Late-night measures of cortisol levels in saliva may not be all that helpful in diagnosing Cushing’s syndrome, a group of physicians discovered upon learning that a difficult to diagnose patient had manipulated the samples.
Although this behavior is extremely rare, the research team from the University of Calgary in Canada, argued that — when a diagnosis becomes difficult — it may be advisable to confirm suspicions using another and more reliable method that can distinguish natural from synthetic glucocorticoids.
The study, “Factitious ACTH- dependent, apparent hypercortisolism: the problem with late night salivary cortisol measurements collected at home,” was published in the journal Clinical Endocrinology.
The case report described a woman who was admitted to a specialist clinic after two endocrinologists had failed to diagnose what they suspected was cyclic Cushing’s syndrome.
The woman had complained of fatigue and weight gain over the past four years despite weight loss banding surgery, and declined taking steroid medications. The examination did not reveal particular Cushing’s symptoms.
Physicians started an investigation, including overnight dexamethasone suppression tests and late-night salivary cortisol tests, which indicate increased levels of cortisol likely caused by abnormal functioning of the ACTH hormone.
Imaging did not show any suspected lesions in the pituitary and adrenal gland, and all further examinations did not reveal any disease changes that might have contributed to the increased cortisol.
The woman was put on a dopamine agonist. This treatment triggered a loss of eight kilograms (almost 18 lbs) over six months, and the woman said she was satisfied with it. But two late-night cortisol measurement showed continuing high cortisol levels.
When the clinic started using a new type of analysis to measure cortisol, however, findings changed. The new test, which was more sensitive, indicated massively higher doses of cortisol in re-analyzed saliva samples compared to the older results.
The new test could detect synthetic glucosteroids, but could not indicate if synthetic steroids were responsible for the higher levels seen in the retest. So the team used a method called liquid chromatography-tandem mass spectrometry. This technique can identify specific molecules, and revealed that the women had manipulated the samples using prednisone.
The woman’s physician also paid a surprise visit to collect a new saliva sample, which turned out to have normal cortisol levels.
The woman neither denied or confirmed manipulating the samples. And the team was contacted two months later by her new physician, requesting confirmation of her Cushing’s syndrome and details on her case.
The researchers believed the woman most likely has what is known as Munchausen’s syndrome, a mental illness that leads patients to feign physical disease. A 1995 report by the National Institutes of Health showed that 0.7 percent of all people investigated for too high cortisol had this syndrome.
Despite the rarity of this case, the team argued that chemical analysis is a valuable tool for both determining sample manipulation in difficult Cushing’s syndrome cases, or a different potential problem.
They also cautioned against putting too much trust in very elevated late-night cortisol, particularly when the symptoms do not match the cortisol increase.