Combination Treatment with T4 and T3: Toward Personalized Replacement Therapy in Hypothyroidism?

Biondi, Bernadette; Wartofsky, Leonard

doi:10.1210/jc.2011-3399

Cited by 125Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryHormonal and reproductive studies

Combination Treatment with T4 and T3: Toward Personalized Replacement Therapy in Hypothyroidism?

Biondi, Bernadette, Wartofsky, Leonard·2012·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2011-3399

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Abstract

Context Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic. Evidence acquisition We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action. Evidence synthesis The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in…

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European guidelines and a narrative review suggested that therapy combining LT4 and LT3 could be considered under certain specific circumstances.
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From Short-Term Time Trends in Prescribing Therapy for Hypothyroidism: Results of a Survey of American Thyroid Association Members (2019) · cites this paper as [3]

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Gumieniak, O., Perlstein, T. S., Williams, J. S., Hopkins, P. N., Brown, N. J., Raby, B. A., & Williams, G. H. (2007) · Hypertension · doi:10.1161/01.hyp.0000256295.72185.fd · Cited by 84 · see citing works
Substitution of Liothyronine at a 1:5 Ratio for a Portion of Levothyroxine: Effect on Fatigue, Symptoms of Depression, and Working Memory Versus Treatment With Levothyroxine Alone
Rodriguez, T., Lavis, V. R., Meininger, J. C., Kapadia, A. S., & Stafford, L. F. (2005) · Endocrine Practice · doi:10.4158/ep.11.4.223 · Cited by 80 · see citing works
Mental improvement after replacement therapy with thyroxine plus triiodothyronine: relationship to cause of hypothyroidism
Bunevičius, R., & Prange, A. J. (2000) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145700001826 · Cited by 78 · see citing works
Are Autoimmune Thyroid Dysfunction and Depression Related?
Pop, V. J. (1998) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.9.3194 · Cited by 76 · see citing works
Hypothyroidism and Thyroid Substitution: Historical Aspects
Lindholm, J., & Laurberg, P. (2011) · Journal of Thyroid Research · doi:10.4061/2011/809341 · Cited by 70 · see citing works
Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations
Woeber, K. A. (2002) · Journal of Endocrinological Investigation · doi:10.1007/bf03343972 · Cited by 67 · see citing works
The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized, double blind, cross‐over study in thyroidectomized patients
Celi, F. S., Zemskova, M., Linderman, J. D., Babar, N. I., Skarulis, M. C., Csako, G., Wesley, R., Costello, R., Penzak, S. R., & Pucino, F. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03700.x · Cited by 65 · see citing works
The Thr92Ala 5′ Type 2 Deiodinase Gene Polymorphism Is Associated with a Delayed Triiodothyronine Secretion in Response to the Thyrotropin-Releasing Hormone–Stimulation Test: A Pharmacogenomic Study
Butler, P. W., Smith, S. M., Linderman, J. D., Brychta, R. J., Alberobello, A. T., Dubaz, O. M., Luzon, J. A., Skarulis, M. C., Cochran, C. S., WESLEY, R. A., et al. (2010) · Thyroid · doi:10.1089/thy.2010.0244 · Cited by 60 · see citing works
A Polymorphism in Type I Deiodinase Is Associated with Circulating Free Insulin-Like Growth Factor I Levels and Body Composition in Humans
Peeters, R. P., van den Beld, A. W., van Toor, H., Uitterlinden, A. G., Janssen, J. A. M. J. L., Lamberts, S. W. J., & Visser, T. J. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1301 · Cited by 60 · see citing works
Treatment of clinical hypothyroidism with thyroxine and triiodothyronine: a literature review and metaanalysis
Joffe, R. T., Brimacombe, M., Levitt, A. J., & Stagnaro-Green, A. (2007) · Psychosomatics · doi:10.1176/appi.psy.48.5.379 · Cited by 57 · see citing works
Fractures in Patients with Primary Idiopathic Hypothyroidism
Vestergaard, P., Weeke, J., Hoeck, H. C., Nielsen, H. K., Rungby, J., Rejnmark, L., Laurberg, P., & Mosekilde, L. (2000) · Thyroid® · doi:10.1089/thy.2000.10.335 · Cited by 57 · see citing works
The Hypothalamic-Pituitary-Thyroid Axis
