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1

Dutt, Rohit, Kailash Chander Malik, Manoj Karwa, and Gaurav Kumar JAIN. "Development and Validation of UPLC-MS/MS Method for Rapid Simultaneous Determination of Levothyroxine and Liothyronine in Human Serum." Journal of Drug Delivery and Therapeutics 10, no. 3-s (2020): 176–81. http://dx.doi.org/10.22270/jddt.v10i3-s.4189.

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A simple ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed and fully validated to simultaneously determine levothyroxine (LT4) and liothyronine (LT3) in human serum. Sample preparation was done through protein precipitation with acetonitrile. HyPURITY C18 column was selected to achieve rapid separation for LT4 and LT3 within 4 min. Electrospray ionization (ESI) under multiple reaction monitoring (MRM) was used to monitor the ion transitions for LT4 (m/z 777.54→731.52), LT3 (m/z 651.64→ 605.65) and internal standard LT4-D3 (m/z
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Vishnumaya, A. M. Anjali Krishna S. S. Alnon L. J*. Shaiju S. Dharan. "Assessment of Quality of Life Among Patients with Hypothyroidism on Levothyroxine: A Review." International Journal of Pharmaceutical Sciences 3, no. 5 (2025): 830–40. https://doi.org/10.5281/zenodo.15345188.

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Hypothyroidism is the most common endocrine disorders that significantly impacts patient health related quality of life (HRQoL). Levothyroxine (LT4) is the primary treatment used alone to restore normal thyroid hormone levels. This review examines how levothyroxine (LT4) treatment influences the quality of life in individuals diagnosed with hypothyroidism. It assesses the effectivity of levothyroxine in symptom resolution, explore factors influencing QoL, and identify possible shortcomings in the current treatment plan. This review evaluates recent observational studies and meta-analyses that
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Bjerkreim, Betty Ann, Sara Salehi Hammerstad, Hanne Løvdal Gulseth, Tore Julsrud Berg, Sindre Lee-Ødegård, and Erik Fink Eriksen. "Thyroid Signaling Biomarkers in Female Symptomatic Hypothyroid Patients on Liothyronine versus Levothyroxine Monotherapy: A Randomized Crossover Trial." Journal of Thyroid Research 2022 (May 4, 2022): 1–10. http://dx.doi.org/10.1155/2022/6423023.

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Background. Levels of thyroid-stimulating hormone (TSH) are believed to reflect degree of disease in patients with hypothyroidism, and normalization of levels is the treatment goal. However, despite adequate levels of TSH after starting levothyroxine (LT4) therapy, 5–10% of hypothyroid patients complain of persisting symptoms with a significant negative impact on quality of life. This indicates that TSH is not an optimal indicator of intracellular thyroid hormone effects in all patients. Our aim was to investigate different effects of LT3 and LT4 monotherapy on other biomarkers of the thyroid
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Meizlik, Paige, Andrew Cucchiara, Lakshmi Kannan, et al. "Physiologic Effects of Levothyroxine and Liothyronine in the in Older Individuals With Persistent Subclinical Hypothyroidism: A Randomized, Double-Blind, Cross-Over Study." Journal of the Endocrine Society 5, Supplement_1 (2021): A976—A977. http://dx.doi.org/10.1210/jendso/bvab048.1996.

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Abstract Background: Subclinical hypothyroidism is common in older individuals, but the physiologic responses to treatment with levothyroxine (LT4) and liothyronine (LT3) are not well defined in this age group. Methods: We conducted a randomized, double-blind, cross-over study of LT4 and LT3 treatment in men and women aged 70 years and over without anti-thyroid peroxidase antibodies with persistent subclinical hypothyroidism, defined as having a TSH level between 4.5 and 19.9 µIU/mL with a normal free thyroxine (FT4) level at two consecutive time points. Physiologic outcome measures assessed a
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Solter, D., and M. Solter. "Benefit of Combined Triiodothyronine (LT3) and Thyroxine (LT4) Treatment in Athyreotic Patients Unresponsive to LT4 Alone." Experimental and Clinical Endocrinology & Diabetes 120, no. 02 (2011): 121–23. http://dx.doi.org/10.1055/s-0031-1297253.

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AbstractDespite some reports, the usefulness of levothyroxine ( LT4) and levotriiodothyronine (LT3) combination therapy in hypothyroidism remains controversial. The objective of this paper is to study a benefit of additional LT3 in athyreotic patients who failed to normalize TSH on LT4 alone even with hyperthyroid serum T4 values.In a survey of 200 athyreotic patients treated between 2006 and 2009, about 7% failed to normalize serum TSH levels following treatment with LT4, though serum T4 values in the hyperthyroid range were achieved. These patients (characterized by serum T4≥160 nmol/L and T
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Shepelkevich, A. P., Yu V. Dydyshka, E. V. Yurenya та ін. "Features of the use of synthetic analogues of thyroid hormones: а 2020 THESIS* questionnaire survey of members of the Belarusian Public Medical Association of Endocrinology and Metabolism". Problems of Endocrinology 68, № 1 (2021): 18–26. http://dx.doi.org/10.14341/probl12828.

