Combined therapy with L-Thyroxine and L-Triiodothyronine compared to L-Thyroxine alone in the treatment of primary hypothyroidism
Tóm tắt
OBJECTIVE: The objective of this study was to compare various parameters in patients with hypothyroidism receiving either monotherapy with L-Thyroxine (L-T4) or combination therapy with L-T4 and L-Triiodothyronine (L-T3). DESIGN: We conducted a randomized, controlled trial in 36 premenopausal women with hypothyroidism. The patients were divided into two groups: Group A (n=20) received only L-T4, while Group B received the combination L-T4 and L-T3. The treatment period lasted for 6 months. RESULTS: At baseline, the various parameters examined did not differ in the two groups. No significant difference between monotherapy and combined therapy was demonstrated on TSH level, ECG monitoring, densitometry, or thyroid symptoms score. The lipid profile was better during combined treatment compared to L-T4 alone; in Group A during treatment with L-T4 the levels of cholesterol and Low Density Lipoprotein (LDL) Cholesterol were unchanged, while in group B total cholesterol and LDL decreased (p<0.05). The changes in osteocalcin levels did not differ in the two groups, whereas the levels of urine deoxypyridinoline at the end of therapy were higher in the group with combination therapy, compared to monotherapy. CONCLUSION: Compared with L-T4 alone, replacement therapy with the combination of L-T4+L-T3 shows favourable changes in serum lipid profile, but higher activation of bone resorption.
Tài liệu tham khảo
Clyde PW, Harari AE, Getka EJ, Shakir KM, 2003 Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. JAMA 290: 2952–2958.
Grozinsky-Glasberg S, Fraser A, Nahshoni E, Weizman A, Leibovici L, 2006 Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 91: 2592–2599.
Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ, Jr, 1999 Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med 340: 424–429.
Bunevicius R, Prange AJ, 2000 Mental improvement after replacement therapy with thyroxine plus triiodothyronine: relationship to cause of hypothyroidism. Int J Neuropsychopharmacol 3: 167–174.
Cassio A, Cacciari E, Cicognani A, et al, 2003 Treatment for congenital hypothyroidism: thyroxine alone or thyroxine plus triiodothyronine? Pediatrics 111: 1055–1060.
Levitt A, Silverberg J, 2002 T4 plus T3 treatment for hypothyroidism: a double-blind comparison with usual T4. 74th Annual Meeting of the American Thyroid Association, Los Angeles, California, October 10–13.
Sawka AM, Gerstein HC, Marriott MJ, MacQueen GM, Gernstein HC, 2003 Does a combination regimen of thyroxine (T4) and 3,5,3′-triiodothyronine improve depressive symptoms better than T4 alone in patients with hypothyroidism? Results of a double-blind, randomized, controlled trial. J Clin Endo crinol Metab 88: 4551–4555.
Siegmund W, Spieker K, Weike AI, et al, 2004 Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14:1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism. Clin Endocrinol (Oxf). 60: 750–757.
Walsh JP, Shiels L, Lim EM, et al, 2003 Combined thyroxine/liothyronine treatment does not improve well-being, quality of life, or cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism. J Clin Endocrinol Metab 88: 4543–4550.
Fadeyev VV, Morgunova TB, Sytch JP, Melnichenko GA, 2005 TSH and thyroid hormones concentrations in patients with hypothyroidism receiving replacement therapy with L-thyroxine alone or in combination with L-triiodothyronine. Hormones (Athens) 4: 101–107.
Cappola AR, Ladenson PW, 2003 Hypothyroidism and Atherosclerosis. J Clin Endocrinol Metab 88: 2438–2444.
Saravanan P, Simmons DJ, Greenwood R, Peters TJ, Dayan CM, 2005 Partial Substitution of Thyroxine (T4) with Tri-Iodothyronine in Patients on T4 Replacement Therapy: Results of a Large Community-Based Randomized Controlled Trial. J Clin Endocrinol Metab 90: 805–812.
Klein I, Ojamaa K, 2001 Thyroid hormone and the cardiovascular system. N Engl J Med 344: 501–509.
Wieshammer S, Keck FS, Waitzinger J, et al, 1989 Acute hypothyroidism slows the rate of left ventricular diastolic relaxation. Can J Physiol Pharmacol 67:1007–1010.
Crowley WF Jr, Ridgway EC, Bough EW, et al, 1997 Noninvasive evaluation of cardiac function in hypothyroidism: response to gradual thyroxine replacement. N Engl J Med 296: 1–6.
Uzzan B, Campos J, Cucherat M, Nony P, Boissel JP, Perret GY, 1996 Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis. J Clin Endocrinol Metab 81: 4278–4289.
Duntas LH, 2005 Reassessment of combined LT4 and LT3 treatment for hypothyroidism: the prospects for slow-release T3 preparations. Hormones (Athens) 4:108-110.
Hennemann G, Docter R, Visser TJ, Postema PT, Krenning EP, 2004 Thyroxine plus low-dose, slow-release triiodothyronine replacement in hypothyroidism: Proof of principle. Thyroid 14: 271–275.
Wiersinga WM, 2009 Do we need still more trials on T4 and T3 combination therapy in hypothyroidism? Eur J Endocrinol 161: 955–959.
Escobar-Morreale HF, Botella-Carretero JI, Gomez-Bueno M, Galán JM, Barrios V, Sancho J, 2005 Thyroid Hormone Replacement Therapy in Primary Hypothyroidism: A Randomized Trial Comparing L-Thyroxine plus Liothyronine with L-Thyroxine Alone. Ann Intern Med 142: 412–424.
Nygaard B, Jensen EW, Kvetny J, et al, 2009 Effect of combination therapy with thyroxine (T4) and 3,5,3′-trii-odothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomized cross-over study. Eur J Endocrinol 161: 895–902.
Appelhof B, Fliers E, Wekking EM, et al, 2005 Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial. J Clin Endocrinol Metab 90: 2666–2674.