RESUMEN
BACKGROUND: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment. METHODS: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and ß-blockers. In sensitivity analyses, the between-group differences of lateralization index values after propensity score matching and the rate of unilateral PA identification in subgroups with undetectable (≤2 mUI/L), suppressed (<8.2 mUI/L), and unsuppressed (≥8.2 mUI/L) direct renin concentration levels were also evaluated. RESULTS: Plasma aldosterone concentration, direct renin concentration, and blood pressure values were similar in non-MRA-treated (n=779) and MRA-treated (n=61) patients with PA, but the latter required more antihypertensive agents (P=0.001) and showed a higher rate of adrenal nodules (82% versus 67%; P=0.022) and adrenalectomy (72% versus 54%; P=0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the receiving operating characteristic curve of lateralization index, both under unstimulated conditions and postcosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels. CONCLUSIONS: At doses that controlled blood pressure and potassium levels, MRAs did not preclude the identification of unilateral PA at AVS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.
Asunto(s)
Glándulas Suprarrenales , Hiperaldosteronismo , Antagonistas de Receptores de Mineralocorticoides , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adrenalectomía/métodos , Aldosterona/sangre , Presión Sanguínea/fisiología , Presión Sanguínea/efectos de los fármacos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/tratamiento farmacológico , Hiperaldosteronismo/cirugía , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Puntaje de Propensión , Renina/sangre , Estudios Retrospectivos , Resultado del Tratamiento , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Adrenal venous sampling is recommended for the identification of unilateral surgically curable primary aldosteronism but is often clinically useless, owing to failed bilateral adrenal vein cannulation. OBJECTIVES: To investigate if only unilaterally selective adrenal vein sampling studies can allow the identification of the responsible adrenal. METHODS: Among 1625 patients consecutively submitted to adrenal vein sampling in tertiary referral centers, we selected those with selective adrenal vein sampling results in at least one side; we used surgically cured unilateral primary aldosteronism as gold reference. The accuracy of different values of the relative aldosterone secretion index (RASI), which estimates the amount of aldosterone produced in each adrenal gland corrected for catheterization selectivity, was examined. RESULTS: We found prominent differences in RASI values distribution between patients with and without unilateral primary aldosteronism. The diagnostic accuracy of RASI values estimated by the area under receiver operating characteristic curves was 0.714 and 0.855, respectively, in the responsible and the contralateral side; RASI values >2.55 and ≤0.96 on the former and the latter side furnished the highest accuracy for detection of surgically cured unilateral primary aldosteronism. Moreover, in the patients without unilateral primary aldosteronism, only 20% and 16% had RASI values ≤0.96 and >2.55. CONCLUSIONS: With the strength of a large real-life data set and use of the gold reference entailing an unambiguous diagnosis of unilateral primary aldosteronism, these results indicate the feasibility of identifying unilateral primary aldosteronism using unilaterally selective adrenal vein sampling results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01234220.
Asunto(s)
Aldosterona , Hiperaldosteronismo , Humanos , Glándulas Suprarrenales/irrigación sanguínea , Adrenalectomía , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirugía , Estudios RetrospectivosRESUMEN
INTRODUCTION: Most of the molybdenum (Mo) is used in metallurgical applications, the tetrathiomolybdate form is an experimental chelating agent for Wilson's disease. Human data of acute Mo exposure are lacking and, no report of no-observed-adverse-effect level (NOAEL) has been described until now. Case-study: We report a case of acute occupational exposure to molybdenum, with the related plasma and urine molybdenum concentrations, caused by an accidental ingestion of a sip of an anti-corrosion liquid for metal containing sodium molybdate. Our purpose was to evaluate potential systemic toxicity of molybdenum and to evaluate the dose-response/dose-effect relationship. We estimated the amount of ingested molybdenum to make a mg/kg relationship and performed repeated urine and plasma molybdenum determinations. The patient was hospitalized for three days to monitor possible development of acute symptoms/biochemical alterations. DISCUSSION: We estimated the amount of the sip around 50 ml, with an estimation of a total of 5 gr of sodium molybdate that, for the patient bodyweight of 80 kg, would mean 62,5 mg/kg of ingested Mo. Blood and urine samples collected 2 hours after ingestion showed 50 mcg/L (reference range: 0.43 - 1.8 mcg/L) and 630 mcg/L (refence range: up to 116 mcg/L) of Mo respectively, confirming acute exposure. The patients remained asymptomatic confirming that an estimated oral dose of Mo of 62.5 mg/kg was not associated with adverse effects. CONCLUSIONS: Our value, being extrapolated by a single case, will require further confirmations from other studies to allow a full evaluation of a NOAEL. Nevertheless, it does not preclude its use in evaluating the probable absence of adverse effect in the context of acute Mo exposure.
