set the response categories for differentiated thyroid cancer (excellent, indeterminate, biochemical incomplete, structural incomplete) largely from thyroglobulin, antibodies and neck ultrasound, and the category decides how intensive follow-up and thyroid hormone suppression should be; an excellent response allows follow-up to be relaxed to yearly and suppression to be eased. In medullary thyroid cancer, an undetectable post-operative calcitonin means cure in most cases; a raised level triggers imaging, and the doubling time of calcitonin and CEA (under six months is ominous, over two years reassuring) is the strongest predictor of survival and the usual trigger for starting a RET or multikinase inhibitor.

Caveats and cost. Thyroglobulin is uninformative before the thyroid is removed and in patients with remaining normal thyroid tissue; assays differ, so serial values should come from one laboratory. Calcitonin is also raised by kidney failure, proton pump inhibitors and other neuroendocrine tumours. Both tests cost a few pounds and are available in any hospital laboratory, and they are the reason most thyroid cancer follow-up needs no scans.