Severity of Proteinuria Is Directly Associated With Risk of Hypothyroidism in Adults

CONTEXT: Proteinuria can cause or exacerbate hypothyroidism, possibly due to urinary loss of protein-bound thyroid hormone. However, the precise relationship between proteinuria and hypothyroidism remains unclear. OBJECTIVE: This work aimed to determine the prevalence of hypothyroidism in patients with proteinuria and the relationship between hypothyroidism and degree of proteinuria. DESIGN: A retrospective cohort study was conducted from December 1979 to March 2015. SETTING: This study was conducted at a large academic hospital. PATIENTS: All paired samples of urine protein and serum thyrotropin (TSH), measured within 24 hours, were obtained from adults (age > 18 years) with at least one instance of urine protein greater than 0.2 g/day or mg/mg creatinine. MAIN OUTCOME MEASURES: Samples were stratified by urine protein tertile. Mean TSH and risk of TSH elevation were compared among tertiles using analysis of covariance and generalized estimating equations controlled for age, sex, samples per patient, and levothyroxine treatment. RESULTS: A total of 2676 samples were identified from 2136 patients. Mean ± SE TSH (mIU/L) was increased in the highest tertile of urine protein (> 1.75g/day) compared to the lower 2 tertiles (2.09 ± 0.07 vs 1.59 ± 0.07, 1.59 ± 0.06, P < .001). The highest tertile had a greater prevalence of TSH greater than 5 mIU/L (17.2% vs 10.5%, 11.9%, P < .001) but a similar risk of TSH greater than 5 mIU/L (odds ratio [OR] 1.44; 95% CI, 0.67-3.09, P = .35). The highest tertile also had a higher prevalence (6.2% vs 3.4%, 2.6%, P = .003) and risk (OR 1.72; 95% CI, 1.05-2.84, P = .008) of TSH greater than 10 mIU/L. Similar results were observed when comparing samples with nephrotic-range proteinuria (> 3.5g/day) to those with lesser proteinuria. CONCLUSION: Hypothyroidism is common among adults with proteinuria, and the risk of hypothyroidism is directly related to the severity of proteinuria.

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