Asunto(s)
Monitoreo Biológico , Molibdeno , Ingestión de Alimentos , Humanos , Molibdeno/toxicidad , Lugar de TrabajoRESUMEN
Many of the patients with primary aldosteronism (PA) are denied curative adrenalectomy because of limited availability or failure of adrenal vein sampling. It has been suggested that adrenal vein sampling can be omitted in young patients with a unilateral adrenal nodule, who show a florid biochemical PA phenotype. As this suggestion was based on a very low quality of evidence, we tested the applicability and accuracy of imaging, performed by computed tomography and/or magnetic resonance, for identification of unilateral PA, as determined by biochemical and/or clinical cure after unilateral adrenalectomy. Among 1625 patients with PA submitted to adrenal vein sampling in a multicenter multiethnic international study, 473 were ≤45 years of age; 231 of them had exhaustive imaging and follow-up data. Fifty-three percentage had a unilateral adrenal nodule, 43% had no nodules, and 4% bilateral nodules. Fifty-six percentage (n=131) received adrenalectomy and 128 were unambiguously diagnosed as unilateral PA. A unilateral adrenal nodule on imaging and hypokalemia were the strongest predictors of unilateral PA at regression analysis. Accordingly, imaging allowed correct identification of the responsible adrenal in 95% of the adrenalectomized patients with a unilateral nodule. The rate raised to 100% in the patients with hypokalemia, who comprised 29% of the total, but fell to 88% in those without hypokalemia. Therefore, a unilateral nodule and hypokalemia could be used to identify unilateral PA in patients ≤45 years of age if adrenal vein sampling is not easily available. However, adrenal vein sampling remains indispensable in 71% of the young patients, who showed no nodules/bilateral nodules at imaging and/or no hypokalemia. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.
Asunto(s)
Adrenalectomía/métodos , Hiperaldosteronismo/cirugía , Glándulas Suprarrenales/irrigación sanguínea , Adulto , Recolección de Muestras de Sangre , Estudios de Factibilidad , Femenino , Humanos , Hiperaldosteronismo/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Cirugía Asistida por Computador , Tomografía Computarizada por Rayos XRESUMEN
AIMS: We aimed at determining the rate of drug-resistant arterial hypertension in patients with an unambiguous diagnosis of primary aldosteronism (PA). Moreover, we sought for investigating the diagnostic performance of adrenal vein sampling (AVS), and the effect of adrenalectomy on blood pressure (BP) and prior treatment resistance in PA patients subtyped by AVS in major referral centres. METHODS AND RESULTS: The Adrenal Vein Sampling International Study-2 (AVIS-2) was a multicentre international study that recruited consecutive PA patients submitted to AVS, according to current guidelines, during 15 years. The patients were over 18 years old with arterial hypertension and had an unambiguous diagnosis of PA. The rate of resistant hypertension was assessed at baseline and after adrenalectomy using the American Heart Association (AHA) 2018 definition. Information on presence or absence of resistant hypertension was available in 89% of the 1625 enrolled PA patients. Based on the AHA 2018 criteria, resistant hypertension was found in 20% of patients, of which about two-thirds (14%) were men and one-third (6%) women (χ2 = 17.1, P < 1*10-4) with a higher rate of RH in men than in women (23% vs. 15% P < 1*10-4). Of the 292 patients with resistant hypertension, 98 (34%) underwent unilateral AVS-guided adrenalectomy, which resolved BP resistance to antihypertensive treatment in all. CONCLUSIONS: (i) Resistant hypertension is a common presentation in patients seeking surgical cure of PA; (ii) AVS is key for the optimal management of patients with PA due to resistant hypertension; and (iii) AVS-guided adrenalectomy allowed resolution of treatment-resistant hypertension.