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BACKGROUND. The standard treatment for hypothyroidism is levothyroxine (LT4), which in the Republic of Belarus is available in tablet form whereas liothyronine (LT3) is not registered, but patients can purchase them on their own abroad.AIM. This study aimed to investigate Belarusian endocrinologists’ attitude of thyroid hormones in hypothyroid and euthyroid patients.MATERIALS AND METHODS. An online survey was conducted, for which members of the Belarusian Medical Association of Endocrinology and Metabolism were invited by posting information in the group chat and by e-mail. The research period
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Razvi, Salman, Sanaa Mrabeti, and Markus Luster. "Managing symptoms in hypothyroid patients on adequate levothyroxine: a narrative review." Endocrine Connections 9, no. 11 (2020): R241—R250. http://dx.doi.org/10.1530/ec-20-0205.

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The current standard of care for hypothyroidism is levothyroxine (LT4) monotherapy to reduce levels of thyrotropin (thyroid-stimulating hormone, TSH) within its reference range and amelioration of any symptoms. A substantial minority continues to report hypothyroid-like symptoms despite optimized TSH, however. These symptoms are not specific to thyroid dysfunction and are frequent among the euthyroid population, creating a therapeutic dilemma for the treating clinician as well as the patient. We present a concise, narrative review of the clinical research and evidence-based guidance on the man
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Meizlik, Paige, Andrew Cucchiara, Lakshmi Kannan, Theresa Scattergood, and Anne Rentoumis Cappola. "TRH Stimulation Testing in Older Individuals with Persistent Subclinical Hypothyroidism: A Randomized, Double-Blind, Cross-Over Study of Levothyroxine and Liothyronine Administration." Journal of the Endocrine Society 5, Supplement_1 (2021): A853—A854. http://dx.doi.org/10.1210/jendso/bvab048.1742.

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Abstract Background: Subclinical hypothyroidism is common in older individuals. To better understand the underlying physiology, we examined the pituitary-thyroid axis using thyrotropin releasing hormone (TRH) stimulation testing both at baseline and after levothyroxine (LT4) and liothyronine (LT3) supplementation. Methods: We conducted a randomized, double-blind, cross-over study in men and women aged 70 years and over without anti-thyroid peroxidase antibodies with persistent subclinical hypothyroidism, defined as having a TSH level between 4.5 and 19.9 µIU/mL with a normal free thyroxine (FT
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Ettleson, Matthew D., and Antonio C. Bianco. "Individualized Therapy for Hypothyroidism: Is T4 Enough for Everyone?" Journal of Clinical Endocrinology & Metabolism 105, no. 9 (2020): e3090-e3104. http://dx.doi.org/10.1210/clinem/dgaa430.

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Abstract Context It is well recognized that some hypothyroid patients on levothyroxine (LT4) remain symptomatic, but why patients are susceptible to this condition, why symptoms persist, and what is the role of combination therapy with LT4 and liothyronine (LT3), are questions that remain unclear. Here we explore evidence of abnormal thyroid hormone (TH) metabolism in LT4-treated patients, and offer a rationale for why some patients perceive LT4 therapy as a failure. Evidence Acquisition This review is based on a collection of primary and review literature gathered from a PubMed search of “hyp
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Vargas-Uricoechea, Hernando, and Leonard Wartofsky. "LT4/LT3 Combination Therapy vs. Monotherapy with LT4 for Persistent Symptoms of Hypothyroidism: A Systematic Review." International Journal of Molecular Sciences 25, no. 17 (2024): 9218. http://dx.doi.org/10.3390/ijms25179218.

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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 s
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Imran, Syed Ali, Obinna Esomchukwu, and Remigius Agu. "Development of Intranasal Levothyroxine Powder Delivery for Hypothyroidism." Journal of the Endocrine Society 5, Supplement_1 (2021): A828—A829. http://dx.doi.org/10.1210/jendso/bvab048.1689.

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Abstract Background: Hypothyroidism affects 3-5% of the general population with oral levothyroxine (LT4) being the predominant replacement therapy. However, significant proportion of hypothyroid patients are unable to absorb oral replacement leading to therapeutic failure and may require injectable thyroxine. Objectives: To develop non-invasive, less costly, and patient-friendly LT4 nasal delivery alternative using mucoadhesive polymers: chitosan and hydroxypropylmethylcellulose (HPMC). Methods: Six nasal LT4 formulations were developed with either chitosan or hydroxypropyl methylcellulose as
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Garayalde Gamboa, María de los Ángeles, Melina Saban, and Marina Ines Curriá. "Treatment with Intramuscular Levothyroxine in Refractory Hypothyroidism." European Thyroid Journal 8, no. 6 (2019): 319–23. http://dx.doi.org/10.1159/000503324.

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Introduction: Orally and daily levothyroxine (LT4) is the treatment of choice for hypothyroidism. In the majority of cases, the lack of effectiveness by this way may be due to poor adherence; however, gastrointestinal malabsorption may explain more cases of thyroxine refractoriness than previously reputed, due to the number of occult forms of these disorders. Case Presentation: A 55-year-old white man with a diagnosis of low risk of recurrence of follicular variant of papillary thyroid carcinoma was treated with total thyroidectomy, 30 mCi iodine 131, and oral LT4. A year before he presented a
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Trimboli, Pierpaolo, Lorenzo Scappaticcio, Annamaria De Bellis, et al. "Different Formulations of Levothyroxine for Treating Hypothyroidism: A Real-Life Study." International Journal of Endocrinology 2020 (January 20, 2020): 1–5. http://dx.doi.org/10.1155/2020/4524759.

