Clonidine suppression test

In the last two months, I have explained why the glucagon stimulation test and adrenal venous sampling should not be used any more for the purpose of pheo diagnosis. In this piece, I will go over a good test that has some value in pheo diagnosis; this is the clonidine suppression test.

First of all, why do we need this test? As I have described in previous postings, the results of pheo markers are not black and white. Most people with normal results do not have pheo. The risk of pheo is substantial if the results are 2-3-fold higher than normal. Those are the easier ones to interpret. The results are harder to digest if they are slightly elevated (higher than normal, but less than 2-3-fold elevated). Clonidine suppression test is intended to clarify the meaning of slightly elevated pheo markers.

Clonidine is a medication used for treating hypertension. It works on the brain to decrease the “sympathetic tone”, that is, the intensity of nerve signals to the adrenal medulla. Clonidine suppresses the release of catecholamines and metanephrines from normal adrenal medulla. Pheo is a tumor of the adrenal medulla and it essentially does things on its own. Catecholamines and metanephrines released from a pheo are less suppressed by clonidine than the normal adrenal medulla. Clonidine is thus used to differentiate pheo from normal.

The test is not really standardized and every center has its own protocol and interpretation criteria. The patient has to be off diuretics, tricyclics, and beta blockers for 1-5 days and off all medications for 12 hours. After an overnight fast, the patient goes to the clinic in the morning, and catecholamines and metanephrines are measured at baseline and 3 hours after taking clonidine. The passing results (no pheo) are 50% decrease and/or back to normal.

The major adverse effect of the test is hypotension, which can be severe.

There are a few caveats about the clonidine suppression test. 1) It should never be considered as a “gold standard” for pheo diagnosis. It is just one of the tests that help diagnosing pheo. 2) The results of the clonidine suppression test can be confusing too. Catecholamines and metanephrines may be trending toward different directions. Some markers may be even higher after clonidine. 3) The test is not needed for most patients. Even in the patient who should benefit most from it, I always find that it confirms my clinical suspicion rather than adds new information. 4) It is contra-indicated if the patients can not be off the medications.

My own experience is that the best use of the clonidine suppression test is for comforting patients who are very anxious about their borderline pheo markers and want all possible reassurance that they do not have pheo.

Dr. Pheo