Literature DB >> 28632526

Persistent hypothyroid symptoms in a patient with a normal thyroid stimulating hormone level.

Jacqueline Jonklaas1.   

Abstract

PURPOSE OF REVIEW: A subset of patients being treated for hypothyroidism do not feel well while taking levothyroxine (LT4) replacement therapy, despite having a normal serum thyroid stimulating hormone level. Pursuing a relative triiodothyronine deficiency as a potential explanation for patient dissatisfaction, has led to trials of combination therapy with liothyronine (LT3), with largely negative outcomes. This review attempts to reconcile these diverse findings, consider potential explanations, and identify areas for future research. RECENT
FINDINGS: Patients being treated with LT4 often have lower triiodothyronine levels than patients with endogenous thyroid function. Linking patient dissatisfaction with low triiodothyronine levels has fueled multiple combination therapy trials that have generally not shown improvement in patient quality of life, mood, or cognitive performance. Some trials, however, suggest patient preference for combination therapy. There continues, moreover, to be anecdotal evidence that patients have fewer unresolved symptoms while taking combination therapy.
SUMMARY: The 14 trials completed to date have suffered from employing doses of LT3 that do not result in steady triiodothyronine levels, and having insufficient power to analyze results based on baseline dissatisfaction with therapy and patient genotype. Future trials that are able to incorporate such features may provide insight into what thyroid hormone preparations will most improve patient satisfaction with therapy.

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Year:  2017        PMID: 28632526      PMCID: PMC5824691          DOI: 10.1097/MED.0000000000000355

Source DB:  PubMed          Journal:  Curr Opin Endocrinol Diabetes Obes        ISSN: 1752-296X            Impact factor:   3.243


  51 in total

1.  Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism.

Authors:  Ellie M Wekking; Bente C Appelhof; Eric Fliers; Aart H Schene; Jochanan Huyser; Jan G P Tijssen; Wilmar M Wiersinga
Journal:  Eur J Endocrinol       Date:  2005-12       Impact factor: 6.664

2.  Prevalent polymorphism in thyroid hormone-activating enzyme leaves a genetic fingerprint that underlies associated clinical syndromes.

Authors:  Elizabeth A McAninch; Sungro Jo; Nailliw Z Preite; Erzsébet Farkas; Petra Mohácsik; Csaba Fekete; Péter Egri; Balázs Gereben; Yan Li; Youping Deng; Mary-Elizabeth Patti; Chantal Zevenbergen; Robin P Peeters; Deborah C Mash; Antonio C Bianco
Journal:  J Clin Endocrinol Metab       Date:  2015-01-08       Impact factor: 5.958

3.  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.

Authors:  Tom Rodriguez; Victor R Lavis; Janet C Meininger; Asha S Kapadia; Linda F Stafford
Journal:  Endocr Pract       Date:  2005 Jul-Aug       Impact factor: 3.443

Review 4.  REVIEW: Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine.

Authors:  Héctor F Escobar-Morreale; José I Botella-Carretero; Francisco Escobar del Rey; Gabriella Morreale de Escobar
Journal:  J Clin Endocrinol Metab       Date:  2005-05-31       Impact factor: 5.958

5.  Increased psychiatric morbidity before and after the diagnosis of hypothyroidism: a nationwide register study.

Authors:  Marianne Thvilum; Frans Brandt; Dorthe Almind; Kaare Christensen; Thomas Heiberg Brix; Laszlo Hegedüs
Journal:  Thyroid       Date:  2014-01-29       Impact factor: 6.568

6.  TSH-suppressive doses of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy.

Authors:  Mitsuru Ito; Akira Miyauchi; Shinji Morita; Takumi Kudo; Eijun Nishihara; Minoru Kihara; Yuuki Takamura; Yasuhiro Ito; Kaoru Kobayashi; Akihiro Miya; Sumihisa Kubota; Nobuyuki Amino
Journal:  Eur J Endocrinol       Date:  2012-06-18       Impact factor: 6.664

7.  Partial substitution of thyroxine (T4) with tri-iodothyronine in patients on T4 replacement therapy: results of a large community-based randomized controlled trial.

Authors:  Ponnusamy Saravanan; Dawn J Simmons; Rosemary Greenwood; Tim J Peters; Colin M Dayan
Journal:  J Clin Endocrinol Metab       Date:  2004-12-07       Impact factor: 5.958

Review 8.  Treatment of clinical hypothyroidism with thyroxine and triiodothyronine: a literature review and metaanalysis.

