RESUMEN
OBJECTIVES: Human T-cell leukaemia virus type 1 (HTLV-1), an STI, is reported to be highly prevalent in Indigenous communities in Central Australia. HTLV-1 is an incurable, chronic infection which can cause Adult T-cell leukaemia/lymphoma (ATL). ATL is associated with high morbidity and mortality, with limited treatment options. We studied the prevalence of HTLV-1 and ATL in the state of Queensland, Australia. METHODS: Serum samples stored at healthcare services in Brisbane, Townsville and Cairns and at haemodialysis units in Brisbane (2018-2019) were screened for HTLV-1/2 antibodies using the Abbott ARCHITECT chemiluminescent microparticle immunoassay (CMIA) for antibodies against gp46-I, gp46-II and GD21 (Abbott CMIA, ARCHITECT). Reactive samples were confirmed through Western blot. Pooled Australian National Cancer Registry surveillance data reporting on cases coded for ATL (2004-2015) were analysed. RESULTS: Two out of 2000 hospital and health services samples were confirmed HTLV-1-positive (0.1%, 95% CI 0.02% to 0.4%), both in older women, one Indigenous and one non-Indigenous. All 540 haemodialysis samples tested negative for HTLV. All samples were HTLV-2-negative. Ten out of 42 (24.8%) reported cases of ATL in Australia were from Queensland (crude incidence rate 0.025/100 000; 95% CI 0.011 to 0.045); most cases were seen in adult men of non-Indigenous origin. Nineteen deaths due to ATL were recorded in Australia. CONCLUSION: We confirm that HTLV-1 and ATL were detected in Queensland in Indigenous and non-Indigenous people. These results highlight the need for HTLV-1 prevalence studies in populations at risk of STIs to allow the implementation of focused public health sexual and mother-to-child transmission prevention strategies.
Asunto(s)
Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto , Linfoma , Masculino , Adulto , Humanos , Femenino , Anciano , Leucemia-Linfoma de Células T del Adulto/epidemiología , Estudios Transversales , Queensland/epidemiología , Estudios Retrospectivos , Australia/epidemiología , Transmisión Vertical de Enfermedad Infecciosa , Infecciones por HTLV-I/epidemiologíaRESUMEN
CONTEXT AND OBJECTIVE: Posture-responsive and posture-unresponsive aldosterone-producing adenomas (APAs) account for approximately 40% and 60% of APAs, respectively. Somatic gene mutations have been recently reported to exist in approximately 90% of APAs. This study was designed to characterize the biochemical, histopathologic, and genetic properties of these 2 types of APA. METHODS: Plasma levels of aldosterone and hybrid steroids (18-oxocortisol and 18-hydroxycortisol) were measured by liquid chromatography-tandem mass spectrometry. Immunohistochemistry for CYP11B2 (aldosterone synthase) and CYP17A1 (17α-hydroxylase) and deoxyribonucleic acid sequencing (Sanger and next-generation sequencing) were performed on APA tissue collected from 23 posture-unresponsive and 17 posture-responsive APA patients. RESULTS: Patients with posture-unresponsive APA displayed higher (P < 0.01) levels of hybrid steroids, recumbent aldosterone and cortisol, larger (P < 0.01) zona fasciculata (ZF)-like tumors with higher (P < 0.01) expression of CYP17A1 (but not of CYP11B2) than patients with posture-responsive APA (most of which were not ZF-like). Of 40 studied APAs, 37 (92.5%) were found to harbor aldosterone-driving somatic mutations (KCNJ5 = 14 [35.0%], CACNA1D = 13 [32.5%], ATP1A1 = 8 [20.0%], and ATP2B3 = 2 [5.0%]), including 5 previously unreported mutations (3 in CACNA1D and 2 in ATP1A1). Notably, 64.7% (11/17) of posture-responsive APAs carried CACNA1D mutations, whereas 56.5% (13/23) of posture-unresponsive APAs harbored KCNJ5 mutations. CONCLUSIONS: The elevated production of hybrid steroids by posture-unresponsive APAs may relate to their ZF-like tumor cell composition, resulting in expression of CYP17A1 (in addition to somatic gene mutation-driven CYP11B2 expression), thereby allowing production of cortisol, which acts as the substrate for CYP11B2-generated hybrid steroids.
