Search Results

You are looking at 1 - 10 of 13 items for

  • Author: Birte Nygaard x
Clear All Modify Search
Sofie Jespersen Department of Internal Medicine and Endocrinology, Copenhagen University Hospital, Herlev, Denmark

Search for other papers by Sofie Jespersen in
Google Scholar
PubMed
Close
,
Birte Nygaard Department of Internal Medicine and Endocrinology, Copenhagen University Hospital, Herlev, Denmark

Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Close
, and
Lars Østergaard Kristensen Department of Internal Medicine and Endocrinology, Copenhagen University Hospital, Herlev, Denmark

Search for other papers by Lars Østergaard Kristensen in
Google Scholar
PubMed
Close

Objective: Graves' ophthalmopathy (GO) is an inflammatory disease in the orbital region. The first-line medical treatment is glucocorticoids. An important potential side effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal (HPA) axis with impairment of endogenous cortisol production, implicating symptoms of adrenocortical insufficiency, especially in the period after cessation of therapy with possible risks in cases of intercurrent illness. The aim of this study was to evaluate HPA axis function before and after methylprednisolone pulse treatment of GO. Study Design: HPA axis function was evaluated by measurements of plasma ACTH and an ACTH stimulation test with plasma cortisol measurements at 0 and 30 min after an intravenous bolus of synthetic ACTH (Synacthen® 250 µg). This was done in 12 patients with GO before and at cessation of methylprednisolone pulse treatment (500 mg i.v. per week for 6 weeks followed by 250 mg i.v. per week for an additional 6 weeks). Results: All patients included fulfilled the criteria of intact HPA axis function before and at cessation of methylprednisolone pulse treatment. Data are given as medians (with ranges). Before glucocorticoid treatment basal plasma cortisol was 290 n<smlcap>M</smlcap> (196-579) and 786 n<smlcap>M </smlcap>(612-1,050) after ACTH stimulation. At cessation of therapy the corresponding values were 309 n<smlcap>M</smlcap> (88-718) and 852 n<smlcap>M</smlcap> (524-1,011), respectively. Thus, all patients passed a 30-min stimulated plasma cortisol of 500 n<smlcap>M</smlcap>. Before treatment plasma ACTH was 4.2 pmol/l (4-16) and at cessation of therapy the corresponding value was 4.8 pmol/l (2-9; p = 0.27). Conclusion: Transient suppression of the HPA axis with secondary adrenocortical insufficiency does not seem to be a common phenomenon after intravenous methylprednisolone pulse therapy for GO. Therefore, routine precautions are not necessary. However, our results do not exclude that transient secondary adrenocortical insufficiency might occur occasionally.

Free access
Birte Nygaard Departments of Endocrinology, Herlev University Hospital, Herlev

Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Close
,
Lars Bastholt Department of Oncology, Odense University Hospital, Odense, Denmark

Search for other papers by Lars Bastholt in
Google Scholar
PubMed
Close
,
Finn Noe Bennedbæk Departments of Endocrinology, Herlev University Hospital, Herlev

Search for other papers by Finn Noe Bennedbæk in
Google Scholar
PubMed
Close
,
Tobias Wirenfeldt Klausen Departments of Haematology, Herlev University Hospital, Herlev

Search for other papers by Tobias Wirenfeldt Klausen in
Google Scholar
PubMed
Close
, and
Jens Bentzen Departments of Oncology, Herlev University Hospital, Herlev

Search for other papers by Jens Bentzen in
Google Scholar
PubMed
Close

Background: It is well known that thyroid hormone withdrawal (THW) in thyroid cancer patients can induce a decrease in quality of life (QOL). Recombinant human thyrotropin (rh-TSH) has been used to avoid this; however, no blinded studies have ever documented the effect. Objective: To compare QOL in patients with differentiated thyroid cancer (DTC) treated with either rh-TSH or liothyronine (L-T<sub>3</sub>) THW for 10 days. Study Design: Double-blind, randomised cross-over. Patients: Fifty-six patients with DTC treated by total thyroidectomy and indication for postsurgery radioiodine (RI) ablation therapy. Intervention: Randomisation to either L-T<sub>3</sub> and rh-TSH prior to the first RI course and following this to ingest placebo tablets and receive placebo injections before a second RI uptake measurement 4-6 months later, or to receive placebo before the primary RI ablation and active therapy 4-6 months later. Main Outcome Measures: QOL was measured by SF-36 and 2 visual analogue scale (VAS) scores at baseline and during RI therapy or RI uptake. Results: A significant difference in QOL was seen in 2 of 4 predefined SF-36 domains (7.2 and 6.6%) and 2 VAS scales (10 and 14%), favouring rh-TSH therapy. Conclusion: This is the first blinded randomised clinical trial describing the effect of rh-TSH compared to L-T<sub>3</sub> THW on QOL in DTC patients. A significant difference was demonstrated, though smaller than described in previous non-blinded studies.

