ABSTRACT
EXTENSIVE AND COSTLY INVESTIGATIONS: Are not warranted in the vast majority of hypertensive patients. Characteristics identifying the patients at risk for secondary hypertension can be used to define the small percentage of patients with hypertension who require more extensive diagnostic testing and management of their condition. Exposure to certain medicines, foods or drugs may cause reversible rises in blood pressure. Renovascular and adrenal diseases cause curable forms of hypertension. IN MANY CASES, THE PATIENT'S HISTORY: Examination and simple tests can detect such exposures and disorders. Checking for secondary hypertension is therefore an early step required for the management of all patients with hypertension, provided it is based on clinical signs and inexpensive tests. This primary screening cannot exclude the possibility of renovascular or adrenal disease in a small number of asymptomatic patients. The risk of missing a diagnosis is acceptable provided that blood pressure is normalized by non-specific antihypertensive treatment. However, more extensive etiologic investigation is required in patients who subsequently develop resistant hypertension. This secondary screening requires imaging and biochemical tests that are not required for primary screening. CORRECTION OF THE CAUSES: Of secondary forms of hypertension may restore blood pressure to normal. The patient's age affects the reversibility of renovascular and adrenal hypertension after etiologic treatment: the younger the patient, the higher the probability of blood pressure normalization.
Subject(s)
Adrenal Gland Diseases/diagnosis , Hypertension, Renovascular/diagnosis , Hypertension/etiology , Adenoma/complications , Adenoma/diagnosis , Adenoma/surgery , Adrenal Gland Diseases/surgery , Adrenal Gland Diseases/therapy , Adrenal Gland Neoplasms/complications , Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/surgery , Adult , Age Factors , Aged , Antihypertensive Agents/therapeutic use , Diagnosis, Differential , Female , Humans , Hyperaldosteronism/complications , Hyperaldosteronism/diagnosis , Hypertension/diagnosis , Hypertension/therapy , Hypertension, Renovascular/therapy , Iatrogenic Disease , Magnetic Resonance Imaging , Male , Middle Aged , Pheochromocytoma/complications , Pheochromocytoma/diagnosis , Pheochromocytoma/surgery , Prospective Studies , Renal Dialysis , Risk FactorsSubject(s)
Hyperkalemia/genetics , Hypertension/genetics , Pseudohypoaldosteronism/genetics , Adult , Family Health , Female , Genes, Dominant , Genetic Heterogeneity , Humans , Hyperkalemia/diagnosis , Hypertension/diagnosis , Male , Middle Aged , Pedigree , Phenotype , Pseudohypoaldosteronism/diagnosisABSTRACT
BACKGROUND: Familial hyperkalaemic hypertension (FHH) is a Mendelian form of low-renin hypertension characterized by hyperkalaemia and hyperchloraemic acidosis despite a normal glomerular filtration rate. To date, three different loci have been identified, on chromosomes 1, 17 and 12. OBJECTIVE: To test for genetic linkage between the three FHH loci and three new affected kindreds. DESIGN AND METHODS: Clinical, biological and genetic analyses were made of three kindreds, including 11 affected individuals among 25 members. Genotyping was performed using four series of microsatellite markers spanning the chromosomes 1, 17 and 12 loci, and the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene. RESULTS: Segregation of the trait in each kindred was compatible with an autosomal transmission, the affected individuals displaying reasonably consistent biochemical abnormalities and the expected variability in arterial hypertension. Multipoint linkage analysis excluded linkage with the four candidate loci in kindreds 1 and 2, but not with the chromosome 1 locus in kindred 3. CONCLUSION: These results demonstrate further genetic heterogeneity and that a fourth gene is responsible for FHH in at least two unrelated kindreds. They suggest a variety of molecular defects leading to FHH.
