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Hypertension with hypokalaemia and suppression of plasma renin activity is known as mineralocorticoid hypertension. Although mineralocorticoid hypertension accounts for a small number of patients labelled as having "essential" hypertension, it is a potentially reversible cause of high blood pressure. The most common cause of mineralocorticoid hypertension is probably primary aldosteronism; controlled posture studies to measure plasma renin activity and aldosterone concentrations, followed by adrenal imaging, will ensure the differential diagnosis between an aldosterone-producing adenoma and idiopathic adrenal hyperplasia in most cases. Three monogenic forms of mineralocorticoid hypertension have been described: glucocorticoid-suppressible hyperaldosteronism, Liddle's syndrome, and apparent mineralocorticoid excess, which have provided new insights into mineralocorticoid hormone action. Many patients with mineralocorticoid-based hypertension are now known to have normal serum potassium concentrations. Until the true prevalence of primary aldosteronism and monogenic forms of mineralocorticoid hypertension are defined, a high index of suspicion is needed in every hypertensive patient. Hypertensive patients with hypokalaemia, together with those with severe hypertension or a family history of hypertension or stroke, should be screened for mineralocorticoid excess.
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PMID:Mineralocorticoid hypertension. 1021 47

Blood pressure homeostasis in humans reflects the coordinate interactions of cardiac output, peripheral vascular resistance, renal volume control, and CNS integration in response to short- and long-term environmental stimuli. Variations in mean arterial pressure within the population include a significant hereditary component. The clearest examples of this genetic contribution occur in rare forms of monogenic hypertension (glucocorticoid remediable aldosteronism, apparent mineralocoid excess, Liddle's syndrome) or hypotension (pseudohypoaldosteronism type I, Bartter's syndrome, Gitelman's syndrome). Primary hypertension, which comprises approximately 95% of hypertensives and is a major risk factor for coronary heart disease, stroke, and renal disease in the U.S., represents a multifactorial and polygenic disease with incremental contributions from genetic and environmental determinants. Efforts to date have identified several candidate genes involved in primary hypertension, including angiotensinogen (AGT), a vasoactive peptide; alpha-adducin, a protein that regulates sodium transport; and the G protein beta 3 subunit, a protein involved in intracellular signal transduction. Advances in knowledge and technology associated with the Human Genome Project, combined with continuing basic research on the physiologic and biochemical causes of hypertension, offer promise for improved diagnosis and therapy of this prevalent disease.
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PMID:Genetic determinants of blood pressure regulation. 1038 72

In familial hyperaldosteronism type I (FH-I), inheritance of a hybrid 11beta-hydroxylase/aldosterone synthase gene causes ACTH-regulated aldosterone overproduction. In an attempt to understand the marked variability in hypertension severity in FH-I, we compared clinical and biochemical characteristics of 9 affected individuals with mild hypertension (normotensive or onset of hypertension after 15 yr, blood pressure never >160/100 mm Hg, < or = 1 medication required to control hypertension, no history of stroke, age >18 yr when studied) with those of 17 subjects with severe hypertension (onset before 15 yr, or systolic blood pressure >180 mm Hg or diastolic blood pressure >120 mm Hg at least once, or > or = 2 medications, or history of stroke). Severe hypertension was more frequent in males (11 of 13 males vs. 6 of 13 females; P < 0.05). All 4 subjects still normotensive after age 18 yr were females. Of 10 other affected, deceased individuals (7 males and 3 females) from a single family, all six who died before 60 yr of age (4 by stroke) were males. Biochemical studies were conducted in 6 mild and 16 severe subjects. The 2 groups were similar in terms of urinary sodium excretion. Mild subjects tended, although not significantly, to have lower urinary 18-oxo-cortisol (mean +/- SD, 27.4 +/- 9.0 vs. 35.2 +/- 12.9 nmol/mmol creatinine x day), higher plasma potassium (4.0 +/- 0.3 vs. 3.6 +/- 0.4 mmol/L), and lower recumbent (0800 h after overnight recumbency) plasma aldosterone levels (498 +/- 279 vs. 744 +/- 290 pmol/L). Upright (midmorning after 2-3 h of upright posture) plasma aldosterone levels were similar (mild, 485 +/- 150; severe, 474 +/- 188 pmol/L). In 1 normotensive female, upright PRA was much higher, and the upright aldosterone/PRA ratio was much lower than that in the other subjects. The remaining mild subjects had similar upright PRA levels (mild, 2.8 +/- 1.4; severe, 3.7 +/- 3.2 pmol/ L x min) and aldosterone/PRA ratios (mild, 199.5 +/- 133.4; severe, 200.6 +/- 150.9) as severe subjects. During angiotensin II (AII) infusion studies (n = 6 mild and 10 severe), performed during recumbency, aldosterone levels were lower in the mild group both basally (404 +/- 144 vs. 843 +/- 498 pmol/L; P < 0.05) and after 60 min AII (2 ng/kg x min; 261 +/- 130 vs. 520 +/- 330 pmol/L; P < 0.05). Aldosterone was unresponsive (rose by <50%) to AII in all subjects. Day curve studies (blood collected every 2 h for 24 h; n = 2 mild and 7 severe) demonstrated abnormal regulation of aldosterone by ACTH rather than by AII in both groups. In conclusion, in this series of patients with FH-I, males had more severe hypertension, and the degree of hybrid gene-induced aldosterone overproduction may have contributed to the severity of hypertension.
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PMID:Severity of hypertension in familial hyperaldosteronism type I: relationship to gender and degree of biochemical disturbance. 1085 45

