KCNJ5 Somatic Mutation Is a Predictor of Hypertension Remission After Adrenalectomy for Unilateral Primary Aldosteronism.

CONTEXT: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure <140/90 mm Hg without antihypertensive drugs) has been reported in approximately 50% of patients with unilateral PA after adrenalectomy. HT duration and severity are predictors of blood pressure response, but the prognostic role of somatic KCNJ5 mutations is unclear. OBJECTIVE: To determine clinical and molecular features associated with HT remission after adrenalectomy in patients with unilateral PA. METHODS: We retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 carcinoma, and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases. RESULTS: KCNJ5 mutations were identified in 33 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.Glu145Gln (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P = 0.0001), and 64.9% had HT duration <10 years (P = 0.0015) compared with those without HT remission. Somatic KCNJ5 mutations were associated with female sex (P = 0.004), larger nodules (P = 0.001), and HT remission (P = 0.0001). In multivariate analysis, only a somatic KCNJ5 mutation was an independent predictor of HT remission after adrenalectomy (P = 0.004). CONCLUSION: The presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.

Tissue-specific inactivation of type 2 deiodinase reveals multilevel control of fatty acid oxidation by thyroid hormone in the mouse.

Type 2 deiodinase (D2) converts the prohormone thyroxine (T4) to the metabolically active molecule 3,5,3'-triiodothyronine (T3), but its global inactivation unexpectedly lowers the respiratory exchange rate (respiratory quotient [RQ]) and decreases food intake. Here we used FloxD2 mice to generate systemically euthyroid fat-specific (FAT), astrocyte-specific (ASTRO), or skeletal-muscle-specific (SKM) D2 knockout (D2KO) mice that were monitored continuously. The ASTRO-D2KO mice also exhibited lower diurnal RQ and greater contribution of fatty acid oxidation to energy expenditure, but no differences in food intake were observed. In contrast, the FAT-D2KO mouse exhibited sustained (24 h) increase in RQ values, increased food intake, tolerance to glucose, and sensitivity to insulin, all supporting greater contribution of carbohydrate oxidation to energy expenditure. Furthermore, FAT-D2KO animals that were kept on a high-fat diet for 8 weeks gained more body weight and fat, indicating impaired brown adipose tissue (BAT) thermogenesis and/or inability to oxidize the fat excess. Acclimatization of FAT-D2KO mice at thermoneutrality dissipated both features of this phenotype. Muscle D2 does not seem to play a significant metabolic role given that SKM-D2KO animals exhibited no phenotype. The present findings are unique in that they were obtained in systemically euthyroid animals, revealing that brain D2 plays a dominant albeit indirect role in fatty acid oxidation via its sympathetic control of BAT activity. D2-generated T3 in BAT accelerates fatty acid oxidation and protects against diet-induced obesity.

Boa evolução da forma granulomatosade Imunodeficiência Comum Variável / Good evolution of granulomatous form of the common variable immunodeficiency

Objetivo: Descrever um caso de forma granulomatosa da imunodeficiência comum variável (ICV) enfatizando a boa evolução da doença granulomatosa durante o acompanhamento em longo prazo. Descrição do caso: Paciente do gênero feminino, atualmente com 26 anos. Apresentava história de otites e amigdalites desde os seis meses e pneumonias desde os três anos de idade. Aos cinco anos foi levada a serviço especializado: apresentava-se desnutrida e com baço palpável a 9 cm e fígado a 2 cm. A investigação laboratorial iniciada nessa ocasião mostrou deficiência de IgG, IgA, IgM séricas, ausência de isohemaglutininas, linfócitos B, T, CD4+ e CD8+ normais. A biopsia hepática revelou doença granulomatosa. Foi então diagnosticada forma granulomatosa da ICV. A paciente foi submetida ao tratamento da imunodeficiência sendo indicado esteroide para a doença granulomatosa. O acompanhamento mensal da paciente durante 21 anos mostrou boa evolução, com regressão da hepatoesplenomegalia e preservação da função hepática. Discussão: A ICV é uma deficiência primária predominantemente de anticorpos, em que há pneumonias de repetição e cujo tratamento principal é a reposição de gamaglobulina. A forma granulomatosa hepática da ICV é rara, mas deve ter diagnóstico precoce, na tentativa de preservar a função hepática. No presente caso, durante os 21 anos de acompanhamento, houve boa evolução da forma granulomatosa da imunodeficiência com o uso de baixas doses de esteroides.

Objective: To describe a case of granulomatous form of common variable immunodeficiency (CVID) with good progress during a longterm monitoring. Case report: Female patient, now 26. She had a history of ear infections and tonsillitis since she was six months and pneumonia as from the age of three years. At the age of five years she was taken to a specialized service: the patient was malnourished and with 9 cms palpable spleen and 2 cms liver. Laboratory investigation initiated at that time showed deficiency of IgG, IgA, IgM serum, absence of isohemaglutininas, and normal B, T, CD4+ and CD8+ lymphocytes. The liver biopsy revealed granulomatous disease. It was then diagnosed as granulomatous CVID. The patient was submitted to immunodeficiency treatment and steroid was indicated for the granulomatous disease. The patient’s monthly monitoring during 21 years showed good outcome, with regression of hepatosplenomegaly and preservation of liver function. Discussion: CVID is predominantly a primary deficiency of antibodies, in which there is recurrent pneumonias and the main treatment recommended is the replacement of gammaglobulin. The granulomatous form of CVID is rare, nevertheless it must be diagnosed early so that the liver function can be preserved. In this 21-year-monitoring case there has been a good evolution of the granulomatous form of immunodeficiency with low doses of steroids.