ResearchPad - hypertension Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Dialysis timing may be deferred toward very late initiation: An observational study]]> The optimal timing to initiate dialysis among patients with an estimated glomerular filtration rate (eGFR) of <5 mL/min/1.73 m2 is unknown. We hypothesized that dialysis initiation time can be deferred in this population even with high uremic burden. A case-crossover study with case (0–30 days before dialysis initiation [DI]) and control (90–120 days before DI) periods was conducted in 1,079 hemodialysis patients aged 18–90 years at China Medical University Hospital between 2006 and 2015. The uremic burden was quantified based on 7 uremic indicators that reached the predefined threshold in case period, namely hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and bicarbonate. Dialysis timing was classified as standard (met 0–2 uremic indicators), late (3–5 indicators), and very late (6–7 indicators). Median eGFR-DI of the 1,079 patients was 3.4 mL/min/1.73 m2 and was 2.7 mL/min/1.73 m2 in patients with very late initiation. The median follow-up duration was 2.42 years. Antibiotics, diuretics, antihypertensive medications, and non-steroidal anti-inflammatory drugs (NSAIDs) were more prevalently used during the case period. The fully adjusted hazards ratios of all-cause mortality for the late and very late groups were 0.97 (95% confidence interval 0.76–1.24) and 0.83 (0.61–1.15) compared with the standard group. It is safe to defer dialysis initiation among patients with chronic kidney disease (CKD) having an eGFR of <5 mL/min/1.73 m2 even when patients having multiple biochemical uremic burdens. Coordinated efforts in acute infection prevention, optimal fluid management, and prevention of accidental exposure to NSAIDs are crucial to prolong the dialysis-free survival.

<![CDATA[Incidence and risk factors for hyperglycemia in pregnancy among nulliparous women: A Brazilian multicenter cohort study]]> To assess the incidence and risk factors for hyperglycemia in pregnancy in a cohort of Brazilian nulliparous pregnant women.Materials and methodsThis is a secondary analysis of a multicenter cohort study that enrolled 1,008 nulliparous pregnant women at 19–21 weeks. Exclusion criteria included chronic exposure to corticosteroids and previous diabetes. Bivariate and multivariate analyses by Poisson regression were used to identify associated factors.ResultsThe incidence of hyperglycemia in pregnancy was 14.9% (150/1,008), and 94.7% of these cases were gestational diabetes mellitus (142/150). Significant associated factors included a family history of diabetes mellitus, maternal overweight or obesity at enrollment, and previous maternal conditions (polycystic ovarian syndrome, thyroid dysfunctions and hypertensive disorders). A BMI ≥ 26.3Kg/m2 (RRadj 1.87 [1.66–2.10]) and a family history of diabetes mellitus (RRadj 1.71 [1.37–2.15]) at enrollment were independent risk factors for HIP.ConclusionsA family history of diabetes mellitus and overweight or obesity (until 19–21 weeks of gestation) may be used as selective markers for HIP in Brazilian nulliparous women. Given the scarcity of results in nulliparous women, our findings may contribute to determine the optimal diagnostic approach in populations of similar socioeconomic characteristics. ]]> <![CDATA[Health profile of adult special immigrant visa holders arriving from Iraq and Afghanistan to the United States, 2009–2017: A cross-sectional analysis]]> Between 2,000 and 19,000 Special Immigrant Visa holders (SIVH) from Iraq and Afghanistan have resettled in the United States annually since 2008.Per the Immigration and Nationality Act, SIVH, like other immigrants and refugees, must be examined by a physician before arriving in the US. Results of these overseas examinations are transmitted by the Centers for Disease Control and Prevention (CDC) to US state and local health departments via CDC’s Electronic Disease Notification system (EDN).Increasing provider knowledge about the health conditions most commonly encountered in SIVH as well as any differences in health conditions between SIVH from Iraq and Afghanistan may facilitate diagnostic screening, examination, and referrals to additional healthcare providers in the US.Information about the health of SIV populations is limited and would be beneficial for US clinicians who see SIVH in their clinics.What did the researchers do and find?In this cross-sectional analysis, we analyzed overseas medical exam data in CDC’s EDN for 19,167 SIV Iraqi and Afghan adults who resettled to the United States from April 2009 through December 2017.Among all SIVH, 56.5% were overweight or had obesity, 2.4% reported hypertension, 1.1% reported diabetes, and 19.4% reported current or previous tobacco use.In general, Iraqi SIVH were more likely to have obesity, diabetes, and be current or former smokers than Afghan SIVH.What do these findings mean?State public health agencies and clinicians screening SIVH should consider screening for diabetes among those with risk factors and prompt referral and management of obesity, hypertension, and smoking.Behavioral risk factor counseling and referral to culturally appropriate chronic disease prevention programs can be initiated at screening visits and subsequently reemphasized with primary care providers and other healthcare professionals.Limitations include the inability to obtain all SIVH records, self-reported medical history of NCDs, and underdiagnosis of NCDs such as hypertension and diabetes because formal laboratory testing for NCDs is not used during overseas medical exams. ]]> <![CDATA[SUN-LB96 Basal Contralateral Aldosterone Suppression Is Rare in Lateralized Primary Aldosteronism and Can Be Useful in Predicting Surgical Outcome]]> Background: Adrenal venous sampling (AVS) is performed to distinguish between unilateral or bilateral source of aldosterone in primary aldosteronism (PA). Unilateral aldosteronomas should lead to suppression of renin and contralateral (CL) aldosterone secretion, assessed by the CL suppression ratio. We recently found that CL aldosterone suppression was relatively rare using the ratio of basal aldosterone concentration of the opposite adrenal vein/periphery (AOPP/AP) in contrast to the traditional cortisol-corrected aldosterone ratio ((A/C)OPP(A/C)P). Pathology studies showed frequent zona glomerulosa (ZG) hyperplasia adjacent to a dominant aldosteronoma, which could also indicate probable ZG hyperplasia in the CL adrenal. The ratio of basal CL suppression could be a usefull parameter to predict cure following unilateral adrenalectomy (UA), but controversy remains in the literature.


