Twenty-four Hour Hormone Profiles of TSH, Free T3 and Free T4 in Hypothyroid Patients on Combined T3/T4 Therapy

Abstract

The benefits of using thyroxine (T4) plus triiodothyronine (T3) in combination in thyroid hormone replacement are unproven but many individuals continue to be treated with this regime. When T3 is used alone for hypothyroidism, it results in wide fluctuations of thyroid hormone levels. However, only limited data exists on combined T3/T4 therapy. In this study, we have compared 24-hour profiles of thyroid stimulating hormone (TSH), free T4 (fT4) and free T3 (fT3) and cardiovascular parameters in 10 hypothyroid patients who had been on once daily combined T3/T4 therapy for more than 3 months with 10 patients on T4 alone. Twenty patients, who were part of a larger study, investigating the long-term benefits of combined T3/T4 therapy, were recruited into this sub-study. Over 24-hours, 12 samples were taken for thyroid hormones. Their 24-hour pulse and BP is also monitored on a separate occasion. On T4 alone, a modest 16% rise in fT4 with no change in fT3 was seen in the first 4-hours post-dose. In contrast, on combined treatment, fT3 levels showed a marked rise of 42% within the first 4-hours post-dose (T3/T4:T4=6.24: 4.63 mU/L, p<0.001). Mean exposure to fT3 calculated by area under the curve (AUC) was higher (T3/T4:T4=1148:1062, p<0.0001) on T3. Circadian rhythm of TSH was maintained on both treatments. No difference in pulse or blood pressure over the 24-hours was seen between the groups. Our data suggests that despite chronic combined T3/T4 therapy, wide peak-to-trough variation in fT3 levels persists. Although no immediate cardiovascular effects were seen, the long-term consequences for patients on combined therapy are unknown.

Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study

“…Whereas a previous study showed that LT4 monotherapy leads to no change in serum free T3 in the first 4 hours post-dose, LT4/LT3 therapy can determine a marked rise by 42% in serum free T3 within the first 4 hours after ingestion of LT4/LT3 (27). This acute rise can cause hyperthyroid symptoms that were not detected by our adapted HRQOL questionnaire.…”

“…Excessive doses of LT4/ LT3 may contribute to increases in resting heart rate (27), bone remodeling markers (24,(28)(29)(30) and serum aminotransferases (30), leading to clinical manifestations of hyperthyroidism (31). In our study, we observed a borderline significant increase in heart rate by 3 beats/minute, which did not lead to adverse events.…”

2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

“…Whereas during L-T4 monotherapy no change in serum free T3 is seen in the first four hours post-dose, during L-T4 + L-T3 combination therapy a marked rise of 42% in serum free T3 has been observed within the first 4 h after ingestion of L-T3 [66]. The increase of serum free T3 may provoke cardiac arrhythmias in susceptible patients.…”

MECHANISMS IN ENDOCRINOLOGY: Impact of isolated TSH levels in and out of normal range on different tissues

“…The finding that intermittent TSH application promotes bone formation in patients supports the hypothesis that a certain extent of fluctuations in TSH levels might be essential for normal bone physiology (53). In hypothyroid patients under therapy with T 3 , T 4 , or T 3 /T 4 aiming to achieve euthyroidism, absolute TSH levels and circadian variations were reduced but not absent (37,54,55). However, loss of response to thyrotropin-releasing hormone (TRH) was observed in almost all TC patients treated with thyroid hormone for suppression of TSH levels (56,57).…”