From Aldosteronism to Fibromuscular Dysplasia

Secondary aldosteronism is rarely observed clinically. Its causes may be physiological or pathological. Renal artery stenosis (RAS) is one of the most common causes. Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory arteriopathy that can lead to RAS. Through the following 2 cases, we investigated the imaging manifestations, diagnosis, and treatment of FMD for better future clinical work. Case 1 was a 35-year-old female patient. Her chief complaint was elevated blood pressure for 2 days. She had elevated blood pressure (maximum of 180/120 mm Hg) during a physical examination 2 days before, accompanied by dizziness, numbness in the left hand, intermittent cough, and occasional sputum. After treatment with Chinese traditional medicine and acupuncture, the patient’s dizziness improved, but her blood pressure remained uncontrolled. She had neither a history of chronic kidney diseases or autoimmune diseases nor a family history. Her plasma K+ concentration was 3.07 mmol/l. Her hormone test results revealed that (Table 1) renin and aldosterone increased significantly, suggesting secondary aldosteronism. Renal artery computed tomography angiography (CTA) indicated multiple severe stenoses of the right renal artery (Figure 1a–c). Her left renal artery was 24.8 mm in length and 5.2 mm in diameter, whereas her right renal artery was approximately 30.8 mm in length and 3.2 mm in diameter. Hormone results of case 1 Hormone results of case 1 CTA of case 1. (a–c) Renal artery CTA (before balloon angioplasty); (d–i) abdominal CTA (after balloon angioplasty); (d) artery period; (e) portal vein period; (f) delay period; (g–i) 3-dimensional reconstruction. After a vascular surgery consultation, she was diagnosed with FMD. Then, she received balloon angioplasty for treatment. Subsequently, her blood pressure and plasma potassium level returned to normal. However, she was not experiencing relief from renal artery stenosis. Her blood pressure remained stable in the succeeding 4 months, and her blood potassium level was within the normal range. Abdominal CTA indicated that renal artery stenosis was relieved (Figure 1d–i). Case 2 was a 31-year-old female patient. Her chief complaint was a weakness for 6 months, and elevated blood pressure was observed with renal artery stenosis for 2 weeks. The patient developed post-activity fatigue without noticeable causes 6 months previously and occasionally experienced headaches that could be relieved after rest, and no special treatment was administered. Physical examination revealed elevated blood pressure (systolic blood pressure up to 200 mm Hg). Abdominal CTA indicated a string-of-beads appearance in the right renal artery and severe local luminal stenosis, which were considered FMD (her examination report was provided but the CTA image was not because the patient underwent this examination in another province). Her aldosterone (standing) level was 800 pg/ml, whereas her renin (standing) level was 613 μIU/ml. The patient was admitted to the hospital because of a blood potassium level of 2.51 mmol/l, which was similar to that of case 1. Because the patient had headache and dizziness, head magnetic resonance angiography (MRA) (Figure 2) examination was further conducted, and limited stenosis in the middle of the basilar artery was considered. The patient also underwent renal arteriography and balloon dilation. Her blood pressure and blood potassium level returned to normal after the operation, and renal artery stenosis was relieved. Head MRA of case 2. Case 1 was a young female patient who was admitted because of hypertension and hypokalemia. Elevated renin and aldosterone levels suggested secondary aldosteronism. Similar conditions were also observed in case 2. Primary aldosteronism is common in clinical practice. It is caused by adrenal-related diseases. However, secondary aldosteronism is due to abnormal hormone levels resulting from activation of the renin–angiotensin-aldosterone system (RAAS) because of factors other than the adrenal glands. Secondary aldosteronism has a low incidence and is clinically uncommon. Among the conditions, RAS is more common. In these 2 cases, neither abnormal liver and kidney function nor hypoproteinemia was observed. The combination of high plasma renin and aldosterone levels and renal artery CTA results led to the diagnosis of RAS. Causes of RAS include atherosclerosis, arteritis, and FMD. Atherosclerosis is more common in middle-aged and elderly people and may be accompanied by obesity, diabetes, hyperlipidemia, or chronic smoking. Arteritis is mostly observed in young women. Patients may also have other immune system disorders simultaneously. FMD diagnosis should be considered after the exclusion of atherosclerosis and arteritis. FMD is a nonatherosclerotic, noninflammatory arteriopathy, predominantly observed in women. It was first observed in the renal arteries of a 5-year-old boy in 1938.1 FMD involves the muscular walls of small- and medium-sized arteries, which may result in serious complications. More than 60%–75% of