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[Bilateral Conn's adenoma. Diagnostic discussions].

Primary hyperaldosteronism represents less tha 1% of all causes of hypertension. We report one case of primary hyperaldosteronism which emphasizes the difficulty of distinguishing tumoral PHA from idiopathic PHA (bilateral adrenal hyperplasia), observed in a 57-year-old man. The diagnosis was suggested by marked hypokalemia, and was confirmed by hyperaldosteronaemia and low and poorly stimulated renin activity. Intravenous saline infusion failed to significantly suppress plasma aldosterone levels. Upright posture for 60 minutes suppressed plasma aldosterone concentration. A Computed tomography (CT) scan showed bilateral adrenal mass. Management consisted of total right adrenalectomy, and enucleation of adenoma from the opposite adenoma. The patient is normotensive 4 years after surgery.

Adenoma↗

[Primary aldosteronism and pregnancy: report of 2 cases].

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.

Adult↗

Heart in adrenal diseases.

The paper reviews the hitherto rather scarce literature concerned with cardiac changes in phaeochromocytoma, primary hyperaldosteronism and Cushing syndrome, and presents the authors' own echocardiographic findings in these diseases. In phaeochromocytoma they found a slight thickening of the interventricular septum which, however, did not fulfil the criteria of asymmetric left ventricular hypertrophy. Also other parameters showed higher values attesting to an increased left ventricular mass, however, without exceeding normal limits. Focal disturbances of left ventricular kinetics and the decrease in LV systolic function were non significant. The picture of obstructive hypertrophic cardiomyopathy, frequently mentioned in the literature, was observed only once, giving grounds to the suspicion that it is only a nonspecific manifestation of the hypercontractile state of the myocardium. In primary hyperaldosteronism only slight posterior LV wall thickening and an increase in the LV mass index were found, compared to control group. No significant changes were found in Cushing syndrome besides a tendency to concentric LV hypertrophy. Echocardiographic changes observed in all three affections disappeared after successful surgical or drug treatment.

Adrenal Gland Neoplasms↗

[Biochemical detection of Conn's adenoma: definition of criteria and reference values].

Primary hyperaldosteronism is a diagnosis which should be considered in refractory hypertension even in the absence of any hypokalaemia. Its detection relies above all on the levels of renin and aldosterone. The aldosterone/renin ratio has been proposed as the most sensitive criterium. The reference values used for the diagnosis of primary hyperaldosteronism are very variable in the literature, depending not only on the method used but also on the criteria used for their determination. In this study we evaluated the defined reference values prospectively by studying a population of patients with a Conn's adenoma treated surgically. The study included an initial retrospective period which allowed identification of 29 cases of Conn's adenoma treated surgically, and a 9 month prospective period during which 212 reports were collected. During this prospective period a further 9 cases of Conn's adenoma were detected, which were successfully treated with surgery. Analysis to discriminate the 38 Conn's adenomata from the rest showed that 3 parameters contributed significantly and independently to the diagnosis: supine plasma renin activity (ARPc), supine aldosteronaemia and the erect aldosterone/renin ratio, allowing correct classification in 88% of the cases. The reference ranges of these 3 parameters were calculated in order to give a sensitivity of 100% and the best possible specificity, therefore allowing a combined criterium involving all 3 parameters to be defined: ARPc < 0.45 ng/ml/h, supine aldosteronaemia >417 pmol/l, and erect aldosterone/renin >1180.

Adenoma↗

[Genetics and arterial hypertension: monogenic forms].

