Hypothyroidism Risk Potentially Related to Proteinuria Severity

Woman holds her throat
The urinary loss of protein-bound thyroid hormone may cause or worsen hypothyroidism. A link between proteinuria and hypothyroidism was explored.

People with severe proteinuria have a significant risk of developing or worsening hypothyroidism, according to a study in the Journal of Clinical Endocrinology & Metabolism.

Researchers assessed the relationship between thyroid function and urinary protein excretion in adults with proteinuria at a large academic medical center.

Eligible participants were aged >18 years who had at least 1 measure of elevated urinary protein excretion recorded in a retrospective cohort study conducted from December 1979 to March 2015. Urinary protein excretion >0.2 g/day or mg/mg creatinine was considered elevated.

In 2136 patients with proteinuria, 2676 samples were identified that consisted of concurrent measurements of serum thyrotropin (TSH) and urinary protein excretion that were included in the analysis. Patients had a median (interquartile range) age of 56.4 years when the samples were obtained, and 63.1% of samples were from women. The samples were divided into 3 tertiles according to urinary protein excretion (0-0.54, 0.55-1.75, and >1.75).

The mean ±SE TSH was significantly greater in the highest tertile of urinary protein excretion (2.09±0.09 mIU/L, P < .001) compared with the lowest and middle tertiles, which were not different from each other (1.59±0.07 vs 1.59±0.06 mIU/L).

Mild TSH elevation (>5 mIU/L) was found in 10.5±1.1% and 11.9±1.1% of samples in the lowest and middle tertiles of urinary protein excretion, respectively, vs 17.2± 1.1% of samples in the highest tertile (P < .001).

The odds of TSH elevation >10 mIU/L were not different in the middle tertile (odds ratio [OR] 0.84; 95% CI, 0.49-1.44; P = .52) but were significantly greater in the highest tertile (OR 1.72; 95% CI, 1.05-2.84; P = .008), compared with the lowest tertile of urinary protein excretion.

The odds of TSH elevation >5 mIU/L were not significantly increased in the middle tertile (OR 0.93; 95% CI, 0.49-1.79; P = .84) or the highest tertile (OR 1.44; 95% CI, 0.67-3.09; P = .35), vs the lowest tertile.

The adjusted prevalence for TSH elevation >10 mIU/L in the lowest, middle, and highest tertiles of urinary protein excretion was 1.6±0.5%, 1.6± 0.5% (P = .96), and 3.9±0.5% (P = .003), respectively.

In sensitivity analyses that included only a single sample from each participant, comparable results were observed, except TSH elevation risk >5 mIU/L was significantly increased in the highest tertile of urinary protein excretion (OR 1.58; 95% CI, 1.13-2.21; P = .008).

The investigators noted that data were not available to control for potential confounders, including treatment with glucocorticoids or other medications that may affect TSH levels, or the presence of other risk factors for hypothyroidism, including thyroid autoantibodies, iodine status,  other autoimmune disease, or type 2 diabetes. Also, institutional changes in laboratory assays occurred during the study period, which may have affected the results.

“This study demonstrates that patients with severe proteinuria have a significant risk of hypothyroidism,” the study authors concluded. “Although this finding is not sufficient to recommend routine thyroid function testing in patients with proteinuria, clinicians should be aware of this risk and should consider thyroid function testing in this high-risk group, particularly if symptoms suggestive of hypothyroidism are present.”


Kwong N, Medici M, Marqusee E, Wassner AJ. Severity of proteinuria is directly associated with risk of hypothyroidism in adults. J Clin Endocrinol Metab. 2021;106(2):e757-e762. doi:10.1210/clinem/dgaa872