Day #328 Cushing Syndrome

Today we had a patient present with weight gain, facial changes, abdominal obesity, psychosis and hypertension with hypokalemia.

The most common cause of Cushing Syndrome is Cushing's Disease (ACTH producing pituitary adenoma 68%). Ectopic ACTH production and adrenal ademomas are the second most common causes at approx 10% each.

The clinical symptoms and physical signs are wonderfully illustrated in the figure below (with thanks to the TWH CMR who drew it)

The diagnostic algorithm (review here) is as follows:

1. Confirm cortisol excess. 24h urine cortisol or the 1mg overnight dexamethasone supression test are the best in terms of sensitivity and specificity.


2. Is the ACTH high? If yes proceed to evaluate for adrenal adenoma or ectopic ACTH. Is ACTH low? Look at the adrenals.

ACTH High (see original publication by Hurst -- former faculty @ Toronto (memorial tribute here) from 1928 lancet)

From the diagnostic algorithm article: "A woman with mild to moderate hypercortisolism, a normal or slightly elevated plasma ACTH, and normokalemia has at least a 95% likelihood of having Cushing’s disease. In contrast, a patient with prodigious hypercortisolism, hypokalemia, and marked elevations of plasma ACTH may be more likely to have an occult ectopic ACTH-secreting tumor. "

Pituitary MRI is the next step:

Adenoma -- likely not ectopic ACTH (above) = resect

No adenoma, or likely ectopic ACTH = more evaluation

The 8mg dexamethasone suppression test is not sensitive or specific.

Petrosal sinus sampling with CRH stimulation is the best diagnostic test, but is invasive.

If ectopic ACTH confirmed:

bronchial, thymic carcinoids or other neuroendocrine tumors (e.g. islet cell, medullary carcinoma of the thyroid, or pheochromocytoma)

CT thorax and abdomen may find the tumor. If negative consider octreotide scan. Sometimes you won't find it.