Desiccated Thyroid (Rx)

INTRODUCTION: Standard levothyroxine (LT4) therapy may not fully address all risks associated with hypothyroidism-especially cognitive decline, dementia, and mortality-even when TSH levels are normalized. Observational studies link hypothyroidism to higher dementia rates; the role of LT4 plus T3 therapies remains uncertain. METHODS: This retrospective cohort study analyzed TriNetX data, comparing 1.26 million patients with hypothyroidism (on LT4, LT4 + T3, or desiccated thyroid extract) to 3.32 million controls. Outcomes included dementia, atrial fibrillation, and mortality over 20 years of follow-up. Propensity score matching was used to balance covariates for age, sex, and comorbidities. Adjusted hazard ratios were obtained via Cox proportional hazard modeling. A parallel systematic review and meta-analysis of 12 studies evaluated dementia risk in hypothyroidism. RESULTS: Patients with hypothyroidism showed a ∼1.4-fold higher risk of dementia and a >2.0-fold increase in mortality-even with normal TSH-and these risks were most pronounced when TSH levels were off-target. A parallel meta-analysis indicated a 1.4-fold heightened dementia risk. In cohorts formed by propensity score matching comparing LT4 monotherapy vs combination therapy, relative risk analysis indicated 27% and 31% lower dementia and mortality risks, respectively, with combination therapy. The adjusted Cox model (hazard ratio) showed 16% and 25% reductions in these outcomes for combination therapy patients. CONCLUSION: Despite standard LT4 therapy, hypothyroidism remains associated with heightened risks of dementia and mortality. Adding T3 may more effectively mitigate these risks than LT4 alone, but further studies are needed to confirm the cognitive and survival benefits of T3-containing regimens. © The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissi

CONTEXT: Levothyroxine (L-T4) monotherapy is the standard of care for the treatment of hypothyroidism. A minority of L-T4-treated patients remain symptomatic and report better outcomes with combination therapy that contains liothyronine (L-T3) or with desiccated thyroid extract (DTE). OBJECTIVE: This work aimed to assess patient preferences in the treatment of hypothyroidism. METHODS: A systematic review, meta-analysis, meta-regression, and network meta-analysis of randomized controlled trials (RCTs) comparing treatments for adults with hypothyroidism (L-T4 vs L-T4 + L-T3 or DTE). Searches were conducted in PubMed, Embase, and Cochrane databases up to April 10, 2024. Data extraction and quality assessment were independently performed by 4 researchers. RESULTS: Eleven RCTs (8 cross-over studies) with a total of 1135 patients were considered. Overall, 24% of patients preferred L-T4 vs 52% who preferred L-T4 + L-T3 or DTE; 24% had no preference. The meta-analysis confirmed the preference for combination therapy over L-T4 monotherapy (relative risk [RR]: 2.20; 95% CI, 1.38-3.52; P = .0009). Excluding 4 studies reduced the high heterogeneity (I2 = 81%) without affecting the results (RR: 1.97; 95% CI, 1.52-2.54; P < .00001; I2 = 24%). This preference profile remained when only crossover studies were considered (RR: 2.84; 95% CI, 1.50-5.39; P < .00001). Network meta-analysis confirmed the preference for DTE and L-T3 + L-T4 vs L-T4 alone. CONCLUSION: Patients with hypothyroidism prefer combination therapy (L-T3 + L-T4 or DTE) over L-T4 monotherapy. The strength of these findings justifies considering patient preferences in the setting of shared decision-making in the treatment of hypothyroidism. © The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected]. See the journal About page for additional terms.

Regardless of the cause, hypothyroidism should be treated with levothyroxine. The objectives of management are the normalization of TSH levels and the relief of symptoms. In general, the vast majority of patients who achieve normalization of TSH levels show a resolution of symptoms; however, for a small number of individuals, symptoms persist (despite adequate control of TSH). This scenario generates a dilemma in the therapeutic approach to these patients, because even when excluding other causes or concomitant diseases that can explain the persistence of symptoms, pharmacological management strategies are scarce. Consequently, the efficacy of some less conventional approaches to therapy, such as the use of LT3 monotherapy, desiccated thyroid extracts, and LT4/LT3 combinations, in addressing persistent hypothyroid symptoms have been evaluated in multiple studies. The majority of these studies did not observe a significant benefit from these "nonconventional" therapies in comparison to results with LT4 monotherapy alone. Nevertheless, some studies report that a significant proportion of patients prefer an alternative to monotherapy with LT4. The most common approach has been to prescribe a combination of LT4 and LT3, and this review describes and analyzes the current evidence of the efficacy of LT4/LT3 combination therapy vs. LT4 monotherapy in addressing persistent hypothyroidism symptoms to provide suggested guidelines for clinicians in the management of these patients.