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Objective. Hypothyroid patients are treated by sodium levothyroxine (LT4). Tablet is the mostly used LT4 formulation, and the fasting regimen is required for the absorption of active principle. Also, gastrointestinal diseases and drugs may impair the LT4 bioavailability when tablet is used. Nonsolid LT4 formulations (i.e., liquid solution (LS) and soft gel (SG) capsule) were manufactured to overcome the limitations of LT4 tablet. This study was conceived to evaluate the performance of nonsolid LT4 formulations in a real-life scenario. Methods. Two institutions participated in the study that wa
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Peterson, Sarah J., Elizabeth A. McAninch, and Antonio C. Bianco. "Is a Normal TSH Synonymous With “Euthyroidism” in Levothyroxine Monotherapy?" Journal of Clinical Endocrinology & Metabolism 101, no. 12 (2016): 4964–73. http://dx.doi.org/10.1210/jc.2016-2660.

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Context: Levothyroxine (LT4) monotherapy is the standard of care for hypothyroidism. Objective: To determine whether LT4 at doses that normalize the serum TSH is associated with normal markers of thyroid status. Design: Cross-sectional data from the US National Health and Nutrition Examination Survey (2001–2012) was used to evaluate 52 clinical parameters. LT4 users were compared to healthy controls and controls matched for age, sex, race, and serum TSH. Regression was used to evaluate for correlation with T4 and T3 levels. Participants: A total of 9981 participants with normal serum TSH were
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Albashaireh, Arwa, and Spyridoula Maraka. "Stopping Levothyroxine Therapy in Subclinical Hypothyroidism, Perhaps We Could Start a Trend." Journal of the Endocrine Society 5, Supplement_1 (2021): A954—A955. http://dx.doi.org/10.1210/jendso/bvab048.1950.

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Abstract Introduction: Subclinical hypothyroidism (SCH) is diagnosed based on elevated thyrotropin (TSH) and normal thyroxine (FT4) levels. Previous guidelines recommended treatment of SCH with levothyroxine (LT4) when TSH is > 10 uIU/mL or if TSH <10 uIU/mL with symptoms suggestive of hypothyroidism, positive thyroperoxidase antibodies (TPO Ab) or evidence/risk factors of cardiovascular disease. There has been an increasing practice of LT4 prescription for SCH, which contributes to making LT4 the second most prescribed drug in the US. Case: This case reviews the course of a pati
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Jonklaas, Jacqueline, Antonio C. Bianco, Anne R. Cappola, et al. "Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document." European Thyroid Journal 10, no. 1 (2021): 10–38. http://dx.doi.org/10.1159/000512970.

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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
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Gupta, Manisha, Hitesh Saraogi, and Amit Kumar Dey. "Combination therapy rationale in the management of hypothyroidism." Thyroid Research and Practice 20, no. 3 (2024): 128–32. https://doi.org/10.4103/trp.trp_35_24.

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Hypothyroidism is a common endocrine disorder marked by insufficient thyroid hormone production, leading to symptoms such as fatigue, weight gain, and cognitive impairment. The standard treatment is levothyroxine (LT4) monotherapy, intended to normalize thyroid hormone levels. However, some patients continue to experience symptoms despite achieving biochemical euthyroidism. This has led to interest in LT4 and liothyronine combination therapy, which may better replicate the body’s natural thyroid hormone profile by providing both thyroxine (T4) and triiodothyronine (T3). We present case reports
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Nedeljkovic-Beleslin, Biljana, Roberto Attanasio, Laszlo Hegedüs, et al. "Use of thyroid hormones in hypothyroid and euthyroid patients: A thesis questionnaire survey of Serbian physicians." Srpski arhiv za celokupno lekarstvo, no. 00 (2022): 110. http://dx.doi.org/10.2298/sarh211221110n.

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Introduction/Aim. Hypothyroidism is a common disease and treatment with levothyroxine (LT4) is effective. However, variations in management are frequent. The aim of this study was to identify practices and attitudes of Serbian physicians relating to the treatment of hypothyroidism. Methods. An anonymized questionnaire was distributed electronically to members of the Serbian Thyroid Society, Serbian Association of Endocrine Surgeons, and Section for Endocrinology of the Serbian Medical Society. Results. Out of 170 invitations, 99 responses were received. LT4 was the first choice for the treatme
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Kraut, Eyal, and Pendar Farahani. "A Systematic Review of Clinical Practice Guidelines’ Recommendations on Levothyroxine Therapy Alone versus Combination Therapy (LT4 plus LT3) for Hypothyroidism." Clinical & Investigative Medicine 38, no. 6 (2015): 305. http://dx.doi.org/10.25011/cim.v38i6.26194.

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Purpose: Patients with hypothyroidism are increasingly enquiring about the benefit of using combination therapy of levothyroxine (LT4) and liothyronine (LT3) as a potential treatment for hypothyroidism. Combination therapy, however, remains controversial. The purpose of this study was to systematically review available hypothyroidism treatment recommendations from clinical practice guidelines from around the world to identify the consensus regarding combination therapy. Source: Clinical practice guidelines were obtained from searches of PubMed, EMBASE, and MEDLINE, using several combinations o
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de Carvalho, Gisah Amaral, Gilberto Paz-Filho, Cleo Mesa Junior, and Hans Graf. "MANAGEMENT OF ENDOCRINE DISEASE: Pitfalls on the replacement therapy for primary and central hypothyroidism in adults." European Journal of Endocrinology 178, no. 6 (2018): R231—R244. http://dx.doi.org/10.1530/eje-17-0947.