Asunto(s)
Neoplasias de la Corteza Suprarrenal , Adenoma Corticosuprarrenal , Aldosterona/metabolismo , Hiperaldosteronismo , Postura/fisiología , Neoplasias de la Corteza Suprarrenal/genética , Neoplasias de la Corteza Suprarrenal/metabolismo , Neoplasias de la Corteza Suprarrenal/patología , Adenoma Corticosuprarrenal/genética , Adenoma Corticosuprarrenal/metabolismo , Adenoma Corticosuprarrenal/patología , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Humanos , Hiperaldosteronismo/genética , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Screening for primary aldosteronism is infrequently performed in primary care. This is partly because screening is complicated by the need to adjust existing antihypertensive medications. This article provides an approach to screening patients who are already taking antihypertensive medication. OBJECTIVE: The objective of this article is to describe how to alter antihypertensive medications to allow accurate screening for primary aldosteronism. DISCUSSION: The ideal time to screen for primary aldosteronism is prior to initiating antihypertensive medications. If the patient is already undergoing treatment, replacing commonly used medications with sustained-release verapamil, prazosin, moxonidine and/or hydralazine results in fewer false positives and false negatives. Accuracy is also improved by ensuring normokalaemia. Screening should be performed six weeks after these conditions are met. A positive result should trigger a referral to an endocrine hypertension unit for further evaluation.
Asunto(s)
Antihipertensivos/efectos adversos , Hiperaldosteronismo/diagnóstico , Antihipertensivos/uso terapéutico , Humanos , Hiperaldosteronismo/fisiopatología , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Masculino , Tamizaje Masivo/métodos , Persona de Mediana EdadRESUMEN
Adrenal venous sampling (AVS) is a key part of the diagnostic workup of primary aldosteronism, distinguishing unilateral from bilateral disease and determining treatment options. Although AVS is a well-established procedure, many aspects remain controversial, including optimal patient selection for the procedure and exactly how AVS is performed and interpreted. Despite the controversies, a growing body of evidence supports the use of AVS in most patients with primary aldosteronism, though some specific patient groups may be able to forego AVS and proceed directly to treatment. Although AVS remains a difficult procedure, success rates may be improved with the use of advanced CT imaging techniques and/or rapid cortisol assays. New advances in nuclear imaging and steroid profiling may also offer alternatives or adjuncts to AVS in the future.
Asunto(s)
Glándulas Suprarrenales/irrigación sanguínea , Recolección de Muestras de Sangre/métodos , Técnicas de Diagnóstico Endocrino , Hiperaldosteronismo/diagnóstico , Glándulas Suprarrenales/patología , Aldosterona/análisis , Aldosterona/sangre , Técnicas de Diagnóstico Endocrino/normas , Técnicas de Diagnóstico Endocrino/tendencias , Humanos , Hidrocortisona/análisis , Hidrocortisona/sangre , Hiperaldosteronismo/sangre , VenasRESUMEN
Context: Current threshold values for primary aldosteronism (PA) diagnostic testing are based on measuring aldosterone (PAC) using immunoassays. Quantification of PAC by liquid chromatography-tandem mass spectrometry (LC-MS/MS) yields lower values. Objective: To compare aldosterone measurement by radioimmunoassay (RIA) with LC-MS/MS and evaluate performances of proposed LC-MS/MS-specific cutoffs for PA screening and confirmatory testing. Patients and Intervention: Forty-one patients underwent aldosterone/renin ratio (ARR) testing to screen for, and fludrocortisone suppression testing (FST) to confirm or exclude, PA. Renin (DRC) was measured by chemiluminescent immunoassay. Results: Median serum PACLC-MS/MS was 27.8% lower (P < 0.05) than plasma PACRIA in 164 pairs of FST samples. A positive correlation (Spearman coefficient, 0.894, P < 0.01; Pearson r coefficient, 0.861, P < 0.01) was observed between the two assays. Thirty-seven patients showed consistent FST diagnoses (29 positive, 8 negative), whereas four showed inconsistent FSTs by the two assays. Good agreement (κ coefficient, 0.736; P < 0.01) was observed between the current FST diagnostic PACRIA cutoff of 165 pmol/L and the proposed PACLC-MS/MS cutoff of 133 pmol/L. Among 37 patients with consistent FST results, no differences were observed in sensitivity (89.7% vs 93.1%) or specificity (87.5% vs 87.5%) for PA screening between the current ARR cutoff of 70 pmol/mU (PACRIA/DRC) and the proposed cutoff of 55 pmol/mU (PACLC-MS/MS/DRC). Conclusions: Adjustment of the current cutoffs for PA diagnostic testing is necessary if PAC is measured by LC-MS/MS. Our preliminary results suggest that the proposed LC-MS/MS cutoffs for ARR and FST perform as well as current RIA cutoffs.