BACKGROUND: Persistent symptoms in hypothyroid patients despite normalized TSH levels suggest the need for alternative treatments. This study aims to evaluate the effectiveness of combined T4 and T3 therapy or desiccated thyroid (DTE) compared to T4 monotherapy, with a focus on thyroid profile, lipid profile, and quality of life metrics. METHODS: We conducted a systematic review in Embase, Medline/PubMed, and Web of Science up to 11/23/2023. We used the following keywords: "Armour Thyroid," OR "Thyroid extract," OR "Natural desiccated thyroid," OR "Nature-Throid," "desiccated thyroid," OR "np thyroid," OR "Synthroid," OR "levothyroxine," OR "Liothyronine," "Cytomel," OR "Thyroid USP," OR "Unithroid." AND "hypothyroidism. " We only included RCTs and excluded non-RCT, case-control studies, and non-English articles. RESULTS: From 6,394 identified records, 16 studies qualified after screening and eligibility checks. We included two studies on desiccated thyroid and 15 studies on combined therapy. In this meta-analysis, combination therapy with T4 + T3 revealed significantly lower Free T4 levels (mean difference (MD): -0.34; 95% CI: -0.47, -0.20), Total T4 levels (mean difference: -2.20; 95% CI: -3.03, -1.37), and GHQ-28 scores (MD: -2.89; 95% CI: -3.16, -2.63), compared to T4 monotherapy. Total T3 levels were significantly higher in combined therapy (MD: 29.82; 95% CI: 22.40, 37.25). The analyses demonstrated moderate to high heterogeneity. There was no significant difference in Heart Rate, SHBG, TSH, Lipid profile, TSQ-36, and BDI Score. Subjects on DTE had significantly higher serum Total T3 levels (MD: 50.90; 95% CI: 42.39, 59.42) and significantly lower serum Total T4 (MD: -3.11; 95% CI: -3.64, -2.58) and Free T4 levels (MD: -0.50; 95% CI: -0.57, -0.43) compared to T4 monotherapy. Moreover, DTE treatment showed modestly higher TSH levels (MD: 0.49; 95% CI: 0.17, 0.80). The analyses indicated low heterogeneity. There was no significant difference in Heart Rate, SHBG, Lipid profile, TSQ-36, GHQ-28, and BDI Score. CONCLUSIONS: Our study revealed that combined therapy and DTE lead to higher T3 and lower T4 levels, compared to T4 monotherapy in hypothyroidism. Howeve

Background: Desiccated thyroid extract (DTE) is no longer recommended for the treatment of hypothyroidism but is still in use. This review aimed to summarize the available literature on treatment with DTE in adult patients with hypothyroidism. Methods: The search was conducted up until January 6, 2024, in six electronic databases. Two reviewers independently screened all the search results. The retrieved studies compared DTE treatment with levothyroxine or combination therapy with liothyronine and levothyroxine. The primary outcome was quality of life (QoL), and the secondary outcomes included symptoms, treatment preference, adverse effects, thyroid hormone levels, thyroid autoantibodies, cardiovascular measures, and gene polymorphisms in deiodinase enzymes. Results: In the qualitative synthesis, we included nine nonrandomized studies of interventions (NRSIs), two randomized clinical trials (RCTs), and three case reports. The overall quality of evidence was moderate to very low for the various outcomes. The RCTs found no difference between treatments regarding QoL and symptom score assessments. In the NRSIs, symptom and QoL assessments were in favor of DTE. The included studies indicated that DTE may cause an increase in heart rate, lower body weight, and lower high-density lipoprotein compared with other treatment regimens, but results were conflicting. Conclusions: Most studies of DTE treatment are hampered by an inferior design, and data on long-term effects and side effects are lacking. Two RCTs could not demonstrate any difference in QoL or symptom scores when comparing DTE with other thyroid hormone substitutions. Future trials of DTE in patients with hypothyroidism should be based on adequate study designs, validated measures of QoL, patients with reduced QoL, and the assessment of biomarkers reflecting long-term adverse effects.

