ODP110 Parathyroid Hormone Independent Hypercalcaemia Secondary to Granulomatous Inflammation: Could This Be Melioidosis?
Authors: Grace Samuel , Currie Bart , Kumar Shanal 
Published: November 2022

Background

Hypercalcemia has been described in patients with most granulomatous disorders, most commonly in sarcoidosis and tuberculosis, but never in melioidosis.

Clinical Case

A 45-year-old woman presented with two-day history of abdominal pain, nausea, lethargy and intermittent fevers during Darwin's wet season. Medications included daily methadone, diazepam and mirtazapine. On examination she was febrile with stable hemodynamics and left upper quadrant tenderness. Investigations revealed pancytopenia, deranged liver function tests with a cholestatic pattern, raised CRP of 53 (&lt;5mg/L) and normal serum calcium. Blood cultures were negative but melioidosis serology was positive (indirect hemagglutination antibody (IHA) titer 1: 1280). Abdominal computed tomography demonstrated hepatosplenomegaly with peripheral splenic infarcts and a 7mm intrasplenic aneurysm, but no abscesses. PET showed no hypermetabolic lesions. After extensive investigation, she was treated for presumptive culture-negative melioidosis with intravenous meropenem. Clinically she improved despite gradual elevation in serum calcium which peaked at 3.31 (2.1-2.6mmol/L) five weeks after presentation. Initial biochemical investigations revealed suppressed PTH at 0.5 (1.4-9.1pmol/L), low 25-hydroxy-Vitamin D of 26 (50-150nmol/L), elevated phosphate at 2.43 (0.75-1.5mmol/L) and moderate renal impairment (eGFR 34mL/min/1.73m 2). Hypercalciuria was present with urine calcium to creatinine ratio of 812 (100-580mmol/mol). Her 1,25-dihydroxy-Vitamin D (calcitriol) was elevated at 219 (48-190pmol/L) suggestive of PTH-independent hypercalcemia. The patient remained asymptomatic of hypercalcemia and aggressive intravenous hydration produced minimal biochemical improvement. Renal impairment precluded bisphosphonate use. She was commenced on prednisolone 50mg while continuing intravenous meropenem. Serum calcium normalized in 10 days and prednisolone dose was gradually tapered. A liver biopsy was performed due to persistent liver derangement and histology showed granulomatous inflammation. She completed six weeks of antibiotics for melioidosis and was discharged on day 50, with a planned six months of eradication therapy. Outpatient follow-up demonstrated normal serum calcium after cessation of prednisolone with decreasing IHA titer (1: 320). We hypothesize that this case reflects PTH-independent hypercalcemia secondary to granulomatous inflammation, presumptively caused by melioidosis. The rise in calcium after commencement of antibiotics and normalization following initiation of glucocorticoid therapy, with no rebound post cessation, is consistent with successful therapy of an infection with granulomatous inflammation. Activated macrophages within granulomas have unregulated 1-alpha-hydroxylase expression which is thought to increase conversion of 25-hydroxy-Vitamin D to calcitriol and therefore increase intestinal calcium absorption. Treatment with glucocorticoids inhibits calcitriol synthesis leading to quick resolution of hypercalcemia. While use of glucocorticoids are commonplace in the management of granulomatous disease due to sarcoidosis, they have been increasingly recognized as an important risk factor for melioidosis, considered to result from suppression of innate immunity. However, use of glucocorticoids if required is not contraindicated once antibiotic therapy for melioidosis has commenced.

Conclusion

In areas where melioidosis is endemic, clinicians should be aware of hypercalcemia and the potential risks associated with its treatment.

Presentation: No date and time listed