Asunto(s)
Aldosterona/sangre , Hiperaldosteronismo/diagnóstico , Hipertensión/etiología , Tamizaje Masivo/normas , Espectrometría de Masas en Tándem/normas , Adulto , Anciano , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Líquida de Alta Presión/normas , Técnicas de Diagnóstico Endocrino/normas , Femenino , Fludrocortisona/administración & dosificación , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/complicaciones , Hipertensión/sangre , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Estudios Prospectivos , Radioinmunoensayo/métodos , Radioinmunoensayo/normas , Renina/sangre , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem/métodosRESUMEN
Primary aldosteronism is an important and common cause of hypertension that carries a high burden of morbidity. Outcomes, however, are excellent if diagnosed and treated appropriately. The diagnostic workup for primary aldosteronism is complex and comprises three steps: (1) screening, (2) confirmatory testing, and (3) subtype differentiation. In this review, we discuss recent advances in the diagnostic workup for primary aldosteronism. The development of accurate mass spectroscopy-based assays for measuring aldosterone will lead to improved confidence in all diagnostic aspects involving measurement of aldosterone, and accurate measurement of angiotensin II may soon advance us beyond the measurement of renin. We now have a greater understanding of hormonal influences on the aldosterone/renin ratio, which are particularly important when screening premenopausal women or those taking estrogen-containing preparations. Confirmatory testing is important, but there are limitations to the commonly used methods that have recently become more apparent, with new approaches offering a way forward. Adrenal venous sampling (AVS) is a challenging procedure but is important for deciding on treatment options. Success rates may be improved by the use of Synacthen stimulation and of rapid intraprocedural measurement of cortisol. Better understanding of AVS interpretation criteria allows improved prognostication and aids treatment decisions. The use of labeled metomidate positron emission tomography computed tomography scanning may also offer an alternative to AVS in some units. Although the diagnostic approach to patients with primary aldosteronism remains a complex multistep process in which attention to detail is important, recent advances will improve patient care and outcomes.
RESUMEN
Widespread application of the plasma aldosterone/renin ratio (ARR) as a screening test has led to the recognition that primary aldosteronism (PA) is the most common specifically treatable and potentially curable form of hypertension, accounting for 5-10% of patients. Maximal detection requires accurate diagnostic approaches and awareness and control of factors that confound results, including most antihypertensives, posture, time of day, dietary salt, and plasma potassium. Recent studies have revealed potential for false positives in patients on beta-adrenoceptor blockers, and, when direct renin concentration (but not plasma renin activity) is used to measure renin, in women during the luteal phase of the menstrual cycle or receiving estrogen-containing contraceptives or hormonal replacement therapy. In addition to verapamil slow release, hydralazine and prazosin, moxonidine has minimal effects on the ARR and can be used to control hypertension during work-up. Fludrocortisone suppression testing, while probably the most reliable means of definitively confirming or excluding PA, is time consuming and expensive, requiring a five day inpatient stay. A novel approach, upright (seated) saline infusion suppression testing (SST), has shown excellent reliability with much greater sensitivity than conventional recumbent SST in a recent pilot study, and requires only a day visit. Accurate measurement of aldosterone is essential for each step of PA workup: introduction of new, highly reliable high-throughput mass spectrometric methods into clinical practice has represented a major advance. In response to concerns raised about accuracy of renin assays, new mass spectrometric methods for measuring angiotensin II are currently being assessed in the clinical setting.
