Rabdomiólisis por hipopotasemia severa en paciente con síndrome de Conn / Rhabdomyolysis and profound hypokalemia in a patient with Conn´s syndrome

El Síndrome de Conn o hiperaldosteronismo primario se caracteriza por hipertensión, hipopotasemia con alcalosis metabólica y una masa adrenal. La rabdomiólisis puede ser secundaria a traumatismos, excesiva actividad muscular, enfermedades musculares hereditarias y otras causas médicas, como la hipopotasemia. Presentamos el caso de un hombre de 46 años con rabdomiólisis secundaria e hipopotasemia severa como expresión de hiperaldosteronismo primario por un adenoma suprarrenal(AU)

Conn's syndrome or primary hyperaldosteronism is characterized by hypertension, hypokalemia with metabolic alkalosis and the presence of an adrenal mass. Rhabdomyolysis can be secon- dary to trauma, excessive muscle activity, hereditary muscle diseases and other medical causas, such as hypokalemia. We present the case of a 46-year-old man with secondary rhabdomyolisis and hypokalemia as an-expresión of primary hyperaldosteronism due to an adrenal adenoma(AU)

Variabilidad fenotípica y estrés oxidativo endotelial en una familia con hiperaldosteronismo familiar tipo I / Phenotypical variability and endothelial oxidative stress in a family with type I familial hyperaldosteronism

Type I familial hyperaldosteronism (HAF-I) is caused by the presence of a chimeric gene CYP11B1/CYP11B2 which encodes an enzyme with aldosterone synthetase activity regulated by ACTH. HAF-I patients present with severe hypertension at young ages and a greater risk of stroke. AIM: To characterize clinical and biochemical presentation of family members with HAF-I. To evaluate endothelial oxidative stress markers before and after glucocorticoid treatment. PATIENTS AND METHODS: We evaluated three family members with HAF-I confirmed with a genetic test (XL-PCR) for chimeric gene CYP11B1/CYP11B2. The index case was a 13 years old boy with stage 2 hypertension (Joint National Committee VIIth report), plasma aldosterone/ plasma renin activity (AP/ARP) ratio of161 and normal plasma potassium. His father had primary hyperaldosteronism diagnosed at 25 years of age with hypertension and hypokalemia. His sister was 15 years old, with a normal blood pressure and an AP/ARP ratio of 37.6. RESULTS: All subjects had plasma xanthine-oxidase levels in the upperlimit of normal. Malondialdehyde was above normal in the index case and his father. These markers returned to normal with glucocorticoid treatment. CONCLUSIONS: We report a HAF-I carrying family with a wide phenotypical variability between affected members. Elevation of endothelial oxidativestress markers and its normalization after glucocorticoid treatment, may indicate that aldosterone produces endothelial damage and increases cardiovascular risk.

Hiperaldosteronismo primário / Primary aldosteronism

O hiperaldosteronismo primário (HAP) é uma síndrome decorrente do aumento da secreção autônoma de aldosterona pela glândula adrenal, independente do controle da renina. O rastreamento do HAP está indicado em indivíduos com hipertensão arterial sistêmica (HAS) e hipocalemia espontânea ou grave com doses moderadas de diuréticos ou HAS refratária ao tratamento (%3 agentes anti-hipertensivos). No presente relato, paciente masculino apresentava diabete melito (DM) de início recente e HAS, emagrecimento, poliúria, polidipsia, e cansaço aos médios esforços. Apresentava hipocalemia grave e investigação laboratorial confirmou a suspeita de HAP, com medida de aldosterona sérica e urinária elevadas com diminuição da atividade da renina plasmática e aumento da razão aldosterona sérica/renina. Tomografia computadorizada de adrenais mostrou adenoma na adrenal esquerda. Após cirurgia, o paciente evoluiu com melhora dos níveis tensionais e normalização do metabolismo da glicose. Embora a prevalência de HAP em pacientes com DM não seja diferente da população de hipertensos não-diabéticos, a sua presença deve ser investigada nos casos de HAS refratária ou quando há hipocalemia. Em pacientes com DM, o metabolismo do cortisol também deve ser investigado para afastar a concomitância de hipercortisolismo decorrente de adenoma misto.