1. To evaluate the prevalence of basal CL suppression using the AOPP/AP ratio as compared to the (A/C)OPP/(A/C)P ratio at previously established cut-offs.

2. To determine the best cut-off to predict clinical and biochemical surgical cure in two Canadian referral centers.

3. To compare the accuracy of the AOPP/AP ratio to the basal lateralization ratio (LR) and the post-ACTH LR in predicting the surgical outcome.

Methods: 330 patients with PA and successful bilateral simultaneous basal and post-ACTH stimulated AVS (selectivity index >2 basally and >5 post-ACTH) were included; 124 patients found to be lateralized underwent UA. The follow-up data were evaluated for clinical and biochemical cure at 3 and 12 months using the PASO criteria.

Results: Using AOPP/AP and (A/C)OPP/(A/C)P at the cut-off of 1, the prevalence of CL suppression is 6% and 45%, respectively. The median CL suppression ratio is 2.3 (1.3-5.1) in lateralized cases of PA using AOPP/AP. Using ROC curves, the AOPP/AP ratio is associated with clinical cure at 3 and 12 months and biochemical cure at 12 months. (A/C)OPP/(A/C)P is associated with biochemical cure only. The cut-offs for AOPP/AP offering the best sensitivity and specificity for clinical and biochemical cures at 12 months are 2.15 (Se 63% and Sp 71%) and 6.15 (Se 84% and Sp 77%), respectively. Basal LR and post-ACTH LR are associated with clinical cure but only the post-ACTH LR is associated with biochemical cure.

Conclusions: Basal CL suppression defined by the AOPP/AP ratio is rare and incomplete compared to the traditional (A/C)OPP/(A/C)P ratio in lateralized cases of PA. This may reflect the frequent micronodular hyperplasia adjacent to dominant aldosteronomas and possibly in the CL adrenal. Basal CL aldosterone suppression may predict clinical postoperative outcome, but with modest accuracy.