Asunto(s)
Técnicas de Diagnóstico Endocrino/normas , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Tamizaje Masivo/normas , Mejoramiento de la Calidad , Aldosterona/sangre , Humanos , Tamizaje Masivo/métodos , Pruebas de Función Adreno-Hipofisaria/normas , Renina/sangreRESUMEN
UNLABELLED: In patients with primary aldosteronism (PA) undergoing adrenal venous sampling (AVS), cortisol levels are measured to assess lateralization of aldosterone overproduction. Concomitant adrenal autonomous cortisol and aldosterone secretion therefore have the potential to confound AVS results. We describe a case where metanephrine was measured during AVS to successfully circumvent this problem. A 55-year-old hypertensive male had raised plasma aldosterone/renin ratios and PA confirmed by fludrocortisone suppression testing. Failure of plasma cortisol to suppress overnight following dexamethasone and persistently suppressed corticotrophin were consistent with adrenal hypercortisolism. On AVS, comparison of adrenal and peripheral A/F ratios (left 5.7 vs peripheral 1.0; right 1.7 vs peripheral 1.1) suggested bilateral aldosterone production, with the left gland dominant but without contralateral suppression. However, using aldosterone/metanephrine ratios (left 9.7 vs peripheral 2.4; right 1.3 vs peripheral 2.5), aldosterone production lateralized to the left with good contralateral suppression. The patient underwent left laparoscopic adrenalectomy with peri-operative glucocorticoid supplementation to prevent adrenal insufficiency. Pathological examination revealed adrenal cortical adenomas producing both cortisol and aldosterone within a background of aldosterone-producing cell clusters. Hypertension improved and cured of PA and hypercortisolism were confirmed by negative post-operative fludrocortisone suppression and overnight 1âmg dexamethasone suppression testing. Routine dexamethasone suppression testing in patients with PA permits detection of concurrent hypercortisolism which can confound AVS results and cause unilateral PA to be misdiagnosed as bilateral with patients thereby denied potentially curative surgical treatment. In such patients, measurement of plasma metanephrine during AVS may overcome this issue. LEARNING POINTS: Simultaneous autonomous overproduction of cortisol and aldosterone is increasingly recognised although still apparently uncommon.Because cortisol levels are used during AVS to correct for differences in dilution of adrenal with non-adrenal venous blood when assessing for lateralisation, unilateral cortisol overproduction with contralateral suppression could confound the interpretation of AVS resultsMeasuring plasma metanephrine during AVS to calculate lateralisation ratios may circumvent this problem.