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Hypothyroidism is one of the most common hormone deficiencies in adults. Most of the cases, particularly those of overt hypothyroidism, are easily diagnosed and managed, with excellent outcomes if treated adequately. However, minor alterations of thyroid function determine nonspecific manifestations. Primary hypothyroidism due to chronic autoimmune thyroiditis is largely the most common cause of thyroid hormone deficiency. Central hypothyroidism is a rare and heterogeneous disorder characterized by decreased thyroid hormone secretion by an otherwise normal thyroid gland, due to lack of TSH. Th
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Lomenick, Jefferson P., Lulu Wang, Steve B. Ampah, Benjamin R. Saville, and Fayrisa I. Greenwald. "Generic Levothyroxine Compared With Synthroid in Young Children With Congenital Hypothyroidism." Journal of Clinical Endocrinology & Metabolism 98, no. 2 (2013): 653–58. http://dx.doi.org/10.1210/jc.2012-3558.

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Abstract Context: Clinicians who prescribe levothyroxine (LT4) for hypothyroidism often feel strongly about using a brand-name drug instead of a generic. Objective: The objective of the study was to determine whether Synthroid resulted in better control of congenital hypothyroidism than generic LT4. Design: This was a 5-year retrospective study. Setting: The study was conducted at 1 tertiary care center. Patients: Children who were 0–36 months old with congenital hypothyroidism followed up at our center from 2006 to 2011 were treated with either Synthroid exclusively (35 subjects) or generic L
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Ahmed, Ziyan, Rinsha P. V. Sherin, Tatiana De Lourdes Fonseca, Thanh Duc Hoang, and Mohamed K. M. Shakir. "Improvement of Treatment Resistant Depression in a Patient With Primary Hypothyroidism and Thr92Ala5’ Type 2 Deiodinase Gene Polymorphism With Multiple Daily Doses of Triiodothyronine." Journal of the Endocrine Society 5, Supplement_1 (2021): A937. http://dx.doi.org/10.1210/jendso/bvab048.1915.

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Abstract Introduction: The augmentation pharmacologic therapy used in patients with treatment-resistant depression (TRD) includes drugs such as lithium, buspirone, triiodothyronine (LT3) and other drugs. We report a patient with TRD and primary hypothyroidism who responded to a combination of LT3, given in divided doses, and levothyroxine (LT4), rather than LT4 alone, even though the serum TSH levels were in the normal range with these treatments. Interestingly, the patient had a Thr92Ala5’ type 2 deiodinase polymorphism. Case Report: A 54-year old male presented to our emergency room with sui
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Mele, Chiara, Maria Antonella Tagliaferri, Loredana Pagano, et al. "Levothyroxine Replacement in Obese Adults: The Role of Metabolic Variables and Aging on Thyroid Testing Abnormalities." Journal of Clinical Endocrinology & Metabolism 104, no. 12 (2019): 6265–74. http://dx.doi.org/10.1210/jc.2019-00773.

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Abstract Context General rates of over- and underreplacement in levothyroxine (LT4) users with primary hypothyroidism are variably high. No information on LT4 adequacy exists in obesity. Objective We explored rates and factors relating to LT4 adequacy in obese patients with primary hypothyroidism. Setting Tertiary care center. Design Among 4954 consecutive obese patients admitted between 2011 and 2014, 691 hypothyroid patients receiving LT4 therapy and 691 body mass index (BMI)-, age-, and sex-matched euthyroid controls underwent analysis of thyroid function, glucolipid profile, body compositi
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Christy, Alap L., Vivian D'Souza, Ruby P. Babu, et al. "Utility of C-terminal Telopeptide in Evaluating Levothyroxine Replacement Therapy-Induced Bone Loss." Biomarker Insights 9 (January 2014): BMI.S13965. http://dx.doi.org/10.4137/bmi.s13965.

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Background Levothyroxine (LT4) therapy has shown to have effects on bone metabolism though its deleterious effect on bone remodeling is debatable. This study was aimed at assessing the diagnostic utility of the bone remodeling marker C-terminal telopeptide (CTx) in detecting early bone loss. Materials and Methods In this case–control study, 84 premenopausal women of 30–45 years of age were selected. Out of them, 28 were recently diagnosed of hypothyroidism (not on LT4), 28 were on LT4 replacement therapy (100–200 μg/day) for more than five years, and 28 had euthyroid. Plasma CTx levels were es
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Park, Chun-Muk. "Management to hypothyroidism in functional medicine." Korean Institute for Functional Medicine 6, no. 2 (2023): 1–13. http://dx.doi.org/10.32581/jkifm.2023.6.2.1.

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Hypothyroidism is a condition in which the thyroid gland does not produce enough thyroid hormones to maintain normal physical activity. Common causes include autoimmune diseases such as Hashimoto's thyroiditis, surgical removal of the thyroid gland, and radiation therapy. It presents with a variety of clinical symptoms, including dry skin, puffiness, intolerance to cold, slowed thinking, and weight gain. However, there are patients who do not show sufficient symptom improvement with LT4 (levothyroxine) alone, the standard treatment for hypothyroidism. As our understanding of thyroid physiology
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Smriti, Bhargava, Singh Vishwajeet, and Sharma Purnima. "Effects of Levothyroxine Therapy on Pregnancy and Neonatal Outcomes in Subclinical Hypothyroidism." International Journal of Pharmaceutical and Clinical Research 16, no. 7 (2024): 956–61. https://doi.org/10.5281/zenodo.13132594.