OBJECTIVE: To determine the association between a transition from levothyroxine (LT4) to combination therapy and change in the Thyroid Symptom Questionnaire (TSQ-36). METHODS: We performed a post hoc subgroup analysis of 2 previous randomized, double-blind, crossover studies (total n = 143) to evaluate patient symptoms on treatment with LT4, desiccated thyroid extract (DTE), and levothyroxine + liothyronine (LT4+LT3). The TSQ-36 was completed at the end of each treatment period in the context of normal thyroid stimulating hormone levels. Patients were stratified based on their TSQ-36 score on LT4: Low Symptoms (TSQ-36: 0-12), Moderate Symptoms (TSQ-36: 13-24), and High Symptoms (TSQ-36: 25-36). Mean TSQ-36 scores were compared on LT4, LT4+LT3, and DTE. Treatment-blinded preference of therapy was also stratified by TSQ-36 score on LT4. RESULTS: In cohort 1, the Moderate-High Symptoms group had significantly lower TSQ-36 scores on DTE vs LT4 (P = .01). In cohort 2, the High Symptoms group had significantly lower TSQ-36 scores on DTE vs LT4 (P < .01) and on LT4+LT3 vs LT4 (P < .001). The Moderate Symptoms group had significantly lower TSQ-36 scores on DTE vs LT4 (P = .02). The Low Symptoms group had significantly lower TSQ-36 scores on LT4 vs DTE (P = .03) and LT4+LT3 (P = .02). Patients who preferred combination therapy had significantly higher TSQ-36 scores than patients who preferred LT4. Persistent symptoms may be due to a relative deficiency in triiodothyronine, which could be remedied by combination therapy. CONCLUSION: The TSQ-36 can potentially be used to quantify patient symptoms and guide thyroid hormone therapy. Patients on LT4, with moderate-to-severe symptoms despite normalization of thyroid stimulating hormone, could consider a trial of combination therapy. Patients with low symptoms on LT4 should generally avoid combination therapy. Published by Elsevier Inc.

INTRODUCTION: Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypothyroid patients, while also exploring the most symptomatic patients. METHODOLOGY: Prospective, randomized, double-blind, crossover study of 75 hypothyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypothyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect. RESULTS: Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypothyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component). CONCLUSIONS: As a group, outcomes were similar among hypothyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE. © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

CONTEXT: Patients previously treated with desiccated thyroid extract (DTE), when being switched to levothyroxine (L-T₄), occasionally did not feel as well despite adequate dosing based on serum TSH levels. OBJECTIVE: Our objective was to investigate the effectiveness of DTE compared with L-T₄ in hypothyroid patients. DESIGN AND SETTING: We conducted a randomized, double-blind, crossover study at a tertiary care center. PATIENTS: Patients (n = 70, age 18-65 years) diagnosed with primary hypothyroidism on a stable dose of L-T₄ for 6 months were included in the study. INTERVENTION: Patients were randomized to either DTE or L-T₄ for 16 weeks and then crossed over for the same duration. OUTCOME MEASURES: Biochemical and neurocognitive tests at baseline and at the end of each treatment period were evaluated. RESULTS: There were no differences in symptoms and neurocognitive measurements between the 2 therapies. Patients lost 3 lb on DTE treatment (172.9 ± 36.4 lb vs 175.7 ± 37.7 lb, P < .001). At the end of the study, 34 patients (48.6%) preferred DTE, 13 (18.6%) preferred L-T₄, and 23 (32.9%) had no preference. In the subgroup analyses, those patients who preferred DTE lost 4 lb during the DTE treatment, and their subjective symptoms were significantly better while taking DTE as measured by the general health questionnaire-12 and thyroid symptom questionnaire (P < .001 for both). Five variables were predictors of preference for DTE. CONCLUSION: DTE therapy did not result in a significant improvement in quality of life; however, DTE caused modest weight loss and nearly half (48.6%) of the study patients expressed preference for DTE over L-T₄. DTE therapy may be relevant for some hypothyroid patients.