RESUMEN
OBJECTIVE: Demonstration of unilateral aldosterone production by adrenal venous sampling (AVS) is required to select appropriate candidates for adrenalectomy in patients with primary aldosteronism (PA). During AVS, aldosterone and cortisol levels are measured to assess successful cannulation and lateralization. In patients with aldosterone-producing adenoma (APA), concurrent autonomous cortisol secretion might confound AVS results. DESIGN AND PATIENTS: We retrospectively examined results in eight patients with cortisol-producing adenoma (CPA), but without PA, who underwent AVS. RESULTS: In all eight, cortisol was higher on the CPA side than contralateral (CL) (median 6·7-fold [range 2·4-27·2]; P = 0·012]). By cortisol criteria, CL catheter placement would have been labelled inadequate in six despite adrenal venous aldosterone levels markedly higher than peripheral (41·6-fold [7·2-510·5]; P < 0·001), suggesting successful cannulation. In all eight, adrenal venous aldosterone/cortisol (A/C) ratios on the CL side were indicative of increased aldosterone production (≥2 times peripheral), but in only three patients on the CPA side (difference CL side 44·5-fold [6·0-109·0] vs CPA side 1·65-fold [1·0-23·0]; P = 0·017). A/C ratios were higher on the CL vs the CPA side in seven (20·0-fold [4·7-76·0]). CONCLUSION: These results in patients with CPA suggest that in patients with APA, concurrent autonomous unilateral cortisol hypersecretion could confound AVS accuracy by increasing cortisol levels (reducing A/C ratio) on the CPA side, while reducing levels (increasing A/C ratio and suggesting failed cannulation) on the CL side. Misclassification of PA subtype or repeat AVS could result, underscoring the importance of adequately assessing cortisol production prior to AVS and the need to consider alternatives.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/patología , Hidrocortisona/metabolismo , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/metabolismo , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
CONTEXT: In primary aldosteronism (PA), adrenal vein sampling (AVS) distinguishes unilateral and bilateral disease by comparison of aldosterone/cortisol (A/F) ratios. There is controversy about the criteria for interpretation, however, and in particular it is not clear whether contralateral suppression (CS) (defined as A/F(adrenal) ≤ A/F(peripheral) on the unaffected side) is important. We therefore performed a retrospective study to determine whether CS in surgically treated unilateral PA was associated with blood pressure (BP) and biochemical outcomes. SETTING AND DESIGN: Patients who underwent unilateral adrenalectomy for PA after successful AVS were included if the lateralization index (A/F(dominant):A/F(nondominant)) was ≥ 2. Cases were reviewed at 6 to 24 months follow-up for outcomes with respect to the presence and degree of CS. RESULTS: Sixty-six of 80 patients had CS. Baseline characteristics were similar. At postoperative follow-up, those with CS had lower systolic BP (SBP) (128 mm Hg vs 144 mm Hg, P = .001), a greater proportion with cure or improvement of hypertension (96% vs 64%, P = .0034), a greater proportion with biochemical cure of PA on fludrocortisone suppression testing (43 of 49 [88%] vs 4 of 9 [44%], P = .002) and were taking a lower median number of antihypertensive medications (0 vs 1.5, P = .0032). In a multivariate model, the degree of CS and preoperative SBP were both significantly correlated with postoperative SBP, but the lateralization index, sex, and age were not. CONCLUSION: In this study, the presence of CS correlated with good BP and biochemical outcomes from surgery. This finding suggests that CS should be a factor in deciding whether to offer surgery for treatment of PA.
Asunto(s)
Aldosterona/sangre , Hidrocortisona/sangre , Hiperaldosteronismo/sangre , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirugía , Adolescente , Glándulas Suprarrenales/irrigación sanguínea , Adrenalectomía , Adulto , Anciano , Recolección de Muestras de Sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: As renin and aldosterone levels vary during the menstrual cycle, and are critical criteria for interpretation of aldosterone suppression tests to confirm or exclude primary aldosteronism, outcome of testing may vary depending on the menstrual cycle phase. We assessed the effect of timing within the menstrual cycle on levels of renin, aldosterone and female sex steroids during fludrocortisone suppression testing (FST). METHODS: In 22 women undergoing FST who experienced regular menstrual cycles, renin (measured as both plasma renin activity and direct renin concentration), aldosterone (mass spectrometry) and cortisol, progesterone, oestradiol, LH and FSH (immunoassay) levels were compared, relative to phase of cycle. Aldosterone levels were compared to those in age-matched males undergoing FST. RESULTS: Progesterone (P < 0·0001) and aldosterone (P = 0·006) levels were higher in nine women (after one of 10 was excluded with anovulatory cycle) studied during the luteal phase than in the 12 studied during the follicular phase. All studied during the luteal phase had positive FST, and all three with negative FST were studied during the follicular phase. There were no significant differences in other parameters measured except FSH, which was higher (P = 0·02) during the follicular phase. Aldosterone was higher (P = 0·01) in women studied in the luteal (but not follicular) phase compared to men. CONCLUSION: The menstrual cycle may affect the outcome of FST and other suppression testing used to diagnose primary aldosteronism. Larger patient numbers and preferably restudy of the same patient in both phases should clarify this and determine the optimum time in the cycle for testing.