Primary aldosteronism (PA) is a syndrome that results from adrenal autonomous secretion of aldosterone. The screening for this syndrome is indicated for individuals with arterial hypertension (AH) and spontaneous or severe hypocalemia after diuretics, and refractory AH (%3 antihypertensive agents). In this report, a male patient presented recent-onset diabetes mellitus (DM) and AH, weight lost, poliuria, polidipsia, and tiredness. Severe hypocalemia was present, and the laboratory workup confirmed the hypothesis of PA, with increased plasmatic and urinary aldosterone levels, low plasma renin activity and increased aldosterone/renin ratio. Adrenal computerized tomography showed a left adrenal adenoma. After the surgical procedure, blood pressure levels and glycemia were brought to normal. Though the prevalence of PA is not increased in patients with DM, it should be screened in patients with refractory AH or persistent hypocalemia. In patients with DM, cortisol metabolism should also be evaluated to rule the presence of hypercortisolism in a mixed adenoma.

Prospective evaluation and characteristics of patients with suspected primary hyperaldosteronism / Evaluación prospectiva y características de los pacientes con sospecha de hiperaldosteronismo primario

Primary hyperaldosteronism (PH), resulting in hypokalaemic hypertension, may be due to an aldosterone-producing adenoma (APA) or bilateral zona glomerulosa hyperplasia. Six patients with suspected PH were identified at the University Hospital of the West Indies and standardized screening was carried out. Plasma renin activity (PRA) and serum aldosterone concentrations (SAC) were measured, followed by confirmatory intravenous saline suppression test. The patients were all women, of median age 48 years (interquartile range, IQR: 41-51.7 years). They tended to be overweight with suboptimal blood pressure control. Median serum potassium was 3.1 mmol/L (IQR 2.7 - 3.3 mmol/l) and kaliuresis was elevated or inappropriately normal. All individuals had suppressed PRA (< 0.6 ng/ml/hr) and elevated SAC (> 30 ng/dl), with SAC/PRA ratios > 50. Five patients had confirmed PH (ie post-saline SAC > 10 ng/dl); PH could not be definitely excluded in the sixth patient (ie post-saline SAC 5 - 10 ng/dl). Imaging studies revealed normal adrenal glands in one patient, unilateral adrenal enlargement in three patients, and unilateral adrenal masses in two patients. Only one of these latter two patients was shown to have an adrenal adenoma on histological examination. In this series, there appears to be fewer cases of the APA subtype of PH than expected. It remains to be seen whether the distribution of PH subtypes in Jamaica is actually different from elsewhere. This, and the cost-effectiveness of different approaches to screening, identification and management of patients suspected of having PH in Jamaica are areas for further study.

El hiperaldosteronismo primario (HP), que trae como resultado hipertensión hipocalémica, puede tener por causa un adenoma productor de aldosterona (APA) o una hiperplasia bilateral de la zona glomerulosa. Seis pacientes con sospecha de HP fueron identificados en el Hospital Universitario de West Indies, y se llevó a cabo un tamizaje estandarizado. Se realizaron mediciones de la actividad de renina plasmática (ARP) y las concentraciones de aldosterona en suero (CAS), seguidas de una prueba confirmatoria de supresión con salina por vía intravenosa. Los pacientes fueron en su totalidad mujeres, con una edad mediana de 48 años (rango intercuartil, IQR: 41­51.7 años). Tenían tendencia al sobrepreso y un control subóptimo de la presión sanguínea. La mediana de potasio sérico fue 3.1 mmol/L (IQR 2.7­3.3 mmol/l) y la caliuresis fue elevada o inadecuadamente normal. Todos los indi-viduos presentaron ARP suprimida (< 0.6 ng/ml/hr) y CAS elevada (> 30 ng/dl), coproporciones CAS/ARP> 50. A cinco pacientes les fue confirmado HP (ie CAS post-salina > 10 ng/dl); el HP no pudo ser definitivamente excluido en el sexto paciente (ie CAS post-salina 5 ­ 10 ng/dl). Estudios de imagen revelaron glándulas suprarrenales normales en un paciente, agrandamiento suprarrenal unilateral en tres pacientes, y masas suprarrenales unilaterales en dos pacientes. Solamente uno de estos dos últimos pacientes mostró tener un adenoma adrenal al realizarse el examen histológico. En esta serie, parece haber menos casos del subtipo APA de HP que lo esperado. Queda por ver si la distribución de los subtipos de HP en Jamaica es en realidad diferente de la de otras partes. Esto, al igual que el costo-efectividad de los diferentes métodos de tamizaje, identificación y tratamiento de pacientes con sospecha de HP en Jamaica, son áreas que requieren ulterior investigación.

