RESUMEN
Essential hypertension is a highly prevalent disease in the general population. Secondary hypertension is characterized by a specific and potentially reversible cause of increased blood pressure levels. Some secondary endocrine forms of hypertension are common (caused by uncontrolled cortisol, aldosterone, or catecholamines production). This article describes rare monogenic forms of hypertension, characterized by electrolyte disorders and suppressed renin-aldosterone axis. They represent simple models for the physiology of renal control of sodium levels and plasma volume, thus reaching a high scientific interest. Furthermore, they could explain some features closer to the essential phenotype of hypertension, suggesting a mechanistically driven personalized treatment.
Asunto(s)
Hiperplasia Suprarrenal Congénita , Artrogriposis , Fisura del Paladar , Pie Equinovaro , Deformidades Congénitas de la Mano , Hipertensión , Síndrome de Liddle , Síndrome de Exceso Aparente de Mineralocorticoides , Hiperplasia Suprarrenal Congénita/complicaciones , Hiperplasia Suprarrenal Congénita/metabolismo , Hiperplasia Suprarrenal Congénita/terapia , Artrogriposis/complicaciones , Artrogriposis/metabolismo , Artrogriposis/terapia , Fisura del Paladar/complicaciones , Fisura del Paladar/metabolismo , Fisura del Paladar/terapia , Pie Equinovaro/complicaciones , Pie Equinovaro/metabolismo , Pie Equinovaro/terapia , Deformidades Congénitas de la Mano/complicaciones , Deformidades Congénitas de la Mano/metabolismo , Deformidades Congénitas de la Mano/terapia , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/etiología , Hipertensión/metabolismo , Hipertensión/fisiopatología , Síndrome de Liddle/complicaciones , Síndrome de Liddle/metabolismo , Síndrome de Liddle/terapia , Síndrome de Exceso Aparente de Mineralocorticoides/complicaciones , Síndrome de Exceso Aparente de Mineralocorticoides/metabolismo , Síndrome de Exceso Aparente de Mineralocorticoides/terapia , Síndrome de Exceso Aparente de MineralocorticoidesRESUMEN
Apparent mineralocorticoid excess (AME) is a genetic disorder causing severe hypertension, hypokalemia, and hyporeninemic hypoaldosteronism owing to deficient 11 beta-hydroxysteroid dehydrogenase type-2 (11ßHSD2) enzyme activity. The 11ßHSD2 enzyme confers mineralocorticoid receptor specificity for aldosterone by converting cortisol to its inactive metabolite, cortisone and inactivating the cortisol-mineralocorticoid receptor complex. The 20year follow-up of a consanguineous Iranian family with three sibs affected with AME shows the successes and pitfalls of medical therapy with spironolactone. The three sibs, (female, male, female) were diagnosed at the ages of 14, 11, and 4 years, respectively. At diagnosis, hypertensive retinopathy and left ventricular hypertrophy were present in the eldest female and retinopathy was noted in the male sib. Spironolactone treatment resulted in decreased blood pressure and rise in serum potassium levels. The older female, age 36, developed reduced left ventricular function with mitral and tricuspid regurgitation and renal failure after her second pregnancy. She was treated with renal transplantation resulting in cure of AME with decreased blood pressure and weaning from antihypertensives. Her younger sibs, age 34 and 26, do not have end organ damage. Early and vigilant treatment improves morbidity in patients with AME. Mineralocorticoid receptor antagonists normalize blood pressure, correct hypokalemia and reduce hypertensive end-organ damage in patients with AME. Low dose dexamethasone can be considered, though the response may be variable. Future directions of therapy include selective mineralocorticoid antagonists.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasas/deficiencia , 11-beta-Hidroxiesteroide Deshidrogenasas/genética , Hipertensión/genética , Hipertensión/terapia , Síndrome de Exceso Aparente de Mineralocorticoides/genética , Síndrome de Exceso Aparente de Mineralocorticoides/terapia , Adolescente , Adulto , Presión Sanguínea , Niño , Preescolar , Análisis Mutacional de ADN , Exones , Salud de la Familia , Femenino , Humanos , Hipertensión/metabolismo , Irán , Trasplante de Riñón , Masculino , Síndrome de Exceso Aparente de Mineralocorticoides/metabolismo , Mineralocorticoides/metabolismo , Mutación , Linaje , Polimorfismo Genético , Embarazo , Insuficiencia Renal/genética , Insuficiencia Renal/terapia , Renina/metabolismo , Espironolactona/química , Espironolactona/uso terapéutico , Síndrome de Exceso Aparente de MineralocorticoidesRESUMEN
