A 54-year-old Chinese man was admitted to the Orthopedics Department of our hospital on 2 October 2021, complaining of weakness in both lower extremities for 2 days, with worsening for half a day. His serum potassium was measured at 1.57 mmol/L (reference value 3.5–5.5 mmol/L), and he was transferred to the intensive care unit for potassium supplementation with a deep venous catheter but without ventilation. After intravenous potassium supplementation at 24 g within 48 hours, his blood potassium was 3.1 mmol/L (reference value 3.5–5.5 mmol/L). The case was complicated by metabolic alkalosis, and the patient was transferred to our department for further treatment due to suspected endocrine disease. The patient was found to have “SH of the left kidney” on physical examination 26 years ago but received no treatment, and 20 years prior, he was diagnosed at another hospital with left congenital ureteral stenosis and severe left kidney hydrops and was given left ureteral dilation, with the left kidney hydrops improving slightly after surgery; 13 years prior, his blood pressure was elevated, with the maximum reaching 150/102 mmHg. He was given 5 mg once a day felodipine sustained-release tablets, and his blood pressure fluctuated between 130–147 mmHg and 85–97 mmHg. He was also diagnosed with obstructive sleep apnea syndrome, and no special treatment was given; 8 years prior, multiple stones in both kidneys and SH in the left kidney and a nodule in the left external adrenal branch were detected by physical examination but were not pursued due to normal ARR values. Ureteroscopic lithotomy and stent implantation in the left ureteral stenosis were performed in the Urology Department of our hospital. The left hydronephrosis improved after surgery, and his blood potassium level measured at admission was 2.6 mmol/L (reference value 3.5–5.5 mmol/L). After discharge, 12–15 g of oral potassium chloride was given daily to maintain his blood potassium between 2.8 mmol/L and 3.3 mmol/L. Severe hypokalemia occurred in the absence of supplementation within 1–2 days, and his lowest blood potassium concentration was 1.6 mmol/L. Several times, a central venous catheter was used to supplement potassium in the intensive care unit due to severe hypokalemia. Because the ARRs were less than 20 on several occasions, the endocrinology department was not invited for consultation to further search for the cause of his hypokalemia. During the course of the disease, the patient had an increased frequency of nocturnal urination (approximately five to eight times per night), no quadriplegia, a round and red face, thin skin, ecchymosis after collision, paroxysmal headache, palpitations, sweating, pale face, and other discomfort. His family history was as follows: his father died at 80 years, and the cause of death was unknown; both his grandmother and mother died of hypertensive cerebral hemorrhage at 60 years; his sister was diagnosed with essential hypertension at age 50 years; and his brother was healthy and had no history of hypertension. His personal history included the following: nonsmoking, average daily alcohol consumption of 100–150 g for approximately 20 years, and one healthy son.
His physical examination results were as follows: pulse, 78 beats per minute; blood pressure, 153/92 mmHg; body mass index, 23.7 kg/m2; no sign of Cushing syndrome; normal muscle strength and muscle tone in both upper limbs; grade 4 in both lower limbs; and no other positive signs. The results of the auxiliary tests were as follows: blood lipids indicating that triglycerides were 3.54 mmol/L; routine blood, coagulation, thyroid function, liver function, kidney function, gonadal hormone, growth hormone, and insulin-like growth factor 1 results; and a cortisol concentration of 13.71 nmol/L after the 1 mg dexamethasone suppression test. Thyroid and parathyroid ultrasound, pituitary magnetic resonance imaging, and dual energy X-ray absorptiometry showed no abnormalities. Abdominal color ultrasound indicated fatty liver, double kidney stones, severe left kidney hydronephrosis, and thinning of the left kidney parenchyma. Renal artery color ultrasound indicated no obvious stenosis in either renal artery. Echocardiography showed that the ventricular septum was 12 mm long, with decreased left ventricular diastolic function. Abdominal computed tomography (CT) revealed severe left renal hydronephrosis (Fig. 1A), and computed tomography angiography (CTA) showed that the vascular network of the left kidney was sparser than that of the right kidney (Fig. 1B). Renal radionuclide imaging indicated poor left renal blood supply, moderately impaired function (glomerular filtration rate, GFR, 30.7 mL/min), and incomplete obstruction of the left upper urinary tract. The blood supply and function of the right kidney were normal (GFR, 47.5 mL/min), and the total GFR was 78.2 mL/min.
A Severe hydronephrosis and thinning of the renal cortex of the left kidney and calculi of the right kidney. B Computed tomography angiography indicated increased volume and sparse vascular network of the left kidney.