Glucocorticoid-remediable aldosteronism

Glucocorticoid-remediable aldosteronism (GRA) is a monogenic form of human hypertension that predisposes to cerebral hemorrhage. As a result of a chimeric gene duplication, aldosterone is ectopically synthesized in the cortisol-secreting zona fasciculata of the adrenal gland under the control of adrenocorticotropin (ACTH). Hypertension frequently has its onset during childhood and is usually refractory to standard anti-hypertensives such as ACE inhibitors and beta-blockers. Hypokalemia can develop in those treated with a potassium-wasting diuretic, but random potassium levels are usually normal. Diagnosis has been facilitated by the availability of a genetic test. Suppression of ACTH release with exogenous dexamethasone is a useful diagnostic and therapeutic strategy. Treatment with the mineralocorticoid receptor antagonists spironolactone and epleronone is also efficacious. The diagnosis of GRA facilitates directed therapies and screening of at-risk individuals and kindreds.

Hiperaldosteronismo primário causado por adenoma adrenal produtor de aldosterona / Primary hyperaldosteronism caused by aldosterone producing adrenal adenoma

Paciente feminina, 59 anos, branca, hipertensa há 20 anos, apresentou hipertensão grave e hipocalemia. Hiperaldosteronismo primário (HAP) foi comprovado após triagem laboratorial, que indicou aldosterona plasmática elevada e renina plasmática baixa. A tomografia computadorizada de abdômen superior detectou a presença de uma massa na glândula adrenal direita. A paciente foi submetida à adrenalectomia por videolaparoscopia. Após a cirurgia, a hipertensão persistiu mas foi controlada com uso de drogas antihipertensivas. HAP é uma das formas mais comuns de hipertensão secundária. Pode ser causada por adenoma produtor de aldosterona (APA) ou hiperplasia adrenal bilateral (HAB). A doença é caracterizada principalmente por retenção de sódio, supressão da atividade da renina plasmática e aumento da secreção de aldosterona. O "padrão-ouro" para confirmar o diagnóstico de HAP é a ausência da supressão de aldosterona em resposta à fludrocortisona e/ou à dieta hipersódica. O cateterismo das veias adrenais é o melhor método para diferenciar APA de HAB, uma vez que a presença de uma massa adrenal unilateral nos estudos por imagem não garante o diagnóstico de APA. O tratamento para APA é a adrenalectomia unilateral, que pode ser realizada por videolaparoscopia ou por cirurgia aberta (AU)