Carlson, H. E., & Hershman, J. M. (1975) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)31955-1 · Cited by 53 · see citing works
Thr92Ala polymorphism in the type 2 deiodinase is not associated with T4 dose in athyroid patients or patients with Hashimoto thyroiditis
Heemstra, K. A., Hoftijzer, H. C., Van Der Deure, W. M., Peeters, R. P., Fliers, E., Appelhof, B. C., Wiersinga, W. M., Corssmit, E. P. M., Visser, T. J., & Smit, J. W. A. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03474.x · Cited by 51 · see citing works
Subclinical Hyperthyroidism -- Just a Low Serum Thyrotropin Concentration, or Something More?
Utiger, R. D. (1994) · New England Journal of Medicine · doi:10.1056/nejm199411103311909 · Cited by 46 · see citing works
Hypothyroidism and mood disorders: integrating novel insights from brain imaging techniques
Pilhatsch, M., Marxen, M., Winter, C., Smolka, M. N., & Bauer, M. (2011) · Thyroid Research · doi:10.1186/1756-6614-4-s1-s3 · Cited by 46 · see citing works
Do we need still more trials on T4 and T3 combination therapy in hypothyroidism?
Wiersinga, W. M. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0879 · Cited by 43 · see citing works
Effect of Levo-Thyroxine Treatment on Weight and Body Mass Index in Children with Acquired Hypothyroidism
Lomenick, J. P., El-Sayyid, M., & Smith, W. J. (2007) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2007.06.006 · Cited by 38 · see citing works
T 3 Augmentation in Major Depressive Disorder: Safety Considerations
Rosenthal, L. J., Goldner, W. S., & O’Reardon, J. P. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10030402 · Cited by 37 · see citing works
The Type 2 Deiodinase ORFa-Gly3Asp Polymorphism (rs12885300) Influences the Set Point of the Hypothalamus-Pituitary-Thyroid Axis in Patients Treated for Differentiated Thyroid Carcinoma
Hoftijzer, H. C., Heemstra, K. A., Visser, T. J., le Cessie, S., Peeters, R. P., Corssmit, E. P. M., & Smit, J. W. A. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0235 · Cited by 36 · see citing works
TSH may not be a good marker for adequate thyroid hormone replacement therapy
Alevizaki, M., Mantzou, E., Cimponeriu, A. T., Alevizaki, C. C., & Koutras, D. A. (2005) · Wiener klinische Wochenschrift · doi:10.1007/s00508-005-0421-0 · Cited by 34 · see citing works
Effects of Either LT4 Monotherapy or LT4/LT3 Combined Therapy in Patients Totally Thyroidectomized for Thyroid Cancer
Regalbuto, C., Maiorana, R., Alagona, C., Paola, R. D., Cianci, M., Alagona, G., Sapienza, S., Squatrito, S., & PEZZINO, V. (2007) · Thyroid · doi:10.1089/thy.2006.0084 · Cited by 32 · see citing works
Free thyroxine, free triiodothyronine, and thyrotropin concentrations in hypothyroid and thyroid carcinoma patients receiving thyroxine therapy
Liewendahl, K., Helenius, T., Lamberg, B. ‐., Mähönen, H., & Wägar, G. (1987) · European Journal of Endocrinology · doi:10.1530/acta.0.1160418 · Cited by 28 · see citing works
Hypothyroidism is associated with signs of endothelial dysfunction despite 1‐year replacement therapy with levothyroxine
Clausen, P., Mersebach, H., Nielsen, B., Feldt‐Rasmussen, B., & Feldt‐Rasmussen, U. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03410.x · Cited by 27 · see citing works
Levothyroxine therapy for hypothyroidism: should we abandon conservative dosage titration?
Wartofsky, L. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.15.1683 · Cited by 23 · see citing works
Self-citation
TSH and thyroid hormones concentrations in patients with hypothyroidism receiving replacement therapy with L-thyroxine alone or in combination with L-triiodothyronine.
(2005) · PubMed · Cited by 22 · see citing works
Combined Levotriiodothyronine and Levothyroxine Therapy for Hypothyroidism: Are We a Step Closer to the Magic Formula?
Wartofsky, L. (2004) · Thyroid · doi:10.1089/105072504323030898 · Cited by 20 · see citing works
Self-citation
For Some, l-Thyroxine Replacement Might Not Be Enough: A Genetic Rationale
Kim, B. W., & Bianco, A. C. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0410 · Cited by 18 · see citing works
Changes within the thyroid axis after long-term TSH-suppressive levothyroxine therapy
Verburg, F. A., Smit, J. W. A., Grelle, I., Visser, T. J., Peeters, R. P., & Reiners, C. (2012) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2011.04262.x · Cited by 14 · see citing works