The treatment process was as follows. After admission to our department, his antihypertensive medication was changed to a 10 mg per day nifedipine sustained-release tablet, which had little influence on the renin–angiotensin–aldosterone system (RAAS), to control his blood pressure; the blood pressure of the patient was controlled within the range of 120–137/72–88 mmHg. Urine potassium was 40.58 mmol and 60.8 mmol for two consecutive days, the serum potassium ion contents of simultaneous blood sampling were 3.01 mmol/L and 3.0 mmol/L, and the pH values were 7.43 and 7.42, respectively; 2 weeks later, the decubitus position test indicated that the plasma renin and ARR values were within the normal range but that aldosterone was significantly increased (Table 1). Further captopril inhibition tests indicated that aldosterone was not inhibited (Table 2), similar to the results of the normal saline load test (Table 3). The midnight 1 mg dexamethasone inhibition test suggested a cortisol level of 13.71 nmol/L, thus excluding Cushing syndrome. Adrenal CT showed a nodule in the left external adrenal branch, which was a possible adenoma with a diameter of approximately 8 mm and a CT value of approximately 17 Hounsfield units (HU). No definite abnormality was found in the right adrenal gland (Fig. 2). For the left adrenal nodule of the patient, we performed segmentation of the adrenal venous sample, which included four points: the left adrenal vein, inferior vena cava (left), right adrenal vein, and inferior vena cava (right). The selection indices on the left and right sides were 37.76 and 4.26, respectively, indicating successful intubation. Comparing the aldosterone-to-cortisol ratios on both sides, the left-sided index was 2.18 (> 2), suggesting that the left side was the dominant side (Table 4). Therefore, the patient was transferred to the urology department and underwent total adrenal resection on the left side via laparoscopy. Pathology and immunohistochemistry analyses of the resected tissue indicated cortical adenoma (Fig. 3). KCNJ5 (inwardly rectifying potassium channel subfamily J, member 5) mutation sequencing of the resected tissue indicated a mutation at the G151R hotspot (Fig. 4). Cytochrome p450 11β-hydroxylase.
Adrenal computed tomography revealing a local nodule in the left external adrenal branch (red arrow) with a diameter of approximately 8 mm and a computed tomography value of approximately 17 Hounsfield units. Considering the possibility of adenoma, no definite abnormality was found in the right adrenal gland
Histopathology of the left adrenal adenoma (300×)
KCNJ5 gene missense mutation (black arrows) detected by next-generation sequencing in the tumor tissue (c.451G > A p.G151R)
CYP11B1 staining was negative, but aldosterone synthase (CYP11B2) staining was positive, indicating small nodules producing aldosterone in the sample, namely, aldosterone-producing micronodules (Fig. 5), which may be the source of the high aldosterone secretion in this patient. A total of 100 mg of hydrocortisone was given intravenously for three consecutive days after surgery for replacement therapy. His plasma aldosterone, renin, and cortisol levels were 18.4 pg/mL (reference value 30–230 pg/mL), 10.89 µIU/mL (reference value 2.8–40 µIU/mL), and 729.67 nmol/L (reference value 118.64–618.02 nmol/L), respectively, and his blood pressure was within the normal range without antihypertensive drugs. The serum creatinine, potassium, sodium, and cortisol concentrations were 156 µmol/L (reference value 58–110 µmol/L), 6.73 mmol/L, 134.7 mmol/L, and 309 nmol/L, respectively, and the adrenocorticotropic hormone (ACTH) concentration was 33.8 pg/mL (reference value 7.0–85.0 pg/mL). These results all suggested that the salt corticosteroids he was taking were insufficient, and after symptomatic rehydration treatment, the patient’s kidney function returned to normal. In the absence of potassium supplementation, the serum potassium concentration was between 3.8 mmol/L and 4.2 mmol/L, and the plasma aldosterone and renin (orthostatic) concentrations were 59.5 pg/mL (reference value 30–400 pg/mL) and 33.64 µIU/mL (reference value 4.4–46 mIU/ml), respectively. At 1-year follow-up, blood pressure and serum potassium were within the normal ranges without any drug administration, and plasma aldosterone (orthostatic) and renin (orthostatic) and serum creatinine and serum potassium were 96.2 pg/mL, 9.34 µIU/mL, 93.4 µmol/L, and 4.08 mmol/L, respectively.
Immunohistochemistry of CYP11B2 (red arrows) in the tumor tissue; A Gross staining of CYP11B2, B–E Local staining of CYP11B2. CYP11B2 = aldosterone synthase
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