Asunto(s)
Hiperaldosteronismo , Hipertensión , Adolescente , Glándulas Suprarrenales/irrigación sanguínea , Glándulas Suprarrenales/cirugía , Adrenalectomía/efectos adversos , Adrenalectomía/métodos , Femenino , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirugía , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Masculino , Estudios RetrospectivosRESUMEN
CONTEXT: Adrenal gland imaging is recommended by the current guidelines for the workup of primary aldosteronism (PA). However, its diagnostic performance has not been established in large, multiethnic cohorts of patients who undergo adrenal vein sampling (AVS) and adrenalectomy. OBJECTIVE: This work aims to assess the diagnostic accuracy of cross-sectional adrenal imaging. METHODS: This international multicenter study took place in tertiary referral centers. A total of 1625 PA patients seeking surgical cure were enrolled in an international study involving 19 centers in North America, Europe, Asia, and Australia. Of these, 1311 (81%) had imaging data available and 369 (23%), who received a final diagnosis of surgically cured unilateral PA, were examined. Patients underwent AVS and imaging by computed tomography and/or magnetic resonance imaging. The accuracy of detection of unilateral PA at imaging was estimated by the area under the receiver operator characteristics curve using cure (biochemical and/or full clinical success) as the reference at follow-up after unilateral adrenalectomy. RESULTS: In the cohort of 1311 patients with imaging data available, 34% and 7% of cases showed no detectable or bilateral nodules, respectively. Imaging did not detect the culprit adrenal in 28% of the surgically cured unilateral PA patients. Moreover, the clinical outcome did not differ significantly between the imaging-positive and imaging-negative patients. CONCLUSION: Cross-sectional imaging did not identify a lateralized cause of disease in around 40% of PA patients and failed to identify the culprit adrenal in more than one-fourth of patients with unilateral PA.
Asunto(s)
Glándulas Suprarrenales/irrigación sanguínea , Glándulas Suprarrenales/diagnóstico por imagen , Adrenalectomía/métodos , Aldosterona/sangre , Hiperaldosteronismo/diagnóstico por imagen , Hiperaldosteronismo/cirugía , Adulto , Asia , Australia , Estudios de Cohortes , Europa (Continente) , Femenino , Humanos , Hiperaldosteronismo/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , América del Norte , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , VenasRESUMEN
PURPOSE: Pheochromocytoma, a catecholamine-secreting tumour leading to neurological and cardiovascular life-threatening conditions through hypertension crisis, occurs in 0.1-0.5% of hypertensive patients, but it is extremely rare in pregnancy (0.0018-0.006%). Some classes of drugs, even commonly used in pregnancy, can trigger catecholamine secretion, precipitating the clinical situation. MATERIALS AND METHODS AND RESULTS: We report a 33-year-old woman, gravida 2 para 1, with previous mild hypertension, was admitted to the emergency room, at 28 2/7 weeks of gestation due to headache, tachycardia and severe arterial hypertension (220/120 mm Hg) triggered by the antiemetic metoclopramide used for a week because of nausea. In the emergency room, a paradoxical rise in blood pressure followed intravenous labetalol infusion was observed. Both metoclopramide and labetalol-triggered hypertensive crisis raised the suspicion of an undiagnosed pheochromocytoma. Diagnostic work-up showed elevated normetanephrine urinary excretion ââand a right adrenal pheochromocytoma by abdominal magnetic resonance imaging. Oral alpha-1 and beta-1-adrenergic antagonist and calcium-channel blocker were started. At 33-weeks of gestation, she underwent a caesarean section giving birth to a female child. Seven weeks later she underwent a video-laparoscopic right adrenalectomy which normalised her blood pressure. CONCLUSIONS: Both metoclopramide, a selective dopamine type-2 receptor antagonist and partial agonist of 5-hydroxytryptamine 4 receptor, and labetalol, a non-selective ß-adrenoreceptor-blocker with weak α1-adrenergic antagonism, exacerbated an acute hypertensive crisis revealing an unrecognised pheochromocytoma in a pregnant patient. Careful attention to potential drug-triggered catecholamine crises and especially early recognition of pheochromocytomas, are mandatory in hypertensive pregnant women. A missed or delayed diagnosis could result in catastrophic results affecting foetal and maternal outcomes.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Hipertensión , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Adrenalectomía , Adulto , Cesárea , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Recién Nacido , Metoclopramida/efectos adversos , Feocromocitoma/complicaciones , Feocromocitoma/cirugía , EmbarazoRESUMEN