Apparent mineralocorticoid excess is a syndrome reflecting the absent or impaired activity of the enzyme 11ß-hydroxysteroid dehydrogenase Type 2. It may be mild when the mutant enzyme retains some activity, or severe when activity is absolutely or essentially absent. Diagnosis relies on a triad of hypertension, hypokalemia and suppressed plasma aldosterone levels, plus an abnormal urinary cortisol to cortisone ratio, either free steroid or metabolites. Treatment is symptomatic in the mild form - correction of hypertension and hypokalemia - but needs to be prompt, vigorous and sustained in the severe form, which usually presents in neonates/infancy. Elucidation of the pathogenesis of apparent mineralocorticoid excess is an example of 'reverse translation', in that it proved prismatic for the demonstration of the physiologic mechanisms underlying the selective activation of epithelial mineralocorticoid receptors by aldosterone.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/genética , Síndrome de Exceso Aparente de Mineralocorticoides/diagnóstico , Aldosterona/sangre , Aldosterona/metabolismo , Antihipertensivos/química , Cortisona/orina , Diagnóstico Diferencial , Dieta , Humanos , Hidrocortisona/orina , Hipertensión/complicaciones , Hipertensión/genética , Hipopotasemia/complicaciones , Hipopotasemia/genética , Síndrome de Exceso Aparente de Mineralocorticoides/terapia , Mineralocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismo , Esteroides/metabolismo , Síndrome de Exceso Aparente de MineralocorticoidesRESUMEN
Hereditary disorders of potassium homeostasis are an interesting group of disorders, affecting people from the newborn period to adults of all ages. The clinical presentation varies from severe hypotension at birth to uncontrolled hypertension in adults, often associated with abnormal potassium values, although many patients may have a normal serum potassium concentration despite being affected by the genetic disorder. A basic understanding of these disorders and their underlying mechanisms has significant clinical implications, especially in the few patients with subtle clinical signs and symptoms. We present a summary of these disorders, with emphasis on the clinical presentation and genetic mechanisms of these disorders.
Asunto(s)
Hiperpotasemia/genética , Hipopotasemia/genética , Potasio/metabolismo , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Hiperplasia Suprarrenal Congénita/terapia , Síndrome de Bartter/diagnóstico , Síndrome de Bartter/genética , Síndrome de Bartter/terapia , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/genética , Síndrome de Gitelman/terapia , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/genética , Hiperaldosteronismo/terapia , Hipoaldosteronismo/diagnóstico , Hipoaldosteronismo/genética , Hipoaldosteronismo/terapia , Síndrome de Liddle/diagnóstico , Síndrome de Liddle/genética , Síndrome de Liddle/terapia , Síndrome de Exceso Aparente de Mineralocorticoides/diagnóstico , Síndrome de Exceso Aparente de Mineralocorticoides/genética , Síndrome de Exceso Aparente de Mineralocorticoides/terapia , Seudohipoaldosteronismo/diagnóstico , Seudohipoaldosteronismo/genética , Seudohipoaldosteronismo/terapiaRESUMEN
Here we describe the case of a patient followed from birth because of a positive family history for apparent mineralocorticoid excess (AME) in an older brother. The patient, a girl, had normal serum electrolyte and blood pressure measurements in the first months after birth. Not until the age of 11 months did she develop anorexia and failure to thrive in combination with hypertension, hypokalemia, and metabolic alkalosis, which are consistent with the diagnosis of AME. This diagnosis was confirmed by mutation analysis of the HSD11B2 gene (C1228T). Treatment with amiloride and furosemide electrolyte disturbances normalized her blood pressure. At the age of 19 years she unexpectedly suffered a stroke. Additional investigations revealed no accepted risk factor for stroke. We discuss the possible underlying mechanisms for the delayed manifestation of hypertension and electrolyte disturbances in AME, propose an additional explanation for the stroke in this patient, and advise treatment with a mineralocorticoid receptor antagonist to reduce stroke risk in patients with AME.