<![CDATA[SAT-553 Use of Optimal Cutting Temperature Compound (OCT)-Embedded Adrenal Tumor Tissue for Intratumoral Steroid Hormone Profiling]]> Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension, accounting for 5-8% of all hypertension. PA is most commonly attributed to an aldosterone-producing adenoma (APA) or to bilateral hyperaldosteronism (BHA). Mutations in the inward-rectifying K+ channel (mKCNJ5), which increase autonomous aldosterone production, are most frequently detected in APAs. APAs with mKCNJ5 display aberrant expression of aldosterone synthase (CYP11B2) and 17α-hydroxylase (CYP17A1), which are involved in aldosterone and cortisol synthesis, respectively. Co-expression of these enzymes results in the production of a set of “hybrid” steroids, which have been proposed as serum biomarkers. The relative production of hybrid steroids in adrenal tumors vs. adjacent normal adrenal (NA) tissue has not been investigated. Objectives: To determine the utility of OCT-embedded adrenal tumor tissue for steroid profiling. To use immunohistochemistry (IHC)-guided OCT tumor capture for intratumoral hybrid steroid profiling in mKCNJ5 APA and NA tissue. Methods: OCT-embedded adrenal tissue from 9 patients (8 women, Age 45.9 ± 3.3 years) with APAs harboring known KCNJ5 mutations were used for the study. Where available OCT-embedded normal adrenal (NA) tissue adjacent to APAs were used as controls (n=4). IHC was performed for CYP11B2 and CYP17A1 on OCT tissue allowing guided APA capture from serial sections. Steroids were extracted from APA and adjacent NA tissue, and quantified by liquid chromatography/tandem mass spectrometry. Steroids measured were normalized to the protein content of the extracted tissue. Results: Compared to NA, APA tissue demonstrated 23-, 5.6- and 6.4-fold higher levels of aldosterone, 11-deoxycorticosterone, and 18-hydroxycorticosterone, respectively (P<0.05). In addition, the “hybrid” steroid products, 18-oxocortisol and 18-hydroxycortisol, were significantly elevated in APA vs. NA (P<0.01). Conversely, the adrenal androgens dehydroepiandrosterone and 11-hydroxyandrostenedione were lower in APA as compared with NA (P<0.05). All mKCNJ5 APAs were also found to co-express CYP11B2 and CYP17A1. Conclusion: IHC-guided mKCNJ5 APA capture and steroid extraction identified a distinct intratumoral hybrid steroid signature that associated with co-expression of CYP11B2 and CYP17A1.These findings also demonstrate that OCT-embedded tissue can be used to accurately define intra-tissue steroid profiles, which will have application for steroid-producing and steroid-responsive tumors.

<![CDATA[MON-208 Age-Dependent Progression of Renal Dysfunction After Adrenalectomy for Aldosterone-Producing Adenomas in Japan]]> Context: In patients with aldosterone-producing adenomas (APAs), adrenalectomy causes a rapid decrease in blood pressure and increase in blood potassium levels; however, the effects of these intensive metabolic changes on kidney function with age have not yet been examined in Japan.

Objective: To investigate factors related to the progression of kidney dysfunction after adrenalectomy in different age groups.

Participants: Fifty Japanese patients with APAs with 27,572 health check-up subjects as controls were examined.

Main Outcome Measures: We investigated changes in eGFR after adrenalectomy and characterized patients who progressed to chronic kidney disease (CKD).Results: Receiver Operating Characteristic and multivariate analyses revealed the postoperative cut-off age of CKD to be 50 years (sensitivity, 57%; specificity; 82%; AUC, 0.69) and identified age as a unique factor for the progression of CKD after adrenalectomy. Among preoperative patients with APAs, CKD was 6% for those younger than 50 years (<50) and 40% for those 50 years and older (≥50). As a control, in 27,572 health check-up subjects, the prevalence of CKD was 4.2% in men and 2.5% in women aged 41-50 years and 18.9% in men and 13.3% in women older than 61 years, clearly demonstrating the higher prevalence of CKD in patients with APAs than in healthy subjects, particularly those with APAs ≥50 years. In patients with APAs <50 years, median eGFR before and after adrenalectomy were 95 mL/min/1.73m2 and 88 mL/min/1.73m2, respectively, indicating that the percentage of the decrease in eGFR was -7%, which was not significant (paired t-test, p=0.13). In contrast, in patients with APAs ≥50 years, median eGFR after adrenalectomy decreased to 42 mL/min/1.73m2 from 67 mL/min/1.73m2 (adjusted by age, paired t-test, p=0.01) (percent decrease in eGFR, -24%) Patients with APAs ≥50 years who progressed to CKD showed higher preoperative aldosterone/renin ratios, lower potassium and chloride levels, lower BMI, and a higher incidence of a history of cardiovascular events and KCNJ5 mutation rates.Conclusion: Age is the most important predictor of the progression of kidney dysfunction after adrenalectomy in Japanese patients with APAs, particularly those with a history of cardiovascular events and positivity for KCNJ5 mutations.