Background: Pheochromocytoma (PHEO) clinical manifestations generally mirror excessive catecholamines secretion; rarely the clinical picture may reflect secretion of other hormones. Watery diarrhea, hypokalemia and achlorhydria (WDHA) is a rare syndrome related to excessive secretion of vasoactive intestinal peptide (VIP). Clinical Case: A 73-year-old hypotensive man affected by adrenal PHEO presented with weight loss and watery diarrhea associated with hypokalemia, hyperchloremic metabolic acidosis (anion gap 15 mmol/l) and a negative urinary anion gap. Abdominal computed tomography scan showed a right adrenal PHEO, 8.1 cm in maximum diameter, with tracer uptake on 68GaDOTA-octreotate positron emission tomography. Metastasis in lumbar region and lung were present. Both chromogranin A and VIP levels were high (more than10 times the normal value) with slightly elevated urine normetanephrine and metanephrine excretion. Right adrenalectomy was performed and a somatostatin analogue therapy with lanreotide started. Immunostaining showed chromogranin A and VIP co-expression, with weak somatostatin-receptor-2A positivity. In two months, patient clinical conditions deteriorated with severe WDHA and multiple liver and lung metastasis. Metabolic acidosis and hypokalemia worsened, leading to hemodynamic shock and exitus. Conclusions: A rare case of WDHA syndrome caused by malignant VIP-secreting PHEO was diagnosed. High levels of circulating VIP were responsible of the rapidly evolving clinical picture with massive dehydration and weight loss along with severe hyperchloremic metabolic acidosis and hypokalemia due to the profuse untreatable diarrhea. The rescue treatment with lanreotide was unsuccessful because of the paucity of somatostatin-receptor-2A on VIP-secreting PHEO chromaffin cells.
Asunto(s)
Acidosis/diagnóstico , Diarrea/diagnóstico , Hipopotasemia/diagnóstico , Feocromocitoma/fisiopatología , Péptido Intestinal Vasoactivo/química , Acidosis/complicaciones , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Adrenalectomía , Anciano , Células Cromafines/citología , Diarrea/complicaciones , Humanos , Hipopotasemia/complicaciones , Masculino , Péptidos Cíclicos/uso terapéutico , Neoplasias del Sistema Nervioso Periférico , Cintigrafía , Receptores de Somatostatina/uso terapéutico , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Síndrome , Tomografía Computarizada por Rayos X , Pérdida de PesoAsunto(s)
COVID-19 , Trombosis , Angiotensina II , Humanos , Factor de Crecimiento Placentario , SARS-CoV-2 , Trombosis/etiologíaRESUMEN
A subset of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) developed a condition of hyper-inflammation, which can cause multi-organ damage and the more severe forms of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) can promote tissue regeneration and modulate immune responses and, thus, have the rational requirements to be used to counteract SARS-CoV-2-induced pneumonia and hyper-inflammation. The aim of the present study was to gain insight into possible mechanisms of action of MSCs obtained from human dental pulp [dental pulp stem cells (DPSCs)] in COVID-19 patients. We investigated the concentrations of 18 cytokines in supernatants of peripheral blood mononuclear cells (PBMCs) obtained from COVID-19 patients cultured in vitro alone and in contact with DPSCs. The modulation of cytokines in PBMCs was confirmed by real-time PCR. IL-6 was the sole cytokine detected in supernatants of DPSCs. In resting conditions, co-culture increased IL-1ß, IL-2, IL-5, IL-6, IL-10, IL-18, TNFα, and granulocyte macrophage colony-stimulating factor (GM-CSF) levels. When PBMCs were activated with anti-CD3/CD28 antibody-coated beads, co-culture increased IL-6 and GM-CSF, whereas it decreased IFNγ, TNFα, IL-2, IL-5, IL-9, IL-10, IL-12 (p70), IL-17A, IL-18, IL-21, IL-23, and IL-27 levels. Concentrations of IL-1ß, IL-4, IL-13, and IL-22 were not affected. The comparison of cytokine concentrations in supernatants of PBMCs from COVID-19 patients vs. healthy subjects revealed lower concentrations of IL-10 and higher concentrations of IL-18 in supernatants of CD3/CD28-activated PBMCs from COVID-19 patients. Results are explorative but indicate that DPSCs can modulate the production of cytokines deregulated in COVID-19 patients, supporting their potential use in COVID-19.
