Case Presentation: A 70-year-old Caucasian male was admitted to our institution with unremitting malaise and difficulty concentrating. He was found to have a serum calcium of 13.8 mg/dl. His medical history was significant for coronary disease treated with a coronary artery bypass graft surgery complicated by a chronic left pleural effusion and a recently treated pneumonia at our institution approximately 50 days prior to admission. Treatment was initiated with pamidronate. A chest x-ray showed similar findings to prior admissions. Parathyroid hormone (PTH) levels were found to be appropriately suppressed leading investigations into alternative causes: medication/supplement use, vitamin A toxicity, HIV infection, lymphoma, paraproteinemias, granulomatous processes, osteolytic bone processes, hyperthyroidism and adrenal insufficiency. The patient had been taking hydrochlorothiazide for hypertension, however, the serum calcium was too elevated to attribute our findings to this medication. Above investigations, including parathyroid hormone-related peptide levels were found to be unyielding. Notably, 25 Hydroxy-vitamin D levels were found to be low at 25.8 pg/mL and 1,25 hydroxy-vitamin D (1,25 VitD) levels were at 77.9 pg/mL—the upper limit of normal.  The patient’s serum calcium responded well and normalized. We repeated vitamin D metabolite levels and found an elevated 1,25 VitD level of 94.8 pg/ml. Concerns for a granulomatous process or lymphoma led to a computed tomography scan of the chest, abdomen and pelvis revealing a left loculated pleural effusion containing gas concerning for an empyema. This was followed by a thoracentesis yielding an exudative effusion with cultures growing Group D non-typhoidal Salmonella. Antibiotics were initiated and tailored as sensitivities returned. The patient had a chest tube placed. His course was then complicated by a cardiac arrest with a successful resuscitation and a transfer to the medical intensive care unit where he was stabilized. Because of the patient’s poor functional status, a video assisted thoracoscopy was considered unsafe and a long term intravenous catheter was placed for antibiotic therapy. The patient suffered a fatal cardiac arrest prior to discharge.

Discussion: Salmonella infections are most well known for enteric fever but non-typhoidal species are also a leading cause of bacterial diarrhea worldwide. Rarely manifesting as pulmonary disease, direct extension from a nearby infection or aspiration of gastric secretions in colonized patients have been cited. Our patient was discovered to be dysphagic and we postulate that he aspirated on prior admission seeding Salmonella which evolved into an empyema. Interestingly, there is growing evidence that chronic inflammation outside of the traditional processes are capable of elevating 1,25 VitD levels through a novel mechanism with a distinct link to intracellular pathogens such as Salmonella. Coupled with hydrochlorothiazide use, we suspect our patient’s serum calcium was shifted towards an elevated range by an elevated 1,25 VitD level which further rose as we removed negative feedback on PTH secretion by decreasing serum calcium levels.

Conclusions: We present a patient with two rare manifestations. Although we cannot objectively prove a link between the patient’s chronic lung infection and hypercalcemia there is growing evidence that any cause of chronic inflammation has effects on vitamin D metabolites. This knowledge can help guide an unyielding hypercalcemia workup.