The principal aim of thyroid hormone replacement in patients with thyroid cancer is to maintain the TSH at a low and generally suppressed level for patients with larger tumors and more aggressive disease. Several studies clearly demonstrate that a suppressed TSH correlates with improved survival in patients with well differentiated (papillary and follicular) thyroid cancer Associations of Serum Thyrotropin Concentrations with Recurrence and Death in Differentiated Thyroid Cancer. J Clin Endocrinol Metab. 2007 Apr 10; [Epub ahead of print]. Conversely, among patients with thyroid nodules having surgery, the level of TSH correlates modestly with the likelihood of having a final diagnosis of thyroid cancer after surgery, as outlined in Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage J Clin Endocrinol Metab. 2008 Mar;93(3):809-14. There is however some randomized prospective trial data with 'lower risk' patients suggesting that TSH suppression may not give substantially different outcomes compared to not suppressing TSH in Japanese subjects without distant spread of thyroid cancer Does postoperative thyrotropin suppression therapy truly decrease recurrence in papillary thyroid carcinoma? A randomized controlled trial J Clin Endocrinol Metab. 2010 Oct;95(10):4576-83
Accordingly, many thyroid cancer patients will require doses of thyroid hormone that are often somewhat higher than those usually required simply to keep the TSH in the normal range in the patient being treated with hypothyroidism. Following radioactive iodine, L-thyroxine is started, often the next day, and a TSH and thyroglobulin are obtained about 4-6 weeks later to ensure that they are both low. Occasionally patients will also receive T3 (Cytomel) for a week or two after the radioactive iodine treatment. There have been no randomized studies to determine whether we should aim for a TSH that is undetectable, versus a TSH of 0.1 or 0.2, and the precise TSH target level should be a matter of discussion between physician and patient. This area remains a matter of debate and discussion in the endocrine community, as illustrated in J Clin Endocrinol Metab 1999 Dec;84(12):4549-53 Levothyroxine suppression of thyroglobulin in patients with differentiated thyroid carcinoma. There is no uniformly agreed upon range for TSH and thyroid hormone levels. Patients with a history of more aggressive/extensive thyroid cancer will likely be maintained on thyoxine levels with a goal of keeping the TSH levels undetectable or close to the lower limit of normal. Patients with smaller thyroid cancers who likely have very low risks of disease recurrence may find recommended levels of TSH close to the lower limit of normal, but not frankly suppressed. Patients are reminded that recommendations for precise thyroxine dosing are based on physician recommendations, but not on results on long term, outcome-based randomized clinical trials. The levels of TSH suppression and optimal thyroid hormone dosing will also depend on the patients age, and associated risk factors for both bone disease and heart disease. See Benefits of thyrotropin suppression versus the risks of adverse effects in differentiated thyroid cancer Thyroid. 2010 Feb;20(2):135-46 for a discussion of this issue.
A useful parameter that is helpful in guiding therapy is the thyroglobulin (Tg) level. If the Tg test is easily detectable when the TSH is 0.3, and falls to an undetectable level when the TSH is 0.1 or lower, this provides information regarding the sensitivity of remaining thyroid cells to TSH suppression.
At times, patients may have difficulty tolerating the doses of thyroid hormone required to keep the TSH suppressed. In these instances, the physician and patient should strive to achieve a level of TSH that keeps the patient healthy and symptom free, yet is not too high so as to engender concern about an increased risk of thyroid cancer recurrence.
If osteoporosis is a concern, then bone density may be measured at periodic intervals and standard measures of osteoporosis prevention and treatment (diet, exercise, smoking cessation, medications) should be considered.
Although a small study suggests that patients on long term thyroxine may exhibit modest abnormalities in parameters of arterial elasticity and left ventricular thickness as assessed by echocardiography, the clinical significance of these observations remains uncertain Long-term thyrotropin-suppressive therapy with levothyroxine impairs small and large artery elasticity and increases left ventricular mass in patients with thyroid carcinoma. Thyroid. 2006 Apr;16(4):381-6
What are the risks of thyroxine therapy that produces slightly higher than normal levels of thyroid hormone, and low levels of TSH?
The principal risks are a) more frequent heart irregularities, especially rapid and sometimes irregular heart beats and b) osteoporosis. Both of these risks are more evident in older individuals. The level of TSH suppression may also be associated with the degree of relative risk. Flynn and colleagues studied 17,684 subjects in Tayside Soctland who received treatment with thyroxine for any indication. The risks of developing cardiovascular disease, dysrhythmias, or fractures were increased for subjects with hypothyroidism (high TSH) or individuals with a completely suppressed undetectable TSH. Patients with a low TSH, in the 0.04-0.4 range, did not have an increased risk for any of these outcomes. See Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy J Clin Endocrinol Metab. 2010 Jan;95(1):186-93.
Is the dose of thyroxine based on body weight?
In general, there is a fairly good relationship between size and weight of an individual and their requirements for thyroxine. Some patients with significant obesity may exhibit abnormalities in the clearance and metabolism of thyroxine that may impact the specific dosing regimen Impaired Pharmacokinetics of Levothyroxine in Severely Obese Volunteers Thyroid. 2011 Mar 21. [Epub ahead of print]