<![CDATA[SAT-559 Patients with Hyperaldosteronism Have Higher Prevalence of Obstructive Sleep Apnea. From the National Inpatient Sample]]> Introduction: Previous studies suggested that aldosterone excess may worsen obstructive sleep apnea (OSA) through causing peri-pharyngeal edema. Objective: In this study we sought to examine if hyperaldosteronism is associated with OSA. Methods: The National Inpatient Sample (NIS) data was queried for adults with diagnosis of primary and secondary hyperaldosteronism during the years 2012 - 2015. Patients with hyperaldosteronism were identified using the international classification of disease (ICD-9). Each patient who was diagnosed with hyperaldosteronism was matched to randomly selected controls at a 1:4 ratio by age, gender and year of hospitalization. A multivariable logistic regression model was used to estimate the adjusted odds ratio (aOR) of OSA among patients with hyperaldosternoism. We adjusted for patient demographics, socioeconomic factors, hospital factors and clinical comorbidities. Subgroup analysis was performed based on gender, race and age groups; young adults (aged 18–35 years), middle aged (> 35-<55 years) and older adults (aged > 55 years). Results: There were 23,465 patients diagnosed with hyperaldosteronism identified. The mean age was 59 (standard error of the mean (SEM): 0.1. Females represented 48.5%. Compared to control, patients with hyperaldosteronism had higher prevalence of hypertension, CHF, stroke, obesity, diabetes, renal failure and lower prevalence of tobacco use and COPD. The proportions of African Americans were higher among patients with hyperaldosteronism compared to the control 30.1 vs 15.5, p<0.001. Patients with hyperaldosteronism had higher prevalence of OSA 16.4 vs 8.3, p<0.001. On multivariate analysis, hyperaldosteronism was independently associated with higher odds for OSA with aOR 2.01 (95%CI: 1.81–2.23) p<0.001. On subgroup analysis, similar findings were observed irrespective of gender, age group or race. Conclusion: Prevalence of OSA is higher among patients with hyperaldosteronism. Physicians may need to consider a case detection of hyperaldosteronism in patients with OSA and hypertension. Similarly we suggest to evaluate patients with hyperaldosteronism for OSA.

<![CDATA[MON-213 Cardiac Damage and Related Risk Factors in Patients with Primary Aldosteronism]]> Primary aldosteronism (PA) is the most common cause of secondary hypertension. Overseas flow surveys show that compared with essential hypertension (EH), the risk of cardiovascular and cerebrovascular diseases and kidney damages in PA patients is increased, and the mortality rate of cardiovascular events is higher than that in EH patients, in addition,this effect is independent of elevated blood pressure. The difference of cardiac damage between PA and EH patients was analyzed by echocardiography. Methods From April 28, 2017 to April 28, 2019, patients with primary aldosteronism diagnosed by ICD in Department of Endocrinology and Metabolism, Department of Cardiology and Urology were extracted from the adrenal group database of the Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, and ICD diagnosis in Department of Endocrinology and Metabolism during the same period was also extracted. In patients with essential hypertension, the differences of clinical indicators and echocardiography between the two groups were compared, and the differences of cardiac damage and related risk factors between the two groups were explored. Results 295 patients were included in this study, including 148 patients in PA group (50.17%) and 147 patients in EH group (49.83%). There was no significant difference in gender, age, BMI, course of disease and average blood pressure between the two groups (P > 0.05). The levels of serum aldosterone and BNP in PA group were significantly higher than those in EH group, and the levels of serum renin and minimum blood potassium were significantly lower than those in EH group (P < 0.05). Left ventricular diameter (LV), left atrial diameter (LA), interventricular septal thickness (IVS), left ventricular posterior wall thickness (LVPW), ascending aorta diameter (AAO), end-diastolic diameter (EDD), end-diastolic volume (EDV) and stroke volume (SV) in PA group were significantly higher than those in EH group (P < 0.05). It was significantly higher than that in EH group (P < 0.05). The correlation analysis of variables with statistical significance between the two groups showed that serum renin activity level was negatively correlated with LV, AAO, EDD and SV, and the lowest serum potassium level was negatively correlated with LVPW and AAO. CONCLUSION Compared with EH of the same age, course of disease and blood pressure level, PA patients are more likely to suffer from cardiac damage, which is manifested by heart growth, ventricular septal thickening and cardiac function decline, and is closely related to the inhibition of serum renin activity and serum potassium level. Clinical attention should be paid to early screening and treatment of PA and its complications in order to reduce the risk of cardiac death.Key words: primary aldosteronism; echocardiography; cardiovascular risk factors