Our laboratory has reported suppression of experimental autoimmune thyroiditis in mice by oral feeding with antigen. Based on these data, we considered it possible that oral feeding of animal thyroglobulin (TG) might induce tolerance to antigen in human autoimmune thyroid disease (AITD). Thirteen patients receiving thyroid hormone replacement with synthetic thyroxine (T4) (five patients with Graves' disease, treated with radioiodine 4 to 11 years ago and eight patients with Hashimoto's thyroiditis) were randomly assigned to a test group (switched to replacement with desiccated thyroid from porcine thyroids) and a control group (maintained on synthetic T4). Humoral and cellular immunologic parameters were evaluated in addition to clinical parameters before and every 3 months after the onset of study for a year. At the onset of study, there was no difference in clinical parameters, or humoral and cellular immunity to thyroid autoantigens, except a finding that one thyroid peroxidase (TPO) peptide (100 approximately 119) appeared to stimulate peripheral blood mononuclear cells (PBMC) during in vitro microproliferation assay more in the test group than control group (p = 0.051 by t test). Additionally, almost all of TPO and thyrotropin receptor extracellular domain (TSHR) peptides were slightly more stimulatory to PBMC from the test group than the control group, although this was not statistically significant. After treatment, all variables were analyzed at each time point between groups (t test), and also were analyzed over time in each group (analysis of variance, ANOVA). Among the clinical parameters, thyrotropin (TSH) levels were unchanged and equal. Total serum T4 levels (p < 0.05 at 6 and 12 months after treatment) and free thyroxine indices (FT4I) (p < 0.05 at all time points after treatment) were lower in the test group than the control group. This is an expected result of treatment with desiccated thyroid. We found no change over time nor any difference between groups at time points for titers of antibodies to thyroid autoantigens, ie, human TG, human TPO, and recombinant human TSHR from Escherichia coli. However, cellular immunity, measured by in vitro mic

Familial dysalbuminemic hyperthyroxinemia (FDH) is a form of euthyroid hyperthyroxinemia caused by ALB gene variants that is commonly misdiagnosed in clinical practice. When coexisting with papillary thyroid carcinoma (PTC), this condition may complicate postoperative management strategies. This study aims to enhance clinical recognition of the coexistence of FDH and PTC and explore evidence-based management approaches. We retrospectively analyzed the diagnostic and therapeutic course of a patient with concurrent FDH and PTC in our clinic and reviewed the current literature. The proband exhibited unsuppressed thyrotropin (TSH) by levothyroxine (L-T4) monotherapy after PTC surgery, with abnormal, persistently elevated total thyroxine (T4) and free T4 levels. Further review of the medical records revealed a similar pattern of thyroid function abnormalities preoperatively. Genetic testing confirmed FDH caused by an ALB gene c.725G>A mutation. Sanger verification confirmed that both the proband's mother and daughter carried the same variant. The proband ultimately achieved adequate TSH suppression with the combination therapy of L-T4 and desiccated thyroid extract (DTE). This case highlights the importance of considering FDH when postoperative T4 and TSH levels show discordance in PTC patients. Increased albumin-T4 binding affinity in these patients may prevent adequate TSH suppression with L-T4 monotherapy, while DTE directly delivers triiodothyronine, without requiring peripheral conversion. Therefore, combination therapy with L-T4 and DTE may achieve effective TSH suppression in these patients. © The Author(s), 2025.

