Background Patients with hypothyroidism are usually treatedwith thyroxine (levothyroxine) only, although both thyroxineand triiodothyronine are secreted by the normal thyroid gland.Whether thyroid secretion of triiodothyronine is physiologicallyimportant is unknown.
Methods We compared the effects of thyroxine alone with thoseof thyroxine plus triiodothyronine (liothyronine) in 33 patientswith hypothyroidism. Each patient was studied for two five-weekperiods. During one period, the patient received his or herusual dose of thyroxine. During the other, the patient receiveda regimen in which 50 µg of the usual dose of thyroxinewas replaced by 12.5 µg of triiodothyronine. The orderin which each patient received the two treatments was randomized.Biochemical, physiologic, and psychological tests were performedat the end of each treatment period.
Results The patients had lower serum free and total thyroxineconcentrations and higher serum total triiodothyronine concentrationsafter treatment with thyroxine plus triiodothyronine than afterthyroxine alone, whereas the serum thyrotropin concentrationswere similar after both treatments. Among 17 scores on testsof cognitive performance and assessments of mood, 6 were betteror closer to normal after treatment with thyroxine plus triiodothyronine.Similarly, among 15 visual-analogue scales used to indicatemood and physical status, the results for 10 were significantlybetter after treatment with thyroxine plus triiodothyronine.The pulse rate and serum sex hormonebinding globulinconcentrations were slightly higher after treatment with thyroxineplus triiodothyronine, but blood pressure, serum lipid concentrations,and the results of neurophysiologic tests were similar afterthe two treatments.
Conclusions In patients with hypothyroidism, partial substitutionof triiodothyronine for thyroxine may improve mood and neuropsychologicalfunction; this finding suggests a specific effect of the triiodothyroninenormally secreted by the thyroid gland.
Source Information
From the Institute of Endocrinology, Kaunas Medical University, Kaunas, Lithuania (R.B., G.K., R.Z.); and the Department of Psychiatry, School of Medicine, University of North Carolina, Chapel Hill (A.J.P.).
Address reprint requests to Dr. Prange at the Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Campus Box 7160, Room 254, Wing D Medical School, Chapel Hill, NC 27599-7160.
Jonklaas, J., Davidson, B., Bhagat, S., Soldin, S. J.
(2008). Triiodothyronine Levels in Athyreotic Individuals During Levothyroxine Therapy. JAMA
299: 769-777
[Abstract][Full Text]
Cooper, D. S.
(2008). Thyroxine Monotherapy After Thyroidectomy: Coming Full Circle. JAMA
299: 817-819
[Full Text]
Slawik, M., Klawitter, B., Meiser, E., Schories, M., Zwermann, O., Borm, K., Peper, M., Lubrich, B., Hug, M. J., Nauck, M., Olschewski, M., Beuschlein, F., Reincke, M.
(2007). Thyroid Hormone Replacement for Central Hypothyroidism: A Randomized Controlled Trial Comparing Two Doses of Thyroxine (T4) with a Combination of T4 and Triiodothyronine. J. Clin. Endocrinol. Metab.
92: 4115-4122
[Abstract][Full Text]
Joffe, R. T., Brimacombe, M., Levitt, A. J., Stagnaro-Green, A.
(2007). Treatment of Clinical Hypothyroidism With Thyroxine and Triiodothyronine: A Literature Review and Metaanalysis. Psychosomatics
48: 379-384
[Abstract][Full Text]
Cooper-Kazaz, R., Apter, J. T., Cohen, R., Karagichev, L., Muhammed-Moussa, S., Grupper, D., Drori, T., Newman, M. E., Sackeim, H. A., Glaser, B., Lerer, B.
(2007). Combined Treatment With Sertraline and Liothyronine in Major Depression: A Randomized, Double-blind, Placebo-Controlled Trial. Arch Gen Psychiatry
64: 679-688
[Abstract][Full Text]
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
[Abstract][Full Text]
Wekking, E. M, Appelhof, B. C, Fliers, E., Schene, A. H, Huyser, J., Tijssen, J. G P, Wiersinga, W. M
(2005). Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism. Eur J Endocrinol
153: 747-753
[Abstract][Full Text]
Eisinger, J.
(2005). L-Thyroxine plus Liothyronine in Hypothyroidism. ANN INTERN MED
143: 543-543
[Full Text]
Escobar-Morreale, H. F., Botella-Carretero, J. I., del Rey, F. E., de Escobar, G. M.
(2005). Treatment of Hypothyroidism with Combinations of Levothyroxine plus Liothyronine. J. Clin. Endocrinol. Metab.