cases occur in the renal artery and 25% of cases occur in the carotid artery.2 Magnetic resonance angiography helps to elucidate FMD pathophysiology by revealing the arterial luminal narrowing with alternating aneurysmal dilation, which gives FMD its classic string-of-beads appearance.3 Hypertension is often observed concurrently with FMD, which requires a more multidisciplinary approach to treatment, particularly if the renal arteries are also involved.4 FMD is a congenital vascular disease commonly involving the renal artery and internal carotid artery, followed by the vertebral artery, mesenteric artery, and external iliac artery.5,6 FMD is also a genetic disease. Genome-wide association studies have identified PHACTR1 (6p24) as a genetic risk locus for 5 vascular diseases: coronary artery disease, migraine headache, carotid artery dissection, FMD, and hypertension.7 This also supports the theory that FMD is congenital in origin. In this article, the authors demonstrated that a common DNA variant associated with 5 vascular diseases regulates the gene EDN1. Selective modulation of endothelin-1 function may prove beneficial in the treatment of such diseases. The vascular morphologies of coronary artery lesions in FMD mostly manifest as coronary dissection. However, multifocal stenotic and aneurysmal lesions can also occur in coronary arteries in some cases of FMD.8 The most common abnormality in the carotid artery vasculature of patients with spontaneous coronary artery dissection is FMD.9 Patients with FMD have a high prevalence of aneurysm and/or dissection before or at the time of FMD diagnosis. Because of the high prevalence and associated morbidity in patients with FMD who have an aneurysm and/or dissection, it is recommended that patients with FMD undergo 1-time cross-sectional imaging from the head to the pelvis, such as CTA or magnetic resonance angiography.10 It has also been reported that 15%–25% of patients with FMD presented with arterial dissection in at least 1 arterial bed.11 However, the exact correlation between FMD and arterial dissection is still unclear. The diagnosis of FMD depends on imaging evidence. Arteriography is the gold standard for the diagnosis of FMD-induced artery stenosis. Based on arteriography, FMD can be classified into 2 types: multifocal FMD (more common) and focal FMD. The hallmark of multifocal FMD is the string-of-beads appearance, and the typical imaging changes of focal FMD are annular or tubular stenosis.12 The diagnosis of renal artery FMD can be considered for adolescent patients (mostly younger than 40 years) with the aforementioned imaging changes of renal artery involvement, excluding atherosclerosis, renal artery spasm, arteritis, or other types of vasculitis and other diseases.13 One study presented a case of a 45-year-old white woman who was admitted to the hospital because of progressive postprandial abdominal pain, and the imaging studies suggested the coexistence of unifocal and multifocal FMD in a single patient.14 To summarize our cases, the course experienced “secondary aldosteronism to FMD.” Interestingly, ultrasonography revealed stenosis of the right renal artery with a markedly elevated maximum blood flow velocity (3.63 m/s) compared with that of the left renal artery (0.80 m/s). According to a recent review of the United States Registry for Fibromuscular Dysplasia,15 cerebrovascular FMD occurs as frequently as renal FMD. Although a significant proportion of FMD patients may present with a serious vascular event, many present with nonspecific symptoms and a subsequent delay in diagnosis. Another study16 presented a rare case of a 27-year-old woman with FMD that primarily affected the circle of Willis. In the treatment of FMD, percutaneous transluminal angioplasty (PTA) is generally preferred. Its early clinical success rate is high, and most studies have reported a PTA success rate of more than 90%. Approximately 10% of the complications are related to vascular access whereas renal artery perforation, dissection, or renal infarction is rare. A new classification of focal renal artery FMD into carotid artery intima–media thickness (IMT) or negative remodeling subtypes based on intravascular ultrasound was described. Patients with renal FMD with the IMT subtype were more likely to be successfully treated for hypertension.17 As doctors specializing in endocrinology and metabolism, when we encounter patients with hypertension coexisting with hypokalemia clinically, we routinely screen the levels of renin, aldosterone, and other hormones. Secondary aldosteronism should not be ignored. We have learned about the imaging manifestations, diagnosis, and treatment of FMD, which is a rare disease. Attention must be focused on avoiding missed diagnoses and misdiagnoses in future clinical work. This project was supported by the National Natural Science Foundation of China (Grant No. 82000763) and the Tianjin Municipal Health Commission (Grant No. KJ20009). The authors declared no conflict of interest. Data are available from the corresponding author upon reasonable request.