Subject(s)
Genetic Variation , Hyperkalemia/complications , Hypertension/etiology , Hypertension/genetics , Receptors, Drug , Symporters , Adolescent , Adult , Aged , Carrier Proteins/genetics , Child , Chromosome Mapping , Chromosomes, Human, Pair 1/genetics , Chromosomes, Human, Pair 12/genetics , Chromosomes, Human, Pair 17/genetics , Female , Genetic Linkage , Genotype , Humans , Infant , Male , Middle Aged , Pedigree , Pseudohypoaldosteronism/classification , Pseudohypoaldosteronism/genetics , Sodium Chloride Symporters , Solute Carrier Family 12, Member 3ABSTRACT
1. Familial hyperkalaemic hypertension (FHH), also called pseudohypoaldosteronism type II (PHA2) or Gordon syndrome, is a rare Mendelian-form of low-renin hypertension. The first cases of FHH were reported approximately 30 years ago and they described the peculiar biochemical abnormalities (i.e. hyperkalaemia and hyperchloraemic acidosis despite a normal glomerular filtration rate). 2. Since then, more than 90 single cases and families have been reported in the literature. These various reports show marked differences in phenotype. 3. Our group has now collected 14 unrelated pedigrees originating from different parts of France and Europe. We confirm the large variations in the age of discovery and in the severity of the biochemical abnormalities from one individual to another and from one family to another one. 4. Blood pressure levels have no significant relationship with hyperkalaemia or hyperchloraemia, but there is a positive relationship with age, as in the normal population. 5. Analyses of clinical features and Mendelian segregation in our families demonstrate autosomal-dominant inheritance, as expected from the literature. 6. Efforts have been made in the past years to unravel the gene responsible for the disease. Until now, a primary responsibility of the gene encoding the thiazide-sensitive Na-Cl cotransporter (SLC12A3) has been excluded in PHA2 families. Three loci have been identified on chromosomes 1 (PHA2A), 17 (PHA2B) and 12 (PHA2C). 7. More recently, analysis of three additional pedigrees, including 10 affected subjects, with over 25 members allowed us to demonstrate further genetic heterogeneity and the existence of at least a fourth locus. 8. The genetic heterogeneity of this syndrome, and thus the variety of molecular defects, suggests the role of either several new components of the same pathway, multiple aldosterone- regulated effectors or direct or indirect partners of the Na-Cl cotransporter.
Subject(s)
Genetic Heterogeneity , Hyperkalemia/genetics , Hyperkalemia/physiopathology , Hypertension/genetics , Hypertension/physiopathology , Adolescent , Adult , Amino Acid Sequence , Female , Humans , Male , Middle Aged , Pedigree , Phenotype , Sodium-Potassium-Exchanging ATPase/genetics , SyndromeABSTRACT
1. Primary aldosteronism is a syndrome consisting of hypertension, suppressed renin activity or concentration and high aldosterone levels in plasma or urine. The main steps in diagnosis are the determination of renin and aldosterone levels, the demonstration of renin-aldosterone dissociation and discrimination between idiopathic hyperplasia and Conn's adenoma, with only Conn's adenoma amenable to surgery. 2. Patients with resistant hypertension and/or hypokalaemia should be screened for primary aldosteronism with simple, redundant hormonal tests. The aldosterone to renin ratio is a logical initial screening test, a high ratio demonstrating renin-aldosterone dissociation. Criteria for a high ratio should be determined in each laboratory. 3. In patients with documented primary aldosteronism, computed tomography scan and adrenal vein sampling help to distinguish between idiopathic hyperplasia and Conn's adenoma. 4. Patients with low renin hypertension, idiopathic hyperplasia and Conn's adenoma have overlapping values for plasma concentrations of potassium, renin and aldosterone and the aldosterone to renin ratio. Because primary aldosteronism subtypes are quantitative diseases, the true prevalence of primary aldosteronism cannot be defined. 5. The use of sensitive screening tests (e.g. aldosterone to renin ratio) gives a higher prevalence of diagnosed cases of primary aldosteronism, but not of surgically correctable forms. Therefore, there is no clinical evidence that primary aldosteronism is underdiagnosed. 6. There is a need for tests to predict the postoperative blood pressure outcome of surgery in subjects with Conn's adenoma.
Subject(s)
Hyperaldosteronism/diagnosis , Practice Patterns, Physicians' , Adrenal Glands/metabolism , Adrenal Glands/pathology , Adrenocortical Adenoma/diagnosis , Adrenocortical Adenoma/metabolism , Adrenocortical Adenoma/pathology , Aldosterone/metabolism , Diagnosis, Differential , Humans , Hyperaldosteronism/metabolism , Hyperaldosteronism/pathology , Hyperaldosteronism/physiopathology , Hyperplasia/diagnosis , Hyperplasia/metabolism , Hyperplasia/pathology , Hypertension/diagnosis , Hypertension/metabolism , Hypertension/pathology , Hypertension/physiopathology , Renin/metabolism , Sensitivity and Specificity , SyndromeABSTRACT
Hypokalaemic hypertension or resistant hypertension justify investigation for primary hyperaldosteronism. The first step of this investigation is to exclude the ingestion of liquorice, alkalis and diuretics. The second is to make sure that the treatment is compatible with the hormonal tests and that the natriuresis and kaliuresis are normal. The diagnosis then depends on an increased plasma or urinary concentration of aldosterone with a low plasma renin activity. The adenoma of Conn is present in 2/3 of cases and surgically curable, and should be distinguished from adrenal hyperplasia which is treatable with distal diuretics. This is a diagnosis which requires computerised tomography or, when inconclusive, demonstration of unilateral secretion of aldosterone. Adrenalectomy, usually by coelioscopy, is indicated in Conn's adenoma when the patient is young and the hypertension severe or recent. Surgical abstention is strongly advised in cases of adrenal hyperplasia.
