Immune reconstitution inflammatory syndrome (IRIS) is an uncommon cause of hypercalcemia in HIV-infected patients recently started on
highly active antiretroviral therapy (
HAART). It is hypothesized that increased granulomatous formation due to IRIS leads to an overproduction of
calcitriol. High levels of
calcitriol, then, can lead to significant
hypercalcemia. We present the case of a 63-year-old male with HIV off HAART presented to the emergency room for
confusion, frequent falls, and
cough. His CD-4 count was noted to be below 35 cells/µL (255-2,496). Over the course of the hospitalization, the patient was found to have disseminated Mycobacterium avium complex (MAC) infection and was initiated on
HAART. Initiation of
HAART was followed by an increase in
calcium up to 14.1 mg/dL. The hypercalcemia did not respond to either
Calcitonin or
Pamidronate. Consideration was then given to IRIS in the setting of MAC
infection leading to increased granulomatous formation. Calcium levels normalized within three days of therapy after initiation of
prednisone for the treatment of IRIS. It is thought that an increase in CD-4 counts leads to the recovery of an immune response. This can lead to granulomatous
inflammation. An increase in
granuloma formation can cause
hypercalcemia due to overproduction of
calcitriol via increased 1-hydroxylase activity from macrophages. Our case report describes IRIS-mediated
hypercalcemia in an HIV-infected individual with MAC
infection. This unusual cause of severe
hypercalcemia should be considered in differential diagnoses for immunocompromised patients in the appropriate setting. Prompt treatment of IRIS with
glucocorticoids can lead to the resolution of
hypercalcemia.