Contralateral suppression in adrenal venous sampling predicts clinical and biochemical outcome in primary aldosteronism.

CONTEXT: The role for hormone parameters at adrenal venous sampling (AVS) in predicting clinical and biochemical outcome remains controversial. OBJECTIVE: To investigate the impact of hormone parameters at AVS under cosyntropin stimulation on lateralization and on complete biochemical and clinical outcome. METHODS: We retrospectively evaluated 150 sequential AVS under cosyntropin infusion. Bilateral successful cannulation rate was 83.3% (n = 140), 47.9% bilateral and 52.1% unilateral. The lateralization index (LI), aldosterone/cortisol ratio (A/C) in the dominant adrenal vein (AV), relative aldosterone secretion index (RASI = A/C in AV divided by A/C in inferior vena cava) were assessed. The contralateral suppression (CS) percentage was defined by (1 - nondominant RASI) *100. RESULTS: A nondominant RASI <0.5 (CS >50%) had 86.84% sensitivity and 92.96% specificity to predict contralateral lateralization. An A/C ratio in dominant AV >5.9 (74.67% sensitivity and 80% specificity) and dominant RASI >4.7 (35.21% sensitivity and 88.06% specificity) had a worst performance to predict ipsilateral lateralization. Complete biochemical and clinical cure were significantly more frequent in the patients with CS >50% [98.41% vs. 42.86% (p < 0.001) and 41.94% vs. 0% (p < 0.001)]. CS correlated with high aldosterone at diagnosis (p < 0.001) and low postoperative aldosterone levels at 1 month (p = 0.019). Postoperative biochemical hypoaldosteronism was more frequent in patients with CS >50% (70% vs. 16.67%, p = 0.014). In multivariable analysis, a CS >50% was associated with complete biochemical cure (OR 125, 95%CI 11.904-5,000; p = 0.001) and hypertension remission (OR 12.19, 95%CI 2.074-250; p = 0.023). CONCLUSION: A CS >50% was an independent predictor of complete clinical and biochemical cure. Moreover, it can predict unilateral PA and postoperative biochemical hypoaldosteronism. Our findings underscore the usefulness of CS for clinical decision-making.

Prostatic Artery Embolization Using Polyethylene Glycol Microspheres: A 1-Year Follow-up Prospective Study Including 30 Patients.

PURPOSE: To evaluate safety and effectiveness of prostatic artery embolization (PAE) using polyethylene glycol (PEG) microspheres in patients with moderate-to-severe benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A single-center, prospective study of 30 patients who underwent PAE from August 2020 to December 2021 using PEG 400-µm microspheres was conducted. Patient evaluation data using International Prostate Symptom Score (IPSS), quality of life (QoL) score, prostate-specific antigen (PSA), peak urinary flow rate (Qmax), postvoid residual volume (PVR), and prostate volume (PV) at baseline and 3 and 12 months after PAE were obtained. RESULTS: Bilateral PAE was performed in all patients. One patient had early clinical failure (3.3%) and another presented with lower urinary tract symptoms (LUTSs) recurrence (3.3%) at the 12-month follow-up. Twenty-eight patients (93.3%) experienced significant and durable LUTS improvement. Mean absolute (and relative) improvement at 3 and 12 months were: IPSS, 14.6 points (-69%) for both; QoL, 3.3 points (-70%) and 3.5 points (-74%); Qmax, 6.3 mL/s (+78%) and 8.6 mL/s (+100%); PSA reduction, 1.2 ng/mL (-22%) and 1.0 ng/mL (-15%); PVR reduction, 48 mL (-56%) and 58.2 mL (-49%); PV reduction, 23.4 cm3 (-29%) and 19.6cm3 (-25%); (P < .05 for all). No major adverse events were observed. Minor adverse events included urinary tract infection (4/30, 13.3%), prostatic tissue elimination (3/30, 10%), penile punctiform ulcer (1/30, 3.3%), and urinary retention (1/30, 3.3%). CONCLUSIONS: PAE using PEG microspheres was observed to be effective with sustained LUTS improvement at the 12-month follow-up. The incidence of urinary infection and prostatic tissue elimination was higher than previously reported for other embolics.

Intra-individual Variability of Serum Aldosterone and Implications for Primary Aldosteronism Screening.

CONTEXT: Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. OBJECTIVE: To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. METHODS: A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. RESULTS: The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level <15 ng/dL, 19.9% had at least 2 aldosterone levels <15 ng/dL, and 16.2% had mean aldosterone levels <15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC >2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. CONCLUSION: Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.