Asunto(s)
Aldosterona/sangre , Técnicas de Diagnóstico Endocrino , Ciclo Menstrual/sangre , Renina/sangre , Adulto , Cromatografía Líquida de Alta Presión , Estradiol/sangre , Femenino , Fludrocortisona/administración & dosificación , Hormona Folículo Estimulante/sangre , Fase Folicular/sangre , Humanos , Hidrocortisona/sangre , Hiperaldosteronismo/sangre , Hiperaldosteronismo/diagnóstico , Hipertensión/sangre , Inmunoensayo , Fase Luteínica/sangre , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Progesterona/sangre , Espectrometría de Masas en Tándem , Factores de TiempoRESUMEN
PURPOSE: A previous clinical trial showed that radiologic insertion of first peritoneal dialysis (PD) catheters by modified Seldinger technique is noninferior to laparoscopic surgery in patients at low risk in a clinical trial setting. The present cohort study was performed to confirm clinical effectiveness of radiologic insertion in everyday practice, including insertion in patients with expanded eligibility criteria and by fellows in training. MATERIALS AND METHODS: Between 2004 and 2009, 286 PD catheters were inserted in 249 patients, 133 with fluoroscopic guidance in the radiology department and 153 by laparoscopic surgery. Survival analyses were performed with the primary outcome of complication-free catheter survival and secondary outcomes of overall catheter survival and patient survival. Outcomes were assessed at last follow-up, as long as 365 days after PD catheter insertion. RESULTS: In the radiologic group, unadjusted 365-day complication-free catheter, overall catheter, and patient survival rates were 22.6%, 81.2%, and 82.7%, respectively, compared with 22.9% (P = .52), 76.5% (P = .4), and 92.8% (P = .01), respectively, in the laparoscopic group. Frequencies of individual complications were similar between groups. Adjusting for patient age, comorbidity, and previous PD catheter, the hazard ratio (HR) for catheter complications by radiologic versus laparoscopic insertion is 0.90 (95% confidence interval [CI], 0.62-1.31); the HR for overall catheter survival is 1.25 (95% CI, 0.59-2.65); and that for death is 2.47 (95% CI, 0.84-7.3). CONCLUSIONS: Radiologic PD catheter insertion is a clinically effective alternative to laparoscopic surgery, although there was poorer long-term survival with radiologic catheter placement, possibly because of preferential selection of radiologic insertion for more frail patients.
