A 29-year-old man is evaluated in the hypertension clinic for persistently elevated blood pressure. He was diagnosed with hypertension at age 21 and is currently taking maximally tolerated doses of amlodipine, lisinopril, and chlorthalidone with poor control. He reports occasional muscle cramps but no headaches, palpitations, or diaphoresis. Family history is notable for his father, who developed severe hypertension in his twenties and died of a hemorrhagic stroke at age 42.
Blood pressure is 168/104 mm Hg and heart rate is 76/min. BMI is 24 kg/m². Physical examination reveals no abdominal bruits, striae, or abnormal fat distribution.
Laboratory results are as follows:
| Laboratory Study | Result | Reference Range |
|---|---|---|
| Sodium | 145 mEq/L | 136-145 mEq/L |
| Potassium | 2.9 mEq/L | 3.5-5.0 mEq/L |
| Chloride | 104 mEq/L | 98-106 mEq/L |
| Bicarbonate | 31 mEq/L | 22-28 mEq/L |
| Creatinine | 0.9 mg/dL | 0.7-1.3 mg/dL |
| Plasma renin activity | 0.1 ng/mL/hr | 0.6-4.3 ng/mL/hr |
| Serum aldosterone | 32 ng/dL | 3-16 ng/dL |
An unenhanced CT scan of the abdomen demonstrates bilateral adrenal enlargement without discrete masses. Following a 4-week therapeutic trial with low-dose oral dexamethasone, the patient's blood pressure decreases to 126/82 mm Hg and serum potassium rises to 4.3 mEq/L.
Which of the following is the most likely molecular mechanism underlying this patient's condition?
- Formation of a chimeric gene combining an ACTH-responsive promoter with the aldosterone synthase coding regionCevap
- BSomatic gain-of-function mutation in the KCNJ5 potassium channel resulting in autonomous cellular depolarization
- CDeficient activity of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme in the renal collecting duct
- DDecreased ubiquitination and degradation of the epithelial sodium channel at the apical membrane
- EDecreased renal arterial perfusion activating the juxtaglomerular apparatus to secrete excess renin