A 60-year-old woman comes to the office due to difficulty climbing stairs and dyspnea on exertion over the last 6 weeks. The patient has a 40-pack-year smoking history. Blood pressure is 160/90 mm Hg and pulse is 78/min. Auscultation of the chest reveals decreased breath sounds over the right lung base. Proximal muscle strength is 4 on a scale of 0-5. Skin examination shows scattered ecchymoses. Laboratory results show mild hyperglycemia and elevated 24-hour urinary free cortisol. Serum cortisol level is at the upper limit of normal and is not suppressed following administration of low-dose dexamethasone. Serum ACTH level is elevated. Chest x-ray reveals a right lower lobe lung mass. Which of the following changes are most likely to occur after administration of high-dose dexamethasone in this patient?

Question

Quizplus · Accepted Answer

11ec160b_390e_6a78_9249_15825ce8b2b0_MD0001_00 This patient's hypertension, proximal muscle weakness, and hyperglycemia are suggestive of excess cortisol (ie, Cushing syndrome [CS]). Hypercortisolism can be confirmed by finding elevated cortisol levels in a late-night salivary sample or 24-hour urine collection. Additionally, low-dose dexamethasone suppression testing can also be useful for confirming the diagnosis; administration of a small dose of a potent glucocorticoid rapidly suppresses ACTH and cortisol secretion in normal individuals, but patients with CS are resistant to low-dose glucocorticoids so serum cortisol remains elevated. Once the diagnosis is confirmed, the next step is establishing the cause of CS, which involves measurement of serum ACTH levels: Low ACTH levels are seen with autonomous adrenal production of cortisol (eg, adrenal adenoma or carcinoma) or exogenous glucocorticoid exposure due to feedback suppression High ACTH levels occur with pituitary adenomas (ie, Cushing disease) or ectopic ACTH production by nonpituitary tumors, which can be further distinguished with the high-dose dexamethasone suppression test: Pituitary sources of ACTH are only relatively resistant to feedback inhibition, and high doses of dexamethasone will suppress ACTH and cortisol levels (Choice A) Nonpituitary ectopic sources of ACTH (eg, small cell lung cancer) are completely resistant to feedback inhibition, and ACTH and cortisol will remain elevated following high doses of dexamethasone This patient's rapid symptom onset, heavy smoking history, and lung mass are consistent with paraneoplastic CS, likely due to small cell lung cancer. ACTH and cortisol production will likely be unchanged following high-dose dexamethasone. (Choices B and C) In normal individuals, dexamethasone suppresses ACTH release from the pituitary. In patients with abnormal pituitary or ectopic ACTH production, dexamethasone affects ACTH levels as described above. However, dexamethasone does not stimulate ACTH release in any setting. (Choice D) The fall in cortisol seen in dexamethasone suppression tests is due to feedback suppression causing decreased ACTH release. A fall in cortisol would not be seen without a corresponding fall in ACTH. Educational objective: Cushing syndrome caused by a pituitary adenoma or ectopic (paraneoplastic) ACTH secretion is associated with elevated ACTH levels. High-dose dexamethasone suppresses ACTH and cortisol secretion when Cushing syndrome is caused by a pituitary adenoma (Cushing disease) but not when it is caused by ectopic ACTH secretion (eg, small cell lung cancer). __________ References: Ectopic Cushing's syndrome in light of modern diagnostic techniques and treatment options. (http://www.ncbi.nlm.nih.gov/pubmed/26313384)

A 60-Year-Old Woman Comes to the Office Due to Difficulty