Two simultaneous operations for off-pump CABG (OPCAB) and abdominal vascular surgery were performed safely and effectively. [Case 1] A 52-year-old man was admitted with the right intermittent claudication and angina pectoris. Coronary angiography and aortography showed 90% stenosis of left anterior descending coronary artery (LAD) and the right external iliac artery. The patient underwent 1 CABG using left internal thoracic artery (ITA) without cardiopulmonary bypass and abdominal aorta--the right external iliac bypass simultaneously. Bleeding volume during the operation was only 150 ml. The operation time was 3 hours 50 minutes. [Case 2] A 57-year-old man was referred from the other hospital with complaints of abdominal aortic aneurysm. He had the history of 4 stroke attacks caused by idiopathic aldosteronism. Preoperative coronary angiography and aortography showed severe 3 vessels disease and abdominal aortic aneurysm. First, we harvested bilateral ITAs, the right gastroepiploic artery (GEA) and saphenous vein (SV). The complete revascularization (left ITA-LAD, right ITA-1st diagonal branch, GEA-seg. 4 posterodescending branch, SV graft-posterolateral branch) was performed on the beating heart. Then we repaired the abdominal aortic aneurysm (56 mm in diameter) using a Gelsealed Y-graft. The operative course was uneventful. The operation time was 6 hours 15 minutes. These cases suggested that OPCAB technique combined with abdominal vascular surgery reduced operation time and prevented complication in the patient with the risk of brain trouble.
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PMID:[Combined off-pump CABG (OPCAB) and abdominal vascular surgery]. 1176 1

Glucocorticoid remediable hyperaldosteronism (GRA) is a monogenic form of inherited hypertension caused by a chimeric gene originating from an unequal cross-over between the 11 beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. GRA is characterized by high plasma levels of aldosterone (regulated by ACTH) with suppressed plasma renin activity and the production of two rare steroids, 18hydroxycortisol and 18oxocortisol. Affected patients usually show severe hypertension and an elevated frequency of stroke at a young age. Affected women have a high risk of developing preeclampsia during pregnancy. Here, we describe a 5-generation pedigree from Sardinia in which the presence of the chimeric gene is demonstrated in 4 generations. This family displays a mild phenotype with average blood pressure levels of 131/86 mm Hg for GRA+ patients. The occurrence of stroke is very low, and preeclampsia was not observed in 29 pregnancies from 8 GRA+ mothers. We investigated whether the cross-over site (between the CYP11B1 and CYP11B2 genes) or biochemical characteristics could explain this phenotype. The cross-over site was located at the end of intron 3, in the same region as described in other families. We found a significant correlation between blood pressure and 18hydroxycortisol, 18oxocortisol, and plasma aldosterone levels, but not with kallikrein. However, none of the biochemical or genetic parameters investigated could explain the mild phenotype of the family.
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PMID:Glucocorticoid remediable aldosteronism: low morbidity and mortality in a four-generation italian pedigree. 1210 22