<![CDATA[Right ventricular pressure overload directly affects left ventricular torsion mechanics in patients with precapillary pulmonary hypertension]]> This study examined the impact of septal flattening on left ventricular (LV) torsion in patients with precapillary pulmonary hypertension (PH). Fifty-two patients with proven precapillary PH and 13 healthy controls were included. Ventricular function was assessed including 4D-measurements, tissue velocity imaging, and speckle tracking analysis. Increased eccentricity index (1.39 vs. 1.08, p<0.001), systolic pulmonary artery pressure (64 vs. 29mmHg, p<0.001) and right ventricular Tei index (0.55 vs. 0.28, p = 0.007), and reduced tricuspid annular plane systolic excursion (19.0 vs. 26.5mm, p<0.001) were detected in PH patients as compared to controls. With increasing eccentricity of left ventricle, LV torsion was both decreased and delayed. Torsion rate paralleled this pattern of change during systole, but not during diastole. In conclusion, right ventricular pressure overload directly affects LV torsion mechanics. The echocardiographic methodology applied provides novel insights in the interrelation of right- and left ventricular function.

<![CDATA[30-year trends in major cardiovascular risk factors in the Czech population, Czech MONICA and Czech post-MONICA, 1985 – 2016/17]]> Compared with Western Europe, the decline in cardiovascular (CV) mortality has been delayed in former communist countries in Europe, including the Czech Republic. We have assessed longitudinal trends in major CV risk factors in the Czech Republic from 1985 to 2016/17, covering the transition from the totalitarian regime to democracy.MethodsThere were 7 independent cross-sectional surveys for major CV risk factors conducted in the Czech Republic in the same 6 country districts within the WHO MONICA Project (1985, 1988, 1992) and the Czech post-MONICA study (1997/98, 2000/01, 2007/08 and 2016/2017), including a total of 7,606 males and 8,050 females. The population samples were randomly selected (1%, aged 25–64 years).ResultsOver the period of 31/32 years, there was a significant decrease in the prevalence of smoking in males (from 45.0% to 23.9%; p < 0.001) and no change in females. BMI increased only in males. Systolic and diastolic blood pressure decreased significantly in both genders, while the prevalence of hypertension declined only in females. Awareness of hypertension, the proportion of individuals treated by antihypertensive drugs and consequently hypertension control improved in both genders. A substantial decrease in total cholesterol was seen in both sexes (males: from 6.21 ± 1.29 to 5.30 ± 1.05 mmol/L; p < 0.001; females: from 6.18 ± 1.26 to 5.31 ± 1.00 mmol/L; p < 0.001).ConclusionsThe significant improvement in most CV risk factors between 1985 and 2016/17 substantially contributed to the remarkable decrease in CV mortality in the Czech Republic. ]]> <![CDATA[MON-219 Prevalence and Incidence of Fractures in Patients with Adrenal Adenomas: A Population-Based Study of 1003 Patients]]> Background: Adrenal adenoma is reported in around 5% of adults undergoing cross-sectional imaging. Although most adenomas are considered non-functioning (NFAT), up to 48% present with mild autonomous cortisol secretion (MACS). Several studies reported increased prevalence and incidence of vertebral fractures in MACS; however conclusions are limited by small sample size, selection bias, inadequate reference population and length of follow up.

Objective: To determine the prevalence and incidence of site-specific fragility fractures in a population-based cohort of patients with adrenal adenomas.

Methods: Residents of local community with a radiographic diagnosis of adrenal adenoma between 1995 and 2017 were identified using a centralized epidemiologic database and matched with reference subjects for sex and age. All subjects were followed through 2017, until death or migration from the community. MACS was diagnosed based on cortisol level ≥1.8 mcg/dl after overnight 1mg dexamethasone suppression, NFAT based on cortisol level <1.8 mcg/dl, and patients not tested with dexamethasone were considered as adenoma with unknown cortisol secretion (AUCS).