Protection of nontarget structures in prostatic artery embolization.

OBJECTIVE: To describe the efficacy and safety of protective embolization during prostatic artery embolization, as well as to discuss its clinical relevance. MATERIALS AND METHODS: This was a retrospective, observational, single-center study including 39 patients who underwent prostatic artery embolization to treat lower urinary tract symptoms related to benign prostatic hyperplasia between June 2008 and March 2018. Follow-up evaluations, performed at 3 and 12 months after the procedure, included determination of the International Prostate Symptom Score, a quality of life score, and prostate-specific antigen levels, as well as ultrasound, magnetic resonance imaging, and uroflowmetry. RESULTS: Protective embolization was performed in 45 arteries: in the middle rectal artery in 19 (42.2%); in the accessory internal pudendal artery in 11 (24.4%); in an internal pudendal artery anastomosis in 10 (22.2%); in the superior vesical artery in four (8.9%); and in the obturator artery in one (2.2%). There was one case of nontarget embolization leading to a penile ulcer, which was attributed to reflux of microspheres to an unprotected artery. There were no complications related to the protected branches. All of the patients showed significant improvement in all of the outcomes studied (p < 0.05), and none reported worsening of sexual function during follow-up. CONCLUSION: Protective embolization can reduce nontarget embolization during prostatic artery embolization without affecting the results of the procedure. In addition, no adverse events other than those expected or previously reported were observed. Therefore, protective embolization of pudendal region is safe.

OBJETIVO: Descrever a eficácia e a segurança da embolização de proteção na embolização de artérias prostáticas e discutir sua relevância clínica. MATERIAIS E MÉTODOS: Estudo retrospectivo, observacional, de um único centro, que inclui 39 pacientes submetidos a embolização de artérias prostáticas para tratamento de sintomas do trato urinário inferior relacionados a hiperplasia benigna da próstata, de junho de 2008 a março de 2018. O acompanhamento foi realizado em 3 meses e 12 meses, incluindo International Prostate Symptom Score, escore de qualidade de vida, antígeno prostático específico, ultrassom, ressonância magnética e urofluxometria. RESULTADOS: Embolização de proteção foi realizada em 45 artérias: artérias retais médias em 19 (42,2%); artérias pudendas internas acessórias em 11 (24,4%); anastomoses com ramos da artéria pudenda interna em 10 (22,2%); artérias vesicais superiores em quatro (8,9%); e artéria obturatória em uma (2,2%). Houve um caso de embolização não alvo que provocou uma úlcera peniana, atribuída a refluxo de partículas para uma artéria não protegida. Não houve complicações relacionadas com os ramos protegidos. Os pacientes apresentaram melhora significativa em todos os resultados estudados (p < 0,05) e não relataram piora da função sexual durante o acompanhamento. CONCLUSÃO: Embolização de proteção pode ser realizada para diminuir embolização não alvo sem interferir nos resultados da embolização de artérias prostáticas. Além disso, não foi observado nenhum evento adverso diferente dos já esperados ou previamente publicados. A embolização de proteção na região pudenda é segura.

Protection of nontarget structures in prostatic artery embolization / Proteção de estruturas não alvo na embolização de artérias prostáticas

Abstract Objective: To describe the efficacy and safety of protective embolization during prostatic artery embolization, as well as to discuss its clinical relevance. Materials and Methods: This was a retrospective, observational, single-center study including 39 patients who underwent prostatic artery embolization to treat lower urinary tract symptoms related to benign prostatic hyperplasia between June 2008 and March 2018. Follow-up evaluations, performed at 3 and 12 months after the procedure, included determination of the International Prostate Symptom Score, a quality of life score, and prostate-specific antigen levels, as well as ultrasound, magnetic resonance imaging, and uroflowmetry. Results: Protective embolization was performed in 45 arteries: in the middle rectal artery in 19 (42.2%); in the accessory internal pudendal artery in 11 (24.4%); in an internal pudendal artery anastomosis in 10 (22.2%); in the superior vesical artery in four (8.9%); and in the obturator artery in one (2.2%). There was one case of nontarget embolization leading to a penile ulcer, which was attributed to reflux of microspheres to an unprotected artery. There were no complications related to the protected branches. All of the patients showed significant improvement in all of the outcomes studied (p < 0.05), and none reported worsening of sexual function during follow-up. Conclusion: Protective embolization can reduce nontarget embolization during prostatic artery embolization without affecting the results of the procedure. In addition, no adverse events other than those expected or previously reported were observed. Therefore, protective embolization of pudendal region is safe.

