Adverse effects of TSH suppression therapy are derived from the induced mild thyrotoxicosis, including cardiovascular and skeletal manifestations. Notably, elderly patients have a higher risk of cardiovascular side effects [18] such as atrial fibrillation, diastolic dysfunction, tachyarrhythmias, increased heart rate or increased left ventricular mass. Likewise, postmenopausal women are most susceptible for skeletal effects such as decreased mineral bone density and fractures [19].
Radioiodine Ablative Therapy
Radioactive iodine (RAI or radioiodine) therapy is based on the capacity of thyroid tissue to take up and retain iodine, specifically, radioiodine. This capacity is present but reduced in papillary and follicular cancer cells.
Radioiodine remnant ablation is performed after surgery, acting as adjuvant therapy by destroying remnant pathological or normal thyroid tissue. The destruction of normal thyroid tissue is useful as it increases the reliability of thyroglobulin testing and radioiodine scanning in the detection of recurrent or metastatic disease. Moreover, remnant ablation has been shown to prevent new thyroid neoplasias in high-risk patients (ie, those with history of radiation exposure). Radioiodine ablative therapy has been shown to reduce recurrence and cause-specific mortality [20] in certain subgroups; however, patients with low mortality risk do not seem to benefit from this therapy [21,22]. Its use is recommended in patients with distant metastases, tumors > 4 cm, or with extrathyroidal extension. It is also recommended for selected patients with tumors 1–4 cm who have high-risk features (such as lymph node involvement, history of radiation, or others previously mentioned) when there is an intermediate to high risk of recurrence or death from thyroid cancer [6]. Lymph node involvement can occur in up to 50% of cases [39] and normally responds to radioiodine therapy.
Since TSH increases radioiodine uptake by normal or pathological thyroid cells, TSH stimulation is required for radioiodine therapy. This can be done by endogenous TSH elevation or by recombinant human TSH (rhTSH). The former can be achieved by either stopping thyroxine 2 to 3 weeks prior to the remnant ablation, or by withdrawing thyroxine and switching to liothyronine for 2 to 3 weeks followed by a discontinuation of liothyronine for 2 weeks. Both approaches seem to produce the same incidence of hypothyroid symptoms [23]. Thyroxine therapy can be resumed 2 to 3 days after radioiodine ablative therapy. Recombinant human TSH can be used with equal efficacy in place of thyroxine withdrawal [24], with the advantage of not producing transitory hypothyroidism. It is especially recommended for patients who are unable to tolerate hypothyroidism or who cannot achieve an adequate TSH level. Short-term recurrence rates are similar in patients treated with rhTSH or thyroxine withdrawal [25].
In addition, a low-iodine diet for 1 or 2 weeks is recommended for patients undergoing radioiodine remnant ablation. The rationale is that a high-iodine diet or iodine exposure (ie, amiodarone treatment or intravenous contrast) can decrease radioiodine uptake by papillary cancer cells due to further dilution of radioactive iodine in an expanded endogenous non-radioactive iodine pool. Patients with suspected high iodine levels can be screened using spot urinary levels [26].