RESUMEN
BACKGROUND AND AIM: Considering the amount of novel knowledge generated in the last five years, a team of experienced hypertensionlogists was assembled to furnish updated clinical practice guidelines for the management of primary aldosteronism. METHODS: To identify the most relevant studies, the authors utilized a systematic literature review in international databases by applying the PICO strategy, and then they were required to make use of only those meeting predefined quality criteria. For studies of diagnostic tests, only those that fulfilled the Standards for Reporting of Diagnostic Accuracy recommendations were considered. RESULTS: Each section was jointly prepared by at least two co-authors, who provided Class of Recommendation and Level of Evidence following the American Heart Association methodology. The guidelines were sponsored by the Italian Society of Arterial Hypertension and underwent two rounds of revision, eventually reexamined by an External Committee. They were presented and thoroughly discussed in two face-to-face meetings with all co-authors and then presented on occasion of the 36th Italian Society of Arterial Hypertension meeting in order to gather further feedbacks by all members. The text amended according to these feedbacks was subjected to a further peer review. CONCLUSIONS: After this process, substantial updated information was generated, which could simplify the diagnosis of primary aldosteronism and assist practicing physicians in optimizing treatment and follow-up of patients with one of the most common curable causes of arterial hypertension.
RESUMEN
CONTEXT: Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients. OBJECTIVES: To investigate in a real-life study the rate of bilateral success and identification of unilateral aldosteronism and their impact on blood pressure outcomes in PA subtyped by AVS. DESIGN AND SETTINGS: In a retrospective analysis of the largest international registry of individual AVS data (AVIS-2 study), we investigated how different cut-off values of the selectivity index (SI) and lateralization index (LI) affected rate of bilateral success, identification of unilateral aldosteronism, and blood pressure outcomes. RESULTS: AVIS-2 recruited 1625 individual AVS studies performed between 2000 and 2015 in 19 tertiary referral centers. Under unstimulated conditions, the rate of biochemically confirmed bilateral AVS success progressively decreased with increasing SI cut-offs; furthermore, with currently used LI cut-offs, the rate of identified unilateral PA leading to adrenalectomy was as low as <25%. A within-patient pairwise comparison of 402 AVS performed both under unstimulated and cosyntropin-stimulated conditions showed that cosyntropin increased the confirmed rate of bilateral selectivity for SI cut-offs ≥ 2.0, but reduced lateralization rates (P < 0.001). Post-adrenalectomy outcomes were not improved by use of cosyntropin or more restrictive diagnostic criteria. CONCLUSION: Commonly used SI and LI cut-offs are associated with disappointingly low rates of biochemically defined AVS success and identified unilateral PA. Evidence-based protocols entailing less restrictive interpretative cut-offs might optimize the clinical use of this costly and invasive test. (J Clin Endocrinol Metab XX: 0-0, 2020).
