The patient was a 50-year-old Chinese man who was diagnosed with hypertension at the age of 42 years. The patient was treated with felodipine alone after he was diagnosed with hypertension, and his blood pressure was ~140-150/90-100 mmHg with felodipine treatment. Approximately 1 month earlier, he felt dizzy and his self-measured blood pressure was found to be 190/120 mmHg. He went to the hospital and was prescribed nifedipine 30 mg three times a day, irbesartan hydrochlorothiazide (150 mg/12.5 mg) one tablet twice a day and, metoprolol 47.5 mg/day. He occasionally measured his blood pressure, which was ~130-150/80-90 mmHg.
The patient had type 2 diabetes mellitus for 6 years, and he currently took gliclazide 30 mg/d and metformin 500 mg twice a day. He was diagnosed with tuberculosis 2 months earlier. Since then, he was regularly taking ethambutol 750 mg/day, isoniazid 100 mg/day, and rifapentine 600 mg twice a day.
Due to his severe hypertension, he was referred to the endocrinology department. The laboratory test showed hypokalemia of 3.1 mmol/L (reference: 3.5-5.5 mmol/L). Two weeks after changing his antihypertensive therapy to nifedipine-controlled released tablet 30 mg/day and doxazosin 4 mg/day, laboratory tests showed a high plasma aldosterone concentration (PAC) of 17.4 ng/dl (to convert to pmol/L, multiply by 27.74), a low plasma renin concentration (PRC) of 4.2 mIU/l (to convert to pmol/L, multiply by 0.0375), and a high aldosterone/renin ratio (ARR) of 41 (ng/dl)/(mIU/l) (reference <2.0) (Table 1), which suggested PA. The saline infusion test and the captopril challenge test (Table 1) confirmed the diagnosis of PA. Adrenal computed tomography (CT) was performed, and a right adrenal nodule (13 mm in diameter) with low density was identified (Figure 1).
Physical examination revealed no full moon face, no centripetal obesity, and no skin purple skin striae. His 24-h urine-free cortisol, plasma cortisol, and plasma adrenocorticotropic hormone levels were normal (Table 1). However, 1 mg overnight and 2 mg/d for 48 h DST yielded positive results (>138 nmol/l). Plasma cortisol levels at 8 a.m. after 1 and 2 mg dexamethasone administration were 218.7 and 384.5 nmol/l, respectively (Table 1). Because some patients with Cushing's syndrome have inconsistent 24-h urine-free cortisol and DST results, subclinical Cushing's syndrome was considered in this patient, although his 24-h urine-free cortisol was not high. According to the guideline, patients younger than 35 years, with spontaneous hypokalemia, marked excess aldosterone, and unilateral adrenal lesions with radiological features consistent with a cortical adenoma on adrenal CT scan may not need adrenal vein sampling before proceeding to unilateral adrenalectomy. For this patient, given PAC and PRC levels as well as his age, adrenal venous sampling was strongly recommended but the patient refused. Laparoscopic total right adrenalectomy was performed. Three nodules were found in the right adrenal resection specimen, and only the largest nodule was observed by CT (Figure 1). Histology showed clear cells with vacuolated cytoplasm. Immunohistochemical staining for the enzymes involved in aldosterone (CYP11B2) and cortisol (CYP11B1) (Figure 2) biosynthesis suggested that all the three nodules secreted aldosterone, whereas none of them secreted cortisol. KCNJ5 mutations were found in two of the three nodules, whereas no PRKACA mutations were found (Figure 3).
One month after surgery, the patient's serum potassium was normal. The PAC decreased to 3.9 ng/dl and PRC increased to 9.2 mIU/L, resulting in a normal ARR, 0.4 (ng/dl)/(mIU/l) (Table 2). However, the patient was still found with resistant hypertension. Despite administration of nifedipine-controlled released tablet 30 mg twice a day, irbesartan hydrochlorothiazide (150 mg/12.5 mg) one tablet twice a day, and metoprolol 47.5 mg/day, his blood pressure was remained uncontrolled. In addition, 1 mg overnight DST yielded positive results (with 8 a.m. plasma cortisol levels of 369.8 nmol/l after administration of 1 mg dexamethasone). This situation disturbed the patients, and we discussed the possible cause with him. Rifapentine-induced false positive in DST as well as uncontrolled blood pressure was considered. Two months after he completed the tuberculosis treatment, 1 mg overnight DST results were negative (8 a.m. plasma cortisol levels of 29.8 nmol/l after administration of 1 mg dexamethasone). His blood pressure was well-controlled with nifedipine alone (30 mg/day). Finally, the patient was diagnosed with right APA and, he was satisfied with the treatment effect.
Informed consent was obtained from the patient for publication of the case report and accompanying images.