Cushing’s disease and IPSS.

From Lewis S Blevins, Jr. MD –  Ninety per-cent of ACTH-dependent causes of hypercortisolism are related to pituitary adenoma. The remaining 10% are related to ectopic, or non pituitary, sources of ACTH secretion.

One-third of pituitary adenomas are not visible on MRI.

How does one proceed with treatment in these patients who have all the hallmarks of pituitary Cushing’s but do not have demonstrable tumors? Should surgery be performed on blind faith?

Fortunately, there are ways to increase the pre-treatment probability of the proper identification of the source of ACTH production.

History and physical can lend a few clues. Smokers, for example, are more likely to have an ACTH-producing lung tumor. Men may be more likely to have the syndrome of ectopic ACTH production. There are other clues to some of the other underlying causes of ectopic ACTH secretion.

Biochemical tests can also be helpful. For example, after high dose secs methadone administration, pituitary adenomas will decrease ACTH secretion and cortisol levels will fall in about 90% of cases whereas levels fall in only 8-10% of patients with ectopic ACTH hypersecretion. Further, pituitary adenomas often respond to CRH stimulation whereas most ectopic ACTH-producing tumors are nonresponsive. In my experience, biochemical tests can increase the accuracy of diagnosis to about 95% when a tumor is not present on MRI.

IPSS, or inferior petrosal sinus sampling, a procedure that involves obtaining blood from the pituitary and a peripheral vein before and after CRH administration, can often differentiate between a pituitary and a nonpituitary source. This test is not, however, without risk and the accuracy is estimated to be only 97-98%. In my opinion, this test should only be performed in the absence of a pituitary adenoma on MRI and especially if biochemical tests are inconclusive.

I was recently asked to comment on a set of data from a patient with documented moderates severe ACTH- dependent hypercortisolism. IPSS had been advised. ACTH and cortisol levels did not suppress with low-dose dexamethasone but suppressed markedly with high-dose dexamethasone. These observations were strongly in favor of a diagnosis of a pituitary source for ACTH hypersecretion. MRI clearly demonstrated an anteriorly located pituitary adenoma. It seemed unnecessary to proceed with IPSS in this situation. Instead, transsphenoidal pituitary surgery seemed warranted.

Much of the practice of medicine is based on a gestalt derived from review and analysis of data including, history and physical, as well as laboratory investigations, coupled with an understand of patterns of diseases and a lot of experience with medical decision-making. Cushing’s disease and related disorders exemplify this approach in every realm from diagnosis and treatment planning to long-term follow-up.


visual by Oliver Tacke

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