Phase II Prospective Evaluation of Desmopressin Stimulation Test Performance in ACTH-dependent Cushing s Syndrome
Background: Cushing syndrome (CS) is a set of diseases that develop when the body produces too much adrenocorticotropic hormone (ACTH). ACTH stimulates the production of a hormone called cortisol. Excess cortisol can cause serious issues, such as diabetes, high blood pressure, weight gain, and mood changes. Diagnosing CS early can be difficult. One test used to diagnose CS, the desmopressin (Desmo) stimulation test (DesmoST), has not been studied in enough people to know how accurate it is.
Objective: To find ways to improve the DesmoST. Researchers especially want to learn more about how well the DesmoST identifies people with specific ACTH CSs: Cushing disease (CD) and ectopic ACTH syndrome (EAS).
Eligibility: People aged 18 to 70 years who have or may have CS, especially CD or EAS. Healthy volunteers are also needed.
Design: Participants with CS will have 3 DesmoSTs at least 48 hours apart. The procedure for each is as follows: They will limit their fluid intake the day before each test. They will have nothing to eat or drink for 12 hours before the test. For 1 of the tests, they will take a pill that contains a hormone (dexamethasone). They will take it around 11 pm the day before the test. Desmo is given through a tube attached to a needle inserted into a vein. Blood will be drawn a total of 6 times before and after the desmo is given. Healthy volunteers will have 4 DesmoSTs. These will be 2 to 14 days apart. All participants will have follow-up visits 3 to 5 days after each test. These visits may be by phone.
∙ To be eligible to participate in this study, an individual must meet all of the following criteria:
• Aged 18-70 years
• Agreement to adhere to Lifestyle Considerations throughout the study.
• Evidence of acceptable laboratory testing results within four weeks of the first test day, as shown by medical record review:
‣ Hematocrit at entry \>=33 %
⁃ Plasma sodium 136-145 mmol/L (unless taking a drug that can cause hyponatremia, see below) eGFR \>=60 ml/min/1.73 sq.m, calculated based on serum creatinine
• For subjects taking any drug that could worsen hyponatremia, a normal plasma sodium (136-145 mmol/L) must have been obtained within seven days of the first test day.
∙ In addition, an individual must meet all the criteria listed for their diagnostic group below, based on medical record review:
∙ A. Patients with possible ACTH-dependent Cushing Syndrome (where the results of further work up will classify the patient as having CD, EAS or pseudo-CS):
⁃ A. Hypercortisolemia as evidenced by physician note or laboratory report: at least one screening modality (1 mg dexamethasone suppression test, 24-hour urinary free cortisol (UFC), bedtime or late night (2200h - 2359h) salivary or serum cortisol) within 4 weeks of screening. In patients suspected to have cyclic CS any previous abnormal result will suffice.
⁃ A. Normal or increased plasma ACTH (\>20 pg/mL) as evidenced by physician note or laboratory report.
∙ B. Patients with recurrent ACTH-dependent Cushing Syndrome (previous CD or EAS):
∙ 1B. Evidence of previous remission of CD or EAS after resection of a causative pituitary or ectopic tumor, evidence of current ACTH-dependent hypercortisolism, and willingness to undergo repeat surgery.
∙ C. Healthy volunteers:
∙ C1. In good general health as evidenced by medical history and physical examination; and in a stable state of health without ongoing acute/temporary illness per the clinical judgement of the investigator.