Question:  I have had persistent Cushing’s since 2012.  I’ve had a couple of surgeries, radiation, and about 18 months of medical therapy.  I came off that when the radiation seemed to be working – I was losing weight, my hair was growing back, and I could sleep.  I’m currently just shy of three years post radiation.  I’ve had “low cortisol” feelings enough that I take a small dose of hydrocortisone on most days (5mg in the morning probably 4 times a week) but a recent salivary cortisol test came back at double the normal limit.  My doctor asked me to stop taking the HC but some days I feel like complete garbage and take one anyway.  Without the ability to test my cortisol constantly, I feel like the occasional test is not an accurate picture of what the cortisol in my body is actually doing.  Neither continuing the daily HC nor completely stopping it feels like the right decision.  I continue to lose weight and have no problems sleeping or other Cushing’s symptoms.  Do you have any advice for managing this “grey area”?

Answer 1:  One concern is that the cumulative effect of all the treatments has also destroyed the normal pituitary cells that make ACTH, and that you may be slightly adrenally insufficient. It’s important to recognize that radiation therapy does not restore the normal rhythm of ACTH production (and hence cortisol rhythms).  Normally, if people have relatively routine sleep-waking habits, the ACTH and cortisol reach a low point just after falling asleep, and begin to increase before waking, so that morning values are much higher than bedtime values.  By contrast, radiation reduces the level in the blood at all times of the day.  In the most extreme case, when there is no difference in morning (waking) and nighttime (sleeping) ACTH/cortisol during Cushing’s syndrome, the change after radiation is that the numbers remain similar but decrease.  For this reason, a late night/bedtime salivary cortisol value will be similar to a morning value, and will be considered “abnormal” for nighttime.  If the question is whether the Cushing’s syndrome is not entirely in remission, it is better to get a 24-hour urine cortisol or to perform a 1 mg dexamethasone suppression test, which are not affected by the radiation.  If your “elevated” evening salivary cortisol level was at the low end of the morning normal range, then it’s possible that you do need cortisol.  An ACTH stimulation test can help identify this problem.  Remember too, that low cortisol levels are associated with weight loss, decreased appetite, fatigue and joint aches, which may be other clues as to your situation.  (Dr. Lynnette Nieman, NIH)

Answer 2:  Was the cortisol test (salivary cortisol) done while you were taking hydrocortisone? If so, the test could be falsely high. In that case, it would be prudent for you to repeat the salivary cortisol test after avoiding taking hydrocortisone for at least 24 hours. It is certainly possible that radiation therapy can make the pituitary underactive over time, which can also make the adrenal glands underactive. Your doctor can measure your cortisol levels in the blood (for example, with a cosyntropin stimulation test) and determine if you need to take hydrocortisone every day.  (Dr. Nicholas Tritos, Massachusetts General Hospital)

(Winter-Spring 2019)