(28) Arginine Vasopressin Deficiency as a Rare Sequela of CNS Blastomycosis in an Adolescent with a STAT1 Mutation

Background: Central nervous system (CNS) blastomycosis is a rare complication of disseminated Blastomyces dermatitidis infection. Hypothalamic-pituitary axis (HPA) involvement causing arginine vasopressin deficiency (AVPD), previously known as central diabetes insipidus, is extremely uncommon. We present a case of AVPD secondary to CNS blastomycosis.

Objectives: To describe a rare case of CNS blastomycosis with hypothalamic involvement leading to AVPD

Design/Methods: Retrospective chart review

Results: A 14-year-old boy with a STAT1 gain-of-function mutation and chronic mucocutaneous candidiasis presented with acute mental status changes and a one-week history of profound polyuria and polydipsia. Brain MRI showed diffuse leptomeningeal enhancement, numerous cerebellar and brainstem microabscesses, and a hypothalamic lesion. Whole body MRI revealed multiorgan involvement, including lungs, skin, spleen, liver and kidneys, as well as chorioretinitis.
Labs revealed serum sodium that increased from 140 to 160 mmol/L, elevated serum osmolality (321 mOsm/kg), and low urine osmolality (initially 408 then 148 mOsm/kg), indicating AVPD. His TSH was 2.002 µIU/mL and Free T4 was 1.0 ng/dL
Desmopressin was initiated at 0.1 mg BID and was escalated to 0.1 mg AM and 0.2 mg PM, with only partial control of symptoms. His clinical course required a two-month hospitalization for management of disseminated fungal infection, hydrocephalus, and AVPD.
At follow-up, he showed significant weight gain from 35.2 kg (3.2nd percentile) to 60.5 kg (77.3rd percentile) over 6 months, raising concern for impending hypothalamic obesity.
CNS blastomycosis typically presents as meningitis or meningoencephalitis with HPA involvement causing AVPD being extremely rare. There has been only one previously reported case of CNS blastomycosis leading to AVPD which occurred in an adult. To our knowledge, ours is the first pediatric case of AVPD in the setting of disseminated blastomycosis.

Conclusions: This case highlights the importance of including CNS fungal infections in the differential diagnosis of neurologic symptoms in immunodeficient patients. Moreover, it emphasizes the need to consider HPA dysfunction in patients with CNS fungal infections when symptoms like polyuria and polydipsia occur, and expands the clinical spectrum of disseminated blastomycosis. Whether our patient’s AVPD will be transient or permanent remains to be seen.