The purpose of this study was to elucidate the effects of dietary sodium restriction on diurnal blood pressure (BP) variation in primary aldosteronism. We studied the diurnal variation in the systemic hemodynamic indices and in baroreflex sensitivity (BRS). In 13 subjects with aldosterone-producing adenomas (2 males; mean age, 39+/-2 years), intra-arterial pressure was monitored telemetrically on a normal salt diet (NaCl 10-12 g/day). Non-dippers were defined as those with a nocturnal reduction in systolic BP (SBP) of less than 10% of daytime SBP. Ten subjects showed a non-dipper pattern. Six of these "non-dippers" underwent repetitive hemodynamic studies on the last day of a 1-week low salt diet regimen (NaCl 2-4 g/day). Stroke volume was determined using Wesseling's pulse contour method, calibrated with indocyanine green dilution. BRS was calculated every 30 min as delta pulse interval/delta SBP on spontaneous variations. Nocturnal reduction of SBP was 4.1% on the normal salt diet. With sodium restriction, urinary sodium excretion decreased from 187+/-8 to 46+/-8 mmol/day, and body weight decreased from 57.9+/-2.1 to 56.6+/-1.9 kg. Night-time BP significantly decreased with dietary modification from 154+/-7/88+/-4 to 140+/-6/78+/-4 mmHg, whereas daytime BP was unaltered. With sodium restriction, cardiac index and stroke index decreased throughout the day. No significant difference was seen in either daytime or nighttime BRS between the two diets. We conclude that the non-dipper pattern is common in patients with an aldosterone-producing adenoma on a normal salt intake, and under such conditions, volume expansion appears to play a major role in the impairment of nocturnal BP reduction.
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PMID:Dietary sodium restriction restores nocturnal reduction of blood pressure in patients with primary aldosteronism. 1245 27

Based on two patients, we discuss the difficulties in diagnosing and managing primary aldosteronism in pregnancy, which derive from changes of the renin-angiotensin-aldosterone axis, from the uncertainty regarding blood pressure control along gestation and postpartum, and from the contraindication to the use of spironolactone. The first case is a 27 years old woman with a long standing refractory hypertension, a hemorrhagic stroke with left brachial hemiplegia and crural hemiparesia, two miscarriages, one stillbirth and one offspring with intrauterine growth retardation. Due to hypokalemia, a plasma aldosterone/renin activity ratio of 91, and a negative genetic screening for glucocorticoid remediable aldosteronism (GRA), a primary hyperaldosteronism with normal adrenals in CT scan was diagnosed, and good blood pressure control was attained with spironolactone. After two and a half years of normotension, a fifth pregnancy, managed with methyldopa evolved with satisfactory blood pressures, plasma potassium, fetal growth, uterine and umbilical arterial resistance indexes, and maternal endothelial function. At 37 1/2 weeks of pregnancy the patient delivered a healthy newborn weighing 2,960 g. Blood pressure rose during the 48 hours of postpartum in the absence of proteinuria and required i.v. hydralazine. The second patient is a 37 years old woman, with known refractory hypertension for 7 years, hypokalemia, plasma aldosterone/renin activity ratio greater than 40, normal adrenals in the CAT scan, and a negative genetic screening for GRA. She had normotensive pregnancies 5 and 3 years prior to the detection of hypertension, with hypertensive crisis in both postpartum periods, retrospectively considered as expressions of primary hyperaldosteronism.
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PMID:[Primary aldosteronism and pregnancy: report of 2 cases]. 1261 Dec 41

