Bilateral adrenal histoplasmosis in an immunocompetent man
Mark Sutton-Smith, Shamaila Zaman, Fatima Saleh, Niels Larsen, Hardeep Singh, Georgina Russell, Onn Min Kon, Laura Martin, Stephen Robinson
A 75 year old man, a UK resident born in West Bengal presents with a seven month history of lethargy, dizziness, nausea and weight loss. He also has T2DM and prostatism. Initially investigated by ENT for a hoarse voice and a right vocal cord lesion later shown to be chronic granulation tissue with Actinomycosis; treated with Co-Amoxiclav. Cross sectional imaging (CT-CAP) demonstrated incidental indeterminate adrenal and mediastinal lesions. PET imaging showed intense metabolically active adrenals with low volume, but moderately active mediastinal and hilar lymphadenopathy. HIV, Hepatitis B and C screen were negative. Hb 116 g/L, WCC 5.6x109/L, Na 132x109/L, K 4.6x109/L. CRP 23.5 mg/L, ESR 27 mm/hr. In a Short Synacthen Test cortisol response was attenuated (381, 377 and 369 nmol/L) with an elevated ACTH 376 ng/L, Renin 5.3 pmol/mL/hr and low Aldosterone (< 60 pmol/L). Necrotising granulomatous disease was identified on adrenal biopsies. Empirical Tuberculosis (TB) treatment was started for an assumed TB adrenalitis and initial histoplasma serology was negative but with an elevated serum beta-D-glucan test. PAS stains were positive for fungal elements and subsequent panfungal PCR revealed Histoplasma capsulatum with negative TB culture and PCR. The overall diagnosis was therefore primary adrenal insufficiency with extensive bilateral adrenal histoplasmosis in an immunocompetent man. Treatment included managing his adrenal insufficiency with hydrocortisone (with education) and fludrocortisone. Broad spectrum anti-fungal treatment was instigated with Ambisome whilst awaiting fungal ID, then Itraconazole treatment trialled but complicated by suspected heart failure, now changed to Voriconazole.
Histoplasmosis is an endemic fungal disease that thrives in the soils of temperate environments worldwide; prevalent Areas include Central and Eastern America, particularly Ohio and Mississippi, South America, Africa, Asia and Australia. West Bengal has a very high rate of Histoplasmosis (9.4%) infection in the general population. Histoplasmosis infection occurs in one of two forms; these can be either manifest as pulmonary disease or disseminated disease commonly involving the adrenals in the immunosuppressed. Bilateral adrenal histoplasmosis in immunocompetent individuals is extremely rare with less than 100 reports of unilateral or bilateral disease worldwide. At a time before HIV became prevalent (1931-1981) necropsy material from 131,466 post-mortem examinations from São Paulo demonstrated 254 (0.2%) adrenalitis cases with only 3 cases (1.2%) caused by histoplasmosis. This case emphasis that histoplasmosis disease should be considered as a differential diagnosis in adrenal insufficiency with bilateral adrenal masses even in the immunocompetent. Diagnosis can be made via histology, PCR tests, serology from blood or urine samples and the limitations of various tests should be taken into account.