Delving into the Latest Updates on Thyroxine/Liothyronine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Levothyroxine/Liothyronine liotrix, Thyroxine and Liothyronine, 左甲状腺素/碘塞罗宁

+ [2]

Target

THR-α x THR-β

Action

agonists

Mechanism

THR-α agonists(Thyroid hormone receptor alpha agonists), THR-β agonists(Thyroid hormone receptor beta agonists)

Therapeutic Areas

Eye Diseases

Active Indication

Cataract

Inactive Indication-

Originator Organization

Wuhan Wujing Pharmaceutical Co. Ltd.

Active Organization

Shaanxi Youngbao Pharmaceutical Co., Ltd.

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date

China (13 Jan 2005),

Cataract

Regulation-

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Structure/Sequence

Molecular FormulaC15H13I4NNaO5

InChIKeyVSGRWOHSMUGJIF-LTCKWSDVSA-N

CAS Registry6106-07-6

View All Structures (2)

Hypothyroidism is a common condition, more frequent in females, associated with excess of cardiovascular risk and poor quality of life not completely abrogated by treatment with levothyroxine.
There is an unmet need to define a safe, effective, and feasible regimen to be applied in large trials aimed at assessing levothyroxine/liothyronine combination therapy in patients living with hypothyroidism.
To address this knowledge gap we propose a randomized, three-arm, double-blind, controlled, escalating dose parallel pilot study whose results will lay the foundation of large multicenter trial(s) able to demonstrate the effectiveness (or lack thereof) of levothyroxine/liothyronine combination therapy.

Start Date10 Dec 2024

Sponsor / Collaborator

University of Connecticut Health Center

NCT01848171

/ Unknown statusPhase 4IIT

Effects of Long-term L-thyroxine Replacement on Serum Lipid and Atherosclerosis in Patients With Hypothyroidism

Hypothyroidism is a common clinical entity which is often complicated by dyslipidemia. It is also reported increased risk for incidence of atherosclerosis and resulting coronary heart disease(CHD), heart failure(HF) and cardiovascular(CV) death. The effect of L-thyroxine replacement treatment on serum lipid and atherosclerosis is controversial in hypothyroid patients, especially in those with mild or moderate subclinical hypothyroidism. The present study was designed to investigate whether L-thyroxine replacement was effective in improving serum lipid profiles and retarding atherosclerosis progress.
Studies have shown that hypothyroidism increased the risk of COVID-19 composite poor outcomes. This study also aimed to investigate whether L-thyroxine replacement therapy was effective in reducing the incidence and mortality of COVID-19, and in improving the severity of COVID-19 and COVID-19 related complications.

Start Date01 Jul 2013

Sponsor / Collaborator

Shandong Provincial Hospital

NCT01831869

/ Unknown statusPhase 4IIT

The Beneficial Effect of L-Thyroxine Long -Term Replacement on Lipid Profiles and Atherosclerosis in Subclinical Hypothyroidism: A Prospective Study

Subclinical hypothyroidism (SCH) is a common condition affecting 3-10% of the general population, especially in women older than 50 years old. It is controversial whether SCH can lead to increased risks of cardiovascular (CV) disease and whether treatment with L-thyroxine reverses these risks. The present study was designed to evaluate the effect of L-thyroxine treatment in SCH on lipid profile, atherosclerosis, endothelial function, serum inflammatory factors and adipocytokines.

Start Date01 Apr 2013

Sponsor / Collaborator

Shandong Provincial Hospital

100 Clinical Results associated with Thyroxine/Liothyronine

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100 Translational Medicine associated with Thyroxine/Liothyronine

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100 Patents (Medical) associated with Thyroxine/Liothyronine

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186

Literatures (Medical) associated with Thyroxine/Liothyronine

18 Apr 2025·JCEM Case Reports

Pseudo-Malabsorption in High Dose Levothyroxine–Resistant Hypothyroidism

Article

Author: Tsuchiya, Kyoichiro ; Hosokawa, Tadatsugu ; Shimba, Ryo ; Yamazaki, Miku ; Harai, Nozomi

AbstractA 38-year-old woman was diagnosed with hypothyroidism during pregnancy at age 35 years and started on levothyroxine (LT4). Despite increasing the dose to 400 μg/day and adding liothyronine, her thyroid function did not improve, leading to hospitalization. Upon admission, her thyroid-stimulating hormone (TSH), free triiodothyronine (T3), and free thyroxine (T4) levels were 255 μIU/mL (255 mIU/L) (reference range [RR]: 0.35–4.94 μIU/mL; 0.35–4.94 mIU/L), 3.42 pg/mL (5.27 pmol/L) (RR: 1.71-3.71 pg/mL; 2.63-5.70 pmol/L), and 0.153 ng/dL (1.97 pmol/L) (RR: 0.70-1.48 ng/dL; 9.01-19.05 pmol/L), respectively. She reported good adherence to medication and not consuming interfering food or medication. Endoscopic examination revealed no malabsorption. A 1000-μg oral LT4 loading test showed an increase in free T4 level from 0.787 (10.1 pmol/L) to 2.40 ng/dL (30.9 pmol/L), indicating pseudo-malabsorption. After presenting the loading test results, she admitted to nonadherence. A multidisciplinary team intervened, conducting individual counseling and simplifying treatment. Post-discharge, with LT4 200 μg/day, her TSH, free T3, and free T4 levels improved to 0.496 μIU/mL (0.496 mIU/L), 5.23 pg/mL (8.05 pmol/L), and 2.19 ng/dL (28.2 pmol/L), respectively. When addressing treatment-resistant hypothyroidism, it is crucial to evaluate patient history and medication schedule and to check for malabsorption. Comprehensive interventions are recommended if nonadherence is suspected.

