Ask Dr. Karen – Answers
#1 – Treatment protocol for patients who are cyclical but still struggling to find the Source
Dear Dr. Karen,
I wonder if I may have your advice please.
I am a 39 year old female, have finally been diagnosed with cyclical Cushing’s. Showing cycles in a 30 day salivary test. I cycle every few days with peaks lasting around three days. Sometimes, I will have a very high peak. I also show high cortisol in urine, and variable ACTH. My pituitary MRI came back normal, so they will now test my adrenals. I am in the UK and the US seems to lead the way with treatment, are there any drug protocols or treatment options that may help symptoms. I have been testing for a year, probably had Cushing’s near on a decade now, my body is exhausted.
A. E., UK
Dr. Karen’s answer:
First of all, let me say that I am so sorry for what you are facing now. The journey with Cushing’s is not easy at all, as you know. It sounds like you are exhausted and that your body is exhausted! Cushing’s causes so much damage. There is a myth that Cyclical Cushing’s patients have less significant symptoms than Florid Cushing’s patients. This is false. The damage that the Cortisol has done to your body is real and I imagine that you are ready to move forward after over a decade. It sounds like you have already caught your high cycles which is a good thing. This is the first step.
As you probably already know, the person with Cyclical Cushing’s
“cylces” between seemingly normal or low Cortisol levels and high enough cortisol levels to cause Cushing’s symptoms. Adequate and appropriate testing requires multiple test measures over an extended period of time. Studies have shown that the prevalence of Cushing’s patients who cycle is much higher
than was once thought. There is a myth that just one normal test results warrants the suspension of testing, even when a patient presents with
symptoms of Cushing’s. Experts in the field have found that patients who Cycle are still impacted by their periods of high Cortisol. For this reason,
many people argue that Cyclical Cushing’s is an even more rare form of Cushing’s Syndrome.
With that said, it is also a myth that one should rule out a pituitary source if it is not found on an MRI. Adele, I want you to know that 60% of pituitary tumors in Cushing’s patients are not seen on an MRI. They are usually referred to as micro adenomas and are so small that the imaging does not pick them up in majority of cases. The tumor can also be hidden in some cases, as was the case in my personal situation. A non-expert from a facility that is not a high volume center may not know how to identify these kinds of tumors, easily. It is possible that your Cushing’s comes from an adrenal source. However, before a pituitary source is completely ruled out, there are other ways to assess if your pituitary is the culprit.
Typically, when there is evidence of high ACTH, even if variable, the next step is what we call an IPSS. Like I said, in the case of pituitary tumors, Cushing’s tumors tend to be microscopic which means they are very small. Because of this, 60% of Cushing’s tumors in the pituitary cannot be seen on imaging such as an MRI, even if it is done repeatedly. In these cases, another test, called an Inferior Petrosal Sinus Sampling or IPSS, is done. In short, this test must be done by an experienced radiologist. The endocrinology team usually accompanies the radiology team during this procedure. Vanderbilt Pituitary Center describes the IPSS:
“The inferior petrosal sinus sampling procedure is performed in the radiology department. This is an outpatient procedure where the patient is awake throughout the test. Patients are typically given a mild sedative and a local anesthetic. Catheters are inserted through the femoral veins and threaded to the petrosal sinuses. These sinuses lie along the internal aspect of the skull base and drain blood from the pituitary gland. Serum ACTH samples are drawn from the left and right pertrosal sinuses and peripheral vein. Thereafter, corticotrophin-releasing hormone is administered through the peripheral vein. Repeat serum ACTH samples from all three locations are obtained at 2, 5 and 10 minutes after the administration of CRH. Additional X-rays are taken to confirm the catheters are not dislodged from their site during the sampling procedure. After the catheters are removed, patients are observed for 4 hours following the procedure ensuring that no bleeding from the femoral vein puncture sites occur….To interpret the results, the ACTH from the left petrosal and right petrosal samples are compared to the peripheral samples. The ratios help to determine whether or not a patient’s Cushing’s syndrome is pituitary or from a non-pituitary source. ”
I would discuss this with your medical team as the next step. The IPSS can be an effective way to adequately rule out a pituitary source if you are having high ACTH readings. Not all hospitals have the staff or expertise to perform the IPSS so you may need to do some research on what facilities, locally, are able to move forward with this procedure. Your doctor must refer you for this procedure.
In the meanwhile, there are a number of medical interventions that have been tried to help alleviate the symptoms of Cushing’s. One of the older school medications used is Ketoconazole. This is actually not a first line treatment for Cushing’s. It is primarily used for fungal infections. However, it has been found effective to decrease Cushing’s symptoms. Again, this is not a long term solution, as it has been known to impact liver enzymes.
Two other newer drugs include Korlym and Signifor. They work in different ways and have been used, more experimentally, more recently to block Cortisol and decrease symptoms. There are side effects from both of these medications that may make it difficult to continue long term. More information about pharmaceutical interventions can be found on an article written by our Pharmaceutical expert, Dr. Tanya Warren here: http://www.epictogether.org/medication/
To my knowledge, still today, the most effective way to treat Cushing’s, including Cyclical Cushing’s, is to remove the tumor from whatever source.
I hope I have answered your question adequately. Please know that we are here for you at The EPIC Foundation. The answer to your question will also be posted on the website after the 15th of the month. Thank you for taking the time to ask it, as I know that many people will benefit from getting this information. Please always feel free to contact us at firstname.lastname@example.org
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