A 75-year-old Japanese man was hospitalized for hypokalemia. Levels of plasma adrenocorticotropic hormone (ACTH) and free cortisol in urine were elevated to 220 pg/mL (normal, 9 to 52 pg/mL) and 793 mg/d (normal, 30 to 100 mg/d), respectively. Blood concentration of corticotropin-releasing factor was 13.8 pg/mL (normal, <40 pg/mL). Chest radiographs and computed tomographic examinations showed an enlarged thymic gland and normal-sized adrenal glands. Venous samplings in the superior and inferior vena cava at several levels showed markedly increased plasma atrial natriuretic peptide concentrations near the thymic tumor (from 120 to 620 pg/mL). By contrast, plasma ACTH concentrations were constant at all sites sampled. Pathologic study results were compatible with carcinoid. Immunohistochemical staining for atrial natriuretic peptides and ACTH in the dissected tumor tissue showed several cells to be positively stained for the peptides. No ACTH-containing cells were detected. After the tumor was removed, both ACTH and atrial natriuretic peptide concentrations returned to normal (ACTH, from 220 to 34 pg/mL; atrial natriuretic peptides, from 180 to 25 pg/mL), as did the levels of cortisol and potassium.

We conclude that this thymic carcinoid produced atrial natriuretic peptides, a condition not previously shown. That thymic gland can produce atrial natriuretic peptide has been shown by Vollman and Schulz [1] and Throsby and colleagues [2]. Our findings provide evidence that an increased number of atrial natriuretic peptides can cause chronic stimulation of ACTH secretion, resulting in the Cushing syndrome.