EFFECT OF LEVOTHYROXINE ON COGNITIVE FUNCTIONS AND CORRELATION WITH NT-PROBNP IN SUBCLINICAL HYPOTHYROIDISM

ABSTRACT Background: Subclinical hypothyroidism (SCH) affects cardiovascular and neurocognitive function. N-terminal pro-B-type natriuretic peptide (NT-proBNP) serves as both a cardiac biomarker and cognitive function marker, reflecting cerebrovascular dysfunction impacting cognitive performance. Objective: To evaluate levothyroxine treatment effects on cognitive function, thyroid functions and NT-proBNP levels in SCH. Methods: A prospective observational study included 40 SCH patients stratified into levothyroxine-treated (n=21) and untreated (n=19) groups. Cognitive function was assessed using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Addenbrooke’s Cognitive Examination (ACE) scales over a minimum of 3 months follow-up or when the patient became euthyroid for the treatment arm. Results: Both groups showed comparable baseline cognitive scores. Baseline differences included higher TSH levels (8.10 ± 1.44 vs 6.53 ± 1.42 mcIU/mL, p=0.001), elevated NT-proBNP concentrations (111.33 ± 46.84 vs 84.05 ± 35.40 pmol/L, p=0.046), and increased anti-thyroid peroxidase antibodies (421.52 ± 281.52 vs 84.95 ± 102.16 IU/mL, p=0.001) in the treated group. Following treatment, the levothyroxine group demonstrated TSH normalization (8.10 ± 1.44 to 2.38 ± 0.86 mcIU/mL, p=0.001) and significant NT-proBNP reduction (111.33 ± 46.84 to 91.10 ± 39.67 pmol/L, p=0.001). The untreated group showed no significant changes in TSH or NT-proBNP levels on follow-up. Despite biochemical improvements, treated group did not demonstrate statistically significant cognitive function changes across assessment tools. Conclusion: Levothyroxine therapy in subclinical hypothyroidism significantly reduced NT-proBNP, while standard cognitive assessment scales showed no significant improvement. This suggests these cognitive scales may lack sensitivity and are subjective, not detecting early cognitive changes, hence more detailed cognitive assessment scales are needed for detecting subtle cognitive improvement. However, NT-proBNP proved to be a more sensitive and objective biomarker, indicating potential early cardiovascular and neurocognitive benefits of therapy that precede measurable changes on traditional cognitive tests.