Prevalence of Hypercalcemia in Patients With Pulmonary Tuberculosis and Impact of Treatment

Background and aim Hypercalcemia is a recognized metabolic complication in patients with pulmonary tuberculosis (TB), attributed to extrarenal synthesis of 1,25-dihydroxyvitamin D (1,25(OH)₂D or calcitriol) by activated macrophages within granulomatous lesions. Biochemical characterization, including parathyroid hormone (PTH) measurement, is essential for excluding alternative etiologies. Serum calcitriol measurement is critical for directly confirming the postulated mechanism. The aim of the study was to determine the prevalence, severity pattern, biochemical profile, including serum calcitriol, risk factors, and treatment response of hypercalcemia in adults with pulmonary TB. Methods Medical records of 100 adults with microbiologically confirmed pulmonary TB confirmed by sputum acid-fast bacilli (AFB) smear, mycobacterial culture (MC), or Mycobacterium tuberculosis rifampicin resistance (MTB/RIF) treated between January 1, 2022, and December 31, 2022, at Brar Multispecialty Hospital, Ludhiana, India, were reviewed. Corrected serum calcium was recorded at baseline, one, two, three, and six months. Hypercalcemia was defined as corrected calcium >10.5 mg/dL (2.62 mmol/L) and graded as mild (10.6-11.5 mg/dL), moderate (11.6-12.5 mg/dL), or severe (>12.5 mg/dL). All hypercalcemic patients underwent measurement of serum calcitriol (1,25-dihydroxyvitamin D), PTH, and 25-hydroxyvitamin D (25(OH)D) as per standard hypercalcemia evaluation protocol, with direct calcitriol measurement enabling confirmation of the granulomatous mechanism. Results Hypercalcemia (>10.5 mg/dL) occurred in 22 patients (22%; 95% CI: 14.6-31.6%) at baseline, with 16 (72.7%) classified as mild and six (27.3%) moderate. All hypercalcemic patients demonstrated suppressed PTH (6.2±2.0 pg/mL, range 3.3-9.6 pg/mL; reference range 10-65 pg/mL), confirming a non-parathyroid-mediated mechanism and excluding primary/secondary hyperparathyroidism. Serum 25(OH)D levels were within normal range (37.0±6.0 ng/mL; reference range 20-50 ng/mL). Serum phosphate was measured in all hypercalcemic patients with a mean of 3.1±0.5 mg/dL (reference range 2.5-4.5 mg/dL), supporting the granulomatous mechanism. Critically, direct measurement of serum calcitriol in all hypercalcemic patients revealed uniform elevation (78.5±15.2 pg/mL; reference range 15-65 pg/mL), directly confirming the extrarenal 1α-hydroxylase mechanism. Disseminated TB (multivariate OR: 2.4, 95% CI: 1.1-5.3, p=0.028) and chronic kidney disease (multivariate OR: 3.8, 95% CI: 1.3-11.1, p=0.015) were independent risk factors. Complete calcium normalization occurred in all hypercalcemic patients by six months of anti-TB therapy (median time 2.0 months, IQR: 1.3-2.9 months). Conclusion Hypercalcemia affects approximately 22% of patients with pulmonary TB. Suppressed PTH with normal 25(OH)D, normal phosphate, and elevated calcitriol confirms the characteristic biochemical pattern of granulomatous hypercalcemia resulting from extrarenal calcitriol synthesis. Complete resolution with anti-TB therapy supports calcium and vitamin D metabolite screening in high-risk TB populations.