Mendelian forms of hypertension have delivered a treasure trove of novel genes. To date, the molecular mechanisms of five such syndromes have been largely clarified, including glucocorticoid-remediable aldosteronism, Liddle's syndrome, apparent mineralocorticoid excess, an activating mutation of the mineralocorticoid receptor, and pseudohypoaldosteronism type 2. Each of these conditions features salt sensitivity with increased sodium and volume reabsorption by the kidney and low plasma renin activity. None of the gene loci for these syndromes has been convincingly linked to hypertension in the general population. We are investigating kindreds who have autosomal-dominant hypertension and brachydactyly. Affected persons invariably have both anomalies. The hypertension is severe and results in death at about age 50 years from stroke. The condition resembles essential hypertension, because renin, aldosterone, and norepinephrine responses are normal and no salt sensitivity is present. The response to antihypertensive drugs is general. Another feature is diminished baroreflex sensitivity with markedly impaired blood pressure buffering. Furthermore, the ventrolateral medulla may be compromised in these patients, because neurovascular anomalies are a regular finding. We mapped the gene(s) for this disease to chromosome 12p and narrowed the chromosomal region by studying more affected families. Interestingly, the same locus was recently mapped in Chinese families with essential hypertension. Our 3-centimorgan region contains genes encoding a phosphodiesterase, an ATP-dependent potassium channel, and its regulator the sulfonylurea receptor 2. Screening of the coding regions revealed that none of these candidate genes harbor obvious mutations; however, other genetic mechanisms may nevertheless compromise their function. Our study underscores the importance of regulatory physiology to the understanding of a complex genetic syndrome.
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PMID:Mendelian hypertension with brachydactyly as a molecular genetic lesson in regulatory physiology. 1295 13

The paper deals with hemorrhagic stroke (HS) pathogenesis and diagnosis in young people. Among cerebrovascular diseases in the young acute hemorrhagic strokes take noticeable place. Arterial hypertension, diabetes mellitus, smoking, alcoholism are among risk factors of subarachnoidal hemorrhage (SAH). Massive hemorrhages occur in the rupture of arterial aneurysms and arteriovenous malformations. HS in the young may be caused by blood diseases, i.e. leukemias, hemophilias, idiopathic thrombocytopenic purpura, coagulopathies; vasculitis in diffuse diseases of the connective tissue; non-inflammatory arteriopathies; drug addiction. Genetic predisposition to HS development is discussed with focus to such diseases as a family form of moya-moya disease, glucocorticoid-depressed hyperaldosteronism, elastic pseudoxanthoma, Marfan's syndrome, renal olycystosis, Sturge-Veber syndrome. It is recommended to use wider updated methods of neurovisualization (CT, MRT, angiography) in diagnosis of HS. The conclusion is made that HS diagnosis, especially in the young, needs a multidisciplinary approach with active participation of neurologist, neurosurgeon, therapist, endocrinologist, hematologist.
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PMID:[Specific features of pathogenesis and diagnosis of hemorrhagic stroke in young patients]. 1511 67

Primary aldosteronism (PA) is the most common cause of mineralocorticoid hypertension. Different studies, using the plasma aldosterone concentration to plasma renin activity ratio (PAC/PRA) for the screening of patients with hypertension, have shown a marked increase in the detection rate of PA. Idiopathic bilateral adrenal hyperplasia (IHA) and aldosterone-producing adrenal adenoma (APA), are the leading causes of primary aldosteronism. Glucocorticoid-remediable aldosteronism (GRA), also called familial hyperaldosteronism type I, familial hyperaldosteronism type II and carcinomas are rare causes of PA. Patients with hypertension and hypokalemia, those with a family history of hypertension and stroke at an early age, or patients with medication-resistant hypertension should be screened for PA using the PAC/PRA ratio. If a high ratio is found, a sodium loading test or a captopril test is warranted to confirm the diagnosis. Adrenal gland imaging is important in subtype differentiation (APA vs IHA). Adrenal venous sampling should be used when other tests prove inconclusive. Genetic testing has facilitated detection of GRA. Surgery is considered the treatment of choice for patients with APA, while bilateral hyperplasia subtypes are treated medically. Normalization of aldosterone levels or aldosterone receptor blockade are necessary to prevent the morbidity and mortality associated with hypertension, hypokalemia, and cardiovascular damage.
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PMID:Detecting and treating primary aldosteronism: primary aldosteronism. 1742 5


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