In the elderly population, thyroid hormone levels can help monitor health status, predict short-term and long-term clinical prognoses, predict disease severity, and assess quality of life and survival status. In previous studies, the frequency of thyroid dysfunction increased with advancing age in the hospitalised elderly patients. The prevalence of NTIS in hospitalised severely or debilitated elderly patients can be as high as 32%-62% [7, 9, 10]. In the present study, among the 931 elderly male patients hospitalised for various reasons, there were 193 NTIS patients (20.73% prevalence rate). After matching by age and BMI, the Alb levels were significantly lower, and the renal function indices and FBG levels higher, in the NTIS group than in the non-NTIS group. In addition, the 2-year survival rate was significantly lower in the NTIS group than in the non-NTIS group. A reduced free T3 level was strongly associated with all-cause mortality in NTIS patients, a similar finding of previous studies [11, 12].
NTIS is often associated with nutritional deficiencies or acute and chronic diseases. Protein and UA levels are indicators of nutritional status. Proteins also play an important role in the synthesis and transport of thyroid hormones. In several studies, the serum Alb level was reduced, and the free T3 level was positively correlated with the Alb level, in patients with NITS [13, 14]. In the present study, the Alb levels were also significantly reduced in the NTIS group compared with the non-NTIS group. Correlation analysis showed that TP, Alb, and PA levels decreased as the total T3 and free T3 levels decreased. Hypothetically, decreased Alb levels leads to a decrease in the conversion of T4 to T3, resulting in a decrease in T3 levels or a decrease in T4 binding to the protein, which accelerates the removal of thyroid hormones [15, 16]. In the present study, the free T3 level was also positively correlated with the UA and Hb levels, further confirming that fasting and hunger can cause NTIS .
The T4 level is strongly associated with CKD. NTIS is a common thyroid dysfunction in CKD patients [13, 17], and its mechanism is associated with the kidney's involvement in the synthesis, secretion, and metabolism of thyroid hormones. In kidney disease, chronic metabolic acidosis and inflammatory factors lead to the inhibition of deiodinase activity, and the conversion of T4 to T3 in peripheral tissues is reduced . Hypothalamic–pituitary–thyroid axis dysfunction  combined with loss of T4 in the urine causes total T3 and total T4 levels to decrease. A decrease in the glomerular filtration rate (GFR) reduces iodine excretion, resulting in an iodine-blocking effect (Wolff–Chaikoff effect) . Song et al.  retrospectively analysed 2,284 subjects with normal TSH levels and found that as the estimated GFR (eGFR) decreased in CKD patients, the prevalence of low T3 syndrome gradually increased; the eGFR was positively correlated with the serum T3 level and was independent of age and serum protein levels. In another study, reduced free T3 levels predicted an increased risk of cardiovascular events in CKD patients with proteinuria . In patients with chronic haemodialysis, reduced free T3 levels were a strong predictor of all-cause mortality . In the present study, among hospitalised elderly male patients, the UN and Cr levels in the NTIS group were higher than in the non-NTIS group. Correlation analysis showed total T3 and free T3 levels were negatively correlated with UN and Cr levels. After adjusting for confounding factors, all-cause mortality was significantly increased in CKD patients.
Compared with young, short-term diabetic patients, the elderly are more likely to develop NTIS. Some studies have compared the thyroid function status of diabetic patients according to age, disease course, and blood glucose control status and found lower free T3 levels in diabetic patients than in normal controls [23, 24]; furthermore, the incidence of cardiovascular events in patients with type 2 diabetes and NTIS was significantly increased . Aging, long diabetes duration, poor blood sugar control, and several complications can increase the prevalence of NTIS, especially in patients with diabetic nephropathy and ketoacidosis [26, 27]. In the present study, total T3 and free T3 levels were also negatively correlated with the FBG level.
In this study, at the end of the 2-year follow-up, a total of 157 patients had died (18.43% mortality rate). Kaplan–Meier survival analyses showed that the survival rate was significantly lower in the NTIS group (64.58%) than in the non-NTIS group (86.52%). Cox proportional hazards models showed that after removing confounding factors, reduced free T3 levels increased the risk of all-cause death. The ROC analysis showed that when using a free T3 cut-off level of 3.45 pmol/L, the Youden index was highest, with a sensitivity of 0.675 and specificity of 0.642, indicating that when free T3 levels are less than 3.45 pmol/L, the risk of death increases. In a recent study of 1,190 patients with acute heart failure, the survival rates were significantly lower in patients with low free T3 compared with normal levels, and a multivariate Cox proportional hazards model showed that a low free T3 level was an independent predictor of mortality . Studies on ICU patients and hospitalised chronic patients reported the free T3 level to be an independent predictor of all-cause mortality [11, 29]. Similar to previous studies, a lower free T3 level in the present study was associated with a worse prognosis in elderly male patients with chronic diseases.
The present study had several limitations including failure to evaluate many factors that affect the patient prognosis. Although age and BMI were matched between the two groups, the treatment plan, treatment timing, severity of the patient's condition, and response to the treatment plan could have affected the patient’s condition. Due to the small sample size, many influencing factors were difficult to quantify. The patients were not stratified according to the above-mentioned factors. In addition, only elderly male inpatients were analysed in the study. Whether the above study results can be generalised to the general population requires further research.