Free access
Allan Carlé Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark

Search for other papers by Allan Carlé in
Google Scholar
PubMed
Close
,
Jens Faber Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Jens Faber in
Google Scholar
PubMed
Close
,
Rudi Steffensen Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark

Search for other papers by Rudi Steffensen in
Google Scholar
PubMed
Close
,
Peter Laurberg Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark

Search for other papers by Peter Laurberg in
Google Scholar
PubMed
Close
, and
Birte Nygaard Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Close

Objectives: In previous studies, around half of all hypothyroid patients preferred levo-thyroxine (L-T4) + levo-triiodothyronine (L-T3) combination therapy, 25% preferred T4, and 25% had no preference. The reason for this is yet to be explored. Methods: A total of 45 overtly autoimmune, hypothyroid patients – now euthyroid on ≥6 months’ L-T4 therapy – participated in a prospective, double-blind, cross-over study. The patients were randomized into 2 groups of either 3 continuous months’ L-T4 therapy followed by 3 months’ combination therapy or vice versa. In all periods, 50 μg L-T4 was blindly replaced by either (identical) 50 μg L-T4 or by 20 μg T3. L-T4 was hereafter adjusted to obtain normal serum TSH values. We investigated 3 single nucleotide polymorphisms (SNPs) on the type II iodothyronine deiodinase (DIO2) gene (rs225014 (Thr92Ala), rs225015, and rs12885300 (ORFa-Gly3Asp)) and 1 SNP on the cellular membrane transport-facilitating monocarboxylate transporter (MCT10) gene (rs17606253), and asked in which of the 2 treatment periods patients felt better (i.e., which treatment was preferred). Results: 27 out of 45 patients (60%) preferred the combination therapy. Two polymorphisms (rs225014 (DIO2, Thr92Ala) and rs17606253 (MCT10)) were combined yielding 3 groups: none vs. 1 of 2 vs. both SNPs present, and 42 vs. 63 vs. 100% of our patients in the 3 groups preferred the combined treatment (Jongheere-Terpstra trend test, p = 0.009). Conclusion: The present study indicates that the combination of polymorphisms in DIO2 (rs225014) and MCT10 (rs17606253) enhances hypothyroid patients’ preference for L-T4 + L-T3 replacement therapy. In the future, combination therapy may be restricted or may be even recommended to individuals harbouring certain polymorphisms.

Free access
Maria Rossing Department of Endocrinology, Herlev University Hospital, Herlev
Center of Genomic Medicine, Rigshospitalet, Copenhagen University, Copenhagen, Denmark

Search for other papers by Maria Rossing in
Google Scholar
PubMed
Close
,
Birte Nygaard Department of Endocrinology, Herlev University Hospital, Herlev

Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Close
,
Finn Cilius Nielsen Center of Genomic Medicine, Rigshospitalet, Copenhagen University, Copenhagen, Denmark

Search for other papers by Finn Cilius Nielsen in
Google Scholar
PubMed
Close
, and
Finn Noe Bennedbæk Department of Endocrinology, Herlev University Hospital, Herlev

Search for other papers by Finn Noe Bennedbæk in
Google Scholar
PubMed
Close

We aimed to investigate the diagnostic accuracy of ultrasound (US)-guided fine-needle aspirates (FNAs) obtained from 854 consecutive Danish patients with a scintigraphically cold thyroid nodule in a borderline iodine-deficient area. Clinical, sonographic, and pathological findings in patients with a cold thyroid nodule undergoing US-guided FNA were prospectively registered. 408 patients underwent thyroid surgery, resulting in 50 cancers and in addition 37 patients had an incidental finding of papillary thyroid microcarcinomas. Based on the diagnostic FNA, we found sensitivity and specificity for malignancy of 73.9 and 99.2%, respectively. The positive and negative predictive values of a diagnostic FNA for malignancy were 89.5 and 97.7%. We identified 6 false-negative and 2 false-positive diagnoses. Solid versus cystic feature of the nodule, as well as >2 high-risk US features, were predictive for malignancy. Cancer incidence was 13% among females and 9% among males. The accuracy of a diagnostic set-up based on clinical examination, scintigraphy, US, and US-guided FNA was determined with a 48% rate of histopathological validation in the cohort. The overall thyroid cancer incidence has increased worldwide, but our results suggest that the most frequent occurring cancer is an incidental papillary thyroid microcarcinoma of which the clinical significance has yet to be established.