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<strong>Background:</strong>&nbsp;Subclinical hypothyroidism (SCH) during pregnancy has been associated with adverse maternal and fetal outcomes. This study aimed to investigate the effects of levothyroxine (LT4) therapy on pregnancy and neonatal outcomes in women with SCH.&nbsp;<strong>Methods:</strong>&nbsp;A prospective, randomized controlled trial was conducted on 200 pregnant women with SCH, who were allocated to either the LT4 treatment group (n=100) or the control group (n=100). Thyroid function tests were monitored throughout pregnancy, and pregnancy and neonatal outcomes were assessed
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Washington, Kris, Michelle Baron, and Sunil Vandse. "RF23 | PSAT258 Comparable Bioavailability of a Novel Levothyroxine Solution taken 10 or 30 minutes prior to a High-Fat, High-Calorie Breakfast." Journal of the Endocrine Society 6, Supplement_1 (2022): A856—A857. http://dx.doi.org/10.1210/jendso/bvac150.1771.

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Abstract Levothyroxine (LT4) is the recommended treatment for hypothyroidism and the second most prescribed medication in the US. Several formulations are available, however most patients take LT4 tablets. Evidence suggests that absorption of levothyroxine tablets is decreased when taken with food, especially those rich in soy, iodine, and fiber. In order to avoid erratic absorption of LT4, it is recommended that oral formulations are taken on an empty stomach, 30-60 minutes before breakfast. However, compliance with this recommendation is often difficult for patients with busy schedules or on
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Raj, Rishi, Ayesha Ghayur, Qurrat Elahi, and Chinmaya Patel. "Severe Rhabdomyolysis and Acute Renal Failure Due to Noncompliance to Levothyroxine Therapy." Journal of the Endocrine Society 5, Supplement_1 (2021): A953. http://dx.doi.org/10.1210/jendso/bvab048.1947.

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Abstract Background: Noncompliance to levothyroxine (LT4) is common however only rarely it leads to severe side effects. We report a case of rhabdomyolysis leading to acute kidney injury (AKI) requiring hemodialysis (HD) due to noncompliance to LT4 therapy for one month. Clinical Case: A 68-year-old Caucasian male presented with a 2-week history of worsening fatigue and generalized weakness, accompanied by pain in bilateral lower extremities. Medical history included coronary artery disease, heart failure with reduced ejection fraction, hypertension, dyslipidemia, hypothyroidism, type 2 diabet
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Washington, Kris, Michelle Baron, and Sunil Vandse. "RF23 | PSAT259 Comparable Bioavailability of a Novel Levothyroxine Solution when Administered with Coffee." Journal of the Endocrine Society 6, Supplement_1 (2022): A857. http://dx.doi.org/10.1210/jendso/bvac150.1772.

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Abstract Levothyroxine (LT4) is the treatment of choice for hypothyroidism and the second most prescribed medication in the United States. Despite its established efficacy and widespread availability, approximately 40% of patients treated with LT4 fail to achieve thyroid stimulating hormone (TSH) levels within the normal range. Current LT4 product guidelines recommend administration in the fasting state 30-60 minutes before breakfast to avoid a food interaction leading to reduced intestinal absorption of LT4. This recommendation may impact compliance, as over 50% of adult Americans drink coffe
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Uzun, Kerem, and Cüneyt Ardıç. "Evaluation of the correct use of levothyroxine in patients with hypothyroidism." Journal of Turkish Family Physician 12, no. 2 (2021): 57–65. http://dx.doi.org/10.15511/tjtfp.21.00257.

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İntroduction: Standard treatment for hypothyroidism is replacement with synthetic Levothyroxine (LT4) sodium preparations. LT4 should be taken on an empty stomach at least 30 minutes before a meal, as maximal absorption occurs when taken on an empty stomach. Protein Pump Inhibitor (PPI), iron sulphate, calcium carbonate have been shown to reduce the absorption of LT4 when taken together with LT4. Therefore, patients receiving LT4 should be informed to take their drugs at least 4 hours before drugs that interact with thyroid hormone absorption. Objective: The aim of this study is to evaluate th
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Berta, Eszter, Inez Mercédesz Lengyel, László Hegedűs, et al. "Pajzsmirigyhormon-kezelési szokások Magyarországon." Orvosi Hetilap 163, no. 12 (2022): 463–72. http://dx.doi.org/10.1556/650.2022.32412.

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Összefoglaló. Bevezetés: A pajzsmirigy-alulműködés gyakori betegség. Kezelésében a levotiroxin (LT4)-pótlás a szokásos eljárás, mely tabletta vagy gélkapszula formájában áll rendelkezésre Magyarországon. A nemzetközi trendeknek megfelelően az esetek korai felismerése miatt már a kevésbé kifejezett hormonális eltérések idején elindul a kezelés. Az endokrinológusok hypothyreosiskezelési szokásaival kapcsolatban Magyarországon és Európában felmérés eddig nem történt. Célkitűzés: A THESIS (Treatment of Hypothyroidism in Europe by Specialists: an International Survey) célja, hogy felmérjük az európ
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Sun, Xiaodong, Ningning Hou, Hongsheng Wang, Lin Ma, Jinhong Sun, and Yongping Liu. "A Meta-Analysis of Pregnancy Outcomes With Levothyroxine Treatment in Euthyroid Women With Thyroid Autoimmunity." Journal of Clinical Endocrinology & Metabolism 105, no. 4 (2019): 1009–19. http://dx.doi.org/10.1210/clinem/dgz217.

