Skip to main content
main-content
Erschienen in: Endocrine 2/2020

22.06.2020 | Viewpoint

Targeting the right population for T3 + T4 combined therapy: where are we now and where to next?

verfasst von: Tommaso Porcelli, Domenico Salvatore

Erschienen in: Endocrine | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Abstract

The universal applicability of levothyroxine (LT4) monotherapy for the treatment of hypothyroidism has been questioned in recent years. Indeed, it is now clear that about 10–15% of LT4-treated hypothyroid patients are dissatisfied with their treatment. It is plausible that this subset of hypothyroid patients may need T3 + T4 combined therapy to restore peripheral euthyroidism. To address this issue, many clinical trials have investigated the effect of T3 + T4 combinations versus standard LT4-based therapy. However, to date, results have been inconclusive, mainly due to the lack of markers that identify candidates for combination therapy. A breakthrough in this field came with the recent finding that several single-nucleotide polymorphisms in the deiodinase genes are associated with the persistence of hypothyroid symptoms in biochemically euthyroid LT4-treated patients, and are thus markers of candidates for combination therapy. In addition, whole-genome association studies are expanding our knowledge of other genes of the thyroid hormone (TH) pathway that affect serum TH levels. To target the right population for the T3 + T4 combined therapy, the next step is to translate these new findings into prospective trials. Hopefully, this will pave the way to personalized therapy for each hypothyroid patient.
Literatur
12.
Zurück zum Zitat V. Panicker, C. Cluett, B. Shields, A. Murray, K.S. Parnell, J.R.B. Perry, M.N. Weedon, A. Singleton, D. Hernandez, J. Evans, C. Durant, L. Ferrucci, D. Melzer, P. Saravanan, T.J. Visser, G. Ceresini, A.T. Hattersley, B. Vaidya, C.M. Dayan, T.M. Frayling, A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine. J. Clin. Endocrinol. Metab. 93, 3075–3081 (2008). https://​doi.​org/​10.​1210/​jc.​2008-0397 CrossRefPubMedPubMedCentral V. Panicker, C. Cluett, B. Shields, A. Murray, K.S. Parnell, J.R.B. Perry, M.N. Weedon, A. Singleton, D. Hernandez, J. Evans, C. Durant, L. Ferrucci, D. Melzer, P. Saravanan, T.J. Visser, G. Ceresini, A.T. Hattersley, B. Vaidya, C.M. Dayan, T.M. Frayling, A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine. J. Clin. Endocrinol. Metab. 93, 3075–3081 (2008). https://​doi.​org/​10.​1210/​jc.​2008-0397 CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat F.J. de Jong, R.P. Peeters, T. den Heijer, W.M. van der Deure, A. Hofman, A.G. Uitterlinden, T.J. Visser, M.M.B. Breteler, The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe. J. Clin. Endocrinol. Metab. 92, 636–640 (2007). https://​doi.​org/​10.​1210/​jc.​2006-1331 CrossRefPubMed F.J. de Jong, R.P. Peeters, T. den Heijer, W.M. van der Deure, A. Hofman, A.G. Uitterlinden, T.J. Visser, M.M.B. Breteler, The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe. J. Clin. Endocrinol. Metab. 92, 636–640 (2007). https://​doi.​org/​10.​1210/​jc.​2006-1331 CrossRefPubMed
16.
Zurück zum Zitat M. Medici, W.M. van der Deure, M. Verbiest, S.H. Vermeulen, P.S. Hansen, L.A. Kiemeney, A.R.M.M. Hermus, M.M. Breteler, A. Hofman, L. Hegedüs, K. Ohm Kyvik, M. den Heijer, A.G. Uitterlinden, T.J. Visser, R.P. Peeters, A large-scale association analysis of 68 thyroid hormone pathway genes with serum TSH and FT4 levels. Eur. J. Endocrinol. 164, 781–788 (2011). https://​doi.​org/​10.​1530/​EJE-10-1130 CrossRefPubMed M. Medici, W.M. van der Deure, M. Verbiest, S.H. Vermeulen, P.S. Hansen, L.A. Kiemeney, A.R.M.M. Hermus, M.M. Breteler, A. Hofman, L. Hegedüs, K. Ohm Kyvik, M. den Heijer, A.G. Uitterlinden, T.J. Visser, R.P. Peeters, A large-scale association analysis of 68 thyroid hormone pathway genes with serum TSH and FT4 levels. Eur. J. Endocrinol. 164, 781–788 (2011). https://​doi.​org/​10.​1530/​EJE-10-1130 CrossRefPubMed