A 59-year-old female white patient, hipertensive for 20 years, presented severe hipertension and hipokalemia. Primary hiperaldosteronism (PHA) was confirmed after laboratory screening, which indicated high plasmatic aldosterone and low plasmatic renin. Computerized tomography (CT) of the upper abdomen detected the presence of a mass in the right adrenal gland. The patient underwent a videolaparoscopic adrenalectomy. After surgery, hypertension persisted but was controled by use of anti-hypertensive drugs. PHA is one of the most common forms of secondary hypertension. It can be caused by aldosterone producing adenoma (APA) or bilateral adrenal hyperplasia (BAH). The disease is characterized mainly by sodium retention, supression of plasma renin activity and increased aldosterone secretion. The "gold-standard" to the diagnosis of PHA is the absence of aldosterone supression in response to fludrocortisone and/or high sodium diet. The catheterism of adrenal veins is the best method to differentiate APA from BAH since the presence of a unilateral adrenal mass as confirmed by imaging studies does not warrant the diagnosis of APA. The treatment of APA is unilateral adrenalectomy, which can be performed by videolaparoscopy or open surgery (AU)

Hiperaldosteronismo primario y embarazo: lecciones obtenidas de 2 casos clínicos / 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.

La hipertensión arterial mineralocorticoidea: ¿una nueva forma de hipertensión secundaria? / Mineralcorticoid hypertension: a new form of secondary hypertension?

There is a group of genetic alterations that are phenotypically related to mineralocorticoid hypertension. They include, among others, some forms of primary hyperaldosteronism and of hyporeninemic aldosteronism that can be specifically treated, thus becoming secondary forms of hypertension. These could account for 10 to 15 percent of cases of essential hypertension, but more studies are required to accept these figures. The screening for these forms of hypertension should be done measuring aldosterone levels and plasma renin activity. An aldosterone/plasma renin activity ratio over 25 should lead to the suspicion of the disease. However, the cost effectiveness of the widespread measurement of these parameters would be very low. Therefore it is mandatory to determine the epidemiological features of these diseases to perform a selective screening among subjects with essential hypertension

Alteraciones en la enzimología de la producción de aldosterona / Alterations in the enzymology of aldosterone production

El último paso para la producción de aldosterona (11-desoxicorticosterona a aldosterona) en mitocondrias de zona glomerulosa de adrenal de rata es catalizado por la enzima CYP11B2. CYP11B1, en zona fasciculata, transforma 11-desoxicorticosterona en corticosterona o 18-hidroxi-11-desoxicorticosterona. CYO11B1 y CYP11B2 tienen alta homología y sus genes se hallan en tándem en el cromosoma 8q22. Mutaciones en el gen de CYP11B2 y recombinaciones genéticas entre éste y el gen de CYP11B1 serían las responsables de las alteraciones en la enzimología de la producción de aldosterona, dando una nueva denominación y explicación a las deficiencias anteriormente conocidas como de CMOI y CMOII

Síndrome de Conn. Una causa rara de hipertensión arterial de corrección quirúrgica / Conn's syndrome. a rare cause of arterial hypertention for surgical treatment

Se informa el caso de un adenoma de la gándula suprarrenal productor de aldosterona. Pacientes femenina de 54 años de edad que acude a consulta médica por presentar hipertensión arterial, debilidad extrema, y parestesias. Sus estudios de laboratorio demostraron hipokalemia severa, hipernatremia, hiperaldosteronemia e hiporreninemia. La tomografía de abdomen demostró un nódulo en la glándula suprarrenal derecha el cual fue resecado con abordaje posterior. El reporte histopatológico fue de un adenoma suprarrenal producto de aldosterona compatible con síndrome de Conn. El hiperaldosteronismo primario es una enfermedad rara, causante de hipertensión aterial en el 0.5 por ciento de los pacientes hipertensos, habitualmente es secundario a un adenoma de la glándula suprarrenal. El manejo quirúrgico revierte los trastornos metabólicos en la mayoría de los casos

Hiperaldosteronismo primário com angina e arritmia / Primary hyperaldosteronism with angina and arrhythmia

Hiperaldosteronismo primário em homem de 43 anos, sabidamente portador de hipertensäo arterial há 2 anos, com comprometimento cardiovascular manifestado por precordialgia, arritmia ventricular e hipocalemia. A tomografia computadorizada evidenciou adenoma da supra renal esquerda. O paciente foi submetido cirurgia para retirada do tumor, permanecendo assintomático, em período de seguimento de 11 meses