90: 4946-4954
[Abstract][Full Text]
Appelhof, B. C., Fliers, E., Wekking, E. M., Schene, A. H., Huyser, J., Tijssen, J. G. P., Endert, E., van Weert, H. C. P. M., Wiersinga, W. M.
(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
[Abstract][Full Text]
Escobar-Morreale, H. F., Botella-Carretero, J. I., Gomez-Bueno, M., Galan, J. M., 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
[Abstract][Full Text]
Saravanan, P., Simmons, D. J., Greenwood, R., Peters, T. J., Dayan, C. M.
(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
[Abstract][Full Text]
JOFFE, R. T., SAWKA, A. M., MARRIOTT, M. J., MACQUEEN, G. M., GERNSTEIN, H. C.
(2004). Does Substitution of T4 with T3 Plus T4 for T4 Replacement Improve Depressive Symptoms in Patients with Hypothyroidism?. Ann. N. Y. Acad. Sci.
1032: 287-288
[Abstract][Full Text]
(2004). Thyroid Disorders and Women's Health. JWatch Women's Health
2004: 3-3
[Full Text]
Burger, A. G.
(2004). Environment and Thyroid Function. J. Clin. Endocrinol. Metab.
89: 1526-1528
[Full Text]
Blanchard, K. R.
(2004). Dosage Recommendations for Combination Regimen of Thyroxine and 3,5,3'-Triiodothyronine. J. Clin. Endocrinol. Metab.
89: 1486-1487
[Full Text]
Clyde, P. W., Harari, A. E., Getka, E. J., Shakir, K. M. M.
(2003). Combined Levothyroxine Plus Liothyronine Compared With Levothyroxine Alone in Primary Hypothyroidism: A Randomized Controlled Trial. JAMA
290: 2952-2958
[Abstract][Full Text]
Cooper, D. S.
(2003). Combined T4 and T3 Therapy--Back to the Drawing Board. JAMA
290: 3002-3004
[Full Text]
Kaplan, M. M., Sarne, D. H., Schneider, A. B.
(2003). In Search of the Impossible Dream? Thyroid Hormone Replacement Therapy That Treats All Symptoms in All Hypothyroid Patients. J. Clin. Endocrinol. Metab.
88: 4540-4542
[Full Text]
Walsh, J. P., Shiels, L., Lim, E. M., Bhagat, C. I., Ward, L. C., Stuckey, B. G. A., Dhaliwal, S. S., Chew, G. T., Bhagat, M. C., Cussons, A. J.
(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
[Abstract][Full Text]
Sawka, A. M., Gerstein, H. C., Marriott, M. J., MacQueen, G. M., Joffe, R. T.
(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. Endocrinol. Metab.
88: 4551-4555
[Abstract][Full Text]
Cassio, A., Cacciari, E., Cicognani, A., Damiani, G., Missiroli, G., Corbelli, E., Balsamo, A., Bal, M., Gualandi, S.
(2003). Treatment for Congenital Hypothyroidism: Thyroxine Alone or Thyroxine Plus Triiodothyronine?. Pediatrics
111: 1055-1060
[Abstract][Full Text]
Toft, A. D, Beckett, G. J
(2003). Thyroid function tests and hypothyroidism. BMJ
326: 295-296
[Full Text]
Hindmarsh, P C
(2002). Optimisation of thyroxine dose in congenital hypothyroidism. Arch. Dis. Child.
86: 73-75
[Full Text]
PEARL, P. L., WEISS, R. E., STEIN, M. A.
(2001). Medical Mimics: Medical and Neurological Conditions Simulating ADHD. Ann. N. Y. Acad. Sci.
931: 97-112
[Abstract][Full Text]
Reed, H. L., Reedy, K. R., Palinkas, L. A., Van Do, N., Finney, N. S., Case, H. S., LeMar, H. J., Wright, J., Thomas, J.
(2001). Impairment in Cognitive and Exercise Performance during Prolonged Antarctic Residence: Effect of Thyroxine Supplementation in the Polar Triiodothyronine Syndrome. J. Clin. Endocrinol. Metab.
86: 110-116
[Abstract][Full Text]
Berga, S. L.
(2001). Systemic Benefits of Cyclic Ovarian Function. Reproductive Sciences
8: S3-S6
[Abstract]
Woeber, K. A.
(1999). The Year in Review: The Thyroid. ANN INTERN MED
131: 959-962
[Abstract][Full Text]
(1999). Should We Treat Hypothyroidism with Thyroxine Plus T3?. Journal Watch Dermatology
1999: 17-17
[Full Text]
(1999). Should We Treat Hypothyroidism with Thyroxine Plus T3?. JWatch General
1999: 6-6
[Full Text]
Toft, A. D.
(1999). Thyroid Hormone Replacement -- One Hormone or Two?. NEJM
340: 468-470
[Full Text]