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Abstract Context Thyroid autoimmunity (TAI), the most common cause of (sub)clinical hypothyroidism, is associated with adverse pregnancy outcomes. The benefits of levothyroxine (LT4) intervention in women with TAI remain controversial. Objective The purpose of this analysis is to determine the effect of LT4 on pregnancy outcomes in euthyroid women with TAI. Data sources Databases were searched up to May 2019. Study selection Randomized controlled trails (RCTs) and retrospective studies that reported effects of LT4 administration on pregnancy outcomes in euthyroid women with TAI were screened.
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Ramírez Stieben, Luis Agustín, Estefanía Pustilnik, Rodolfo Feldman, et al. "Optimal levothyroxine dose to achieve euthyroidism in patients with primary hypothyroidism: analysis according to etiology." Revista de la Facultad de Ciencias Médicas de Córdoba 79, no. 4 (2022): 353–57. http://dx.doi.org/10.31053/1853.0605.v79.n4.35157.

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Introduction. Levothyroxine (LT4) has been considered the standard of care for treatment of hypothyroidism. Current recommendations suggest a LT4 dose between 1.6–1.8 µg/kg/day. The aim of this study was to evaluate the LT4 dose for adult patients with primary hypothyroidism of different etiologies who reached euthyroidism.&#x0D; Methods. A cross-sectional study was performed from the retrospective review of the charts of patients with primary hypothyroidism in treatment with LT4. Subjects were classified according to TSH level in overtreated (TSH &lt; 0.4 µIU/ml), euthyroid (TSH 0.40-4.20), a
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Albassam, Mustafa Mohammed, Noor Mohammed Obaid, and Yasser Kadhim Hashem Al-Zwaini. "Differentiation Between Clinical and Subclinical Hypothyroidism in Pathophysiology, Symptoms, Diagnosis and Treatment – A Narrative Review." Baghdad Journal of Biochemistry and Applied Biological Sciences 5, no. 3 (2024): 144–61. https://doi.org/10.47419/bjbabs.v5i03.285.

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Subclinical hypothyroidism is characterized by elevated thyroid-stimulating hormone (TSH) levels with normal serum free thyroxine (fT4) and free triiodothyronine (fT3) concentrations. In contrast, overt primary hypothyroidism occurs when fT4 levels fall below the normal reference range. Diagnosing subclinical hypothyroidism is challenging due to varying upper limits of normal for TSH. This review explores the differentiation between clinical and subclinical hypothyroidism in pathophysiology, symptoms, diagnosis, and treatment. Overt hypothyroidism lacks a singular identifying symptom, while su
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Samuels, Mary H., Irina Kolobova, Meike Niederhausen, Jonathan Q. Purnell, and Kathryn G. Schuff. "Effects of Altering Levothyroxine Dose on Energy Expenditure and Body Composition in Subjects Treated With LT4." Journal of Clinical Endocrinology & Metabolism 103, no. 11 (2018): 4163–75. http://dx.doi.org/10.1210/jc.2018-01203.

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Abstract Background It is unclear whether variations in thyroid status within or near the reference range affect energy expenditure, body mass, or body composition. Methods 138 subjects treated with levothyroxine (LT4) for hypothyroidism with normal TSH levels underwent measurement of total, resting, and physical activity energy expenditure; thermic effect of food; substrate oxidation; dietary intake; and body composition. They were assigned to receive an unchanged, higher, or lower LT4 dose in randomized, double-blind fashion, targeting one of three TSH ranges (0.34 to 2.50, 2.51 to 5.60, or
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Juiz-Valiña, Paula, María Cordido, Elena Outeiriño-Blanco, et al. "Evaluation of Thyroid Hormone Replacement Dosing in Morbidly Obese Hypothyroid Patients after Bariatric Surgery-Induced Weight Loss." Journal of Clinical Medicine 10, no. 16 (2021): 3685. http://dx.doi.org/10.3390/jcm10163685.

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The most frequent endocrine disease in obese patients is hypothyroidism. To date, there are no clear data regarding what happens to the dose of levothyroxine (LT4) after bariatric surgery (BS). The objective of the present study was to evaluate thyroid hormone replacement dose in morbidly obese hypothyroid patients after BS-induced weight loss. We explore the best type of measured or estimated body weight for LT4 dosing. We performed an observational study evaluating patients with morbid obesity and hypothyroidism who underwent BS. We included 48 patients (three men). In morbidly obese hypothy
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Law, Lawrence Siu-Chun, Nicholas Kuu, Melissa Hui Ting Leong, Siang Fei Yeoh, and Samantha Peiling Yang. "A CASE REPORT AND LITERATURE REVIEW OF SUBCUTANEOUS LEVOTHYROXINE ABSORPTION TESTING IN A PATIENT WITH REFRACTORY PRIMARY HYPOTHYROIDISM." Journal of the ASEAN Federation of Endocrine Societies 40, S1 (2025): 48–49. https://doi.org/10.15605/jafes.040.s1.079.

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INTRODUCTION/BACKGROUND We present a case of refractory primary hypothyroidism in which the patient failed an oral levothyroxine (LT4) absorption test under optimised conditions. Given limited formulary options and the patient's complex clinical background, an off-label trial of subcutaneous LT4 was initiated as an alternative treatment strategy. CASE A 51-year-old male underwent total thyroidectomy with right central neck dissection and radioactive iodine ablation for papillary thyroid carcinoma. He was maintained on a supraphysiologic dose of oral LT4 (approximately 3.16 mcg/kg/day) with sup
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Nakano, Yujiro, Koshi Hashimoto, Noriaki Ohkiba, et al. "A Case of Refractory Hypothyroidism due to Poor Compliance Treated with the Weekly Intravenous and Oral Levothyroxine Administration." Case Reports in Endocrinology 2019 (February 5, 2019): 1–6. http://dx.doi.org/10.1155/2019/5986014.

