Primary adrenal insufficiency due to infiltrative fungal infections, such as Cryptococcus neoformans is rare, particularly in immunocompetent patients. We present a case of an immunocompetent 61-year-old man who presented with adrenal insufficiency and persistent bilateral adrenal enlargement due to disseminated cryptococcus infection.
Our patient presented with a three-month history of generalised weakness, fatigue, weight loss, and dizziness. He did not have a significant background medical history. Investigations revealed hyponatraemia (123mmol/L), hyperkalaemia (5.6mmol/L), low-normal cortisol 193nmol/L, elevated ACTH (216.2ng/L), low-normal aldosterone 34pmol/L, and an elevated renin 262mU/L. Short synacthen testing was positive (one-hour cortisol 200 nmol/L), consistent with primary adrenal insufficiency. Autoimmune adrenalitis was initially suspected; however, autoantibodies were negative (<10 titre). An abdominal CT scan revealed markedly enlarged adrenal glands, suggestive of hypertrophy of unclear cause. Quantiferon gold testing was negative excluding tuberculosis and HIV antigens were negative. Plasma metanephrines were normal. An FDG-PET scan revealed avidity in the right (SUV 5.1) and left (SUV 3.3) adrenal glands as well as rectal region (SUV 6.7). There was concern about possible colorectal cancer with adrenal metastases, although colonoscopy revealed a benign colonic polys.
The patient was commenced on hydrocortisone (20mg mane, 10mg midday) and fludrocortisone 100mcg mane, with improvement in symptoms and normalisation of electrolyte abnormalities. A surveillance abdominal CT scan revealed persistently enlarged bilateral adrenals. Adrenal biopsies revealed cryptococcus organisms and cryptococcus neoformans DNA was detected by PCR. Serum cryptococcal antigen testing was strongly positive (titres 1:1280) as was cerebrospinal fluid analysis (titre 1:160). Mycolytic blood cultures were negative. Treatment involved induction therapy with intravenous liposomal amphotericin-B 4mg/kg daily and 5-flucytosine 25mg/kg four times daily for two weeks, followed by consolidation therapy with fluconazole.
This case highlights the importance of considering disseminated cryptococcosis in immunocompetent individuals presenting with adrenal insufficiency. Early diagnosis and appropriate antifungal therapy are crucial.