Case Discussion <Brief History> A 34-year-old woman who denied any systemic disease had suffered from persistent high blood pressure for a half year. She was quiet well-being before this event and no abnormality was detected in previous annual health examinations, except for incidentally found high blood pressure (SBP was between 140-160 mmHg). Since she had no typical manifestations such as headache, blurred vision, dyspnea, chest tightness or epistaxis, she paid no attention to it. However, the blood pressure was still high several months later, and she visited the out-patient department (OPD) for help. She denied any oral contraceptive or glucocorticoid use, renal disease or abdominal trauma history. Physical examination showed a woman of 157 cm in height and 60 kg in weight. Her body temperature was 37.2 o C, blood pressure 152/86 mmHg, and pulse rate was 102 bpm. A systolic murmur was heard over the cardiac apex and obvious abdominal bruits were auscultated in the periumbilical area. The pulses in the four limbs were intact and there's no blood pressure discrepancy between them. The other examinations were unremarkable. <Laboratory and Image Study> 1. CBC/DC & coagulation profiles: Day after admission WBC K/μL RBC M/μL Hgb g/dL Hct % MCV fL Plt K/μL 0 8.51 4.55 10.8 33.4 92.3 470 5th 8.43 4.71 11.0 33.5 92.2 450 2. Biochemistry Day after admission BUN mg/dl Cre mg/dl Na mmol/l K mmol/l GOT U/l T-Bil mg/dl Alb g/dL 0 9.3 0.7 141 3.8 34 1.0 4.3 5th 10 0.9 138 4.1 33 0.9   3. Urine analysis: Day after admission Appearance Sp. gr pH Protein mg/dL Glu g/dL Ketones O.B Urobil EU/dL Bil 0 Y;C 1.02 7.0 >300 － － － 0.1 － 5th Y;C 1.02 7.0 >300 － － － 0.1 － Day after admission Nitrite WBC RBC /HPF WBC /HPF EpithCell /HPF Cast /LPF Crystal Bact 0 － － 0-1 0-1 0-3 － － － － － 0-1 0 3-5 － － － 4. Renal echo: Size R't 10.2 cm ; L't 10.9 cm Shape Bilaterally normal Cortical thinkness R't: 9 mm; L't: 9 mm (within normal limit) Central sinus No hydronephrosis Solid or cystic lesion Nil 5. CXR: normal heart size and clear lung fields. 6. Magnetic Resonance Imaging and Angiography without/with Gadolinium-ABDOMEN Bilateral renal sizes are intact but showing the zig-zag appearance. The orifices are intact. Focal collateral vessels are noted around the right renal hilum. Fibromuscular dysplasia (FMD) should be excluded. The pattern could be also dissection, or unknown etiology. No evidence of focal lesions in the liver, spleen, pancreas, both adrenal and kidneys. No evidence of paraaortic LAPs in abdomen; no ascites. 7. Computer tomography angiography-Brain: negative for aneurysm 8. Serology 24 hours urine VMA: within normal limit Plasma aldosterone/Plasma rennin activity: high Thyroid function: within normal limit Adrenal function: within normal limit and normal diurnal change <Course and Treatment> Initially, her blood pressure was controlled by max. dose of Amlodipine and Losartan. Because of the clinical presentations and MR angiography finding, FMD was highly suspected. Renal angiography was performed which showed a bead-like appearance of the right distal renal arteries. Besides, significant stenosis of the right renal arteries was also noted. (80% stenosis, Figure A) Then she underwent percutaneous transluminal angioplasty (PTA) with stenting smoothly and was discharged and followed up at our OPD. Her blood pressure improved gradually during the follow-up period and all drugs for hypertension were withdrawn finally. <Analysis> Generally speaking, investigations to rule out the possibility of secondary hypertension (HTN) are needed in people who are younger than 30 years or older than 60 years having hypertension, HTN is refractory to more than 3 drugs with max. dose control, abdominal bruits and other specific clinical presentations etc. Five categories should be considered in diagnosing 2nd HTN: 1. Renal vascular disease 2. Renal parenchymal disease 3. Endocrinopathy 4. Congential heart disease 5. Drugs like oral contraceptives, Erythropoietin, Cocaine, Amphetamine. Usually, the congenital heart disease could be diagnosed by pediatrists in patient's early life, but we should still pay attention to it. In HTN resulting from renal parenchymal disease, glomerulonephritis (GN) is the main reason. GN-related 2nd HTN is often associated with renal dysfunction (high BUN and Creatinine), proteinuria, hematuria and/or pyuria. Renal imaging study may be normal. Most of the diagnosis should be made by renal biopsy. In endocrinopathy, like pheochromocytoma, Cushing's syndrome, Graves' disease, acromegaly, aldosteronism etc. should also be considered. However, each disease has its distinct clinical presentations and could be diagnosed by serology tests. Besides, she also denied any drug abuse history. Although her blood pressure was not refractory to drug therapy and not exceeding 3 drugs, 2nd HTN