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Refractory hypothyroidism is caused by decreased gut absorption, increased metabolism, and poor compliance. Previous studies suggested that the weekly oral, suppository, or intramuscular administration of levothyroxine (LT4) is an effective treatment for refractory hypothyroidism. However, limited information is currently available on treatment involving the weekly intravenous administration of LT4. We managed a case of refractory hypothyroidism due to poor compliance, for which, by weekly intravenous LT4 administration, LT4 was intravenously administered weekly at a dose of 300 μg without any
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Gluvic, Zoran, Emina Sudar, Jelena Tica, et al. "Effects of Levothyroxine Replacement Therapy on Parameters of Metabolic Syndrome and Atherosclerosis in Hypothyroid Patients: A Prospective Pilot Study." International Journal of Endocrinology 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/147070.

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The aim of this study was to investigate the effect of levothyroxine (LT4) replacement therapy during three months on some parameters of metabolic syndrome and atherosclerosis in patients with increased thyroid-stimulating hormone (TSH) level. This study included a group of 30 female patients with TSH level &gt;4 mIU/L and 15 matched healthy controls. Intima media complex thickness (IMCT) and peak systolic flow velocity (PSFV) of superficial femoral artery were determined by Color Doppler scan. In hypothyroid subjects, BMI, SBP, DBP, and TSH were significantly increased versus controls and dec
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Sullivan, Shannon D., Erin Downs, Geanina Popoveniuc, Alexander Zeymo, Jacqueline Jonklaas, and Kenneth D. Burman. "Randomized Trial Comparing Two Algorithms for Levothyroxine Dose Adjustment in Pregnant Women With Primary Hypothyroidism." Journal of Clinical Endocrinology & Metabolism 102, no. 9 (2017): 3499–507. http://dx.doi.org/10.1210/jc.2017-01086.

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Abstract Context Regulation of maternal thyroid hormones during pregnancy is crucial for optimal maternal and fetal outcomes. There are no specific guidelines addressing maternal levothyroxine (LT4) dose adjustments throughout pregnancy. Objective To compare two LT4 dose-adjustment algorithms in hypothyroid pregnant women. Design Thirty-three women on stable LT4 doses were recruited at &amp;lt;10 weeks gestation during 38 pregnancies and randomized to one of two dose-adjustment groups. Group 1 (G1) used an empiric two-pill/week dose increase followed by subsequent pill-per-week dose adjustment
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Muraca, Emanuele, Stefano Ciardullo, Alice Oltolini, et al. "Resting Energy Expenditure in Obese Women with Primary Hypothyroidism and Appropriate Levothyroxine Replacement Therapy." Journal of Clinical Endocrinology & Metabolism 105, no. 4 (2020): e1741-e1748. http://dx.doi.org/10.1210/clinem/dgaa097.

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Abstract Context Growing evidence suggests that appropriate levothyroxine (LT4) replacement therapy may not correct the full set of metabolic defects afflicting individuals with hypothyroidism. Objective To assess whether obese subjects with primary hypothyroidism are characterized by alterations of the resting energy expenditure (REE). Design Retrospective analysis of a set of data about obese women attending the outpatients service of a single obesity center from January 2013 to July 2019. Patients A total of 649 nondiabetic women with body mass index (BMI) &amp;gt; 30 kg/m2 and thyrotropin
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Gullu, Sevim, Hasan Sav, and Nuri Kamel. "Effects of levothyroxine treatment on biochemical and hemostasis parameters in patients with hypothyroidism." European Journal of Endocrinology 152, no. 3 (2005): 355–61. http://dx.doi.org/10.1530/eje.1.01857.

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Objective: The aims of the study were to evaluate the disturbances in the coagulation system in patients with overt hypothyroidism (OH), to assess the effects of levothyroxine (LT4) on the coagulation parameters, and to determine whether subclinical hypothyroidism (SH) affects concentrations of coagulation markers and several biochemical parameters, thereby supporting early substitution. Design: The study included 15 patients with SH (TSH levels 5–10 mU/l), 15 patients with OH and 15 euthyroid controls. Methods: Blood urea nitrogen, creatinine, creatine phosphokinase, aspartate aminotransferas
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Pedrosa Astudillo, Diana Lorena, Inés Patricia Jara Tapia, Lizbeth Carolina López García, et al. "Impact of hormone replacement therapy on cardiovascular risk in patients with hypothyroidism: a systematic review." Ibero-American Journal of Health Science Research 4, s (2024): 39–46. http://dx.doi.org/10.56183/iberojhr.v4is.613.

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Hypothyroidism, which is developed in 4-10 % of the population, and subclinical hypothyroidism found in more than 10 % of people which are highly associated with cardiovascular pathophysiology at some level. Hypothyroidism, which is the most frequent endocrine disorder with a lack of enough thyroid hormones, presents a wide range of cardiovascular complications, including coronary artery disease, heart failure, and dyslipidemia. Thyroid hormone replacement therapy, particularly levothyroxine (LT4), continues to be the central management of hypothyroidism, which aims to restore euthyroidism and
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Sachmechi, Issac, Kenneth D. Burman, Giuseppe Mautone, et al. "RF23 | PSAT365 An Open-Label Therapeutic Efficacy Study of Tirosint (Levothyroxine Sodium) Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors." Journal of the Endocrine Society 6, Supplement_1 (2022): A859—A860. http://dx.doi.org/10.1210/jendso/bvac150.1777.

