Adrenocorticotropic Hormone-Independent Cushing Syndrome with Bilateral Cortisol-Secreting Adenomas
A 48-year-old woman.\nIncidentally found bilateral adrenal masses.\nThe patient had been diagnosed with hypertension 3 years prior, and had been receiving carvedilol 25 mg as prescribed by a private clinic. However, the patient's blood pressure (BP) had not been under control for about 3 months prior to the visit at our hospital. A year prior, the patient's menstrual cycle had become irregular and her weight had increased by 5 kg in the last year. The patient had visited our hospital due to the identification of bilateral adrenal masses from abdominal CT during a routine health examination.\nNothing specific except hypertension.\nNothing specific.\nAt the time of the visit to our hospital, the patient's height was 150 cm, weight was 53.8 kg, BP was 145/95 mm Hg, pulse rate was 72 beats per minute, respiratory rate was 20 times per minute, and body temperature was 37.1℃. She had an alert mental state, no visible signs for acute or chronic illness and no abnormal findings for skin, sclera and conjunctiva. Examination of the head and neck revealed a moon face, while a buffalo hump deformity was observed upon thoracic examination. There was no specific finding on the abdominal examination and no edema of extremities was identified. The patient had no accompanying muscle weakness or sensory deterioration.\nThe peripheral blood test performed at the time of visit to the hospital showed the following; white blood cell, 6,450/mm3; hemoglobin, 12.9 g/dL; hematocrit, 41.6%; and platelet, 289,000/mm3. The serum biochemical assay showed the following; calcium, 9.4 mg/dL; phosphorus, 3.3 mg/dL; total protein, 7.0 g/dL; albumin, 4.2 g/dL; aspartate aminotransferase, 21 IU/L; alanine aminotransferase, 19 IU/L; alkaline phosphatase, 43 IU/L; blood urea nitrogen, 10 mg/dL; creatinine, 0.7 mg/dL; sodium, 144 mEq/L; potassium, 3.4 mEq/L; and chlorine, 102 mEq/L.\nThe hormone test indicated that the morning baseline blood cortisol was 15.7 µg/dL and ACTH was less than 5 pg/mL. The 24-hour urine free cortisol excretion increased to 198.7 µg/day (normal range, 23 to 135). In addition, the following were in the normal range; metanephrine, 63 µg/day (normal range, 52 to 341); normetanephrine, 176 µg/day (normal range, 88 to 444); epinephrine, 3.1 µg/day (normal range, 0 to 20); norepinephrine, 28.9 µg/day (normal range, 15 to 80); and vanillylmandelic acid, 5.4 mg/day (normal range, 0 to 8). The 24-hour urine creatinine was 0.5 g/day (normal range, 0.8 to 1.8) and the creatinine clearance was calculated to be 122.4 mL/min (normal range, 75 to 125), indicating that the urine sampling was done relatively well. The plasma aldosterone concentration was 7.5 ng/dL and plasma renin activity was 0.4 ng/mL/hr, indicating that the aldosterone/renin activity ratio was 18.7 and there was no finding of primary aldosteronism.\nThe serum cortisol after an overnight 1 mg dexamethasone suppression test was 14.5 µg/dL, which was not suppressed. The low-dose dexamethasone suppression test demonstrated that the 24-hour urine free cortisol excretion increased to 397.8 µg/day and the blood cortisol concentration increased to 21.1 µg/dL, so we diagnosed the patient's condition as Cushing Syndrome. In the high-dose dexamethasone suppression test, the urine free cortisol excretion and blood cortisol concentration were not suppressed ().\nBilateral adrenal tumors were identified on adrenal CT, with one sized 2.8×2.0 cm on the right side and the others sized 2×2.3 cm and 1.7×1.4 cm, respectively, on the left side (). There were no abnormal findings from the Sella MRI.\nAdrenal vein sampling (AVS) was done in order to identify the location of a functional tumor secreting cortisol in between the bilateral adrenal tumors. AVS was conducted without an ACTH stimulus on the day after the high-dose dexamethasone suppression test. The blood cortisol concentration was measured by sampling the blood twice from catheterization to the femoral vein and bilateral adrenal veins ().\nWhen the bone density was measured by dual energy X-ray absorptiometry, osteopenia was found based on the finding that the T score of lumber spine was -2.1, T score of femoral neck was -1.0 and T score of the total hip was -0.7.\nAs the adrenal vein cortisol measured from AVS was eight times higher than that of the inferior vena cava, it was determined that the AVS was done selectively. The blood cortisol concentration was measured as high from the bilateral adrenal veins with AVS. Therefore, we diagnosed the patient with Cushing Syndrome induced by bilateral cortisol-secreting adenomas. To treat the patient, we removed all of the bilateral adrenal tumors by laparoscopic bilateral adrenalectomy. Immediately after the surgery, the patient was discharged because there was no specific complication while implementing supplementary therapy with prednisolone and fludrocortisone, and we had discontinued the antihypertensive agent as the BP had improved to 120/80 mm Hg at the 2-month follow-up observation. At 5 months postoperatively, the blood cortisol concentration was 5.0 µg/dL, ACTH was 19.0 pg/mL, the plasma aldosterone concentration was 15.0 ng/dL, and the plasma renin activity was 3.0 ng/mL/hr, indicating no evidence of recurrence. The patient is currently under follow-up study as an outpatient while receiving prednisolone 5 to 2.5 mg and fludrocortisone 0.1 mg.\nA single mass was found on each of the adrenal glands and their sizes were 2.6×2.3×1.7 cm for the left side mass and 2.6×2.5×1.6 cm for the right side mass. Based on the visual findings, the left mass was in the shape of a dumbbell with a narrowed mid-part, showing a light brown cross-section, and the right mass had a brown cross-section ().\nFrom the optical microscopic findings, the bilateral adenomas were composed of large round vacuolar cells of consistent shape and size, and with good differentiation, whereas the normal tissues of the adrenal cortex around the adenoma were atrophic. As an atypical nucleus and necrosis, hemorrhage, or reverse differentiation were not found, the findings were appropriate for adrenal adenoma ().