Open access
Wilmar M. Wiersinga Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Wilmar M. Wiersinga in
Google Scholar
PubMed
Close
,
Leonidas Duntas Endocrine Unit, Evgenidion Hospital, University of Athens Medical School, Athens, Greece

Search for other papers by Leonidas Duntas in
Google Scholar
PubMed
Close
,
Valentin Fadeyev Federal Endocrinological Scientific Center, Moscow, Russia

Search for other papers by Valentin Fadeyev in
Google Scholar
PubMed
Close
,
Birte Nygaard Department of Endocrinology, Herlev Hospital, Herlev, Denmark

Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Close
, and
Mark P.J. Vanderpump Department of Endocrinology, Royal Free Hampstead NHS Trust, London, UK

Search for other papers by Mark P.J. Vanderpump in
Google Scholar
PubMed
Close

Background: Data suggest symptoms of hypothyroidism persist in 5–10% of levothyroxine (L-T4)-treated hypothyroid patients with normal serum thyrotrophin (TSH). The use of L-T4 + liothyronine (L-T3) combination therapy in such patients is controversial. The ETA nominated a task force to review the topic and formulate guidelines in this area. Methods: Task force members developed a list of relevant topics. Recommendations on each topic are based on a systematic literature search, discussions within the task force, and comments from the European Thyroid Association (ETA) membership at large. Results: Suggested explanations for persisting symptoms include: awareness of a chronic disease, presence of associated autoimmune diseases, thyroid autoimmunity per se, and inadequacy of L-T4 treatment to restore physiological thyroxine (T4) and triiodothyronine (T3) concentrations in serum and tissues. There is insufficient evidence that L-T4 + L-T3 combination therapy is better than L-T4 monotherapy, and it is recommended that L-T4 monotherapy remains the standard treatment of hypothyroidism. L-T4 + L-T3 combination therapy might be considered as an experimental approach in compliant L-T4-treated hypothyroid patients who have persistent complaints despite serum TSH values within the reference range, provided they have previously received support to deal with the chronic nature of their disease, and associated autoimmune diseases have been excluded. Treatment should only be instituted by accredited internists/endocrinologists, and discontinued if no improvement is experienced after 3 months. It is suggested to start combination therapy in an L-T4/L-T3 dose ratio between 13:1 and 20:1 by weight (L-T4 once daily, and the daily L-T3 dose in two doses). Currently available combined preparations all have an L-T4/L-T3 dose ratio of less than 13:1, and are not recommended. Close monitoring is indicated, aiming not only to normalize serum TSH and free T4 but also normal serum free T4/free T3 ratios. Suggestions are made for further research. Conclusion: L-T4 + L-T3 combination therapy should be considered solely as an experimental treatment modality. The present guidelines are offered to enhance its safety and to counter its indiscriminate use.

Free access
Luba Freja Michaelsson Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Luba Freja Michaelsson in
Google Scholar
PubMed
Close
,
Jeppe Lerche  la Cour Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Jeppe Lerche  la Cour in
Google Scholar
PubMed
Close
,
Bjarke Borregaard Medici Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Bjarke Borregaard Medici in
Google Scholar
PubMed
Close
,
Torquil Watt Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Torquil Watt in
Google Scholar
PubMed
Close
,
Jens Faber Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Jens Faber in
Google Scholar
PubMed
Close
, and
Birte Nygaard Department of Endocrinology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Close