Asunto(s)
Glándulas Suprarrenales/irrigación sanguínea , Hiperaldosteronismo/clasificación , Manejo de Especímenes/normas , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/patología , Adrenalectomía , Cosintropina/administración & dosificación , Diagnóstico Diferencial , Estudios de Seguimiento , Hormonas/administración & dosificación , Humanos , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patología , Hiperaldosteronismo/cirugía , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Mutations of genes related to Krebs cycle enzymes, kinases or to pseudohypoxic signaling pathways, including Von-Hippel-Lindau (VHL) and transmembrane-protein-127 predispose to pheochromocytoma and paraganglioma development. Homozygous loss of function mutation of VHL (VHL 598C>T) gene can associate with polycythemia because of an altered hypoxia sensing. PATIENT: A 19-year-old normotensive man presented with headache, fatigue associated with severe erythrocytosis (hematocrit 76%), high hemoglobin (25.3âg/dl) in normoxic condition. Bone marrow biopsy showed marked hyperplasia of erythroid series. The Janus kinase 2 (V617F) mutation was absent. Abdominal computed tomography scan showed a 8-mm left adrenal pheochromocytoma with tracer uptake on GaDOTA-octreotate PET. Twenty-four-hour urinary metanephrine excretion was slightly increased, while normetanephrine, 3-methoxytyramine were normal. Adrenal veins sampling showed high left-side erythropoietin secretion. RESULTS: Next-generation sequencing genetic analysis evidenced two concurrent heterozygous mutation of VHL598C>T and of transmembrane-protein-127 c.268G>A. Left side adrenalectomy improved symptoms, erythrocytosis, hemoglobin, and erythropoietin circulating levels. Adrenal histologic sections showed a pheochromocytoma with extensive immunostaining for erythropoietin, but also coexpression of chromogranin A, a marker of chromaffin tissue. CONCLUSION: Congenital polycythemia was clinically diagnosed, mimicking Chuvash polycythemia. Chuvash polycythemia is an autosomal recessive disorder that usually harbors a homozygous mutation of VHL598C>T but not predispose to pheochromocytoma development; in contrast our patient showed for the first time that the concurrent heterozygous VHL and TMEM mutations, resulted in a clinical phenotype of a normotensive patient with polycythemia due to erythropoietin-secreting pheochromocytoma that improved after adrenalectomy.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/genética , Eritropoyetina/metabolismo , Heterocigoto , Mutación , Feocromocitoma/genética , Policitemia/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Neoplasias de las Glándulas Suprarrenales/complicaciones , Genotipo , Humanos , Masculino , Fenotipo , Feocromocitoma/complicaciones , Policitemia/complicaciones , Adulto JovenRESUMEN
We sought to measure the clinical benefits of adrenal venous sampling (AVS), a test recommended by guidelines for primary aldosteronism (PA) patients seeking surgical cure, in a large registry of PA patients submitted to AVS. Data of 1625 consecutive patients submitted to AVS in 19 tertiary referral centers located in Asia, Australia, Europe, and North America were collected in a large multicenter international registry. The primary end points were the rate of bilateral success, ascertained lateralization of PA, adrenalectomy, and of cured arterial hypertension among AVS-guided and non AVS-guided adrenalectomy patients. AVS was successful in 80.1% of all cases but allowed identification of unilateral PA in only 45.5% by the criteria in use at each center. Adrenalectomy was performed in 41.8% of all patients and cured arterial hypertension in 19.6% of the patients, 2-fold more frequently in women than men (P<0.001). When AVS-guided, surgery provided a higher rate of cure of hypertension than when non-AVS-guided (40.0% versus 30.5%; P=0.027). Compared with surgical cases, patients treated medically needed more antihypertensive medications (P<0.001) and exhibited a higher rate of persistent hypokalemia requiring potassium supplementation (4.9% versus 2.3%; P<0.01). The low rate of adrenalectomy and cure of hypertension in PA patients seeking surgical cure indicates suboptimal AVS use, possibly related to issues in patient selection, technical success, and AVS data interpretation. Given the better outcomes of AVS-guided adrenalectomy, these results call for actions to improve the diagnostic use of this test that is necessary for detection of surgical PA candidates. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01234220.
