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: Evaluation of 68Ga-DOTATATE PET/CT, Octreotide and F-DOPA PET Imaging in Patients With Ectopic Cushing Syndrome

Eligibility criteria:
-  INCLUSION CRITERIA:

          -  Adults with possible ectopic Cushing syndrome

          -  Age 18-90

          -  Patients must be willing to return to NIH for follow-up studies.

        EXCLUSION CRITERIA:

          -  Pregnant or lactating women. A pregnancy test is performed in women of childbearing
             potential (up to age 55) unless they have a history of hysterectomy and/or bilateral
             oophorectomy.

          -  Children (age less than 18) are excluded. Because ectopic ACTH secretion is rare in
             this age group, the likelihood of benefit is less and does not balance the risk of
             radiation.

          -  Very elderly patients (> 90 years)

          -  For the mifepristone studies only: Patients taking medications that alter CYP3A4
             activity will not be eligible for the mifepristone study, since this P450 system
             metabolizes mifepristone. Patients with hypokalemia (K < 3.5 mEq/L), despite medical
             therapy with replacement or mineralocorticoid antagonists will also be excluded from
             the mifepristone studies. Such patients may participate in other components of the
             protocol. Medications affecting CYP3A4 may be adjusted to allow participation in the
             mifepristone component, with a one week washout period.

          -  The presence of severe active infection.

          -  clinically significantly impaired cardiovascular (e.g. history of abnormally low
             ejection fraction, the presence of moderate pulmonary fluid overload, and/or blood
             pressure over 190/100), abnormal coagulation in the absence of medically-indicated
             treatment (PT and PTT elevated by 30% above the normal values), hematopoietic
             (hematocrit less than 30%, hemoglobin below 10 g/dl, white count below 3000 K/UL, and
             platelets below 100,000 K/mm(3)), hepatic (liver enzymes elevated by 4-fold above
             normal values), or renal function (plasma creatinine level over 2.1).

          -  Based on the clinical judgment of the attending physician, other medical problems may
             prompt exclusion.

          -  impaired mental capacity or markedly abnormal psychiatric condition that precludes
             informed consent.

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

          -  combined blood withdrawal during the six weeks preceding the study greater 450 ml.

          -  known allergy to [(111)In-DTPA-D-Phe]-pentetreotide or other somatostatin analogues.

          -  strong evidence for Cushing s disease. This includes those with a central to
             peripheral ACTH gradient during IPSS or a lesion on pituitary MRI. We anticipate that
             these exclusion criteria will increase the ratio of patients with ectopic ACTH
             syndrome to those with Cushing s disease from the usual 1: 8 to 1: 2, thus we would
             accrue 3 patients to identify one with ectopic ACTH secretion.
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 90 Years

Eligibility (NLI label): Entailment