Flagged first, then by citations

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Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement
Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928 · see citing works
Treatment with thyroid hormone
Biondi, B., & Wartofsky, L. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1083 · Cited by 259 · see citing works
Self-citation
Papillary thyroid microcarcinoma: time to shift from surgery to active surveillance?
Leboulleux, S., Tuttle, R. M., Pacini, F., & Schlumberger, M. J. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(16)30180-2 · Cited by 234 · see citing works
Understanding and managing toxicities of vascular endothelial growth factor (VEGF) inhibitors
Schmidinger, M. (2013) · European Journal of Cancer Supplements · doi:10.1016/j.ejcsup.2013.07.016 · Cited by 159 · see citing works
Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study
Hoang, T. D., Olsen, C. H., Mai, V. Q., Clyde, P. W., & Shakir, M. K. M. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-4107 · Cited by 151 · see citing works
Defending plasma T3 is a biological priority
Abdalla, S. M., & Bianco, A. C. (2014) · Clinical Endocrinology · doi:10.1111/cen.12538 · Cited by 147 · see citing works
TSH and thyrotropic agonists: key actors in thyroid homeostasis
Dietrich, J. W., Landgrafe, G., & Fotiadou, E. H. (2012) · Journal of Thyroid Research · doi:10.1155/2012/351864 · Cited by 146 · see citing works
Homeostatic control of the thyroid-pituitary axis: perspectives for diagnosis and treatment
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00177 · Cited by 143 · see citing works
Hypothyroidism and Thyroiditis
Brent, G. A., & Davies, T. F. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-0324-5.00013-4 · Cited by 115 · see citing works
Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism
Wiersinga, W. M. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.258 · Cited by 114 · see citing works
DIAGNOSIS OF ENDOCRINE DISEASE: How reliable are free thyroid and total T3 hormone assays?
Welsh, K. J., & Soldin, S. J. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0193 · Cited by 124 · see citing works
The administration of l -thyroxine as soft gel capsule or liquid solution
Vita, R., Fallahi, P., Antonelli, A., & Benvenga, S. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.918101 · Cited by 93 · see citing works
Management of Adverse Events Associated with Cabozantinib Therapy in Renal Cell Carcinoma
Schmidinger, M., & Danesi, R. (2017) · The Oncologist · doi:10.1634/theoncologist.2017-0335 · Cited by 87 · see citing works
Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment
Hoermann, R., Midgley, J. E. M., Giacobino, A., Eckl, W. A., Wahl, H. G., Dietrich, J. W., & Larisch, R. (2014) · Clinical Endocrinology · doi:10.1111/cen.12527 · Cited by 82 · see citing works
Printing T3 and T4 oral drug combinations as a novel strategy for hypothyroidism
Alomari, M., Vuddanda, P. R., Trenfield, S. J., Dodoo, C. C., Velaga, S., Basit, A. W., & Gaisford, S. (2018) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2018.07.062 · Cited by 77 · see citing works
Compounded Bioidentical Hormones in Endocrinology Practice: An Endocrine Society Scientific Statement
Santoro, N. F., Braunstein, G. D., Butts, C. L., Martin, K. A., McDermott, M., & Pinkerton, J. V. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1271 · Cited by 72 · see citing works
The emergence of levothyroxine as a treatment for hypothyroidism
Hennessey, J. V. (2017) · Endocrine · doi:10.1007/s12020-016-1199-8 · Cited by 66 · see citing works
Thyroid Disease and Cognition
Samuels, M. H. (2014) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2014.02.006 · Cited by 66 · see citing works
Gender differences in symptoms of hypothyroidism: a population‐based <scp>D</scp>an<scp>T</scp>hyr study
Carlé, A., Bülow Pedersen, I., Knudsen, N., Perrild, H., Ovesen, L., & Laurberg, P. (2015) · Clinical Endocrinology · doi:10.1111/cen.12787 · Cited by 59 · see citing works
Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2013) · European Journal of Endocrinology · doi:10.1530/eje-12-0819 · Cited by 59 · see citing works
