The impact of severe nephrotic syndrome on thyroid function, nutrition and coagulation

Abstract

Background: Nephrotic syndrome (NS) is characterized by urinary loss of proteins, including hormones and their carrier proteins, potentially resulting in endocrine disorders. This study aimed to assess thyroid dysfunction frequency and potential implications in NS.

Methods: In this case-control study, patients with severe NS (serum albumin ≤2.5 g/dl) and controls without proteinuria were evaluated for thyroid, haemostatic and nutritional parameters, including body composition.

Results: A total of 42 nephrotic and 40 non-proteinuric patients were enrolled. The NS group showed higher thyroid-stimulating hormone and lower free hormones, corresponding to a higher frequency of both euthyroid sick syndrome {ESS; 36% versus 5%; odds ratio [OR] 10.6 [95% confidence interval (CI) 2.2-50.0]} and hypothyroidism [31% versus 5%; OR 8.5 (95% CI 1.8-40.7)] compared with the control group. Levothyroxine supplementation was required for 11 NS patients (26% of the NS group). In addition, compared with control individuals, NS patients exhibited lower lean tissue mass and a trend towards hypercoagulability, which was evidenced by higher levels of most coagulation factors and fibrinolysis inhibitors, and reduced endogenous anticoagulants activities. Furthermore, NS patients with ESS presented with a 10.4 kg (95% CI -18.68 to -2.12) lower lean tissue mass. Those with hypothyroidism had significantly reduced activity of coagulation factor X [by -30% (95% CI -47 to -13)] and protein S [by -27% (95% CI -41 to -13)] compared with euthyroid NS individuals.

Conclusions: Thyroid dysfunction is common in severe NS, often necessitating levothyroxine supplementation, which supports routine thyroid workup. A potential link between thyroid, nutritional and coagulation disorders in NS requires further investigation.

Keywords: coagulation; hypothyroidism; nephrotic syndrome; nutrition; thyroid dysfunction.

Graphical Abstract

Figure 1:

Heat map of correlations between thyroid hormones, carrier proteins and nutritional and coagulation parameters in severe NS. *Spearman's rank correlations of statistical significance (P < .05). The exact R and P-values are provided in Supplementary Table S2.

Figure 2:

The effect of thyroid dysfunction on (a) lean tissue mass, (b) factor X and (c) free protein S activity in severe NS in the multivariate models. β: standardized coefficient of the linear regression model. A subgroup of patients with NS and euthyroidism serves as the reference group.