Circulating Citrate is Elevated During Profound Hypothyroidism: An Observational Study

Purpose: We conducted an observational study on how profound hypothyroidism affects circulating citrate, a potential biomarker of mitochondrial dysfunction linked to mortality. Methods: Sixteen differentiated thyroid carcinoma patients were first studied during hypothyroidism, i.e., 4-6 weeks after total thyroidectomy, and subsequently after 20 weeks of thyroid hormone supplementation. 5 patients were also studied during euthyroidism, i.e., before total thyroidectomy. Circulating citrate and total ketone bodies were measured by nuclear magnetic resonance spectroscopy. Results: During profound hypothyroidism (mean thyroid stimulating hormone [TSH] 106 ± 77 mU/L), circulating citrate was 72% higher (95% CI: 48%-96%), reaching 157 ± 48 µmol/L, compared to 93 ± 25 µmol/L during thyroid hormone administration (mean TSH 0.20 ± 0.53 mU/L). This increase remained significant after adjusting for estimated glomerular filtration rate (eGFR) (P < 0.001) and body mass index (BMI) (P < 0.001). Citrate during hypothyroidism was also higher compared to five euthyroid patients studied before total thyroidectomy (P = 0.014). Total ketone bodies did not significantly change during hypothyroidism (P = 0.62). Conclusion: Short-term profound hypothyroidism gives rise to a major increase in circulating citrate, also when adjusted for changes in eGFR and BMI, conceivably attributable to hypothyroidism-related mitochondrial dysfunction. It is suggested that thyroid function status should be taken into consideration when evaluating the association of circulating citrate with adverse health outcomes.