A 24-year-old man with a protein-losing gastroenteropathy due to an intestinal lymphangiectasia was treated with glucocorticoids (prednisolone, 7.5 mg/day) and developed low-grade fevers 7 months before admission. He did not have any remarkable life histories. Five months before admission, the man complained of headaches, fatigue, and a hearing abnormality. Then, he experienced nausea, diarrhea, and drowsiness for 6 days and subsequently sought evaluation at our hospital. The physical examination at the time of admission revealed that he was slow to respond (Japan Coma Scale 1-1). The following measurements were obtained: height, 161.2 cm; weight, 51.0 kg; BMI, 19.6 kg/m2; blood pressure, 119/78 mmHg; heart rate, 62 bpm; and body temperature, 37.4 C. The remainder of the examination findings were normal, without any signs of meningitis.
The initial laboratory data showed a white blood cell count of 11700/muL, with 87.0% neutrophils (86% segmented and 1% band neutrophils), 2.0% lymphocytes, 10%monocytes, 0% eosinophils, 1% metamyelocytes, hemoglobin = 15.7 g/dL, and a platelet count of 157,000/muL. The serum C-reactive protein level was slightly elevated (0.80 mg/dL). Although the serum sodium level was slightly decreased (130 mEq/L), the potassium (4.6 mEq/L), chloride (97 mEq/L), creatinine (0.59 mg/dL), fasting glucose (85 mEq/L), and HbA1c (5.1%) concentrations were normal.
An abdominal computed tomography (CT) showed bilateral adrenal enlargement (right, 10.0 x 20.0 mm; left, 29.0 x 29.0 mm). A retrospective analysis of the CT images revealed that the enlargement in the left adrenal gland developed 5 months before admission (Figure 1(A)), which coincided with the onset of fevers and headaches. Subsequently, the bilateral adrenal enlargement progressed (Figure 1(B)). The differential diagnosis of adrenal enlargement includes metastatic carcinoma, bilateral adrenal hyperplasia, tuberculosis, and fungal infections. A whole-body examination failed to find a primary malignant lesion. The QuantiFERON-TB test and HIV antibody titer were negative.Although there were no signs of meningeal irritation, a diagnostic lumbar puncture was performed. The cerebrospinal fluid revealed an increased white blood cell count (240/muL), a normal protein level, a decreased glucose level (0.10 g/l), and a positive cryptococcal antigen titer. The pathologic specimen showed the presence of yeast-like organisms, such as Cryptococcus spp. on Alcian blue staining, which was subsequently determined to be Cryptococcus neoformans.
Although the level of serum adrenocorticotropic hormone (ACTH) was elevated (131.3 pg/mL; normal range, 7.2-63.3 pg/mL) at the time of the diagnosis of cryptococcosis (Table 1), cortisol release in response to ACTH (Cortrosyn), which was evaluated 1 day after prednisolone cessation, was increased (Table 2). Oral prednisolone (7.5 mg/day) was then resumed as treatment for the protein-losing gastroenteropathy. The other endocrinological data of adrenal gland ruled out the possibility of pheochromocytoma and aldosterone-secreting tumors in this patient (Table 2).
Amphotericin B (250 mg/day) was initiated, followed by the addition of fluconazole (400 mg/day). The symptoms improved gradually after beginning antifungal treatment. Fluconazole alone was continued after discharge. After the initiation of antifungal treatment, the elevated ACTH levels were decreased and varied during the treatment (Table 1), suggesting a stressed condition with infection at the diagnosis and unstable absorption of prednisolone due to the protein-losing gastroenteropathy. Mild hyponatremia probably due to relative adrenal insufficiency was improved to the normal range (138 mEq/L) one month after the initiation of the antifungal treatment.
An abdominal CT, which was routinely obtained during follow-up, showed that the size of the adrenal glands decreased following antifungal therapy and became normal without any abnormal findings, including calcifications, 6 months after starting treatment (Figure 1(C)).