Effects of Long-term Combination LT4 and LT3 Therapy for Improving Hypothyroidism and Overall Quality of Life

Anam Tariq, DO; Yijin Wert, MS; Pramil Cheriyath, MD; Renu Joshi, MD


South Med J. 2018;111(6):363-369. 

In This Article


Of the 100 patients with a mean age of 54 years (range 20–81 years), 95 were women and 5 were men (57 women and 3 men receiving DTE and 38 women and 2 men receiving LT4/LT3). Six patients were excluded because they had ceased therapy. Discontinuation of DTE was caused by pregnancy, minimal hyperthyroid adverse effects, and lack of improvement with continued signs and symptoms of hypothyroidism. Discontinuation of LT4/LT3 therapy was caused by adverse effects, preference, and being lost to follow-up.

The mean follow-up duration was 27 months (range 1–111 months, median 22 months). Only 1 patient had a range of 111 months duration because she had come to the clinic while undergoing combination therapy after failing LT4 monotherapy for several years. The average dose of DTE was 30 mg. The average LT4/LT3 dose was 75 μg/5 μg to obtain physiologic thyroid levels. Fifty-two percent had Hashimoto disease, 22% had surgical hypothyroidism, 10% had ablation for either Graves disease or thyroid cancer, and 16% had miscellaneous etiologies.

Baseline laboratory values for 25[OH]D on LT4 monotherapy were normal in 69% of the DTE population and in 75% of the LT4/LT3 population. For patients with abnormal 25[OH]D levels, appropriate treatment was provided with supplementation per AACE guidelines to levels >30 ng/mL before starting on combination therapy.

The Table compares thyroid function tests between LT4 monotherapy and combination therapies, natural and synthetic. The average TSH remained normal in 89.47% after LT4/LT3 compared with monotherapy alone (P < 0.05), and the average FT3 remained normal in 90% compared with monotherapy (P < 0.05). The average FT4 remained normal in 92.5% after LT4/LT3 compared with LT4 (P > 0.05).

For the DTE population, the average TSH postextract remained normal in 96.49% of patients (P < 0.05). The average FT3 remained normal in 93.62% (P < 0.005). The average FT4 remained normal in 96.49% of patients (P > 0.05).

Although some patients undergoing either combination therapy had abnormal TSH for a short duration, the data were not statistically significant (P > 0.05). The ones who had abnormally low TSH were the patients with thyroid cancer requiring a lower TSH.

Neither natural nor synthetic therapies produced higher TSH levels than the normal values. None of the patients with low TSH or high FT4 and FT3 were hospitalized for adverse effects or arrhythmias. We also compared natural therapy with synthetic therapy and did not find one to be of a better value with TSH, FT3, and FT4.

Fifty-one patients receiving DTE and 26 patients receiving LT4/LT3 participated in the SF-20 questionnaire; 92% of patients receiving DTE and 100% of patients receiving LT4/LT3 answered feeling "excellent, very good, or good" when questioned about self-health; in addition, 80% to 100% on both FT3 therapies were not limited at all in their daily activities (ie, eating, dressing, bathing, carrying groceries, climbing stairs, running, walking, strenuous sports, housework). More than 70% receiving either DTE or LT4/LT3 reported being as "healthy as anybody [they knew]" (Figure). On DTE, 86.8% reported "feeling calm and peaceful," and 88.2% reported "being a happy person." With LT4/LT3, 76.9% reported "feeling calm and peaceful," and 92.31% reported "being a happy person." Approximately 84.6% receiving LT4/LT3 and 100% receiving DTE denied any sense of "hopelessness."


Survey results of the combination therapies. SF-20 Questions, Medical Outcomes Study Short Form-20 questionnaire.