Objectives: According to one hypothesis, the popularity of levothyroxine (L-T<sub>4</sub>)/liothyronine (L-T<sub>3</sub>) combination therapy relates to weight loss. The purpose of this study was to detect a possible correlation between thyroid-related quality of life (QoL) and weight loss in hypothyroid patients switched from L-T<sub>4</sub> monotherapy to L-T<sub>4</sub>/L-T<sub>3</sub> combination therapy. Methods: In an open-label cohort study, all hypothyroid patients referred to the University Hospital endocrine clinic due to persistent symptoms despite adequate L-T<sub>4</sub> monotherapy (without other explanations for the symptoms) were switched from L-T<sub>4</sub> monotherapy to L-T<sub>4</sub>/ L-T<sub>3</sub> combination therapy at a ratio of approximately 17/1. At baseline and after 3 months of treatment we measured: QoL by the Thyroid Patient-Reported Outcome (ThyPRO-39) questionnaire, thyroid hormones, body weight, body composition by a DEXA-scan, and cognitive function by evaluating participants’ reaction time as well as working memory by the California Computerized Assessment Package (CalCAP®). QoL was re-evaluated after 12 months. Results: Twenty-three patients participated (91% women, median age 47 years). The ThyPRO-39 composite score decreased from a median of 54 (quartiles: 34, 74) to 15 (11, 28) after 3 months (p < 0.0001), and 20 (14, 26) after 12 months, indicating a better QoL. There was no change in body weight, and no correlations between QoL and weight. There was a slight improvement in cognitive function, whereas body composition, heart rate, and serum TSH did not change. Conclusion: Our study on hypothyroid patients switched from L-T<sub>4</sub> monotherapy to L-T<sub>4</sub>/L-T<sub>3</sub> combination therapy showed a substantial improvement in QoL measured by the ThyPRO-39. This improvement could not be explained by weight loss.

Free access
Birte Nygaard Departments of Endocrinology, Herlev Hospital, Copenhagen

Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Close
,
Jens Bentzen Departments of Oncology, Herlev Hospital, Copenhagen

Search for other papers by Jens Bentzen in
Google Scholar
PubMed
Close
,
Peter Laurberg Department of Endocrinology, Aalborg Hospital, Aalborg

Search for other papers by Peter Laurberg in
Google Scholar
PubMed
Close
,
Susanne Møller Pedersen Departments of Biochemistry, Odense University Hospital, Odense

Search for other papers by Susanne Møller Pedersen in
Google Scholar
PubMed
Close
,
Lars Bastholt Departments of Oncology, Odense University Hospital, Odense

Search for other papers by Lars Bastholt in
Google Scholar
PubMed
Close
,
Aase Handberg Departments of Biochemistry, Aarhus Hospital, Aarhus, Denmark

Search for other papers by Aase Handberg in
Google Scholar
PubMed
Close
,
Carsten Rytter Departments of Oncology, Aarhus Hospital, Aarhus, Denmark

Search for other papers by Carsten Rytter in
Google Scholar
PubMed
Close
,
Christian Godballe ENT Head and Neck Surgery, Odense University Hospital, Odense

Search for other papers by Christian Godballe in
Google Scholar
PubMed
Close
, and
Jens Faber Departments of Endocrinology, Herlev Hospital, Copenhagen

Search for other papers by Jens Faber in
Google Scholar
PubMed
Close

During follow-up on patients treated for differentiated thyroid cancer, thyroglobulin (Tg) antibodies can interfere with the Tg assay, making the use of Tg less reliable as a tumor marker. Purpose: To compare Tg and Tg autoantibodies (Tg-Ab) methods used in Denmark, regarding the number of patient samples being accepted for evaluating the result of a serum thyroglobulin (s-Tg) measurement. Design: 95 consecutive blood samples drawn from patients in 2006 in one center were selected according to the following criteria: s-Tg <1µg/l and accepted BRAHMS Tg+ recovery test using 50 ng of Tg. Samples were retested with: (1) DPC IMMULITE 2000 Tg and Tg-Ab, (2) BRAHMS Tg and Tg-Ab on Kryptor, (3) BRAHMS Tg+ and Dynotest anti-Tg, (4) DELFIA hTg and recovery test using 25 ng of Tg, and (5) BRAHMS Tg+ with recovery test using 1 and 50 ng of Tg. Results: The number of patient samples that was not accepted for Tg evaluation varied from 2 to 26% when the reference values suggested by the manufacturers of the assay were used. When using the detection limit to the cutoff seen in epidemiological studies the number increased to 40%. Conclusion: We found large discrepancies in acceptance of patient samples for s-Tg evaluation, thus illustrating a diagnostic dilemma.

