A 56-year-old woman comes to the office due to progressive weight gain and fatigue over the last 4 months. She also has had increasing difficulty in lifting heavy objects and climbing stairs. The patient has moderate, persistent bronchial asthma for which she uses inhaled corticosteroids and beta-2 agonists. Family history is significant for colon cancer in her father. Blood pressure is 160/90 mm Hg and pulse is 80/min. On physical examination, there is symmetric proximal muscle weakness of the upper and lower extremities. Fasting plasma glucose level is 135 mg/dL and 24-hour urinary cortisol is increased. Further evaluation reveals that high-dose, but not low-dose, dexamethasone suppresses serum cortisol levels. Serum ACTH levels are high-normal. Which of the following is the most likely cause of this patient's symptoms?

Question

A 56-year-old woman comes to the office due to progressive weight gain and fatigue over the last 4 months.  She also has had increasing difficulty in lifting heavy objects and climbing stairs.  The patient has moderate, persistent bronchial asthma for which she uses inhaled corticosteroids and beta-2 agonists.  Family history is significant for colon cancer in her father.  Blood pressure is 160/90 mm Hg and pulse is 80/min.  On physical examination, there is symmetric proximal muscle weakness of the upper and lower extremities.  Fasting plasma glucose level is 135 mg/dL and 24-hour urinary cortisol is increased.  Further evaluation reveals that high-dose, but not low-dose, dexamethasone suppresses serum cortisol levels.  Serum ACTH levels are high-normal.  Which of the following is the most likely cause of this patient's symptoms?

Quizplus · Accepted Answer

11ec160b_3ab2_f300_9249_0dec870ed47d_MD0001_00 This patient has weight gain, proximal muscle weakness, hypertension, and hyperglycemia, which are prominent features of Cushing syndrome. Screening tests for endogenous Cushing syndrome include low-dose dexamethasone suppression testing. In normal individuals, low doses of dexamethasone (a potent glucocorticoid) suppress ACTH and cortisol levels through negative feedback. However, in endogenous Cushing syndrome, ACTH and cortisol levels are not suppressed. The most common causes of Cushing syndrome are shown in the flowchart and can be categorized on the basis of serum ACTH levels as either ACTH dependent (ACTH is high or inappropriately normal) or ACTH independent (ACTH is suppressed). In ACTH-dependent Cushing syndrome, if high-dose dexamethasone suppresses ACTH and cortisol secretion, a pituitary source of ACTH (ie, ACTH-secreting pituitary adenoma) is likely. In contrast, ectopic ACTH production (eg, from malignant tumors such as small cell lung cancer) is not suppressed by high-dose dexamethasone (Choice E). This patient has excessive cortisol production that is suppressed by high-dose but not low-dose dexamethasone. This is consistent with an ACTH-secreting corticotroph pituitary adenoma (Cushing disease), the most common cause of endogenous Cushing syndrome. (Choices A and B) Excess cortisol production due to an autonomously functioning adrenal adenoma, adrenal carcinoma, or primary adrenocortical hyperplasia will cause Cushing syndrome with a suppressed ACTH level (ACTH independent). This patient's ACTH is elevated. (Choice C) Administration of exogenous glucocorticoids is a common cause of Cushing syndrome. This is most common with systemic agents (eg, prednisone), but can occasionally be seen with topical or inhaled glucocorticoids. However, ACTH is suppressed in these cases. Educational objective: In Cushing syndrome due to an ACTH-secreting pituitary adenoma (Cushing disease), ACTH is high and cortisol production can be suppressed by high-dose, but not low-dose, dexamethasone. In patients with ectopic ACTH production (eg, from malignant tumors), cortisol and ACTH production are not suppressed by low- or high-dose dexamethasone. __________ References: Cushing's disease. (http://www.ncbi.nlm.nih.gov/pubmed/25248590)

A 56-Year-Old Woman Comes to the Office Due to Progressive