Hypertension is a complex, multifactorial disease; genetic factors represent one third to half of the inter-individual variability of blood pressure values. The study of genes involved in rare forms of monogenic hypertension led to the identification of pivotal pathophysiological pathways of kidney sodium and water reabsorption that can influence blood pressure values when changed. Glucocorticoid-Remediable Aldosteronism (GRA) is characterised by normal to high aldosterone levels, despite plasma renin activity suppression, and by the fact that these alterations are corrected by exogenous glucocorticoid administration. Apparent Mineralocorticoid Excess (AME) is due to a mutation of the gene encoding the renal isoform of 11 â HSD enzyme; the non-conversion of cortisol to cortisone result in increasing cortisol levels that activate the mineralocorticoid receptor. Early onset hypertension exacerbating during pregnancy is caused by a mutation leading to a conformational change in the mineralocorticoid receptor. Therefore, substances that are normally inactive at this level, such as progesterone, become potent agonists of the mutated receptor. Liddle's syndrome (or type I pseudo-hyperaldosteronism (PHA1), is characterised by a constitutive activation of the epithelial sodium channels in the distal tubule, causing an increase in sodium and chloride reabsorption. Gordon syndrome (Type II pseudo-hyperaldosteronism, PHA2) differs from the other forms because of the presence, in addition to hypertension, of hyperkaliemia and hyperchloremic acidosis that can be normalized with thiazide diuretics. Finally, a large pedigree of Turkish origin has been described: these patients are affected by an uncertain form of monogenic hypertension associated with brachydactyly.

Glucocorticoids↗

Aldosterone synthase cytochrome P-450 expressed in the adrenals of patients with primary aldosteronism.

A human cytochrome P-450 with aldosterone synthase activity was purified from the mitochondria of an aldosterone-producing adenoma. It was recognized by an anti-bovine cytochrome P-450(11 beta) IgG and by a specific antibody raised against a portion of the CYP11B2 gene product, one of the two putative proteins encoded by human cytochrome P-450(11 beta)-related genes (Mornet, E., Dupont, J., Vitek, A., and White, P. C. (1989) J. Biol. Chem. 264, 20961-20967). A similar and probably the same aldosterone synthase cytochrome P-450 was detected in the adrenal of a patient with idiopathic hyperaldosteronism. These aldosterone synthases were distinguishable from cytochrome P-450(11 beta), the product of another cytochrome P-450(11 beta)-related gene, i.e. CYP11B1, by their catalytic, molecular, and immunological properties and also by their localization. The latter enzyme was unable to produce aldosterone and did not react with the specific antibody against the CYP11B2 gene product. It was present both in tumor and non-tumor portions of the adrenals carrying the adenoma and in normal adrenal cortex. On the other hand, aldosterone synthase cytochrome P-450 localized in the tumor portions of the adrenals or in the adrenal of a patient with idiopathic hyperaldosteronism. Thus aldosterone synthase cytochrome P-450, a distinct species from cytochrome P-450(11 beta), is responsible for the biosynthesis of aldosterone in the human, at least in patients suffering from primary aldosteronism.

Adenoma↗

Severe hypertension in a ten-year-old boy secondary to an aldosterone-producing tumour identified by adrenal sonography.

Severe hypertension discovered incidentally in a 10 year-old boy was associated with persistent hypokalaemia and metabolic alkalosis. Primary hyperaldosteronism was diagnosed by demonstrating elevated plasma aldosterone levels and increased urinary aldosterone excretion with concomitant depressed plasma renin activity. Adrenal sonography identified a left adrenal adenoma which was removed surgically; normotension and normalization of plasma renin and aldosterone values ensued. This appeared to be the first use in children of sonography to identify adrenal adenoma and it is suggested to be the first step in the differential diagnosis of primary hyperaldosteronism.

Adenoma↗

[Tomodensitometry: localizing value in hypertension of adrenal origin (author's transl)].

Computarized axial tomography has shown the localization of adrenal lesions in four cases of hypertension of adrenal origin: two phaeochromocytomas, one primary hyperaldosteronism, one Cushing's syndrome. This method has the advantage of being neither invasive, nor time-consuming. Unfortunately, it cannot localize tumors smaller than two cm in diameter. It seems to be highly beneficial in phaeochromocytoma, where it can advantageously take the place of arteriography. It is less fruitful in primary hyperaldosteronism and in Cushing's syndrome because lesions are smaller.

Adrenal Gland Neoplasms↗

[The effect of aldosterone antagonists in juvenile heart surgery].

In children with congenital heart disease duration and extent of hyperaldosteronism and the influence of spironolactone after surgery with a heart-lung-machine, were evaluated by direct measurement of plasma aldosterone levels. Secondary hyperaldosteronism as seen in 11 patients without spironolactone-therapy after surgery did not persist very long. 14 children receiving spironolactone immediately after surgery showed an onset of drug efficacy at a period when plasma aldosterone in the group without spironolactone had begun to fall. As a practical consequence, spironolactone treatment should be initiated a few days prior to surgery in order to achieve full efficacy on the day of surgery.

