QUESTION-He is a 63 yo male who was referred to me on 10/30/2014  to evaluate his 2.5 cm left adrenal adenoma which was found incidentally on a ct scan done to evaluate abdominal pain. He has a h/o chronic back pain and had been on opiates and was weaned off of them about 9 months ago in our chemical dependency program. He continues to take ativan for anxiety, lisinopril and amlodipine for hypertension, and kcl 10 meq twice daily for hypokalemia.
He is anxious and has lost 10-15 pounds in the past 9 months. He reports insomnia, headaches, leg weakness, decreased appetite, loss of smell, and chronic back pain. He denies taking herbal supplements, steroids, or any recent steroid injections
Past Medical History:
Anxiety disorder, Spinal stenosis, opioid dependence, Fatty liver , htn
Past Surgical History: None
Family History: No adrenal disease Father with htn and cva, paternal uncles with htn
Social History: Quit tob, occas etoh, retired from construction
Physical Exam
BP 140-160/80-100, No buffalo hump, possible supraclavicular fullness bilat
No abdominal striae
10/17/14 --24 hour urine free cortisol 382 mcg (<137 mcg/24 hours)
11/4/14 ---24 hour urine free cortisol 321 (<137 mcg/24 hours)
10/30/14 --random cortisol 13.8 mcg/dl  @ 10:14 am, ACTH 10.0 pg/ml @ 10:14 am
11/6/2014--random cortisol 19.3 mcg/dl @ 12:24 noon , ACTH 19.7 pg/ml @ 12:24 noon
11/10/2014 --1 mg over night dexamethasone suppression test , cortisol 2.7 mcg/dl @ 8 am
11/17/14 --random cortisol 6.5 mcg/dl @17:46 , ACTH 8.7 pg/ml @17:46
11/19/14 --Late night LABS done with patient waiting at the lab for several hours but done from stick not indwelling IV ==cortisol 16.4 mcg/dl @ 22:30 , ACTH 17.6 @ 22:30 .
late night salivary cortisol performed by Quest diagnostics
11/18/14 --salivary cortisol 0.08 mcg/dl at midnight  (< 0.09)
11/19/14 -salivary cortisol 0.04 mcg/dl at midnight (0.09)

In summary I have a patient with nonspecific symptoms/physical findings, left adrenal adenoma, ACTH that is not low, and  2 high 24 hour urine free cortisols, a 1 mg over night dexamethasone suppression test that is not high, a high late night serum cortisol not done from an indwelling IV, and 2 normal late night salivary cortisol levels.
Do you think this patient has cushing's syndrome or know how I could establish this? Any recommendations would be greatly appreciated. Sincerely, Robert Heymann, MD

RESPONSE- Many thanks for presenting this interesting case. There are two main issues with your patient who has (1) High UFC levels on 2 occasions, and (2) Unexplained hypokalemia.
Your patient has an anxiety disorder on medication and a history of opiate dependence. His clinical phenotype does not fulfil the specific features of Cushing's syndrome besides the elevated UFC levels which are almost 3 times the upper limit of normal. In addition, his cortisol secretory dynamics do not seem to be altered as he has normal salivary cortisols whereas the serum cortisol was not done while the patient was asleep. Although his cortisol level following the 1mg dexamethasone suppression test is not less than 1.8mcg/dl he is known to have anxiety and a history of opiate dependence. The relatively high ACTH levels (compared to the high UFC levels) makes it unlikely that he has an adrenal source of cortisol hypersecretion (it would be usefull to evaluate the other adrenal to see if it is suppressed). So, if he has Cushing's syndrome it may be cyclical and most probably not from an adrenal source.

In such case a formal low dose dexamethasone suppression test following elevated UFC levels will provide high sensitivity and specificity to make the diagnosis or a midnight serum cortisol while the patients is asleep aiming at a cortisol value of less than 1.8 mcg/dl. An unsettled issue is his low K levels that if remain unexplained should be looked in the context of his apparent hypercortisolemia (check urinary K levels). If a discrepancy remains between serum cortisol levels and UFC values a concomitant measurement of serum cortisol day curve and UFC levels would be of value. In addition, medication that may affect UFC levels should be considered

In summary if further tests remain non-diagnostic follow up with repeating of the investigations may be required.   Your sincerely, Dr Gregory Kaltsas