Neudesin alterations in hypothyroidism with and without metabolic syndrome and type 2 diabetes: association with metabolic disturbances and potential biomarker value.

Abstract

Hypothyroidism is one of the common endocrine disorders that often coexists with metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), affecting glucose metabolism, lipids balance and insulin resistance. Neudesin, neuron-derived neurotrophic factor (NENF), is a protein responsible for neurotrophic and metabolic effects; however, the role of neudesin in the development of metabolic disorders associated with thyroid disorders is still unknown. The aim of the study was to investigate the association between the blood neudesin level and metabolic changes in hypothyroid patients with or without MS. The case-control study was performed by comparing three groups of patients: hypothyroidism + metabolic syndrome; hypothyroidism only, and control group. Clinical and biochemical parameters were evaluated: glycemic indices, insulin resistance (HOMA-IR), lipid profile, and thyroid hormone test (TSH, total triiodothyronine [TT3] and total thyroxine [TT4]). Serum neudesin was detected and the level was compared between three groups. The greatest metabolic changes in patients with hypothyroidism and MS include increased fasting glucose, triglyceride, HOMA-IR, TSH, and decreased HDLC, TT4. Although all patients receive levothyroxine 100 μg daily, TSH remained elevated in both patient groups (12.94 ± 4.26 and 11.83 ± 3.79 μIU/mL vs. 1.47 ± 0.74 μIU/mL in controls). Patients with MS had the least favorable profile, with greater adiposity, blood pressure, glycemia, triglycerides, and HOMA-IR and lower HDLC. Serum neudesin was approximately 4.5-fold higher in both hypothyroid groups (6.47 ± 2.21 and 6.11 ± 1.27 ng/mL) than in controls (1.39 ± 0.50 ng/mL; p < 0.001) but did not differ between patients with and without MS (p = 0.720) and did not discriminate between them (AUC 0.509, 95% CI 0.356-0.663). Serum neudesin is therefore raised in treated, incompletely controlled hypothyroidism irrespective of MS status. Because both patient groups were also dysglycemic, the rise cannot be attributed to thyroid status alone, and the separation from controls requires independent validation. Increased level of serum neudesin is associated with hypothyroidism in presence of MS and reflects the association between thyroid disorders and metabolic disorders. Therefore, neudesin could be considered as a biomarker of metabolic risks in hypothyroid patients.