Levothyroxine (T4) monotherapy remains the standard of care for hypothyroidism worldwide. However, a subset of patients continues to report persistent symptoms, such as fatigue, depression, and cognitive difficulties, despite normalized thyroid-stimulating hormone (TSH) levels. This has reignited clinical interest in the active thyroid hormone triiodothyronine (T3) and combination T4/T3 therapies. This review explores the physiological distinctions between T4 and T3, emphasizing the importance of peripheral T4-to-T3 conversion and the role of deiodinase polymorphisms (e.g., DIO2 Thr92Ala) that may impair this process in certain individuals. The evidence for T3-containing therapies is critically evaluated, including synthetic liothyronine and desiccated thyroid extract, comparing their pharmacokinetics, clinical outcomes, and safety profiles with T4 monotherapy. Emerging data suggest that some patients may benefit from combination therapy, particularly in symptom resolution and quality-of-life measures, although robust long-term outcomes remain under debate. Current clinical guidelines from major thyroid societies continue to endorse T4 monotherapy, citing inconsistent trial results and potential cardiovascular risks associated with T3. Nonetheless, a growing movement toward personalized medicine, including genetic profiling, patient-reported outcomes, and individualized dosing, may pave the way for more nuanced treatment strategies. This review underscores the need for a balanced, patient-centered approach to thyroid hormone replacement, integrating evolving science with clinical experience to optimize care for individuals with hypothyroidism.

6. Thyroid. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. 2026 Oct 15. Thyroid is an animal-derived mixture of levothyroxine (T4) and liothyronine (T3), which are normal components of human milk. Limited data on exogenous replacement doses of levothyroxine during breastfeeding indicate no adverse effects in infants. If the mother requires thyroid, it is not a reason to discontinue breastfeeding. The American Thyroid Association recommends that subclinical and overt hypothyroidism should be treated with levothyroxine in lactating women seeking to breastfeed.[1] Thyroid dosage requirement may be increased in the postpartum period compared to prepregnancy requirements patients with Hashimoto’s thyroiditis.[2] Women with treated hypothyroidism appear to have milk with macronutrient content comparable to that of women without thyroid disease.

OBJECTIVE: The practice of treating hypothyroid and euthyroid patients with thyroid hormones varies between countries, as observed in the recent surveys of European thyroid experts, THESIS. As part of the THESIS initiative, we investigated Canadian endocrinologists' perspectives on this topic, focusing on combination therapy with either liothyronine (LT3) plus levothyroxine (LT4) or desiccated thyroid extract (DTE). DESIGN: Members of the Canadian Society of Endocrinology and Metabolism (CSEM) were invited to participate in an anonymous online survey. RESULTS: Out of 348 eligible CSEM members, 68 (19.5%) respondents were included in the analysis. All respondents used LT4 as the first-line treatment for hypothyroid patients. Many respondents (64.7%) would consider LT4 + LT3 for patients on LT4 with persistent symptoms, whereas fewer would consider DTE (16.2%). Most respondents attributed persistent symptoms in LT4-treated patients to psychosocial factors, comorbidities, or unrealistic expectations. Approximately half of the respondents stated that thyroid hormone therapy is never indicated for euthyroid patients. The remaining respondents considered thyroid hormones for euthyroid women with infertility and high thyroid antibody levels (36.8%), depression (13.2%), and growing goiter (7.4%). CONCLUSIONS: Following current guidelines, LT4 tablet is the preferred treatment for hypothyroidism. Most respondents would consider triiodothyronine-containing therapy for patients with persistent symptoms, preferring LT4 + LT3 over DTE. The number of endocrinologists considering combination therapy for hypothyroid patients in Canada was higher than in Europe. Finally, at variance with current guidelines, a fraction of the respondents would consider thyroid hormones in patients with non-thyroidal conditions. © 2025 The Author(s). Clinical Endocrinology published by John Wiley & Sons Ltd.

AIM: The present guideline (GL) is aimed to improve and standardize the treatment of primary hypothyroidism in non-pregnant adults and to offer all the patients the best possible care across the Italian country. TARGET POPULATION: Non-pregnant adults with hypothyroidism. EXCLUDED POPULATION: This GL does not cover the treatment of hypothyroidism in children and adolescents under 18 years of age, in women who are pregnant or breastfeeding, nor in subjects with central hypothyroidism. Also patients who require suppressive therapy with levothyroxine after thyroidectomy for thyroid cancer and those with transient iatrogenic hypothyroidism were not considered in this GL. METHODS: The direct costs and the utilization of resources over time were evaluated for the implementation of the appropriate management within the National Health Service. Recommendations were based on the analysis, according to the GRADE methodology, of the evidence from literature. Patients preferences were collected and verified by means of specific bibliographic research and the active participation of two patients' representatives in the GL development group. RESULTS: The present GL provides 4 formal graded recommendations and 16 ungraded indications for good clinical practice. An elevated agreement was consistently obtained among the panel members. CONCLUSIONS: The present GL provides operative recommendations-based on the best available evidence and cost-effectiveness analysis-for the treatment of adult patients with primary hypothyroidism. The expected benefits from the dissemination, application and implementation of this GL are the improvement of the quality of care, its homogenization across the national territory and the rationalization of health expenditure in the respect of patient preferences. © 2025. The Author(s).