Free access
Bjarke Borregaard Medici Department of Endocrinology, Herlev University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Bjarke Borregaard Medici in
Google Scholar
PubMed
Close
,
Jeppe Lerche la Cour Department of Endocrinology, Herlev University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Jeppe Lerche la Cour in
Google Scholar
PubMed
Close
,
Luba Freja Michaelsson Department of Endocrinology, Herlev University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Luba Freja Michaelsson in
Google Scholar
PubMed
Close
,
Jens Oscar Faber Department of Endocrinology, Herlev University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Jens Oscar Faber in
Google Scholar
PubMed
Close
, and
Birte Nygaard Department of Endocrinology, Herlev University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Close

Background: Despite biochemical euthyroidism, some levothyroxine (L-T<sub>4</sub>)-treated hypothyroid patients report persisting symptoms and some of these patients are tentatively treated with a combination of L-T<sub>4</sub> and liothyronine (L-T<sub>3</sub>). Combination therapy and the appropriate choice of blood tests to monitor treatment are highly debated among specialists and patients. Aim: To evaluate whether measuring serum triiodothyronine (S-T<sub>3</sub>) at baseline or during combination therapy can be used as an indicator of a positive effect from L-T<sub>4</sub>/L-T<sub>3</sub> combination therapy. Materials and Methods: Observational retrospective study of patients (n = 42) with persisting symptoms of hypothyroidism despite L-T<sub>4</sub> therapy who had normal TSH levels and did not have any comorbidities that could explain their symptoms. All were then treated with L-T<sub>4</sub>/L-T<sub>3</sub> combination therapy at a dose ratio of 17/1 according to European Thyroid Association guidelines. Based on patient-reported outcome, they were divided into responders and nonresponders. Results: Five patients were lost to follow-up and thus excluded. At the 3-month follow-up, 11 were classified as nonresponders and 26 as responders. At 12 months these figures had changed to 13 (35%) and 24 (65%), respectively. When comparing responders versus nonresponders, no differences were seen at baseline or during follow-up in S-T<sub>3</sub> and in free T<sub>3</sub> estimates. Further, logistic regression showed no correlation between S-T<sub>3</sub> and free T<sub>3</sub> estimates and responder/nonresponder status. Conclusion: Our data indicate that serum T<sub>3</sub> measurements are not suitable to predict which patient will benefit from L-T<sub>4</sub>/L-T<sub>3</sub> combination therapy, and treatment response cannot be followed by repeated T<sub>3</sub> measurements either.

Free access
Jeppe Lerche la Cour Center for Endocrinology and Metabolism, Department of Internal Medicine, Herlev and Gentofte Hospitals, Herlev, Denmark

Search for other papers by Jeppe Lerche la Cour in
Google Scholar
PubMed
Close
,
Line Tang Møllehave Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Capital Region, Denmark

Search for other papers by Line Tang Møllehave in
Google Scholar
PubMed
Close
,
Bjarke Røssner Medici Center for Endocrinology and Metabolism, Department of Internal Medicine, Herlev and Gentofte Hospitals, Herlev, Denmark

Search for other papers by Bjarke Røssner Medici in
Google Scholar
PubMed
Close
,
Christian Zinck Jensen Center for Endocrinology and Metabolism, Department of Internal Medicine, Herlev and Gentofte Hospitals, Herlev, Denmark

Search for other papers by Christian Zinck Jensen in
Google Scholar
PubMed
Close
,
Anne Ahrendt Bjerregaard Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Capital Region, Denmark

Search for other papers by Anne Ahrendt Bjerregaard in
Google Scholar
PubMed
Close
, and
Birte Nygaard Center for Endocrinology and Metabolism, Department of Internal Medicine, Herlev and Gentofte Hospitals, Herlev, Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Close

Introduction

High compared with low educational level increases the odds of starting levothyroxine (L-T4) with a normal thyroid-stimulating hormone – the mechanism is most likely patient request. The use of liothyronine (L-T3) and desiccated thyroid extract (DTE) is also speculated to be initiated at patients’ request. Therefore, the primary aim of this study was to evaluate if educational level influences treatment with L-T3 and DTE.

Material and methods

In this register-based cross-sectional study, we included all Danish citizens ≥30 years with redeemed prescription of L-T4, L-T3, or DTE during 2017–2020. We defined educational levels as short, medium, and long (<10 years, 10–12 years, and above 12 years, respectively). The association between educational level and treatment with LT3 or DTE vs only LT4 was analyzed in logistic regression models adjusted for age and sex.