Results: Of 1003 patients with adrenal adenomas (581 women (58%), median age of diagnosis 63 years (20–96)), 136 (14%) were diagnosed with NFAT, 86 (9%) with MACS, and 781(78%) with AUCS. At the time of diagnosis, patients had higher BMI (median 30 vs 28 kg/m2, p<0.001), and higher prevalence of tobacco use (70% vs 54%, p<0.001) than reference subjects. Of 154 patients and 113 reference subjects with BMD available at baseline, patients had a higher median BMD at the total hips (0.93 vs 0.89, p=0.02) but similar median BMD at lumbar spine (1.05 vs 1.03, p=0.49) when compared to reference subjects. However, patients had a higher prevalence of fractures than reference subjects (any fracture: 50% vs 42%, p<0.001, vertebral fracture: 6.5% vs 3.7%, P=0.004). When adjusted for age, sex, and prior history of fracture, patients with adenoma had HR of 1.24 (CI 95% 1.04–1.48) for developing a new fracture and HR of 1.18 (CI 95% 0.97–1.44) when also adjusted for BMI and smoking. Subgroup analysis demonstrated that the prevalence of fractures at the time of diagnosis was higher in all 3 subgroups at any fragility fracture site when compared to reference subjects (NFAT: 44% vs 37%, MACS: 48% vs 43%, AUCS: 51% vs 43%); patients with MACS had the highest incidence of new fracture after 5 years of follow up when compared to AUCS and NFAT (cumulative incidence: MACS 25% vs NFAT 19% vs AUCS 16%), though the differences were not significant.

Conclusions: Patients with adrenal adenomas have higher prevalence of fractures at the time of diagnosis. During follow up, patients with adenoma have a higher incidence of fractures even when adjusted for sex, age, and prior history of fracture, possibly due to underlying undiagnosed abnormal cortisol secretion.

<![CDATA[MON-202 Germline SDHB Exon 1 Deletion Is Associated with Absence of <sup>131</sup>I-metaiodobenzylguanidine (MIBG) Uptake in Malignant Paragangliomas]]> Introduction: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells. More than 30% of patients with PPGLs have a hereditary predisposition. Malignancy in PPGLs is defined by the presence of local invasion or metastasis in nonchromaffin tissues. Germline SDHB mutations are found in approximately 40% of malignant PPGLs, mainly paragangliomas (PGLs). However, SDHB mutations are not a prognostic factor in malignant PPGLs. To date, no genotype-phenotype correlation has been reported in malignant PPGLs associated with SDHB mutations. Aim: To investigate clinical and imaging features of patients with malignant PGLs harboring germline SDHB exon 1 deletion or splicing site mutation. Methods: We retrospectively evaluated 22 unrelated individuals with malignant PPGLs. Six out of 22 (27%) malignant PPGLs harbored germline SDHB mutations. Three patients had SDHB exon 1 deletion and 3 splicing site mutation (2 with c.201-2A>G and one with c.423 + 1G>A). All SDHB defects were classified as likely pathogenic. Results: In the exon 1 deletion group, 2 patients had abdominal PGLs (one also had a neck PGL) and one had only head and neck PGLs. In the splicing site mutation group, all 3 patients had abdominal PGLs (one also had a neck PGL). Median age at diagnosis was 26 yrs (16 to 45) and 33 yrs (26 to 53) in the exon 1 deletion and splicing mutation groups, respectively. Two patients (one in each group) had metastasis at diagnosis. All 6 patients had bone metastasis, but liver and/or lung metastasis were more frequent in patients with SDHB exon 1 deletion (66 vs. 33%). Interestingly, metastasis from malignant PGLs harboring SDHB splicing site mutations were 131I-metaiodobenzylguanidine (MIBG) avid in all cases, whereas metastatic lesions from malignant PGLs harboring SDHB exon 1 deletion did not present any MIBG uptake on diagnostic imaging studies. Therefore, all 3 patients with SDHB exon 1 deletion were treated with chemotherapy (cyclophosphamide, vincristine and dacarbazine). In contrast, all 3 patients with splicing site mutations have been treated with MIBG therapy. Median follow-up was 87 months (8 to 360 months). Only one patient (exon 1deletion group) died because of disease progression. Conclusion: We first demonstrated here that germline SDHB exon 1 deletion is associated with absence of MIBG uptake in malignant PGLs. This finding needs to be confirmed in an expanded cohort of malignant PPGLs.

