calcitriol and Tuberculosis--Pulmonary

Hypercalcemia is usually secondary to one etiology, although two coexisting etiologies can rarely cause hypercalcemia. Here, we report a 47-year-old woman with hypercalcemia caused by comorbid parathyroid adenoma and pulmonary tuberculosis. Primary hyperparathyroidism is the most common cause of hypercalcemia. Tuberculosis is a rare cause of hypercalcemia, but Japan continues to have an intermediate tuberculosis burden. Therefore, tuberculosis should be considered as a cause of hypercalcemia in Japan. Patients with tuberculosis are often asymptomatic, making the diagnosis difficult. In the previous cases in which these diseases coexisted, one disease was diagnosed after treatment of the other. In our case, the very high 1,25-dihydroxyvitamin D level (162 pg/mL) helped us to diagnose asymptomatic tuberculosis and both diseases were diagnosed promptly. It is necessary to consider comorbidities, including tuberculosis in a case with a very high 1,25-dihydroxyvitamin D level. We report a valuable case in which the early diagnosis and treatment of tuberculosis and primary hyperparathyroidism prevented the spread of tuberculosis.

Topics: Antitubercular Agents; Bone Density; Comorbidity; Early Diagnosis; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Middle Aged; Parathyroid Neoplasms; Parathyroidectomy; Treatment Outcome; Tuberculosis, Pulmonary; Vitamin D

Vitamin D deficiency (low plasma 25-hydroxyvitamin D [25D] concentration) is often reported in tuberculosis. Adjunctive vitamin D has been tested for its potential to improve treatment outcomes, but has proven largely ineffective. To better understand vitamin D in tuberculosis, we investigated determinants of 25D and its immunologically active form, 1,25-dihydroxyvitamin D (1,25D), their inter-relationship in tuberculosis, longitudinal changes and association with outcome.. In a prospective observational study of adults with smear-positive pulmonary tuberculosis in Sabah, Malaysia, we measured serial 25D, 1,25D, vitamin D-binding protein (VDBP), albumin, calcium, parathyroid hormone, chest x-ray, week 8 sputum smear/culture and end-of-treatment outcome. Healthy control subjects were enrolled for comparison.. 1,25D was elevated in 172 adults with tuberculosis (mean 229.0 pmol/L, 95% confidence interval: 215.4 - 242.6) compared with 95 controls (153.9, 138.4-169.4, p < 0.001), directly proportional to radiological severity (p < 0.001), and fell rapidly within one week of treatment commencement. Tuberculosis patients with higher baseline 1,25D achieved significantly higher percentage weight gain over time, including when controlling for baseline weight, however persistently elevated 1,25D was associated with worse residual x-ray changes and lower end-of-treatment BMI. 1,25D was inversely associated with PTH (p < 0.001), consistent with the extra-renal origin of the 1,25D. 25D did not differ between tuberculosis patients (mean 63.9 nmol/L, 95% CI: 60.6 - 67.3) and controls (61.3, 57.2- 65.3, p = 0.24), and was unassociated with outcomes. Among tuberculosis patients in multivariable analyses, sex, age and VDBP were associated with 25D, and age and albumin with 1,25D. 1,25-dihydroxyvitamin was not significantly asscociated with 25D. Vitamin D deficiency <25 nmol/L was uncommon, occurring in only five TB patients; 1,25D was elevated in three of them.. In an equatorial setting, high extra-renal production of 1,25D was seen in tuberculosis, including in individuals with 25D in the deficient range; however, severe 25D deficiency was uncommon. Baseline elevation of 1,25D, a marker of macrophage activation, was associated with better weight gain but persistent elevation of 1,25D was associated with worse radiological and BMI outcomes. 1,25D warrants testing in larger datasets including TB patients less responsive to treatment, such as multi-drug resistant TB, to test its utility as a marker of tuberculosis severity and treatment response.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Female; Humans; Malaysia; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Treatment Outcome; Tuberculosis, Pulmonary; Vitamin D; Vitamin D Deficiency; Young Adult

1,25-Dihydroxy vitamin D3 [1,25(OH)2D3] is a potent immunomodulator and regulates various immune responses to Mycobacterium tuberculosis (Mtb). The present study aimed to understand the effect of 1,25(OH)2D3 on pro-inflammatory cytokine response to Mtb antigen. Peripheral blood mononuclear cells from 42 healthy controls (HCs) and 42 pulmonary tuberculosis (PTB) patients were cultured with culture filtrate antigen (CFA) of Mtb with and without 1,25(OH)2D3 at 10(-7)M concentration for 72 h. The levels of IL-1α, IL-1β, TNF-α, TNF-β, IL-17 and IL-23 were estimated in the culture supernatants by ELISA. 1,25(OH)2D3 significantly suppressed all the CFA induced pro-inflammatory cytokines (p<0.05) studied except IL-1β in both HCs and PTB patients. Among the PTB patients, the observed suppression was visible both in patients with and without cavitary tuberculosis. The present study results suggest that 1,25(OH)2D3 downregulates the production of pro-inflammatory cytokines and may control the exacerbated inflammatory response that may protect the host from excessive tissue damage at the site of infection.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Bacterial Proteins; Cells, Cultured; Cytokines; Down-Regulation; Female; Humans; Immunologic Factors; Inflammation Mediators; Male; Middle Aged; Mycobacterium tuberculosis; Tuberculosis, Pulmonary; Vitamin D