Subject(s)
Adrenal Gland Diseases/complications , Hyperaldosteronism/complications , Hypertension/drug therapy , Adenoma/complications , Adenoma/diagnosis , Adenoma/therapy , Adrenal Gland Diseases/diagnosis , Adrenal Gland Diseases/therapy , Adult , Age Factors , Aged , Diagnosis, Differential , Humans , Hyperaldosteronism/diagnosis , Hyperaldosteronism/therapy , Middle Aged , Renin/metabolismABSTRACT
Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory vascular disease that primary involves medium-sized and small arteries, most commonly the renal and carotid arteries. Dysplasic stenoses can be classified by angiography into three main subtypes, multifocal (multiple contiguous stenoses with the "string of beads" appearance), unifocal (single stenosis in a given renal artery), or tubular. The multifocal subtype is the most frequent and is usually associated with medial dysplasia, whereas unifocal and tubular stenoses are associated with intimal and perimedial dysplasia, respectively. Renovascular hypertension, mainly in women aged 30 to 50 years, is the most common manifestation of renal artery fibromuscular dysplasia. Its prevalence in hypertensive patients is estimated to less than 1 percent. The true prevalence of the disease is probably higher, however, because many cases can go undetected in normotensive or asymptomatic hypertensive patients. The first line treatment is percutaneous transluminal angioplasty that usually allows blood pressure improvement or normalization. Stenosis progression is slow and rarely leads to ischemic renal failure. Recognition of renal artery fibromuscular dysplasia should lead to screening for associated carotid artery lesions. Fibromuscular dysplasia can be a familial disease.
Subject(s)
Fibromuscular Dysplasia/complications , Hypertension, Renovascular/etiology , Renal Artery Obstruction/etiology , Adult , Aneurysm/etiology , Angioplasty, Balloon, Coronary , Cerebrovascular Disorders/etiology , Disease Progression , Female , Fibromuscular Dysplasia/diagnostic imaging , Fibromuscular Dysplasia/epidemiology , Fibromuscular Dysplasia/therapy , Humans , Hypertension, Renovascular/diagnostic imaging , Ischemia/etiology , Kidney/blood supply , Kidney Failure, Chronic/etiology , Male , Middle Aged , Prevalence , Radiography , Renal Artery Obstruction/diagnostic imaging , Renal Artery Obstruction/epidemiology , Tunica Intima/pathologyABSTRACT
OBJECTIVE: To describe phenotypes and estimate the prevalence of familial cases of renal artery fibromuscular dysplasia (FMD). PATIENTS AND SETTING: One hundred and four unrelated hypertensive patients (94 women) with renal artery fibromuscular dysplasia documented on angiography and classified as having multifocal or unifocal lesions. Familial cases were defined as those with angiographic evidence of renal artery FMD in at least one sibling. RESULTS: Eighty-one patients had multifocal and 16 had unifocal FMD. Both types of stenosis were present in seven patients. Fifty-four patients had bilateral FMD, including the seven patients with both unifocal and multifocal lesions. The 16 patients with unifocal FMD were younger, more likely to be men, and more commonly had unilateral stenoses, stenoses exceeding 75% and a small ischemic kidney than the 81 patients with multifocal lesions. Eleven cases were identified as familial on the basis of FMD having been documented in at least one sibling (eight sibling pairs and three trios). All probands were women and exhibited multifocal lesions. FMD was more often bilateral in familial than it was in apparently sporadic cases. CONCLUSIONS: Multifocal FMD was mostly found in women and unifocal FMD in young men with more severe stenosis and kidney ischemia. The documented prevalence of familial cases was 11% in this series, the true prevalence being probably higher because only a few siblings were examined by angiography. Familial cases all exhibited the multifocal type and were more commonly bilateral than were sporadic cases.