Results

We included 154,360 individuals using thyroid medication of whom 3829 were treated with L-T3 (2.48%) and 430 with DTE (0.28%). The usage was highest among women (3.15%) and the age group 40–49 (5.6%). Longer education compared with short increased the odds of being treated with DTE or L-T3 (medium education odds ratio (OR) 1.61 (95% CI 1.50–1.8) and long education OR 1.95 (95% CI 1.79–2.13)). Test for trend: OR: 1.37 (95% CI 1.31–1.42). Adjustment for other covariates did not affect the results substantially.

Conclusion

Persons with a longer compared to a shorter education are more often treated with either DTE or L-T3, and the usage of these drugs is limited to less than 3% of thyroid hormone users.

Open access
Jacqueline Jonklaas Division of Endocrinology, Georgetown University, Washington, District of Columbia, USA

Search for other papers by Jacqueline Jonklaas in
Google Scholar
PubMed
Close
,
Antonio C. Bianco Section of Adult and Pediatric Endocrinology and Metabolism, University of Chicago, Chicago, Illinois, USA

Search for other papers by Antonio C. Bianco in
Google Scholar
PubMed
Close
,
Anne R. Cappola Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Search for other papers by Anne R. Cappola in
Google Scholar
PubMed
Close
,
Francesco S. Celi Division of Endocrinology, Diabetes and Metabolism, Virginia Commonwealth University, Richmond, Virginia, USA

Search for other papers by Francesco S. Celi in
Google Scholar
PubMed
Close
,
Eric Fliers Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center, Amsterdam, The Netherlands

Search for other papers by Eric Fliers in
Google Scholar
PubMed
Close
,
Heike Heuer Department of Endocrinology, Diabetes and Metabolism, University Duisburg-Essen, Essen, Germany

Search for other papers by Heike Heuer in
Google Scholar
PubMed
Close
,
Elizabeth A. McAninch Division of Endocrinology, Rush University, Chicago, Illinois, USA

Search for other papers by Elizabeth A. McAninch in
Google Scholar
PubMed
Close
,
Lars C. Moeller Department of Endocrinology, Diabetes and Metabolism, University Duisburg-Essen, Essen, Germany

Search for other papers by Lars C. Moeller in
Google Scholar
PubMed
Close
,
Birte Nygaard Center for Endocrinology and Metabolism, Department of Internal Medicine, Herlev and Gentofte Hospitals, Herlev, Denmark

Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Close
,
Anna M. Sawka Division of Endocrinology, University Health Network and University of Toronto, Toronto, Ontario, Canada

Search for other papers by Anna M. Sawka in
Google Scholar
PubMed
Close
,
Torquil Watt Department of Endocrinology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

Search for other papers by Torquil Watt in
Google Scholar
PubMed
Close
, and
Colin M. Dayan Thyroid Research Group, School of Medicine, Cardiff University, Cardiff, United Kingdom

Search for other papers by Colin M. Dayan in
Google Scholar
PubMed
Close

Background: Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies. Methods: The American Thyroid Association (ATA), British Thyroid Association (BTA), and European Thyroid Association (ETA) held a joint conference on November 3, 2019 (live-streamed between Chicago and London) to review new basic science and clinical evidence regarding combination therapy with presentations and input from 12 content experts. After the presentations, the material was synthesized and used to develop Summary Statements of the current state of knowledge. After review and revision of the material and Summary Statements, there was agreement that there was equipoise for a new clinical trial of combination therapy. Consensus Statements encapsulating the implications of the material discussed with respect to the design of future clinical trials of LT4/LT3 combination therapy were generated. Authors voted upon the Consensus Statements. Iterative changes were made in several rounds of voting and after comments from ATA/BTA/ETA members. Results: Of 34 Consensus Statements available for voting, 28 received at least 75% agreement, with 13 receiving 100% agreement. Those with 100% agreement included studies being powered to study the effect of deiodinase and thyroid hormone transporter polymorphisms on study outcomes, inclusion of patients dissatisfied with their current therapy and requiring at least 1.2 µg/kg of LT4 daily, use of twice daily LT3 or preferably a slow-release preparation if available, use of patient-reported outcomes as a primary outcome (measured by a tool with both relevant content validity and responsiveness) and patient preference as a secondary outcome, and utilization of a randomized placebo-controlled adequately powered double-blinded parallel design. The remaining statements are presented as potential additional considerations. Discussion: This article summarizes the areas discussed and presents Consensus Statements to guide development of future clinical trials of LT4/LT3 combination therapy. The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations.

Free access