<![CDATA[SAT-551 Sparing Confirmatory Tests in Primary Aldosteronism]]> Context: The current clinical guidelines suggest that confirmatory tests for primary aldosteronism (PA) may be excluded in some of patients who have elevated plasma aldosterone concentration (PAC) under plasma renin suppression. However, this has low priority evidence and is under debate in use of serum potassium. Objective: This study aimed to investigate an appropriate setting for sparing confirmatory tests in PA. Design and Setting: A retrospective cross-sectional study in a single referral center. Participants: This study included 327 patients who had hypertension under plasma renin suppression and underwent captopril challenge test (CCT) between January 2007 and April 2019. CCT results were used to diagnose PA. Main outcome measure: Diagnostic value of PAC and serum potassium in confirmation of PA. Results: Of the studied patients, 252 of 327 (77%) were diagnosed with PA. All 61 patients with PAC >30 ng/dl were diagnosed with PA. In patients with PAC between 20 and 30 ng/dl, 44 of 55 (80%) were diagnosed with PA, while all 26 with PAC between 20 to 30 ng/dl who had spontaneous hypokalemia were diagnosed with PA. Areceiver operator curve analysis showed that the sensitivity of diagnosis of PA is 100% in our patients, when PAC set at > 28.8 ng/dl and showed that the sensitivity of diagnosis of PA is 100% in our patients with spontaneous hypokalemia, who had PAC < 30 ng/dl, when PAC was set at > 19.2 ng/dl. While, the prevalence of PA was higher in patients with hypokalemia, who had PAC between 10 and 20 ng/dl than in those with PAC < 10 ng/dl. Collectively, 100 out of 102 (98%) with hypokalemia, who had PAC > 10 ng/dl were diagnosed as PA. The proportion of unilateral PA determined by adrenal vein sampling (AVS) was higher in patients who had PAC >30 ng/dl or those with spontaneous hypokalemia who had PAC between 20 and 30 ng/dl than those who did not meet the criteria (76% vs. 17%, P<0.001). Conclusion: Confirmatory tests in PA could be spared in patients who have typical features of PA and these patients had a high probability of unilateral PA on AVS.

<![CDATA[MON-209 Identification of a New Heterozygous Germline ARMC5 Deletion in a Familial Case of Primary Bilateral Macronodular Adrenal Hyperplasia Co-Secreting Cortisol and Aldosterone]]> Context. Approximately 50% of familial cases of primary bilateral macronodular adrenal hyperplasia (PBMAH) are caused by mutations in the ARMC5 gene.

Case report. We report the case of a 37 year-old patient of Haitian origin, who presented with resistant hypertension. His workup showed high aldosterone (410 pmol/L) with suppressed renin levels (0.2 ng/mL/h) with an aldosterone to renin ratio (ARR) of 2050. Patient also had suppressed ACTH levels (<0.5 pmol/L (N: 2-12)) and high UFC (1103 nmol/d (N: <330)). He had an aberrant cortisol and aldosterone response to catecholamines and vasopressin (V1R). An abdominal CT scan showed bilateral enlargement of adrenal glands and a 3.3cm dominant nodule on the right gland. Moreover, a 2.8cm mass on the pancreatic tail was present. Patient underwent left laparoscopic adrenalectomy and distal pancreatectomy; the pathology confirmed PBMAH and a pancreatic neuroendocrine tumor (NET). Following surgery, ARR and UFC remained high and patient was treated successfully with B-blockers and MR antagonists. A head MRI showed no sign of intracranial meningiomas.

Genetic analyses. Following genetic counselling, MEN1 gene analysis was performed using sequencing/MLPA techniques but did not reveal a mutation. Initial genetic testing included ARMC5 gene analysis using direct Sanger sequencing which was negative. However, using Next-Generation Sequencing (NGS) and MLPA analysis, a heterozygous germline ARMC5 deletion of exons 5-8 was identified. The deletion is predicted to prematurely truncate the protein product and cause loss of function. The ARMC5 deletion segregated with the disease in his 24 yo son who had bilateral adrenal adenomas that appeared to be non-functional. The patient’s father was also known for having bilateral adrenal masses and hypertension.