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Abstract Levothyroxine sodium (LT4) absorption is known to be affected by proton pump inhibitors (PPIs). Normal gastric acid secretion is important for the subsequent intestinal absorption of LT4. A reduced gastric acidity may diminish the dissolution of the LT4 tablet in the stomach and the release of LT4 to the gut. The dissolution profile of LT4 soft capsules has been reported to be less affected by pH than that of tablets. Previous studies in healthy subjects administered with LT4 and PPIs, as well as in hypothyroid patients with atrophic gastritis confirmed little or no impact of increase
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Cazacu, Nicoleta, Claudia G. Chilom, Melinda David, and Monica Florescu. "Conformational Changes in the BSA-LT4 Complex Induced by the Presence of Vitamins: Spectroscopic Approach and Molecular Docking." International Journal of Molecular Sciences 23, no. 8 (2022): 4215. http://dx.doi.org/10.3390/ijms23084215.

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Levothyroxine (LT4) is known for its use in various conditions including hypothyroidism. LT4 interaction with serum albumin may be influenced by the presence of vitamins. For this reason, we investigated the effect of vitamin C, vitamin B12, and folic acid on the complex of Bovine Serum Albumin with LT4 (BSA-LT4). UV-Vis spectroscopy was used to monitor the influence of vitamins on the BSA-LT4 complex. Fluorescence spectroscopy revealed a static quenching mechanism of the fluorescence of BSA-LT4 complex by the vitamin C and folic acid and a combined mechanism for vitamin B12. The interaction o
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Phan, Giao Q., Sahzene Yavuz, Angeliki M. Stamatouli, et al. "A feasibility double-blind trial of levothyroxine vs. levothyroxine-liothyronine in postsurgical hypothyroidism." Frontiers in Endocrinology 16 (March 10, 2025). https://doi.org/10.3389/fendo.2025.1522753.

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ContextDespite normalization of Thyrotropin (TSH), some patients with hypothyroidism treated with Levothyroxine (LT4) report residual symptoms which may be attributable to loss of endogenous triiodothyronine (T3).ObjectiveFeasibility trial LT4/liothyronine (LT3) combination vs. LT4/placebo in post-surgical hypothyroidism.DesignDouble-blind, placebo-controlled, 24-week study.SettingAcademic medical centerPatientsIndividuals with indications for total thyroidectomy and replacement therapy.InterventionsLT4/LT3 5 mcg (twice daily) vs. LT4/placebo (twice daily). LT4 was adjusted at 6- and 12-weeks
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Shakir, Mohamed K. M., Daniel I. Brooks, Elizabeth A. McAninch, et al. "Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism." Journal of Clinical Endocrinology & Metabolism, June 29, 2021. http://dx.doi.org/10.1210/clinem/dgab478.

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Abstract 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 sy
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Chaudhury, Nadia, Winston Crasto, Ponnusamy Saravanan, and Vinod Patel. "Intramuscular and Subcutaneous Levothyroxine: Success in Treating Refractory Hypothyroidism." European Thyroid Journal, March 2025. https://doi.org/10.1530/etj-25-0012.

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Introduction: Refractory hypothyroidism often poses a clinical problem as treatment regimens are difficult to individualise to the patient and feasibility of its delivery is difficult to organise within a health care system. We present a patient who became intolerant of intramuscular (IM) levothyroxine (LT4) after 18 years of treatment, thus subcutaneous (SC) LT4 was initiated. Case Presentation: 13-year-old female with newly-diagnosed hypothyroidism, remained hypothyroid despite escalating doses of oral LT4 and LT3. Thyroxine malabsorption was further suggested by nasogastric administration o
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Bianco, Antonio C. "Emerging Therapies in Hypothyroidism." Annual Review of Medicine 75, no. 1 (2023). http://dx.doi.org/10.1146/annurev-med-060622-101007.

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Levothyroxine (LT4) is effective for most patients with hypothyroidism. However, a minority of the patients remain symptomatic despite the normalization of serum thyrotropin levels. Randomized clinical trials including all types of patients with hypothyroidism revealed that combination levothyroxine and liothyronine (LT4+LT3) therapy is safe and is the preferred choice of patients versus LT4 alone. Many patients who do not fully benefit from LT4 experience improved quality of life and cognition after switching to LT4+LT3. For these patients, new slow-release LT3 formulations that provide stabl
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Baran, Julia, Amber Isaza, Mya Bojarsky, et al. "Triiodothyronine levels in athyreotic pediatric patients during levothyroxine therapy." Frontiers in Endocrinology 15 (August 14, 2024). http://dx.doi.org/10.3389/fendo.2024.1443394.

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ObjectiveLevothyroxine (LT4) monotherapy is the current recommended approach for treating pediatric patients post-total thyroidectomy (TT) based on the assumption that peripheral conversion of thyroxine (T4) to triiodothyronine (T3) normalizes thyroid hormone levels. In adults, approximately 15% of post-TT patients on LT4 monotherapy have altered T4:T3 ratios with ongoing debate in regard to the clinical impact with respect to health-related quality of life (hrQOL). The ability to normalize T3 and T4 levels on LT4 monotherapy for pediatric patients’ post-TT is important but not previously desc
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