Adolescent↗

[A review of ten cases of aldosteronoma. Diagnostic and therapeutic conclusions (author's transl)].

Ten patients with primary hyperaldosteronism resulting from a functioning adrenocortical adenoma were studied. The high incidence of hypertension and/or renal disease in the families of these patients suggests that hereditary factors play a part in the genesis of aldosteronomas. In patients with hypertension and hypokalemia the diagnosis of primary hyperaldosteronism is established by measurements of serum renin activity and serum aldosterone concentrations under normal conditions and during pharmacodynamic tests. The adenoma is demonstrated by radioactive iodocholesterol scintigraphy and computerized tomography. In nearly two-thirds of the patients, unilateral adrenalectomy is followed by complete definitive recovery.

Adenoma↗

[Radioimmunoassay in the diagnosis of arterial hypertension].

The paper is concerned with the results of a study of the aldosterone concentration and renin activity, the general level of catecholamines and their fractions (epinephrine, norepinephrine and dopamine) in the peripheral blood and blood taken at selective venography from the vena cava inferior, renal and adrenal veins of 108 patients with hypertension, aldosteroma and idiopathic hyperaldosteronism, adrenal and extraadrenal pheochromocytoma, renovascular and renoparenchymatous arterial hypertension. The aldosterone concentration and renin activity were determined with radioimmunoassay, and the general content of catecholamines and their fractions with a radioenzymatic method using standard kits. It has been shown that the radioimmunoassay to determine the aldosterone concentration and renin activity in the blood from the vena cava inferior, renal and adrenal veins makes it possible to resort to differential diagnosis of hypertension, aldosteroma, idiopathic and secondary hyperaldosteronism. A considerable increase in the blood plasma renin activity on the affected side was revealed in the patients with renovascular hypertension, and in renoparenchymatous hypertension it was equal in both renal veins. The study of the total content of catecholamines and their fractions in the blood from different parts of the venous system can be used for topical diagnosis of adrenal and extraadrenal pheochromocytoma.

Adrenal Gland Neoplasms↗

Primary aldosteronism is comprised of primary adrenal hyperplasia and adenoma.

Primary aldosteronism due to primary adrenal hyperplasia (PAH) is described. Hypertension, hypokalaemia, hyperaldosteronism and renin suppression were corrected by unilateral adrenalectomy in 3/5 patients and by spironolactone treatment in 2/5. Blood pressure and hormonal parameters have remained normal for up to seven years after surgery and spironolactone management. Four patients had bilateral micro- and macronodular hyperplasia and one had unilateral hyperplasia. While hormonally and biochemically identical to patients with aldosterone producing adenoma, PAH can be distinguished from idiopathic hyperaldosteronism (adrenal hyperplasia). The inability to demonstrate a tumour by computed tomography but the presence of bilateral elevations of aldosterone concentration in adrenal venous blood identifies PAH.

Adenoma↗

Primary aldosteronism -- screening, diagnosis and therapy.

Criteria for the screening, diagnosis and therapy of primary aldosteronism (PA) were defined on the basis of its symptoms analysis in 40 PA patients. A diagnosis of PA was proved in 4.12% of 970 patients admitted for arterial hypertension. The presence of polyuria, nocturia, neuromuscular disorders, hypertension, hypopotassaemia, alkalosis, elevated urinary potassium excretion, improving after Spironolactone, was most valuable for the purposes of screening. High plasma aldosterone concentration (PAC) and suppressed renin activity (PRA) provided evidence of the presence of PA. The most successful technique to differentiate aldosterone producing adenoma (APA) from idiopathic hyperaldosteronism (IHA) proved to be adrenal phlebography combined with determination of PAC in the adrenal veins. APA was associated with a 5.9 fold higher PAC in the vein of the adenoma - affected adrenal in contrast with a symmetric PAC rise in both adrenal veins in IHA. A paradoxical decrease of PAC occurred in the peripheral blood of most patients with APA after standing up, but 23.8% exhibited the same orthostatic increase as IHA patients. In all APA patients, unilateral adrenalectomy eliminated the symptoms of hyperaldosteronism and improved or cured hypertension. Spironolactone was indicated preoperatively for all surgical candidates, for non-operated APA patients, and for all IHA patients.

