A 75-year-old man was hospitalized for mental confusion, muscular weakness, and severe hypokalaemia (2.5 mEq/L). The patient's medical history included hypertension and benign prostatic hyperplasia; he took ramipril 5 mg and dutasteride 0.5 mg daily. Few months before he had felt an increasing asthenia, he noted weight gain and the worsening of hypertension control and he experienced some episodes of low urinary tract infections. The laboratory tests evidenced the onset of diabetes (fasting glycaemia 160 mg/dL and HBA1C 50 mmol/L); prostate-specific antigen (PSA) was normal (2.39 mug/L). His wife reported that lastly he was physically exhausted and mentally confused. At physical examination the patient was 165 cm in height and he weighed 70 kgs (BMI 25.7); he showed slight round face and thin arms and legs; his arterial pressure was 160/105 mmHg. Digital evaluation revealed that the prostate was enlarged and firm in consistency. Laboratory tests (Table 1) confirmed severe hypokalaemia (2.3 mmol/L) and documented high levels of midnight salivary cortisol (50.6 mug/L), elevated levels of plasma ACTH (155.4 ng/L), and plasma cortisol (398 mug/L). The overnight 8 mg dexamethasone suppression test did not properly suppress plasma cortisol (198 mug/L); high levels of plasma chromogranin A and calcitonin (272 ng/L) were also documented; PSA was confirmed to be normal (1.7 mug/L) (Table 1).
Magnetic Resonance Imaging (RMI) of the pituitary gland was normal; no nodules were found by thyroid ultrasonography. Total body computed tomography (TBCT) (Figures 1(a)-1(b)) revealed a voluminous prostate gland (maximum diameter of 10 cm) heterogeneously enhancing the contrast medium. The tumour of the prostate had invaded the bladder; the rectum and multiple pathological retroperitoneal lymph nodes as well as bilateral enlarged adrenal glands were evident. A subsequent 68 Gallium DOTATATE PET/CT found a high uptake of the whole prostate (SUV max 12.7) and of the adjacent lymph nodes, confirming the presence of a neuroendocrine tumour in that site and excluding other distant metastases (Figure 2). The patient underwent a transurethral prostate biopsy that showed a small cell prostate cancer focally positive for ACTH and calcitonin and negative for chromogranin A and PSA at immunocytochemistry (Figures 3(a) and 3(b)). Continuous intravenous potassium infusion, potassium sparing drugs (Aldactone), and antihypertensive drugs were administered to the patient. Ketoconazole was also administered with an uptitrating dose of 400 mg/twice daily for 5 weeks and because of the poor control of cortisol secretion, octreotide 0.1 mg every 8 hours subcutaneously was added for further 13 days. Despite a reduction of plasma cortisol (195 mcg/L) after 6 weeks of treatment, no significant clinical benefit was achieved; in fact the patient continued rapidly to worsen becoming more asthenic and confused since he developed a glucocorticoid induced psychosis. The surgeon urologist excluded prostate resection and bilateral surrenectomy because they were considered too dangerous for the patient. The patient started a cycle of chemotherapy with epirubicin and carboplatin, but few weeks after the first cycle, febrile neutropenia, sepsis, and intestinal perforation occurred and the patient died.