Endocrine Abstracts

Context: Numerous studies propose a potential role of PTH in uric acid (UA) metabolism, particularly through its impact on the ABCG2 transporter, which is responsible for UA excretion in the intestines and kidneys. Another suggested mechanism involves increased tubular reabsorption of UA due to hypercalcemia-induced extracellular volume contraction. Elevated UA levels constitute a well-established risk factor for cardiovascular disease, nephrolithiasis, and chronic kidney disease – conditions prevalent in individuals with primary hyperparathyroidism (PHPT). Despite current international guidelines not advocating routine UA-level measurements in PHPT, addressing hyperuricemia could potentially safeguard renal and cardiovascular health in these patients.

Objective: To assess UA levels in patients with PHPT.

Design: Case-control study.

Setting: Academic, outpatient.

Patients: From February 2021 to December 2023, we consecutively evaluated 206 women with classical hypercalcemic asymptomatic PHPT. These underwent comprehensive assessments, including blood and urinary analysis, dual-energy X-ray absorptiometry (DXA), and renal ultrasound. From this group, 116 patients with thorough testing, including UA measurement, were selected. Of these, patients with known interfering drugs (e.g. diuretics) or drugs affecting PTH or serum calcium (bisphosphonates, denosumab, and cinacalcet) were excluded, obtaining a final cohort of 59 patients. Women without primary or secondary hyperparathyroidism enrolled during the same period (n=251), without interfering medications, and with full mineral, serum UA, and DXA evaluation were used as controls.

Results: Both groups had similar age, BMI, and blood creatinine levels, but showed significant differences in biochemical and densitometric parameters as expected. UA level proved notably higher in PHPT patients than controls (5.0 mg/dl vs 4.6 mg/dl, P=0.015). Correlation analyses unveiled an inverse relationship between elevated UA and reduced eGFR (ρ=−0.809, P<0.001), and a positive correlation emerged with PTH levels (ρ=0.217, P<0.001). Univariate analysis in PHPT individuals identified significant associations of UA levels with eGFR (P=0.012), and serum calcium levels (P=0.007). Instead, in the control group, UA levels showed significant associations with BMI (P<0.001) and eGFR (P<0.001), but not with serum calcium levels (P=0.725). In a logistic multinomial regression model, hyperuricemia was predicted by higher BMI (OR=1.087, CI:1.005–1.167, P=0.037), serum creatinine (OR=67.949, CI:6.745–684.535), and serum calcium (OR=2.371, CI:1.348–4.172, P=0.003), regardless of age, PTH levels or diagnosis of PHPT.

Conclusions: Asymptomatic PHPT is associated with elevated serum uric acid, which seems dependent on the degree of hypercalcemia and renal dysfunction, irrespective of PTH levels. Further studies are needed to determine if uric acid levels might have an impact on the clinical management of PHPT.