still needs to be ruled out in this woman because of her age of HTN onset. Based on the general classification, this patient fell into the category of renal vascular disease. Renal artery stenosis (RAS) is the main constituent of renal vascular diseases. It can be divided into two main types: atherosclerotic RAS and FMD. Atherosclerotic RAS usually occurs in elderly with both renal arteries proximal parts involvement. However, FMD is an angiopathy that affects medium-sized arteries predominantly in young women of childbearing age at distal 2/3 parts of renal artery. Of patients with identified FMD, renal involvement occurs in 60-75%, cerebrovascular involvement occurs in 25-30%. The etiology of FMD is not known and the frequency of FMD in Taiwan is also unknown. FMD lesions likely predispose the artery to dissect through weakening of the arterial wall. It ever hints of a genetic cause of FMD, such as collagen or elastin mutation, epidemiologic data suggesting familial transmission are generally weak. It generally follows a benign course and is frequently an incidental finding. However, cranial involvement bears worse prognosis because of the occurrence of dissection and strokes and the coexistence of saccular aneurysms. Most patients with FMD are asymptomatic. Others report nonspecific problems like headache, dizziness, but FMD most commonly affects the renal arteries and can cause refractory renovascular hypertension. No serology exam is useful but the imaging exam like CT angiography, MR angiography. Conventional angiography c remains the criterion standard to detect FMD and its associated vascular lesions but it could be postponed when intervention is needed. The medical treatment is similar to general HTN therapy. Because it is usually one side involvement, the mechanism of 2nd HTN angioplasty is mainly Angiotensin II dependent HTN. And Angiotensin II receptor blocker can be considered first. By performing angioplasty with/without stenting, the success rate has been reported to exceed 90%. So, in patients with definite diagnosis of FMD, angioplasty with/without stenting should be considered first. <Reference> Harrison's principles of internal medicine 15 edition Comprehensive Clinical Nephrology 2nd edition NEJM 2004;350(18):1862-1871 4. eMedicine, Fibromuscular dysplasia. Last Updated: October 6, 2005 繼續教育考題 1. (E) 會造成 2nd HTN 的原因如下，何者正確？ A Renal parenchymal disease B Renal vascular disease C Endocrinopathy D Congenital heart disease E All of above 2. (B) 常見的 renal artery stenosis 中有關 artherosclerotic RAS何者錯誤？ A Mainly in elderly B Mainly in distal part C Mainly bilateral D All of above 3. (C) Renal artery stenosis 中有關 fibromuscular dysplasia 何者錯誤？ A Mainly in young people B Mainly in distal 2/3 parts of renal artery C Mainly in male D Mainly unilateral 4. (D) 對 fibromuscular dysplasia 一般的描述何者錯誤？ A Mainly for medium-size artery B Severe symptoms like stroke, myocardial infarction is not often C Mainly in renal artery D Family transmission is strong 5. (C) 由於一般 fibromuscular dysplasia 是侵犯單側腎動脈,所以依制病機轉可優先考慮何種內科藥物治療？ A Diuretics B Calcium channel blocker C  Angiotensin II receptor blocker D Beta blocker 6. (B) 何者不可能是 2nd HTN 的臨床表現？ A Refractory HTN B Controlled by max dose of only a beta blocker and a Calcium channel blocker C Having abdominal bruits D All of above 答案解說 【E】Five categories should be considered in diagnosing 2nd HTN: Renal vascular disease Renal parenchymal disease Endocrinopathy Congential heart disease Drugs like oral contraceptives, Erythropoietin, Cocaine, Amphetamine. 【B 】Atherosclerotic RAS usually occurs in elderly with both renal arteries proximal parts involvement. 【C】FMD most commonly affects the renal arteries and can cause refractory renovascular hypertension. FMD is an angiopathy that affects medium-sized arteries predominantly in young women of childbearing age at distal 2/3 parts of renal artery. 【A】FMD is an angiopathy that affects medium-sized arteries predominantly in young women of childbearing age at distal 2/3 parts of renal artery. Most patients with FMD are asymptomatic. Of patients with identified FMD, renal involvement occurs in 60-75%, cerebrovascular involvement occurs in 25-30%. Familial transmission are generally weak. 【C】The medical treatment is similar to general HTN therapy. Because it is usually one side involvement, the mechanism of 2nd HTN angioplasty is mainly Angiotensin II dependent HTN. And Angiotensin II receptor blocker can be considered first. 【B】General speaking, investigations to rule out the possibility of secondary hypertension (HTN) are needed in people who are younger than 30 years or older than 60 years having hypertension, HTN is refractory to more than 3 drugs with max. dose control, abdominal bruits and other specific clinical presentations etc. Beta blocker and Calcium channel blocker are only 2 species.