Asunto(s)
Glándulas Suprarrenales/irrigación sanguínea , Adrenalectomía , Aldosterona/sangre , Hiperaldosteronismo/sangre , Adulto , Recolección de Muestras de Sangre , Femenino , Humanos , Hiperaldosteronismo/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Primary aldosteronism (PA) causes cardiovascular damage in excess to the blood pressure elevation, but there are no prospective studies proving a worse long-term prognosis in adrenalectomized and medically treated patients. We have, therefore, assessed the outcome of PA patients according to treatment mode in the PAPY study (Primary Aldosteronism Prevalence in Hypertension) patients, 88.8% of whom were optimally treated patients with primary (essential) hypertension (PH), and the rest had PA and were assigned to medical therapy (6.4%) or adrenalectomy (4.8%). Total mortality was the primary end point; secondary end points were cardiovascular death, major adverse cardiovascular events, including atrial fibrillation, and total cardiovascular events. Kaplan-Meier and Cox analysis were used to compare survival between PA and its subtypes and PH patients. After a median of 11.8 years, complete follow-up data were obtained in 89% of the 1125 patients in the original cohort. Only a trend (P=0.07) toward a worse death-free survival in PA than in PH patients was observed. However, at both univariate (90.0% versus 97.8%; P=0.002) and multivariate analyses (hazard ratio, 1.82; 95% confidence interval, 1.08-3.08; P=0.025), medically treated PA patients showed a lower atrial fibrillation-free survival than PH patients. By showing that during a long-term follow-up adrenalectomized aldosterone-producing adenoma patients have a similar long-term outcome of optimally treated PH patients, whereas, at variance, medically treated PA patients remain at a higher risk of atrial fibrillation, this large prospective study emphasizes the importance of an early identification of PA patients who need adrenalectomy as a key measure to prevent incident atrial fibrillation.
Asunto(s)
Adrenalectomía , Antihipertensivos , Fibrilación Atrial , Tratamiento Conservador , Hiperaldosteronismo , Hipertensión , Adrenalectomía/efectos adversos , Adrenalectomía/métodos , Adulto , Cuidados Posteriores/métodos , Cuidados Posteriores/estadística & datos numéricos , Antihipertensivos/clasificación , Antihipertensivos/uso terapéutico , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/etiología , Tratamiento Conservador/efectos adversos , Tratamiento Conservador/métodos , Femenino , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/epidemiología , Hiperaldosteronismo/fisiopatología , Hiperaldosteronismo/cirugía , Hipertensión/sangre , Hipertensión/diagnóstico , Hipertensión/etiología , Hipertensión/terapia , Italia/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Sistema Renina-Angiotensina/efectos de los fármacos , TiempoRESUMEN
Sprue-like enteropathy associated with olmesartan medoxomil use has been recently reported. Its clinical manifestations include diarrhea, weight loss and malabsorption. Duodenal biopsies show villous atrophy (VA) with or without intraepithelial lymphocytosis and inflammation of the lamina propria. Serology for celiac disease (CD) is negative and gluten-free diet does not result in clinical improvement. Symptoms resolve after olmesartan discontinuation. Follow-up biopsies show recovery/improvement of the duodenum. Whether sprue-like enteropathy is a specific adverse reaction to olmesartan or rather a class effect of angiotensin-receptor blockers (ARBs) remains a controversial issue. We report a case of sprue-like enteropathy associated with telmisartan. A 52-year-old man presented with chronic diarrhea, abdominal discomfort and significant weight loss. In the last 3 years, he had been treated with telmisartan 40 mg/day for hypertension after right adrenalectomy for an aldosterone-producing adenoma. Laboratory investigations showed no significant abnormalities: Hb 13.6 g/dL, serum albumin 3.9 g/dL, total cholesterol 193 mg/dL, serum creatinine 0.99 mg/dL, sodium 143.6 mmol/L, K+ 4.3 mmol/L, calcium 9.3 mg/dL, phosphorus 3.9 mg/dL and 25-OH-D3 27.7 ng/mL. Duodenal histology showed subtotal VA and inflammation of the lamina propria. CD serology was negative. HLA-DQ typing showed absence of the DQ2/DQ8 haplotypes. After telmisartan discontinuation, patient's symptoms subsided, and his body weight increased despite persistence of a gluten-containing diet. Follow-up biopsies at 3 showed progressive duodenal recovery. Very few cases of sprue-like enteropathy associated with ARBs other than olmesartan have been reported. Our case of telmisartan-associated enteropathy further suggests that sprue-like disease may be a class effect of ARBs.
