The most appropriate next diagnostic test for this patient is the 1-mg dexamethasone suppression test. She has the typical clinical features and findings of cortisol excess, or Cushing syndrome. The most common cause of Cushing syndrome is exogeneous glucocorticoid use; however, she has not received glucocorticoids. To evaluate for Cushing syndrome, biochemical evidence of hypercortisolism must be confirmed by use of several screening tests. Three screening tests are used for Cushing syndrome: the 1-mg dexamethasone suppression test (given late at night with assessment of cortisol suppression the next morning), 24-hour urine free cortisol excretion (to quantify total daily cortisol secretion), and measurement of evening salivary cortisol (which normally reaches a nadir at that time but remains elevated in patients with Cushing syndrome). At least two abnormal first-line screening tests are required for diagnosis. Only after establishing biochemical hypercortisolism should the source of excess cortisol production be sought.

Measurement of adrenocorticotropic hormone (ACTH) is not a screening test for Cushing syndrome. After documentation of excess cortisol production, ACTH levels may be useful in determining if hypercortisolism is ACTH-dependent or –independent; however, it is not an appropriate initial screening test.

An 8-mg dexamethasone suppression test is helpful in differentiating between Cushing disease (pituitary tumor–secreting ACTH) and ectopic ACTH production. However, it is not a screening test for Cushing syndrome and would be appropriate only in specific situations after Cushing syndrome is diagnosed.

A pituitary MRI should be ordered only after hypercortisolism and Cushing syndrome are diagnosed and a pituitary adenoma is suspected as a cause.

Measurement of serum cortisol levels lacks sensitivity and specificity for diagnosing Cushing syndrome, primarily due to the pulsatile nature of cortisol secretion, and is not used as a screening test.