Is this PCOS or Cushing’s syndrome?
I use two tests to make sure I do not miss patients who may have Cushing’s syndrome
Low dose (1 mg) dexamethasone suppression test is used to rule out Cushing’s syndrome
24-hour urine free cortisol is used to rule in Cushing’s syndrome
After reading “What is not PCOS?”, Megan, one of our residents, asked me to elaborate on Cushing’s syndrome.
Cushing’s syndrome refers to any etiologies leading to excess cortisol. It can be divided into endogenous or exogenous. The following discussion pertains to the endogenous Cushing’s syndrome, which may be caused by ACTH-secreting tumor of the pituitary gland (a.k.a. Cushing’s disease), cortisol-secreting tumor of the adrenal gland, ectopic ACTH-secreting tumor (such as small cell lung cancer), or Corticotropin-releasing hormone (CRH)-secreting tumor (see diagram below). The exogenous Cushing’s syndrome, most commonly due to ingestion of prescribed glucocorticoids, is not the focus of this discussion.
I use low dose dexamethasone suppression test and (if indicated) 24 hours urine free cortisol to identify individuals who may have endogenous Cushing’s syndrome. I have no plan to determine the source of excess cortisol, because these patients will be referred to my medical endocrinologist colleagues.
The low dose dexamethasone suppression test is performed as follows: after taking 1 mg dexamethasone at 11 P.M., the patient returns for a cortisol blood test next morning between 8 and 9. A cortisol level of < 1.8 µg/dL (50 nmol/L) is considered normal. It confirms that the negative feedback loop of the hypothalamus-pituitary-adrenal axis is intact and, therefore, rules out endogenous Cushing’s syndrome.
In case the cortisol is equal to or > 1.8 µg/dL (50 nmol/L), a 24-hour urine is collected and tested for free cortisol and creatinine. If urine free cortisol in the sample is equal to or > 200 µg, endogenous Cushing’s syndrome is ruled in, and patients are referred to medical endocrinologist (see diagram below). Testing creatinine ensures the compliance in collecting urine - total creatinine in 24 hours should be 955 - 2,936 mg for males, and 601 - 1,689 mg for females.
(Below is added on 10/9/2023)
After listening to the above, Megan asked “Is the low dose dexamethasone suppression test necessary? Isn’t it more straightforward to collect 24 hours urine for free cortisol determination? After all, Cushing’s syndrome is conditions with excess cortisol. Once excess cortisol (> 200 µg) is confirmed in the 24-hour collection, a diagnosis of Cushing’s syndrome is established.”
My answer is as follows. Many physiological conditions are associated with an elevated cortisol. One such example is depression. Depressed individuals have elevated corticotropin releasing hormone (CRH). As a result, their cortisol is elevated. Unlike individuals with true Cushing’s syndrome, their hypothalamus-pituitary-adrenal axis has an intact negative feedback loop. Their cortisol level is suppressible by 1 mg dexamethasone. A low dose dexamethasone suppression test identifies these individuals, eliminates unnecessary referrals.
Thus, the low dose dexamethasone test rules out Cushing’s syndrome. If the cortisol is not suppressed, a 24-hour urine free cortisol test rules in Cushing’s syndrome.