Targeting Hormones for Improving Cognition in Major Mood Disorders and Schizophrenia: Thyroid Hormones and Prolactin
PNECAT Group, Tost, M., Monreal, J. A., Armario, A., Barbero, J. D., Cobo, J., García‐Rizo, C., Bioque, M., Usall, J., Huerta‐Ramos, E., et al. (2019) · Clinical Drug Investigation · doi:10.1007/s40261-019-00854-w · Cited by 53 · see citing works
The Effects of Levothyroxine Replacement or Suppressive Therapy on Health Status, Mood, and Cognition
Samuels, M. H., Kolobova, I., Smeraglio, A., Peters, D., Janowsky, J. S., & Schuff, K. G. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3686 · Cited by 48 · see citing works
Advancements in the treatment of hypothyroidism with L-T4 liquid formulation or soft gel capsule: an update
Fallahi, P., Ferrari, S. M., Ruffilli, I., Ragusa, F., Biricotti, M., Materazzi, G., Miccoli, P., & Antonelli, A. (2016) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2016.1227782 · Cited by 48 · see citing works
Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines
Balasubramanian, V., Liu, Z., Hirvonen, J. J., & Santos, H. A. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700432 · Cited by 46 · see citing works
Recommendations for treatment of hypothyroidism with levothyroxine and levotriiodothyronine: a 2016 position statement of the Italian Society of Endocrinology and the Italian Thyroid Association
Biondi, B., Bartalena, L., Chiovato, L., Lenzi, A., Mariotti, S., Pacini, F., Pontecorvi, A., Vitti, P., & Trimarchi, F. (2016) · Journal of Endocrinological Investigation · doi:10.1007/s40618-016-0511-z · Cited by 44 · see citing works
Self-citation
Effects of Long-Term Combination LT4 and LT3 Therapy for Improving Hypothyroidism and Overall Quality of Life
Tariq, A., Wert, Y., Cheriyath, P., & Joshi, R. (2018) · Southern Medical Journal · doi:10.14423/smj.0000000000000823 · Cited by 43 · see citing works
“This classic monotherapy of levothyroxine (LT4) provides adequate control of symptoms for a majority of the population; however, approximately 5% to 10% of patients continue to have symptoms of hypothyroidism, despite normal TSH and FT4 levels.(4) This may occur because of dysfunctional deiodinase in a subset of hypot…”
Background
Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study
Kaminski, J., Miasaki, F. Y., Paz-Filho, G., Graf, H., & Carvalho, G. A. D. (2016) · Archives of Endocrinology and Metabolism · doi:10.1590/2359-3997000000192 · Cited by 42 · see citing works
Physician Choice of Hypothyroidism Therapy: Influence of Patient Characteristics
Jonklaas, J., Tefera, E., & Shara, N. (2018) · Thyroid · doi:10.1089/thy.2018.0325 · Cited by 41 · see citing works
MANAGEMENT OF ENDOCRINE DISEASE: Pitfalls on the replacement therapy for primary and central hypothyroidism in adults
de Carvalho, G. A., Paz-Filho, G., Mesa, C. O., & Graf, H. (2018) · European Journal of Endocrinology · doi:10.1530/eje-17-0947 · Cited by 41 · see citing works
Managing Terrorism or Accidental Nuclear Errors, Preparing for Iodine-131 Emergencies: A Comprehensive Review
Braverman, E. R., Blum, K., Loeffke, B., Baker, R. J., Kreuk, F., Yang, S. P., & Hurley, J. R. (2014) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph110404158 · Cited by 39 · see citing works
Italian association of clinical endocrinologists statement-replacement therapy for primary hypothyroidism: a brief guide for clinical practice
Guglielmi, R., Frasoldati, A., Zini, M., Grimaldi, F., Gharib, H., Garber, J. R., & Papini, E. (2016) · Endocrine Practice · doi:10.4158/ep161308.or · Cited by 39 · see citing works
Novel thyroid hormones
Zucchi, R., Rutigliano, G., & Saponaro, F. (2019) · Endocrine · doi:10.1007/s12020-019-02018-4 · Cited by 37 · see citing works
Patient-reported outcomes in adequately treated hypothyroidism – insights from the German versions of ThyDQoL, ThySRQ and ThyTSQ
Quinque, E. M., Villringer, A., Kratzsch, J., & Karger, S. (2013) · Health and Quality of Life Outcomes · doi:10.1186/1477-7525-11-68 · Cited by 36 · see citing works
TSH Measurement and Its Implications for Personalised Clinical Decision-Making
