*Purpose: Cryptococcal meningitis is a potentially fatal invasive fungal infection in solid organ transplant recipients. Meningoencephalitis is the most common clinical manifestation of cryptococcal infection. Unusual presentations may delay diagnosis. We present a rare case of hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH) with cryptococcal meningitis in a heart transplant recipient.

*Methods: A 72-year-old male, three years post orthotopic heart transplantation on an immunosuppressive regimen consisting of tacrolimus and mycophenolate mofetil, presented with a subacute onset of headache, malaise, and anorexia. He reported no recent travel or known sick contacts. He lives in a rural area with extensive bird exposure, and recently began smoking marijuana. His vital signs were normal on admission and his physical exam was without localizing infectious signs. He was fully oriented, had no nuchal rigidity, and his neurologic exam was non-focal. He was hyponatremic to 123 mmol/L, had an elevated absolute neutrophil count to 8.4 K/mm³, and his urine studies were consistent with SIADH. A head CT showed only chronic microvascular changes.

*Results: Infectious work up on admission was unremarkable, however on day 4 blood cultures returned with budding yeast. A serum cryptococcal antigen test was positive and his blood cultures speciated to C. neoformans. A lumbar puncture (LP) was performed with an elevated opening pressure of 26 cm H2O, a positive cerebrospinal fluid (CSF) cryptococcal antigen, with CSF cultures growing C. neoformans. He received a 30-day induction phase of flucytosine plus amphotericin B and underwent 8 serial LPs until his CSF cultures were consistently negative. His 30-day induction phase was longer than the standard 14 days due to persistent growth of C. neoformans in CSF cultures at 14 days as well as elevated opening pressures. He was then transitioned to the consolidation phase of fluconazole for an 8-week course to complete as an outpatient. Repeat urine studies following treatment initiation showed resolution of his SIADH.

*Conclusions: To our knowledge, this is the first reported case of SIADH secondary to cryptococcal meningitis from elevated intracranial pressure in a patient who underwent heart transplantation. Recognition of this condition is critical given the devastating neurologic consequences if left untreated. The serum cryptococcal antigen test is an excellent test to quickly diagnose cryptococcosis given the slow rate of growth in cultures. This can lead to earlier treatment initiation and reduction of the neurologic sequalae of this infection.

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