Asunto(s)
Cateterismo/métodos , Fallo Renal Crónico/terapia , Laparoscopía/métodos , Diálisis Peritoneal/métodos , Radiografía Intervencional/métodos , Anciano , Cateterismo/efectos adversos , Cateterismo/instrumentación , Cateterismo/mortalidad , Catéteres de Permanencia , Supervivencia sin Enfermedad , Femenino , Fluoroscopía , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Laparoscopía/efectos adversos , Laparoscopía/mortalidad , Masculino , Persona de Mediana Edad , Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/instrumentación , Diálisis Peritoneal/mortalidad , Radiografía Intervencional/efectos adversos , Radiografía Intervencional/mortalidad , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: Reninomas are rare juxtaglomerular tumours which can cause severe hypertension and hypokalaemia. Diagnosis can be problematic and these tumours can be difficult to locate on imaging. In this report we aim to demonstrate the value of carefully performed renal vein renin ratios (RVRRs) to assist in locating these tumours. METHOD/RESULTS: We report on 3 patients diagnosed with reninoma in our unit. The patients were all female, young (17, 16 and 30 years), severely hypertensive and hypokalaemic (2.5, 2.5 and 3.1 mmol/l). Plasma renin activity (PRA) was elevated (31.9, 274 and 175 ng/ml/h), and aldosterone was high-normal (19.9 ng/dl) or elevated (207 and 109.3 ng/dl). Renal artery stenosis was excluded by renal artery Doppler, DTPA scan and angiography. Renal CT detected the lesion in 2 patients, with one lesion visible on pre- and post-contrast CT and the other on post-contrast CT only. RVRRs were performed several weeks after withdrawing interfering medications, maintaining a <40 mmol/day low-sodium diet and maintaining recumbency overnight the night before and during the procedure. Ratios before and after captopril or enalaprilat administration were obtained and lateralised the tumours in all 3 cases (dominant/non-dominant ratios of 2.3, 4.3 and 3.8). All of the patients underwent nephrectomy yielding a typical juxtaglomerular tumour and resulting in cure of hypertension and hypokalaemia. CONCLUSIONS: Reninoma should be suspected in young hypertensives (especially females) with significant hypokalaemia and high PRA or direct renin concentration after renovascular hypertension has been excluded. CT imaging and carefully performed RVRRs provide the highest likelihood of locating these tumours.
Asunto(s)
Glomérulos Renales/patología , Neoplasias Renales/diagnóstico , Neoplasias/diagnóstico , Venas Renales/patología , Adolescente , Adulto , Aldosterona/sangre , Antihipertensivos/administración & dosificación , Captopril/administración & dosificación , Enalaprilato/administración & dosificación , Femenino , Humanos , Hipertensión/complicaciones , Hipopotasemia/complicaciones , Nefrectomía , Arteria Renal/patología , Renina/sangre , Tomografía Computarizada por Rayos X , Ultrasonografía DopplerRESUMEN
Primary aldosteronism (autonomous aldosterone production with suppressed renin) plays an important pathophysiological role in what has been previously labeled as essential hypertension. Besides the recently described germline mutations in the KCNJ5 potassium channel associated with familial primary aldosteronism, somatic mutations in the same channel have been identified within aldosterone-producing adenomas. In this study, we have resequenced the flanking and coding region of KCNJ5 in peripheral blood DNA from 251 white subjects with primary aldosteronism to look for rare variants that might be important for the pathophysiology of sporadic primary aldosteronism. We have identified 3 heterozygous missense mutations (R52H, E246K, and G247R) in the cohort and found that 12 (5% of the cohort) were carriers for the rare nonsynonymous single nucleotide polymorphism rs7102584 causing E282Q substitution of KCNJ5. By expressing the channels in Xenopus oocytes and human adrenal H295R cells, we have shown that the R52H, E246K, and E282Q substitutions are functional, but the G247R mutation is indistinguishable from wild type. Although the functional substitutions are remote from the selectivity filter, they affect the inward-rectification, the ability of the KCNJ5 channels to conduct Na(+) currents and ATII-induced aldosterone release from the H295R cell line. Together these data suggest that germline variation in the KCNJ5 gene has a role to play in the common sporadic form as well as the much rarer syndromic forms of primary aldosteronism.
