Patient case (clinical description): A 47-year-old man comes to the office due to weight gain and fatigue.  He is not able to lift heavy objects or climb stairs. Family history is positive for DM type 2 and HTN in his father.  Blood pressure is 165/90 mm Hg and pulse is 85/min.  On physical examination, there is symmetric proximal muscle weakness of the upper and lower extremities.  Fasting plasma glucose level is 138 mg/dL and 24-hour urinary cortisol is twice the upper normal limit.  Further evaluation reveals that high-dose, but not low-dose, dexamethasone suppresses serum cortisol levels.  Serum ACTH levels are high-normal. This patient's findings are consistent with endogenous Cushing Syndrome.

Patient's own account: I'm a 47-year-old man. I went to the clinic because I had been gaining weight and had increased fatigue over the past few weeks. I was not able to lift heavy objects or even climb the stairs. My dad was diagnosed with type 2 diabetes and high blood pressure. During the exam, they took my blood pressure, which was 165/90 mm Hg, and my pulse was 85/min. They found out that I have weaknesses in both of my arms and legs. I also did a blood test on an empty stomach, and I had a glucose level of 138 mg/dL, and twice the upper normal limit of cortisol. I had high-normal levels of ACTH. The doctor said I suffer from endogenous Cushing Syndrome.

Clinical trial: Prospective, Open-Label, Multicenter, International Study of Mifepristone for Symptomatic Treatment of Cushing's Syndrome Caused by Ectopic Adrenal Corticotrophin Hormone (ACTH) Secretion

Eligibility criteria:
-  INCLUSION CRITERIA:

        Subjects will be included if they have ALL of the three following criteria:

          1. Hypercortisolism from Cushing's syndrome caused by ACTH ectopic secretion

             AND

          2. Glycemic disorder that is considered to be caused or worsened by the hypercortisolism

             AND

          3. At least one symptom attributable to the Cushing's syndrome.

             EXCLUSION CRITERIA:

               -  Evidence for Cushing's disease as judged by positive inferior petrosal sinus
                  sampling or a lesion on pituitary MRI with positive CRH test

               -  Suspected or known adrenocortical cancer or adenomas, as judged by ACTH values
                  less than 10 pg/ml and adrenal mass

               -  Subjects with cyclic Cushing's syndrome defined by any measurement of Urinary
                  Free Cortisol over the previous 2 months less than 2 N

               -  Children (age less than 18) and patients over 85 years

               -  Pregnant or lactating women. A urinary pregnancy test will be performed in women
                  of childbearing potential unless they have a history of menopause prior to
                  Cushing's syndrome or hysterectomy

               -  Life expectancy less than two months

               -  Surgery planned within 8 weeks after inclusion, especially bilateral
                  adrenalectomy

               -  Uncontrolled diabetes (plasma glucose greater than 15.0 mmol/L (270 mg/L) and/or
                  HbA1c greater than 10%)

               -  Uncontrolled hypertension (blood pressure greater than 180/110 mmHg)

               -  Recent (less than two weeks prior to inclusion) initiation of corrective
                  treatments for depression

               -  Clinically significantly impaired cardiovascular function (e.g. stage IV cardiac
                  failure)

               -  Severe liver disease (liver enzymes greater than or equal to 3 x the
                  institutional upper limit of normal range)

               -  Severe renal impairment (serum creatinine greater than or equal to 2.2 mg/dl or
                  creatinine clearance less than 30 ml/min)

               -  Severe hypokalemia (plasma K below 3.0 mmol/L)

               -  Uncontrolled severe active infection

               -  In women, known endometrial cancer, history of endometrial hyperplasia or vaginal
                  bleeding of unknown cause

               -  Premenopausal women with hemorrhagic disorders or on anticoagulants

               -  Recent (less than two weeks prior to inclusion) initiation of or significant
                  change in dose of anti-tumor therapy

               -  Previous treatment with approved or experimental steroidogenesis inhibitors,
                  somatostatin analogues within one week of admission (eight weeks for patients on
                  octreotide LAR or on lanreotide autogel)

               -  Plasma mitotane concentration greater than 5 microgram/ml

               -  Impaired mental capacity or markedly abnormal psychiatric evaluation that
                  precludes informed consent

               -  Body weight over 136 kg, which is the limit for the tables used in the scanning
                  areas

               -  Inherited porphyria

               -  Positive pregnancy test at inclusion

               -  Use of antiretroviral agents, midazolam, cabergoline, erythromycin, or grapefruit
                  juice within two weeks of the study
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 85 Years

Eligibility (NLI label): Contradiction