18.
Zurück zum Zitat H.C. Hoftijzer, K.A. Heemstra, T.J. Visser, S. le Cessie, R.P. Peeters, E.P.M. Corssmit, J.W.A. Smit, 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. J. Clin. Endocrinol. Metab. 96, E1527–E1533 (2011). https://​doi.​org/​10.​1210/​jc.​2011-0235 CrossRefPubMed H.C. Hoftijzer, K.A. Heemstra, T.J. Visser, S. le Cessie, R.P. Peeters, E.P.M. Corssmit, J.W.A. Smit, 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. J. Clin. Endocrinol. Metab. 96, E1527–E1533 (2011). https://​doi.​org/​10.​1210/​jc.​2011-0235 CrossRefPubMed
19.
Zurück zum Zitat M.Y. Peltsverger, P.W. Butler, A.T. Alberobello, S. Smith, Y. Guevara, O.M. Dubaz, J.A. Luzon, J. Linderman, F.S. Celi, The K258A/G (SNP rs12885300) polymorphism of the human type 2 deiodinase gene is associated with a shift in the pattern of secretion of thyroid hormones following a TRH-induced acute rise in TSH. Eur. J. Endocrinol. 166, 839–845 (2012). https://​doi.​org/​10.​1530/​EJE-11-1073 CrossRefPubMedPubMedCentral M.Y. Peltsverger, P.W. Butler, A.T. Alberobello, S. Smith, Y. Guevara, O.M. Dubaz, J.A. Luzon, J. Linderman, F.S. Celi, The K258A/G (SNP rs12885300) polymorphism of the human type 2 deiodinase gene is associated with a shift in the pattern of secretion of thyroid hormones following a TRH-induced acute rise in TSH. Eur. J. Endocrinol. 166, 839–845 (2012). https://​doi.​org/​10.​1530/​EJE-11-1073 CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat M. Torlontano, C. Durante, I. Torrente, U. Crocetti, G. Augello, G. Ronga, T. Montesano, L. Travascio, A. Verrienti, R. Bruno, S. Santini, P. D’Arcangelo, B. Dallapiccola, S. Filetti, V. Trischitta, Type 2 deiodinase polymorphism (threonine 92 alanine) predicts L-thyroxine dose to achieve target thyrotropin levels in thyroidectomized patients. J. Clin. Endocrinol. Metab. 93, 910–913 (2008). https://​doi.​org/​10.​1210/​jc.​2007-1067 CrossRefPubMed M. Torlontano, C. Durante, I. Torrente, U. Crocetti, G. Augello, G. Ronga, T. Montesano, L. Travascio, A. Verrienti, R. Bruno, S. Santini, P. D’Arcangelo, B. Dallapiccola, S. Filetti, V. Trischitta, Type 2 deiodinase polymorphism (threonine 92 alanine) predicts L-thyroxine dose to achieve target thyrotropin levels in thyroidectomized patients. J. Clin. Endocrinol. Metab. 93, 910–913 (2008). https://​doi.​org/​10.​1210/​jc.​2007-1067 CrossRefPubMed
25.
Zurück zum Zitat S. Jo, T.L. Fonseca, B.M.L.C. Bocco, G.W. Fernandes, E.A. McAninch, A.P. Bolin, R.R. Da Conceição, J.P. Werneck-de-Castro, D.L. Ignacio, P. Egri, D. Németh, C. Fekete, M.M. Bernardi, V.D. Leitch, N.S. Mannan, K.F. Curry, N.C. Butterfield, J.H.D. Bassett, G.R. Williams, B. Gereben, M.O. Ribeiro, A.C. Bianco, Type 2 deiodinase polymorphism causes ER stress and hypothyroidism in the brain. J. Clin. Investig. 129, 230–245 (2019). https://​doi.​org/​10.​1172/​JCI123176 CrossRefPubMed S. Jo, T.L. Fonseca, B.M.L.C. Bocco, G.W. Fernandes, E.A. McAninch, A.P. Bolin, R.R. Da Conceição, J.P. Werneck-de-Castro, D.L. Ignacio, P. Egri, D. Németh, C. Fekete, M.M. Bernardi, V.D. Leitch, N.S. Mannan, K.F. Curry, N.C. Butterfield, J.H.D. Bassett, G.R. Williams, B. Gereben, M.O. Ribeiro, A.C. Bianco, Type 2 deiodinase polymorphism causes ER stress and hypothyroidism in the brain. J. Clin. Investig. 129, 230–245 (2019). https://​doi.​org/​10.​1172/​JCI123176 CrossRefPubMed
Metadaten
Titel
Targeting the right population for T3 + T4 combined therapy: where are we now and where to next?
verfasst von
Tommaso Porcelli
Domenico Salvatore
Publikationsdatum
22.06.2020
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 2/2020
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-020-02391-5

Weitere Artikel der Ausgabe 2/2020

Endocrine 2/2020 Zur Ausgabe

Neu im Fachgebiet Innere Medizin

Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.