11 Feb 2025·Proceedings of the National Academy of Sciences

Variable transduction of thyroid hormone signaling in structures of the mouse brain

Article

Author: Mohácsik, Petra ; Salas-Lucia, Federico ; Fekete, Csaba ; Wittmann, Gábor ; Bianco, Antonio C. ; Fonseca, Tatiana L. ; Sinkó, Richárd ; Egri, Péter ; Bocco, Barbara M. L. C. ; Batistuzzo, Alice ; Gereben, Balázs ; Halmos, Emese

L-thyroxine (L-T4) monotherapy is the standard treatment for hypothyroidism, administered daily to normalize TSH levels. Once absorbed, T4 is converted to T3 to alleviate most symptoms. However, this treatment abnormally elevates plasma T4 levels in over 50% of patients. Using L-T4-treated Thyroid Hormone (TH) Action Indicator mice, which express a T3-regulated luciferase (Luc) reporter, we examined whether these T4 elevations disrupt TH signaling. Hypothyroid mice exhibited reduced Luc expression across brain regions, and L-T4 treatment failed to restore T3 signaling uniformly. There was also variability in the activity of type 2 deiodinase (D2), the enzyme that generates most brain T3. Intracerebroventricular T4 administration achieved higher elevation of Luc expression in the mediobasal hypothalamus compared to the cortex, and studies on cultured cortical astrocytes and hypothalamic tanycytes revealed cell-type-specific responses to T4. In tanycytes, exposure to T4 sustained D2 activity, leading to progressive T3 signaling, whereas in astrocytes, T4 exposure triggered a drop in D2 activity, limiting T3 production through a ubiquitin-dependent, self-limiting mechanism. The sustained D2 activity in tanycytes was linked to rapid deubiquitination by USP33, as confirmed using a ubiquitin-specific protease (USP) pan-inhibitor and USP33 knockout mice. In conclusion, the brain’s response to L-T4 treatment is heterogeneous, influenced by cell-specific regulation of D2-mediated T3 production. While cortical astrocytes exhibit limited T3 signaling due to D2 ubiquitination, tanycytes coexpressing USP33 amplify T3 signaling by rescuing ubiquitinated D2 from proteasomal degradation. These findings provide mechanistic insights into the limitations of L-T4 therapy and highlight the need for tailored approaches to managing hypothyroidism.

26 Feb 2024·Journal of Pediatric Endocrinology and Metabolism

Thyroid hormone resistance and large goiter mimicking infiltrative carcinoma in a pediatric patient

Author: Baxter, Carly ; Martinez-Rios, Claudia ; Ahmet, Alexandra

AbstractObjectivesResistance to thyroid hormone (RTH) is a genetic condition, caused by mutations in the thyroid hormone receptor gene and characterized by impaired end organ responsiveness to thyroid hormone. Here we describe a novel case of THR associated with large goiter mimicking infiltrative c.Case presentationA 13-year-old male with a hyperthyroid phenotype of RTH diagnosed as a toddler, on methimazole and nadolol therapies presented with an increase in goiter size and possible nodule. Thyroid ultrasound was concerning for a diffuse infiltrative process or malignancy. Methimazole was discontinued and he underwent further imaging, fine needle aspiration and core biopsies. Biopsy results were reassuring and imaging findings were subsequently attributed to RTH rather than malignancy. He started every other day liothyronine therapy, which led to a decrease in goiter size, thyroglobulin level, and improvement of hyperthyroid symptoms.ConclusionsThis is the first case to our knowledge describing the above thyroid imaging findings in association with RTH. It also adds important information to the pediatric literature regarding management of the hyperthyroid phenotype of RTH, including the role of liothyronine therapy.

100 Deals associated with Thyroxine/Liothyronine

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	H03AA03	-

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Cataract	China	Shaanxi Youngbao Pharmaceutical Co., Ltd.	13 Jan 2005

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESPE2018	Not Applicable	Hypothyroidism \| Tachycardia, Supraventricular	-	Amiodarone	obakwwiavv(rztfuaxjcw) = dulxdpsqcf mlhewikusz (ypupvscfwg ) View more	-	27 Sep 2018
				L-thyroxine	obakwwiavv(rztfuaxjcw) = wwfixuzogl mlhewikusz (ypupvscfwg )