Possible Cushing’s Disease with High Cortisols


I'm Dr. Noor Lita Adam currently doing my endocrine fellowship in University Malaya Medical Center, Kuala Lumpur. I really hope that somebody may help me and give their opinion on this patient that I saw recently. He's a 32 years old Chinese man who was investigated earlier for secondary cause of hypertension in one of private medical center. He is obese with BMI of 32 kg/m2 and has positive family history of hypertension ( mother at age 50+). He is not diabetic. He has no cushingoid features. His 24 H urine cortisol was markely elevated at 8550 nmol/24H ( 79-590). However his overnight dexamethasone test was suppressed < 50 nmol/L. ACTH level was 42 pg/ml ( < 46). MRI pituitary revealed 3mm R adenoma. We performed a low dose dexamethasone suppression test, baseline cortisol was 646 nmol/l and ACTH was 125 pg/ml. His cortisol suppressed to 12 nmol/l and ACTH 10 pg/ml after LDDST. Is it possible to have Cushing's despite a negative LDDST?

Would inferior petrosal sinus sampling helps in getting a right diagnosis?

I appreciate any opinion on this. Thank you, Dr. Noor Lita Adam


Your patient has a urine free cortisol that is 14-fold higher than the upper limit of normal; normal suppression with overnight dexamethasone, however you don’t mention the dose of dexamethasone used. The LDDST suggests a normal HPA axis and suggests “pseudocushings”. The possible reasons for discrepancies between a high urine free cortisol and normal dexamethasone suppression testing are medications which decrease the metabolism of dexamethasone or substances that interefere with the measurement of cortisol. Furthermore the absence of stigmata on clinical presentation with such a high cortisol makes one suspicious of a false reading in the cortisol – or rapid onset of disease. I would do the following:

1.clarify the medications the patient is taking (rule out: carbamazepine, fenofibrate, licorice, carbenoxolone, exogenous hydrocortisone)

2.Repeat a basal urine free cortisol by HPLC to determine if intermediates are elevated.

3.Measure salivary free cortisol at midnight, twice.

4.If still elevated urine free cortisol perform a low dose dexamethasone suppression/CRF stimulation test (0.5 mg q6h for 2 days and on the morning of the 3rd day do CRF stimulation test). Measure dexamethasone level in the blood to confirm levels.

To answer your specific questions:

5.Is it possible to have CD despite a negative LDDST – unlikely, but possible.

6.IPSS would not be helpful here. First you need to confirm there is hypercortisolism and that it is ACTH dependent.

I look forward to hearing more about your patient. Thank you for allowing me to comment.

Roy Weiss ,MD, PhD, FACP, FACE