Adenoma↗

[Phaeochromocytoma with hypokalaemia (two cases) (author's transl)].

Two cases of phaeochromocytoma with hypokalaemia are reported. In the first, a carcinoma, hypokalaemia was potentially secondary to hyperreninaemia and hyperaldosteronism in association with probably paraneoplastic hypercorticism. The other was benign and the origin of isotopically demonstrated potassium deficiency was less clear, because hyperreninaemia, hyperaldosteronism and hypercortisolism were moderate.

Adrenal Gland Neoplasms↗

[Use of an aldosterone antagonist in abdominal surgery].

Clinical and humoral signs of postoperative stress ore partly related to temporary hyperaldosteronism. The action of an aldosterone-antagonist was therefore studied on 24 abdominal surgical patients. The aldosterone-inhibitor has shown a consistent pharmacological and clinical effect. The drug seems then to be useful and safe-with close clinical and humoral follow-ups for the treatment of the postoperative secondary hyperaldosteronism.

Adult↗

[14C-aldosterone binding by plasma proteins in adolescents with primary arterial hypertension].

The binding 14C-aldosterone by plasma globulins in vitro was studied in healthy adolescents and in those with primary arterial hypertension (PAH). In most of the patients examined hyperaldosteronism was found, which was attended by an increased percentage of 14C-aldosterone binding with aldosterone binding globulin (ABG) and particularly with glucocorticoid binding globulin (GBG). One and half hours of walking caused n changes in the parameters studied in healthy adolescents; in those with hyperaldosteronism the content of aldosterone in blood was considerably reduced, while in patients with a normal initial aldosterone level in blood, it increased with no essential changes in the ability of plasma globulins to bind labelled aldosterone. Two-week treatment of PAH patients with propranolol caused a sharp increase in the plasma aldosterone content and 14C-aldosterone binding with ABG and GBG. It is concluded that the determination of labeled aldosterone binding by plasma proteins is important for indirect judgement of metabolic aldosterone clearance.

Adolescent↗

[New data on mineralocorticoid hormones. Physiopathological implications].

Our better understanding of the terminal steps of aldosterone production based on enzyme cloning has led to new clinical approaches to three aldosterone-related types of hypertension: mineralocorticoid excess, Liddle's disease and glucocorticoid-sensitive hyperaldosteronism. In all three cases, hypertension results from volume expansion due to increased reabsorption of sodium in the distal renal tube with decreased plasma renin activity and hypokaliaemia. Genetic testing now allows early diagnosis of these severe familial diseases and specific treatment. Although both glucocorticoid-sensitive hypertension and Liddle's disease are dominantly inherited diseases, other genes can also modulate the degree of volume expansion, hypokaliaemia and blood pressure levels within a given family. The degree of hypertension observed in a given individual results from the interactions between the expression of "hypertenser" and "hypotenser" genes. Recent progress raises the possibility that other similar genetic mechanisms exist in more common forms of primary hypertension. Systematic exploration of the renin-angiotensin-aldosterone system based on measurement of the renin/aldosterone ratio as proposed in the diagnosis of primary hyperaldosteronism will make it possible to determine whether there exists a relationship between these genes and the hypertension observed.

Aldosterone↗

[A case report of obstructive sleep apnea syndrome associated with primary aldosteronism].

A 60-year-old obese woman was admitted for evaluation of excessive daytime sleepiness, loud snoring, cyanosis, systemic edema, hypertension and diabetes mellitus. Laboratory examination showed severe hypoxemia, hypercapnea, metabolic alkalosis, hypokalemia and hyperaldosteronism. CT scan showed a left adrenal tumor. A diagnosis of obstructive sleep apnea syndrome associated with primary aldosteronism was established. Metabolic alkalosis, hypokalemia and sodium retention due to hyperaldosteronism were thought to be factors exacerbating her sleep apnea.

Female↗