Metabolomic profile of patients on levothyroxine treatment for hypothyroidism

Benabdelkamel, Hicham; Jaber, Malak A.; Dahabiyeh, Lina A.; Masood, Afshan; AlMalki, Reem H.; Musambil, Mohthash; Rahman, Anas M. Abdel; Alfadda, Assim A.

doi:10.1530/etj-23-0062

Cited by 3 publications

(1 citation statement)

References 51 publications

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“…Metabolites were extracted using the protein precipitation reported previously [20,21]. In brief, 100 µL of plasma was mixed with 900 µL of 50% extraction solvent (acetonitrile: methanol).…”

Section: Metabolite Extractionmentioning

confidence: 99%

Metabolomic Profiling of Blood Plasma in Females with Hyperplasia and Endometrial Cancer

Benabdelkamel,

Jaber,

Akkour

et al. 2024

Metabolites

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Uterine cancer is the most prevalent gynecologic malignancy in women worldwide. Endometrial cancer (EC) has an 81% five-year survival rate, depending on disease stage and time of diagnosis. While endometrial cancer is largely treatable when detected early, no established screening techniques are available in clinical practice. As a result, one of the most significant issues in the medical field is the development of novel ways for early cancer identification, which could boost treatment success rates. Liquid chromatography–high-resolution mass spectrometry (LC-HRMS)-based metabolomics was employed to explore the metabolomic markers and pathways unique to this cancer type and link them to the benign endometrial hyperplasia that may progress to cancer in 5% to 25% of patients. The study involved 59 postmenopausal participants, 20 with EC type 1, 20 with benign hyperplasia, and 19 healthy participants. Metabolite distribution changes were analyzed, and 338 of these features were dysregulated and significant. The first two main components, PC1 and PC2, were responsible for 11.5% and 12.2% of the total metabolites, respectively. Compared with the control group (CO), EC samples had 203 differentially expressed metabolites (180 upregulated and 23 downregulated); in hyperplasia (HP), 157 metabolites were dysregulated (127 upregulated and 30 downregulated) compared to the CO group while 21 metabolites exhibited differential regulation (16 upregulated and 5 downregulated) in EC plasma samples compared to the HP group. Hyperplasia samples exhibited similar metabolic changes to those reported in cancer, except for alterations in triglyceride levels, 7a,12 b-dihydroxy-5b-Cholan-24-oic acid, and Hept-2-enedioyl carnitine levels. The metabolites N-heptanoyl glycine and -(Methylthio)-2,3-isopentyl phosphate and formimino glutamic acid can be specific markers for hyperplasia conditions and dimethyl phosphatidyl ethanolamine and 8-isoprostaglandin E2 can be specific markers for EC conditions. Metabolic activities rely on mitochondrial oxidative phosphorylation for energy generation. The changes in metabolites identified in our study indicate that endometrial cancer cells adopt alternative strategies to increase energy production to meet the energy demand, thereby supporting proliferation.

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Section: Metabolite Extractionmentioning

confidence: 99%

Metabolomic Profiling of Blood Plasma in Females with Hyperplasia and Endometrial Cancer

Benabdelkamel,

Jaber,

Akkour

et al. 2024

Metabolites

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Triiodothyronine levels in athyreotic pediatric patients during levothyroxine therapy

Baran,

Isaza,

Bojarsky

et al. 2024

Front. Endocrinol.

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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 described. This study reports data on T3 levels in athyreotic pediatric patients to determine if a similar cohort of patients exists on LT4 monotherapy targeting normalization of TSH (LT4 replacement) or suppression (LT4 suppression).MethodsThyroid function tests (TFTs) were retrospectively extracted from medical charts for patients <19 years old who underwent TT for definitive treatment of Graves’ disease (GD) or differentiated thyroid cancer (DTC) between 2010–2021. LT4 dosing was selected to normalize the TSH in GD patients (LT4 replacement) or suppress TSH in DTC patients (LT4 suppression). Pre- and post-surgical TSH, T3 and T4 levels were compared.ResultsOf 108 patients on LT4 replacement (n=53) or LT4 suppression (n=55) therapy, 94% (102/108) of patients demonstrated T3 levels in the normal range post-TT. However, the majority of patients on LT4 replacement (44/53; 83%) and LT4 suppression (31/55; 56%) displayed post-TT T3 levels in the lower half of the normal range despite 50% (22/44) and 48% (15/31) of these patients, respectively, having post-TT fT4 levels above the upper limit of the normal range.ConclusionA significant number of pediatric patients do not achieve similar T3 and T4:T3 levels pre- and post-TT. Future multi-center, prospective studies evaluating LT4 monotherapy in comparison to combined LT4/LT3 therapy are warranted to determine the potential clinical impact of altered T3 levels in athyreotic pediatric patients.

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Effect of Levothyroxine Therapy on the Lipid Profile of Patients With Hypothyroidism: A Systematic Review

Nishat,

Mueka,

Hassan

et al. 2024

Cureus

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Hypothyroidism, also known as underactive thyroid, is a condition where the thyroid gland does not produce enough thyroid hormone. Deficiency or lack of thyroid hormone causes patients to have a slower metabolism, which may lead to secondary medical issues such as weight gain, fatigue, depression, and increased cardiovascular risk. This systematic review aims to explore the effect of levothyroxine therapy on the lipid profile of hypothyroid patients. Through a comprehensive search, 3096 articles were retrieved using keywords such as Hypothyroidism, Levothyroxine, Lipid, Dyslipidemia, and Cholesterol from PubMed, PubMed Central, Google Scholar, and ScienceDirect databases. The Medical Subject Headings (MeSH) strategy was also leveraged to extensively search the PubMed database. Research articles that were published from the year 2020 until May 2024, including randomized control trials, observational studies, metaanalyses, systematic reviews, literature reviews, and case reports, were included in the research. Research papers published before 2020, written in languages other than English, and animal studies were excluded. The 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used in the design of the systematic review. Levothyroxine therapy is the treatment of choice in patients suffering from hypothyroidism, and based on our review, the treatment has a positive impact, leading to a significant decrease in total cholesterol, low-density lipoproteins, and triglyceride values in hypothyroid patients. The research highlights the importance of starting timely levothyroxine therapy in hypothyroid patients to maintain normal lipid levels and reduce the associated cardiovascular risk.

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Metabolomic profile of patients on levothyroxine treatment for hypothyroidism

Cited by 3 publications

References 51 publications

Metabolomic Profiling of Blood Plasma in Females with Hyperplasia and Endometrial Cancer

Metabolomic Profiling of Blood Plasma in Females with Hyperplasia and Endometrial Cancer

Triiodothyronine levels in athyreotic pediatric patients during levothyroxine therapy

Effect of Levothyroxine Therapy on the Lipid Profile of Patients With Hypothyroidism: A Systematic Review

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