Hoermann, R., & Midgley, J. E. M. (2012) · Journal of Thyroid Research · doi:10.1155/2012/438037 · Cited by 32 · see citing works
Pharmacokinetics of L-Triiodothyronine in Patients Undergoing Thyroid Hormone Therapy Withdrawal
Van Tassell, B., Wohlford, G. F., Linderman, J. D., Smith, S., Yavuz, S., Pucino, F., & Celi, F. S. (2019) · Thyroid® · doi:10.1089/thy.2019.0101 · Cited by 31 · see citing works
Prescribing Therapy for Hypothyroidism: Influence of Physician Characteristics
Jonklaas, J., Tefera, E., & Shara, N. (2019) · Thyroid · doi:10.1089/thy.2018.0369 · Cited by 31 · see citing works
Attitudes and perceptions of health professionals towards management of hypothyroidism in general practice: a qualitative interview study
Dew, R., King, K., Okosieme, O. E., Pearce, S. H., Donovan, G., Taylor, P. N., Hickey, J., Dayan, C. M., Leese, G., Razvi, S., et al. (2018) · BMJ Open · doi:10.1136/bmjopen-2017-019970 · Cited by 31 · see citing works
Effect of Hypothyroidism and Hyperthyroidism on Tissue Thyroid Hormone Concentrations in Rat
Donzelli, R., Colligiani, D., Kusmic, C., Sabatini, M., Lorenzini, L., Accorroni, A., Nannipieri, M., Saba, A., Iervasi, G., & Zucchi, R. (2016) · European Thyroid Journal · doi:10.1159/000443523 · Cited by 31 · see citing works
Treatment of hypothyroidism with levothyroxine or a combination of levothyroxine plus L-triiodothyronine
Escobar-Morreale, H. F., Botella-Carretero, J. I., & Morreale de Escobar, G. (2015) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2014.10.004 · Cited by 30 · see citing works
The effects of perinatal bisphenol A exposure on thyroid hormone homeostasis and glucose metabolism in the prefrontal cortex and hippocampus of rats
Xu, X., Fan, S., Guo, Y., Tan, R., Zhang, J., Zhang, W., Pan, B., & Kato, N. (2019) · Brain and Behavior · doi:10.1002/brb3.1225 · Cited by 28 · see citing works
Patient Requests for Tests and Treatments Impact Physician Management of Hypothyroidism
Esfandiari, N. H., Reyes‐Gastelum, D., Hawley, S. T., Haymart, M. R., & Papaleontiou, M. (2019) · Thyroid · doi:10.1089/thy.2019.0383 · Cited by 26 · see citing works
Critical Approach to Hypothyroid Patients With Persistent Symptoms
Biondi, B., Celi, F. S., & McAninch, E. A. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad224 · Cited by 28 · see citing works
Self-citation
Neither Baseline nor Changes in Serum Triiodothyronine during Levothyroxine/Liothyronine Combination Therapy Predict a Positive Response to This Treatment Modality in Hypothyroid Patients with Persistent Symptoms
Medici, B. B., la Cour, J. L., Michaelsson, L. F., Faber, J. O., & Nygaard, B. (2017) · European Thyroid Journal · doi:10.1159/000454878 · Cited by 25 · see citing works
Successful treatment of myxedema coma with a combination of levothyroxine and liothyronine
Ueda, K., Kiyota, A., Tsuchida, M., Okazaki, M., & Ozaki, N. (2019) · Endocrine Journal · doi:10.1507/endocrj.ej18-0469 · Cited by 25 · see citing works
Active surveillance in low risk papillary thyroid carcinoma
Pitoia, F., & Smulever, A. (2020) · World Journal of Clinical Oncology · doi:10.5306/wjco.v11.i6.320 · Cited by 24 · see citing works
Effect of Liothyronine Treatment on Quality of Life in Female Hypothyroid Patients With Residual Symptoms on Levothyroxine Therapy: A Randomized Crossover Study
Bjerkreim, B. A., Hammerstad, S. S., Gulseth, H. L., Berg, T. J., Omdal, L. J., Lee-Ødegård, S., & Eriksen, E. F. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.816566 · Cited by 24 · see citing works
Short-Term Time Trends in Prescribing Therapy for Hypothyroidism: Results of a Survey of American Thyroid Association Members
Jonklaas, J., Tefera, E., & Shara, N. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00031 · Cited by 23 · see citing works
“In 2012 one guideline from Europe (1), one from North America (2) and one narrative review authored by American and European experts (3) were published.”
BackgroundInfluential
The Hypothalamic-Pituitary-Thyroid Axis: Physiological Regulation and Clinical Implications
Gavrila, A., & Hollenberg, A. N. (2019) · Springer eBooks · doi:10.1007/978-3-319-72102-6_2 · Cited by 19 · see citing works
Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients
Fröhlich, E., & Wahl, R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.587518 · Cited by 20 · see citing works
Is measurement of TT3 by immunoassay reliable at low concentrations? A comparison of the Roche Cobas 6000 vs. LC–MSMS
Masika, L. S., Zhao, Z., & Soldin, S. J. (2016) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2016.02.004 · Cited by 23 · see citing works
Notch signaling in thyrocytes is essential for adult thyroid function and mammalian homeostasis
Mosteiro, L., Nguyen, T. T. T., Hankeová, S., Álvarez‐Sierra, D., Reichelt, M., Vandriel, S. M., Lai, Z., Choudhury, F. K., Sangaraju, D., Kamath, B. M., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00937-1 · Cited by 19 · see citing works
CD5L Constitutes a Novel Biomarker for Integrated Hepatic Thyroid Hormone Action
Nock, S., Johann, K., Harder, L., Wirth, E. K., Renko, K., Hoefig, C. S., Kracke, V., Hackler, J., Engelmann, B., Rauner, M., et al. (2020) · Thyroid · doi:10.1089/thy.2019.0635 · Cited by 19 · see citing works
Peripheral markers of thyroid function: the effect of T4 monotherapy vs T4/T3 combination therapy in hypothyroid subjects in a randomized crossover study
Schmidt, U., Nygaard, B., Jensen, E. W., Kvetny, J., Jarløv, A., & Faber, J. (2013) · Endocrine Connections · doi:10.1530/ec-12-0064 · Cited by 17 · see citing works
Combination Therapy for Hypothyroidism: Rationale, Therapeutic Goals, and Design
Madan, R., & Celi, F. S. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00371 · Cited by 18 · see citing works
Clinical, behavioural and pharmacogenomic factors influencing the response to levothyroxine therapy in patients with primary hypothyroidism—protocol for a systematic review
Dew, R., Okosieme, O. E., Dayan, C. M., Eligar, V. S., Khan, I. N., Razvi, S., Pearce, S. H. S., & Wilkes, S. (2017) · Systematic Reviews · doi:10.1186/s13643-017-0457-z · Cited by 17 · see citing works
Hypothyroidism and Thyroiditis
Brent, G. A., & Weetman, A. P. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00013-7 · Cited by 16 · see citing works
The dynamic pituitary response to escalating-dose TRH stimulation test in hypothyroid patients treated with liothyronine or levothyroxine replacement therapy
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Preliminary Results of a Double-Blind Randomized Controlled Trial Evaluating the Cardiometabolic Effects of Levothyroxine and Liothyronine Compared to Levothyroxine with Placebo in Athyreotic Low-Risk Thyroid Cancer Patients
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Personalized Approaches to Hypothyroidism: The Role of Triiodothyronine (T3) in Thyroid Hormone Replacement
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Authors: Biondi, B., & Wartofsky, L.
Affiliations: Federico II University Hospital (IT)
Corresponding author: Biondi, Bernadette
ORCID: Biondi, Bernadette
Wartofsky, Leonard
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2012-07-01
Volume: 97
Issue: 7
Pages: 2256-2271
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2011-3399
OpenAlex: W2108263652
Cited by: 124
References: 102
Citations by year: 2026: 1 · 2025: 4 · 2024: 4 · 2023: 9 · 2022: 4 · 2021: 10 · 2020: 10 · 2019: 10 · 2018: 10 · 2017: 9 · 2016: 19 · 2015: 7 · 2014: 14 · 2013: 8 · 2012: 4
FWCI: 8.43
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: Università degli Studi di Napoli Federico II
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords: hypothyroidism, thyroid hormone replacement, levothyroxine, triiodothyronine, personalized treatment, T4/T3 ratio, deiodinases, quality of life, cognition, mood, depression, bone turnover markers, sex hormone-binding globulin, body weight, cholesterol
MeSH terms: Drug Combinations, Humans, Hypothalamo-Hypophyseal System, Hypothyroidism, Thyroid Gland, Thyroxine, Triiodothyronine, Hormone Replacement Therapy, Precision Medicine

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Combination Treatment with T4 and T3: Toward Personalized Replacement Therapy in Hypothyroidism?

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