RESUMEN
Peptide receptor radionuclide therapy (PRRT) is a molecular-targeted therapy in which a somatostatin analogue (a small peptide) is coupled with a radioligand so that the radiation dose is selectively administered to somatostatin receptor-expressing metastasized neuroendocrine tumors, particularly gastroenteropancreatic. Reported toxicities include myelotoxicity and nephrotoxicity, the latter manifesting as decreased kidney function, often developing months to years after treatment completion. We present a case of PRRT-induced kidney toxicity manifesting as a severe Gitelman-like tubulopathy with preserved kidney function. Because profound hypokalemia and hypocalcemia can lead to life-threatening arrhythmias, we highlight the necessity for careful monitoring of serum and urine electrolytes in patients receiving PRRT.
Asunto(s)
Síndrome de Gitelman/inducido químicamente , Neoplasias del Íleon/radioterapia , Tumores Neuroendocrinos/radioterapia , Octreótido/análogos & derivados , Compuestos Organometálicos/efectos adversos , Desequilibrio Hidroelectrolítico/inducido químicamente , Acidosis/inducido químicamente , Acidosis/metabolismo , Acidosis/terapia , Anciano , Calcitriol/uso terapéutico , Carbonato de Calcio/uso terapéutico , Quimioradioterapia Adyuvante , Procedimientos Quirúrgicos del Sistema Digestivo , Fluidoterapia , Síndrome de Gitelman/metabolismo , Síndrome de Gitelman/terapia , Humanos , Hipocalcemia/inducido químicamente , Hipocalcemia/metabolismo , Hipocalcemia/terapia , Hipopotasemia/inducido químicamente , Hipopotasemia/metabolismo , Hipopotasemia/terapia , Sulfato de Magnesio/uso terapéutico , Masculino , Octreótido/efectos adversos , Vitaminas/uso terapéutico , Desequilibrio Hidroelectrolítico/metabolismo , Desequilibrio Hidroelectrolítico/terapiaRESUMEN
BACKGROUND: Although primary aldosteronism is considered the most common form of endocrine hypertension, the diagnostic rate of primary aldosteronism in the territory is unknown. OBJECTIVES: The aims of the current study were to compare the number of patients discharged with International Classification of Diseases 9 Clinical Modification codes compatible with primary aldosteronism from all the hospitals in Emilia-Romagna during 16 years (from 2000 to 2015) with the number of expected cases of primary aldosteronism, and to compare the number of patients with primary aldosteronism who underwent adrenalectomy in the period 2000-2015 with the number of expected cases of unilateral primary aldosteronism. METHODS: We accessed the Database of the Emilia-Romagna Health Service to select all patients from the age of 20 years discharged with International Classification of Diseases 9 Clinical Modification codes compatible with primary aldosteronism and, among them, those who underwent adrenalectomy in the same period. The prevalence of hypertension in Emilia-Romagna from the age of 20 years was drawn from the Health Search Database. The population from the age of 20 years in Emilia-Romagna has been drawn from the Italian National Statistical Institute. We hypothesized a prevalence of primary aldosteronism of 5% among hypertensive patients and a prevalence of unilateral subtypes of 30% among the primary aldosteronism patients. RESULTS: A total of 992 patients have been discharged with codes consistent with primary aldosteronism during 16 years in Emilia-Romagna, that is 1.9% of the expected cases of primary aldosteronism. A total of 160 of them underwent adrenalectomy in the same period, which corresponds to 1% of the expected cases of unilateral primary aldosteronism in Emilia-Romagna. CONCLUSIONS: Our results clearly indicate that primary aldosteronism is dramatically underdiagnosed and undertreated.