Amino Acid Metabolic Alterations in Subclinical Hypothyroidism: Comparative Analysis of Plasma Profiles in Patients and Healthy Controls Publisher



Hashemizadeh P ; Rahimi M ; Rajabzadeh S ; Khadembashiri M A ; Alinaghi S A S ; Razi F ; Sani M P ; Mohseni S ; Hemmatabadi M ; Shirzad N
Source: Journal of Diabetes and Metabolic Disorders Published:2026

Abstract

Background: Hypothyroidism is one of the most prevalent endocrine diseases. Subclinical hypothyroidism is characterized by elevated serum TSH levels with normal free T4 concentrations and is often asymptomatic. Emerging evidence suggests that subclinical hypothyroidism is associated with metabolic disturbances and alterations in metabolomic profiles. Therefore, this study aimed to characterize plasma amino acid profiles in treatment-naive individuals with subclinical hypothyroidism and compare them with those of healthy euthyroid controls. Methods: 34 treatment-naive subclinical hypothyroid patients and 31 age-, sex-, and BMI-matched healthy control participants were enrolled in this study. Fasting blood levels of TSH, free T4, free T3, fasting blood glucose (FBG), lipid profile, and liver enzymes were measured. 20 amino acid levels were determined using tandem mass spectrometry (LC-MS/MS). Independent-samples t-test or Mann–Whitney U test, as appropriate, and Chi-square test were used. A logistic regression analysis was also applied. Results: Patients with subclinical hypothyroidism had significantly higher levels of FBG, TG, HDL-C, AST, ALT, and ALP than the control group. Plasma levels of alanine (P = 0.035), asparagine (P = 0.023), glutamine (P < 0.001), and lysine (P < 0.001) were also significantly higher in patients with subclinical hypothyroidism than in the control group. Conclusion: There are significant selective changes in the amino acid profile in treatment-naive subclinical hypothyroid patients. These alterations may reflect that subclinical hypothyroidism influences protein and nitrogen metabolism. These findings suggest that amino acid profiling may serve as a potential adjunctive biomarker for improving the metabolic assessment of patients with subclinical hypothyroidism, although further studies are needed to establish its clinical utility. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2026.