Asunto(s)
Canales de Potasio Rectificados Internamente Asociados a la Proteína G/genética , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/fisiología , Mutación de Línea Germinal/genética , Hiperaldosteronismo/genética , Hiperaldosteronismo/fisiopatología , Polimorfismo de Nucleótido Simple/genética , Neoplasias de la Corteza Suprarrenal/metabolismo , Neoplasias de la Corteza Suprarrenal/patología , Carcinoma Corticosuprarrenal/metabolismo , Carcinoma Corticosuprarrenal/patología , Adulto , Aldosterona/metabolismo , Secuencia de Aminoácidos , Animales , Línea Celular Tumoral , Supervivencia Celular/genética , Supervivencia Celular/fisiología , Estudios de Cohortes , Femenino , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/análisis , Heterocigoto , Humanos , Hiperaldosteronismo/metabolismo , Masculino , Persona de Mediana Edad , Modelos Animales , Datos de Secuencia Molecular , Mutación Missense/genética , Oocitos/citología , Oocitos/metabolismo , Técnicas de Placa-Clamp , Xenopus laevisRESUMEN
OBJECTIVES: In primary aldosteronism, adrenal vein sampling (AVS) suggests unilateral aldosterone-producing adenoma (APA) when the aldosterone/cortisol (A/F) ratio is less than or equal to peripheral on one side and at least two times peripheral on the other. When A/F ratios are lower bilaterally than peripheral despite adequate samples (adrenal venous cortisol ≥3 times peripheral), we recommend repeat AVS. This study aimed to determine the frequency of this occurrence and outcomes in such cases. METHODS: We performed a retrospective observational study of all cases of primary aldosteronism undergoing initial AVS over a 34-year period. RESULTS: Initial AVS in 1397 patients returned satisfactory and discriminatory results in 1066 (76.3%) but 37 patients (2.6%) had adequate samples but bilateral A/F ratios no higher than peripheral. Of the 22 of these 37 who agreed to repeat AVS, 10 demonstrated unilateral aldosterone production, and eight of these had unilateral adrenalectomy disclosing APAs and resulting in cure (3) or improvement (5) in hypertension. Eight had bilateral aldosterone production. Four studies were inconclusive. Patients with initial unsatisfactory AVS because of bilaterally low A/F ratios had significantly (P=0.023) more unilateral disease [10 of 18 satisfactory repeat studies (55.6%) vs. 326 of 1066 satisfactory initial studies (30.6%)] and a significantly higher (67.6 vs. 49.9%, P=0.034) percentage of males. CONCLUSION: As the incidence of APAs was high in a subgroup with low A/F bilaterally on initial AVS, these patients should be offered repeat AVS. This might reflect both a greater dependence of aldosterone production on adrenocorticotrophic hormone (ACTH) in APAs and the pulsatile nature of ACTH secretion.
Asunto(s)
Adenoma/sangre , Adenoma/diagnóstico , Glándulas Suprarrenales/irrigación sanguínea , Aldosterona/sangre , Pruebas Hematológicas/métodos , Hidrocortisona/sangre , Hormona Adrenocorticotrópica/metabolismo , Adulto , Femenino , Humanos , Hiperaldosteronismo/diagnóstico , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Venas , Adulto JovenRESUMEN
Antimicrobial locks (AMLs) are effective in preventing catheter-associated bloodstream infections (CABSI) in hemodialysis (HD) patients, but may increase antibiotic resistance. In our center, gentamicin-heparin locks have been used for all HD central venous catheters since July 1, 2004. We previously reported a significant reduction in CABSI rates, but a short-term trend to increased gentamicin resistance among coagulase-negative staphylococci (CNS). We present a further 3-year follow-up study of bacterial resistance in our dialysis center. We examined the susceptibility of bacterial isolates from CABSI from July 1, 2006 to July 31, 2009, restricting analyses to CNS, gram-negative bacilli, and Staphylococcus aureus. We compared the frequency of gentamicin resistance in these isolates between four groups: CABSI in HD patients, non-CABSI in HD patients, peritonitis in peritoneal dialysis (PD) patients, and bloodstream infection in the non-end-stage kidney failure general population. For CNS isolates, the frequency of gentamicin resistance was similar between the CABSI and PD peritonitis groups, but higher in both groups than the general population. The pattern was similar for S. aureus although the differences were of borderline statistical significance. The frequency of gentamicin resistance among gram-negative bacilli isolates did not differ between groups. Gentamicin resistance was more common than expected in CNS and possibly S. aureus isolates from CABSI, although this resistance may be part of a generally higher frequency of antibiotic resistance in the dialysis population, rather than a direct result of AML use. AMLs remain a valuable clinical tool although surveillance is needed to ensure that benefits continue to outweigh risks.