Sixty-eight-year-old farmer, case of chronic obstructive pulmonary disease, presented to our outpatient department with fatigue, dizziness, pigmentation, and low blood pressure. He had these symptoms for three months. Suspecting adrenal insufficiency, we sent concordant random serum cortisol and plasma adrenocorticotrophic hormone. Low random serum cortisol (3 ug/dl) and elevated plasma ACTH (120 pg/mL) confirmed the diagnosis of primary adrenal insufficiency. As suspicion of adrenal crisis was there, we admitted him to the intensive care unit. He also had acute kidney injury (serum creatinine 2.3 mg/dl, estimated glomerular filtration rate-30 mL/min) with metabolic acidosis (pH-7.1, with bicarbonate 11 meq/l) and hyperkalemia (Serum potassium-6 meq/l). He was given a saline bolus to correct the dehydration. Hydrocortisone infusion was given to cover the glucocorticoid replacement. His blood pressure improved along with the recovery of kidney functions. Computed tomography was done after stabilization showed bilateral adrenomegaly (Figure 1), with the size of the right and left adrenals, 3x2 cm ad 4x3 cm, respectively. Subsequently, the patient had been discharged on 15 mg/m2 hydrocortisone equivalent and 100 microgram fludrocortisones. We planned for the CT guided adrenal biopsy in the follow-up after ruling out pheochromocytoma.
Two months later, he came to the oncology outpatient clinic with a complaint of pain during defecation and an anal mass with ulceration. Before coming to the oncology clinic, he was evaluated by a surgeon and, suspecting anal carcinoma, was referred back to our institute. The oncologist made a diagnosis of metastatic carcinoma anus with paraneoplastic fever. We were called in to have a look. When we saw him, he looked cachectic and more pigmented than the previous admission. His blood pressure was 90/60 mmHg in supine position right arm, with severe orthostasis on standing up from bed. His pulse rate was 110/min, and the axillary temperature was 101-degree Fahrenheit. He stopped treatment in between and stopped five days back.
He had a linear ulcer of 4.0x1.5 cm on the upper anterior gingiva (Figure 2). He had firm hepatomegaly (8 cm below the right subcostal margin). The spleen was enlarged by 6 cm towards the umbilicus. Chest examination revealed rhonchi and inspiratory crepitations throughout the lung fields.
He had an ulcer on the anal verge, covering 240 degrees on the verge (Figure 3). The ulcer had overhanging edges.
Suspecting adrenal crisis due to treatment noncompliance, he was admitted to the medical intensive care unit. He was given normal saline and hydrocortisone infusion. On investigations, the patient had elevated liver enzymes along with elevated serum alkaline phosphatase. He also had non-oliguric acute kidney injury (Table 1). The ultrasonographic examination revealed hepatosplenomegaly with no focal lesions. Chest X-ray showed prominent broncho-vascular markings. The working diagnosis was changed from the carcinoma anus to a systemic infection/inflammation with granulomatous hepatitis and renal injury. 
The differential diagnosis of a patient with an anal ulcer, oral ulcer, primary adrenal insufficiency, granulomatous hepatitis, and kidney injury are disseminated tuberculosis, disseminated fungal infection (histoplasmosis), disseminated CMV infection and syphilis.
The patient was stabilized on the hydrocortisone infusion with a plan to biopsy the anal ulcer. The adrenal biopsy would have been the subsequent investigation if the diagnosis was not confirmed on the anal biopsy. Anal biopsy revealed focally ulcerated squamous mucosa. Underlying stroma showed neutrophils, lymphocytes, plasma cells and macrophages with budding oval yeast forms surrounded by a halo suggesting the diagnosis of Histoplasma capsulatum. The Histoplasma capsulatum was confirmed by PAS positivity (Figure 4). As the diagnosis was established on the anal biopsy and clinically fit into the progressive disseminated histoplasmosis, we kept the adrenal biopsy as a salvage procedure. The nephrologist was in the opinion of wait and watch for the kidney injury as it may improve with the treatment of underlying disease.
The patient was started on oral itraconazole therapy (800 mg a day for three days followed by 200 mg twice a day). He was discharged on 15 mg/m2 of hydrocortisone as a steroid replacement, itraconazole (200 mg twice a day with milk) as an antifungal treatment. The patient was advised to monitor the temperature every six hours and come if any adverse effects. We planned weekly follow-up in the first month to assess the clinical response (resolution of the fever, healing of the ulcers, improvement in kidney injury), steroid replacement (under or over replacement) and treatment side effects (gastritis, hepatitis). The imaging of the adrenals and cortisol reserve will be tested after six months of therapy.
At seven days follow-up, the patient's appetite improved, and he became afebrile.
His renal function and liver function improved when assessed on day seven compared with the status at discharge. The comparison is shown in Table 1. His pain during defecation also decreased.
His fatigue improved, and he gained 2 kg of weight after two weeks. The anal ulcer healed after three weeks of antifungal therapy.