Primary hypothyroidism affects about 3% of the general population in Europe. Early treatments in the late 19th Century involved subcutaneous as well as oral administration of thyroid extract. Until the early 1970s, the majority of people across the world with hypothyroidism were treated with natural desiccated thyroid (NDT) (derived from pig thyroid glands) in various formulations, with the majority of people since then being treated with levothyroxine (L-thyroxine). There is emerging evidence that may account for the efficacy of liothyronine (NDT contains a mixture of levothyroxine and liothyronine) in people who are symptomatically unresponsive to levothyroxine. While this is a highly selected group of people, the severity and chronicity of their symptoms and the fact that many patients have found their symptoms to be alleviated, can be viewed as valid evidence for the potential benefit of NDT when given after careful consideration of other differential diagnoses and other treatment options.

Natural desiccated thyroid (NDT) is a treatment option for many patients with hypothyroidism, but some still exhibit symptoms despite achievement of normal levels of thyroid stimulating hormone (TSH). In this retrospective case series, 13 patients with hypothyroid symptoms were switched from NDT to a liquid formulation of levothyroxine (LT4; Tirosint®-SOL). Laboratory values ≥4 weeks following the switch showed a decrease in TSH levels, maintenance of free triiodothyronine (fT3) levels, and significant increases in free thyroxine (fT4) levels. Patients reported good tolerability, and case summaries are presented for four patients. In summary, this small retrospective case series showed that patients who still had hypothyroid symptoms despite use of NDT can respond well to oral LT4 liquid formulation, including patients who are intolerant of gluten and/or lactose or on hormone replacement therapy or iron supplementation.

OBJECTIVE: Management of hypothyroidism is controversial because of medication cost pressures and scientific uncertainty on how to address treatment dissatisfaction experienced by some patients. The objective was to investigate the experience and preferences of UK endocrinologists in use of thyroid hormones. DESIGN: Web-based survey. PATIENTS: UK endocrinologists were invited to participate. MEASUREMENTS: Responses to questionnaire. RESULTS: The response rate was 21% (272/1295). While levothyroxine monotherapy is regarded as the treatment of choice for hypothyroidism, 51% of respondents stated that combined treatment with levothyroxine and liothyronine could be considered for levothyroxine-treated patients whose symptoms persist despite normalisation of serum thyroid stimulating hormone (TSH) concentration. However, only 40% are currently prescribing such treatment, and just 23% would consider taking it themselves. A small minority prescribe desiccated thyroid extract, and those most likely to do so are aged over 60 years. Most respondents stated that they have no influence over brand or formulation of levothyroxine dispensed to their patients and expect no major differences in efficacy between different formulations. A total of 9% would prescribe levothyroxine for euthyroid enlarging goitre, and 29% for euthyroid female infertility with high titre thyroid peroxidase antibodies, despite recent trials finding no benefit. CONCLUSIONS: UK endocrine practice in management of hypothyroidism is broadly in line with international guidance. However, a minority of respondents would consider thyroid hormone supplementation in euthyroid individuals for female infertility, enlarging goitre, and other indications in which evidence of efficacy is lacking. Willingness to consider prescribing combined levothyroxine and liothyronine, for hypothyroid symptoms which persist despite normalised TSH, has increased in comparison to previous international surveys, despite inconsistent evidence of benefit. © 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

12. Calif Med. 1958 Mar;88(3):206-10. Triiodothyronine; clinical effects in patients with suboptimal response to other thyroid preparations. NEWMAN S, ESCAMILLA RF. Thirty patients with evidence of hypometabolism or a clinically related condition were given triiodothyronine after suboptimal response to thyroxin or desiccated thyroid. DL- and L-isomers of triiodothyronine were used and compared. Thirteen patients (43.3 per cent) were improved and 17 (56.6 per cent) were unimproved or became worse. Side effects occurred in 9 of 34 trials (26 per cent), and could not always be eliminated by decreasing the dosage. The highest percentage of good response occurred in a small group (four of five) who received a combination of desiccated thyroid or thyroxin with supplemental triiodothyronine. Despite careful analysis of the data, no basis was found on which to predict which patients would receive benefit from the triiodothyronine. However, the occasional improvement, sometimes dramatic, suggested that a therapeutic trial with triiodothyronine in difficult or unresponsive cases of hypometabolism or hypothyroidism is justified.