Asunto(s)
Dieta Hiposódica/métodos , Potasio/uso terapéutico , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/genética , ADN/genética , Suplementos Dietéticos , Femenino , Estudios de Seguimiento , Homocigoto , Humanos , Lactante , Síndrome de Exceso Aparente de Mineralocorticoides/diagnóstico , Síndrome de Exceso Aparente de Mineralocorticoides/genética , Síndrome de Exceso Aparente de Mineralocorticoides/terapia , Mutación , Linaje , Factores de Tiempo , Síndrome de Exceso Aparente de MineralocorticoidesRESUMEN
Low-renin hypertension occurs in children as a result of several genetic mutations that cause mineralocorticoid excess or excess stimulation of the mineralocorticoid receptor. This article discusses the genetic disorders that cause low-renin hypertension.
Asunto(s)
Hipertensión/sangre , Hipertensión/genética , Renina/sangre , Hiperplasia Suprarrenal Congénita/genética , Hiperplasia Suprarrenal Congénita/fisiopatología , Hiperplasia Suprarrenal Congénita/terapia , Niño , Preescolar , Femenino , Humanos , Hiperaldosteronismo/genética , Hiperaldosteronismo/fisiopatología , Hiperaldosteronismo/terapia , Hipertensión/fisiopatología , Lactante , Recién Nacido , Masculino , Síndrome de Exceso Aparente de Mineralocorticoides/genética , Síndrome de Exceso Aparente de Mineralocorticoides/fisiopatología , Síndrome de Exceso Aparente de Mineralocorticoides/terapia , Síndrome de Exceso Aparente de MineralocorticoidesAsunto(s)
Hipertensión/etiología , Neoplasias de la Corteza Suprarrenal/complicaciones , Neoplasias de la Corteza Suprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/terapia , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/terapia , Adenoma Corticosuprarrenal/complicaciones , Adenoma Corticosuprarrenal/diagnóstico , Adenoma Corticosuprarrenal/terapia , Síndrome de Cushing/complicaciones , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/terapia , Diagnóstico Diferencial , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Hipertensión/diagnóstico , Hipertensión/terapia , Masculino , Persona de Mediana Edad , Síndrome de Exceso Aparente de Mineralocorticoides/complicaciones , Síndrome de Exceso Aparente de Mineralocorticoides/diagnóstico , Síndrome de Exceso Aparente de Mineralocorticoides/terapia , Feocromocitoma/complicaciones , Feocromocitoma/diagnóstico , Feocromocitoma/terapiaAsunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2 , Síndrome de Exceso Aparente de Mineralocorticoides , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/genética , Diagnóstico Diferencial , Eplerenona , Síndrome de Exceso Aparente de Mineralocorticoides/diagnóstico , Síndrome de Exceso Aparente de Mineralocorticoides/etiología , Síndrome de Exceso Aparente de Mineralocorticoides/fisiopatología , Síndrome de Exceso Aparente de Mineralocorticoides/terapia , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Mutación , Pronóstico , Espironolactona/administración & dosificación , Espironolactona/análogos & derivadosRESUMEN
Adrenal disorders causing hypertension can be related to the dysfunction of either the adrenal cortex or the adrenal medulla. These disorders, including congenital adrenal hyperplasia (CAH), owing to 11B-hydroxylase deficiency and to 17alpha-hydroxylase deficiency; apparent mineralocorticoid excess; familial hyperaldosteronism type I; primary aldosteronism; Cushing's syndrome; and familial glucocorticoid resistance, primarily affect the adrenal cortex and cause low-renin hypertension. The classic disorder of the adrenal medulla resulting in hypertension is pheochromocytoma, although hypertension in obesity might also be associated with catecholamine secretion. In this review, we discuss these etiologies and the most recent advances in our knowledge of their pathophysiology, diagnosis, and treatment.