A 62-year-old man comes to the clinic due to a 2-month history of progressive proximal muscle weakness, fatigue, and a 5-kg (11-lb) weight gain. He has a 40-pack-year smoking history. Blood pressure is 168/98 mm Hg, pulse is 88/min, and respirations are 16/min. Physical examination shows central obesity, facial plethora, and violaceous striae over the abdomen. There is 3/5 strength in the proximal muscles of the upper and lower extremities.
Laboratory studies show the following:
| Test | Result | Reference Range |
|---|---|---|
| Sodium | 146 mEq/L | 136-145 mEq/L |
| Potassium | 2.6 mEq/L | 3.5-5.0 mEq/L |
| Chloride | 96 mEq/L | 98-106 mEq/L |
| Bicarbonate | 34 mEq/L | 22-28 mEq/L |
| Glucose | 185 mg/dL | 70-99 mg/dL |
| Blood urea nitrogen | 18 mg/dL | 7-20 mg/dL |
| Creatinine | 0.9 mg/dL | 0.7-1.3 mg/dL |
Endocrine studies:
| Test | Result | Reference Range |
|---|---|---|
| 24-hour urine free cortisol | 850 µg/day | 10-50 µg/day |
| Morning serum ACTH | 240 pg/mL | 10-60 pg/mL |
A high-dose (8 mg) dexamethasone suppression test is performed. The baseline serum cortisol is 42 µg/dL, and the post-dexamethasone serum cortisol is 40 µg/dL.
Which of the following is the most likely diagnosis?
- AACTH-secreting pituitary adenoma
- BAdrenocortical adenoma
- Ectopic ACTH productionAnswer
- DFactitious glucocorticoid use
- EPrimary hyperaldosteronism
Answer
Ectopic ACTH production
The correct answer is ectopic ACTH production. The patient has clinical signs of Cushing syndrome (weight gain, proximal weakness, striae) and laboratory evidence of severe hypercortisolism (markedly elevated 24-hour urine free cortisol). To determine the etiology of Cushing syndrome, the serum ACTH level is measured. This patient's ACTH is elevated, indicating an ACTH-dependent cause, which narrows the differential to a pituitary adenoma (Cushing disease) or ectopic ACTH production. The high-dose dexamethasone suppression test is then used to differentiate between the two. Ectopic sources of ACTH (such as small cell lung cancer, likely in this heavy smoker) are autonomous and typically do not suppress cortisol production following high-dose dexamethasone administration. In contrast, pituitary adenomas usually retain some negative feedback mechanisms and demonstrate a >50% suppression in cortisol. Furthermore, the patient's severe hypokalemia and metabolic alkalosis are classic for ectopic ACTH production, as massive levels of cortisol overwhelm the renal 11-beta-hydroxysteroid dehydrogenase type 2 enzyme and directly stimulate mineralocorticoid receptors.
Step-by-Step Solution
Key Concept
The high-dose dexamethasone suppression test differentiates between ACTH-dependent causes of Cushing syndrome; pituitary adenomas generally suppress, while ectopic ACTH sources do not.
Estimated Time:1m 30s