BACKGROUND/OBJECTIVE: The management of hypothyroidism has evolved over time as the development of new guidelines and formulations of thyroid hormone have become available. METHODS: A survey of American Association of Clinical Endocrinology members in the United States examining the treatment of hypothyroidism, including questions about initial choice of therapy, use of liothyronine (LT3)-containing regimens, and use of thyroid hormones in hypothyroid and non-hypothyroid patients. RESULTS: Survey links were opened by 387 of 4000 potential respondents and completed by 299 (7%). Respondents unanimously cited levothyroxine (LT4) as the initial treatment choice for hypothyroidism. Forty-seven percent indicated they would use thyroid hormones in patients with euthyroidism with infertility and elevated thyroid antibodies, with smaller numbers for goiter, depression, hypercholesterolemia, fatigue, and obesity. About 60% would consider combination LT4/LT3 in a patient with euthyroidism who does not feel well on treatment or has persistent symptoms. In contrast, a much smaller minority (16% for LT4/LT3 and 5% for desiccated thyroid extract) used such regimens to manage their own hypothyroidism. Persistent symptoms in treated patients with a normal TSH were most often attributed to psychosocial factors, unrealistic patient expectations, and comorbidities. Significant associations were identified between respondent demographics and treatment choices, most notably age, practice setting, and volume of patients with hypothyroidism. CONCLUSIONS: LT4 monotherapy is overwhelmingly employed as first line therapy for hypothyroidism by U.S. clinicians. However, the high usage of thyroid hormones for patients whose symptoms were considered to be unrelated to hypothyroidism is at odds with current international guidelines for the management of hypothyroidism. © 2025 American Association of Clinical Endocrinology. Published by Elsevier Inc.

CONTEXT: Combination therapy with levothyroxine and liothyronine (LT4 + LT3) and desiccated thyroid extract (DTE) make up >10% of new thyroid hormone (TH) prescriptions in the United States. OBJECTIVE: To assess health care utilization related to cardiovascular disease (CVD) and bone health (BH) events (atrial fibrillation [AF], heart failure [HF], myocardial infarction [MI], stroke, and osteoporosis/fractures [FX]) in participants taking LT4+LT3 or DTE surveyed in the Medical Expenditure Panel Survey database. MATERIALS AND METHODS: Multi-year cross-sectional analysis examining 5437 participants (≥18 years old) treated with LT4, LT4+LT3, or DTE between 2016 and 2020. Health care utilization was assessed through outpatient, emergency, and hospital visits for AF, HF, MI, stroke, FX, and a composite index. A weighted analysis provided national estimates of health care utilization parameters. Utilization was re-analyzed following propensity score-based matching to balance sociodemographic and clinical covariates between treatment groups. Additionally, provider type and specialty data were obtained from visits associated with TH prescriptions. RESULTS: 5106 participants were treated with LT4 monotherapy, 252 with DTE, and 79 with LT4 + LT3. Prevalence of combined outpatient CVD and BH-related care utilization was lower among DTE/LT4+LT3 vs LT4 users (3.5% vs 7.7%; P = .008). There were no differences in emergency/hospital events. After covariate balancing, CVD and BH-related care utilization was similar between groups in outpatient and emergency/hospital settings. LT3 and DTE made up 7.6% of all TH prescriptions. For visits associated with DTE prescriptions, nurse practitioners and alternative medicine professionals were more likely to be identified as the primary provider type. CONCLUSION: No significant differences in CVD- and BH-related health care utilization were identified between LT4 and DTE/LT4+LT3 users after covariate balancing. Non-MD providers were more likely to prescribe DTE. © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].