RESUMO Objetivo: Descrever a eficácia e a segurança da embolização de proteção na embolização de artérias prostáticas e discutir sua relevância clínica. Materiais e Métodos: Estudo retrospectivo, observacional, de um único centro, que inclui 39 pacientes submetidos a embolização de artérias prostáticas para tratamento de sintomas do trato urinário inferior relacionados a hiperplasia benigna da próstata, de junho de 2008 a março de 2018. O acompanhamento foi realizado em 3 meses e 12 meses, incluindo International Prostate Symptom Score, escore de qualidade de vida, antígeno prostático específico, ultrassom, ressonância magnética e urofluxometria. Resultados: Embolização de proteção foi realizada em 45 artérias: artérias retais médias em 19 (42,2%); artérias pudendas internas acessórias em 11 (24,4%); anastomoses com ramos da artéria pudenda interna em 10 (22,2%); artérias vesicais superiores em quatro (8,9%); e artéria obturatória em uma (2,2%). Houve um caso de embolização não alvo que provocou uma úlcera peniana, atribuída a refluxo de partículas para uma artéria não protegida. Não houve complicações relacionadas com os ramos protegidos. Os pacientes apresentaram melhora significativa em todos os resultados estudados (p < 0,05) e não relataram piora da função sexual durante o acompanhamento. Conclusão: Embolização de proteção pode ser realizada para diminuir embolização não alvo sem interferir nos resultados da embolização de artérias prostáticas. Além disso, não foi observado nenhum evento adverso diferente dos já esperados ou previamente publicados. A embolização de proteção na região pudenda é segura.

Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism.

Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, 'sporadic' bilateral adrenal hyperplasia (BAH) is the most frequent cause of PA and remains without genetic etiology in most cases. Our aim was to investigate new genetic defects associated with BAH and PA. We performed whole-exome sequencing (paired blood and adrenal tissue) in six patients with PA caused by BAH that underwent unilateral adrenalectomy. Additionally, we conducted functional studies in adrenal hyperplastic tissue and transfected cells to confirm the pathogenicity of the identified genetic variants. Rare germline variants in phosphodiesterase 2A (PDE2A) and 3B (PDE3B) genes were identified in three patients. The PDE2A heterozygous variant (p.Ile629Val) was identified in a patient with BAH and early-onset HT at 13 years of age. Two PDE3B heterozygous variants (p.Arg217Gln and p.Gly392Val) were identified in patients with BAH and HT diagnosed at 18 and 33 years of age, respectively. A strong PDE2A staining was found in all cases of BAH in zona glomerulosa and/or micronodules (that were also positive for CYP11B2). PKA activity in frozen tissue was significantly higher in BAH from patients harboring PDE2A and PDE3B variants. PDE2A and PDE3B variants significantly reduced protein expression in mutant transfected cells compared to WT. Interestingly, PDE2A and PDE3B variants increased SGK1 and SCNN1G/ENaCg at mRNA or protein levels. In conclusion, PDE2A and PDE3B variants were associated with PA caused by BAH. These novel genetic findings expand the spectrum of genetic etiologies of PA.

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.

Treatment of acquired arteriovenous fistula with severe hemodynamic effects: therapeutic challenge / Tratamento de fístula arteriovenosa adquirida com repercussões hemodinâmicas graves: desafio terapêutico

A 34-year-old female patient with severe heart failure and pulmonary hypertension was diagnosed late with a high-output acquired arteriovenous fistula between the right common iliac vein and artery. The most probable cause was an iatrogenic vascular injury inflicted during a prior laparoscopic cholecystectomy. Treatment was conducted by placement of an endoprosthesis in the common iliac artery, achieving total exclusion of the fistula and complete remission of symptoms. Considering the options available for treating this type of lesion, endovascular techniques are becoming ever more effective and are now the option of first-choice for management of this pathology.

Paciente de 34 anos com quadro de insuficiência cardíaca e hipertensão pulmonar severas, com diagnóstico tardio de fístula arteriovenosa adquirida de alto débito entre a veia e a artéria ilíaca comum direita. A provável causa foi relacionada à lesão vascular iatrogênica em colecistectomia laparoscópica realizada previamente. O tratamento foi realizado com endoprótese em artéria ilíaca comum, resultando em exclusão total da fístula e remissão completa dos sintomas. Considerando-se as opções de tratamento para esse tipo de lesão, a técnica endovascular tem se mostrado cada vez mais eficaz e tem se tornado a primeira opção no manejo dessa patologia.