Authors:  Russell T Joffe; Michael Brimacombe; Anthony J Levitt; Alex Stagnaro-Green
Journal:  Psychosomatics       Date:  2007 Sep-Oct       Impact factor: 2.386

9.  Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism.

Authors:  R Bunevicius; G Kazanavicius; R Zalinkevicius; A J Prange
Journal:  N Engl J Med       Date:  1999-02-11       Impact factor: 91.245

10.  Disease-Specific as Well as Generic Quality of Life Is Widely Impacted in Autoimmune Hypothyroidism and Improves during the First Six Months of Levothyroxine Therapy.

Authors:  Kristian Hillert Winther; Per Cramon; Torquil Watt; Jakob Bue Bjorner; Ola Ekholm; Ulla Feldt-Rasmussen; Mogens Groenvold; Åse Krogh Rasmussen; Laszlo Hegedüs; Steen Joop Bonnema
Journal:  PLoS One       Date:  2016-06-03       Impact factor: 3.240

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  14 in total

1.  Cognitive functioning and quality of life in patients with Hashimoto thyroiditis on long-term levothyroxine replacement.

Authors:  Marina Djurovic; Alberto M Pereira; Johannes W A Smit; Olga Vasovic; Svetozar Damjanovic; Zvezdana Jemuovic; Dragan Pavlovic; Dragana Miljic; Sandra Pekic; Marko Stojanovic; Milika Asanin; Gordana Krljanac; Milan Petakov
Journal:  Endocrine       Date:  2018-06-29       Impact factor: 3.633

2.  An Online Survey of Hypothyroid Patients Demonstrates Prominent Dissatisfaction.

Authors:  Sarah J Peterson; Anne R Cappola; M Regina Castro; Colin M Dayan; Alan P Farwell; James V Hennessey; Peter A Kopp; Douglas S Ross; Mary H Samuels; Anna M Sawka; Peter N Taylor; Jacqueline Jonklaas; Antonio C Bianco
Journal:  Thyroid       Date:  2018-04-05       Impact factor: 6.568

Review 3.  Individualized Therapy for Hypothyroidism: Is T4 Enough for Everyone?

Authors:  Matthew D Ettleson; Antonio C Bianco
Journal:  J Clin Endocrinol Metab       Date:  2020-09-01       Impact factor: 5.958

4.  Patient Requests for Tests and Treatments Impact Physician Management of Hypothyroidism.

Authors:  Nazanene H Esfandiari; David Reyes-Gastelum; Sarah T Hawley; Megan R Haymart; Maria Papaleontiou
Journal:  Thyroid       Date:  2019-10-10       Impact factor: 6.568

5.  Optimal Thyroid Hormone Replacement.

Authors:  Jacqueline Jonklaas
Journal:  Endocr Rev       Date:  2022-03-09       Impact factor: 25.261

Review 6.  Thyroid hormone therapy for hypothyroidism.

Authors:  Bernadette Biondi; David S Cooper
Journal:  Endocrine       Date:  2019-08-01       Impact factor: 3.633

7.  Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A Thesis* Questionnaire Survey of Romanian Physicians *Thesis: Treatment of Hypothyroidism in Europe by Specialists: an International Survey.

Authors:  D A Niculescu; R Attanasio; L Hegedüs; E V Nagy; R Negro; E Papini; P Perros; C Poiana
Journal:  Acta Endocrinol (Buchar)       Date:  2020 Oct-Dec       Impact factor: 0.877

8.  Lessons from Randomised Clinical Trials for Triiodothyronine Treatment of Hypothyroidism: Have They Achieved Their Objectives?

Authors:  Rudolf Hoermann; John E M Midgley; Rolf Larisch; Johannes W Dietrich
Journal:  J Thyroid Res       Date:  2018-07-16

9.  Predicting Optimal Combination LT4 + LT3 Therapy for Hypothyroidism Based on Residual Thyroid Function.

Authors:  Joseph DiStefano; Jacqueline Jonklaas
Journal:  Front Endocrinol (Lausanne)       Date:  2019-11-15       Impact factor: 5.555

10.  No Effect of Thyroid Dysfunction and Autoimmunity on Health-Related Quality of Life and Mental Health in Children and Adolescents: Results From a Nationwide Cross-Sectional Study.

Authors:  Raphael Hirtz; Anne Keesen; Heike Hölling; Berthold P Hauffa; Anke Hinney; Corinna Grasemann
Journal:  Front Endocrinol (Lausanne)       Date:  2020-09-02       Impact factor: 5.555

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