To our knowledge we report the second case of ARMC5 deletion in familial PBMAH. Suzuki et al. reported two patients, a mother and her son, carrying ARMC5 deletion of exons1-5 and interestingly they were also affected by PBMAH co-secreting cortisol and aldosterone (1). As in this case report, the ARMC5 deletion was missed using Sanger sequencing initially.

Conclusion. These cases demonstrate that large deletions may be missed by Sanger sequencing and that the real prevalence of ARMC5 mutations may have been underestimated. The link between deletion of ARMC5 and correlation with PBMAH co-secreting aldosterone and cortisol remains to be determined but may be a step forward for genotype-phenotype correlation.

1.Suzuki S, et al. Endocrine practice: official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2015;21 (10):1152-60.

<![CDATA[SAT-563 The Unsuppressed Plasma Renin Activity May Not Enough for Management of Non-Surgically Treated Primary Aldosteronism]]> It is well known the primary aldosteronism (PA) is most common endocrinological hypertension and accounted for 10% among all hypertension population, and it develops cardiovascular disease more frequently than blood pressure matched essential hypertension. Those patients with bilateral hyperaldosteronism, called idiopathic hyperaldosteronism (IHA), or unwilling for surgical treatment are treated by mineralcorticoid receptor antagonists (MRAs). Although it had been unclear how titrate MRAs to prevent atherosclerotic cardiovascular events, a managemental target for those patients was recently reported as plasma renin activity (PRA) ≥ 1.0 ng/ml/hr to prevent cardiovascular events (Hundemer GL, et. al. Lancet Diabetes Endocrinol. 2018 Jan;6(1):51-59).

Thus, we investigated 77 cases of adrenal venous sampling performed patients with PA and followed up for 3 years in our hospital since 2007, including 24 males and 53 females, and their mean age was 56.3 ± 12.5 years old. All patients underwent AVS and showed bilateral hyperaldosteronism and treated with MRAs and followed up more than 3 years. We collected blood pressure, serum sodium and potassium concentration, estimated glomerular filtration ratio (eGFR), PRA, plasma aldosterone concentration (PAC), atherosclerotic parameter, such as mean intima media thickness (IMT), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). We evaluated the relationship of those patients’ PRA and aldosterone to renin ratio (ARR) with eGFR, IMT, baPWV, and ABI. The change of mean IMT after 3 year-follow up were 0.03 ± 0.11 mm vs. 0.06 ± 0.09 mm for well controlled (PRA ≥ 1.0 ng/ml/hr) and poorly controlled (PRA < 1.0 ng/ml/hr), respectively, and no significant difference between them. In the other hand, the change of mean IMT after 3 year-follow up showed 0.03 ± 0.10 mm vs. 0.08 ± 0.10 mm for well controlled (PRA ≥ 1.0 ng/ml/hr and ARR <20) and poorly controlled (PRA < 1.0 ng/ml/hr or ARR ≥ 20), respectively, and the mean IMT increase was significantly lower in this group.

The mean IMT increase showed significantly lower only with PRA ≥ 1.0 ng/ml/hr and ARR <20 rather than PRA ≥ 1.0 ng/ml/hr alone.

In our results, both PRA ≥ 1.0 ng/ml/hr and ARR<20 are important to prevent or improve atherosclerosis, rather than only PRA ≥ 1.0 ng/ml/hr and should be titrated MRAs to achieve this target.

In conclusion, our result revealed the titration of MRAs is important to prevent atherosclerotic cardiovascular event and not only PRA ≥ 1.0 ng/ml/hr, but both PRA and ARR <20 should be achieved.

<![CDATA[MON-206 Diagnosis of Non-Functional Masses in Adrenal Gland Topography - Experience of a Tertiary Health Center]]> Introduction: Masses in adrenal topography are diagnosed frequently due to the increase in radiological imaging in clinical practice. Adrenal incidentalomas occur between 4% and 10% of the patients above 50 years undergoing abdominal imaging, and the majority are benign pathologies. Objective: To analyze the characteristics of the masses located in adrenal gland topography not originating from the adrenal gland. Methods: We retrospectively assessed patients from our tertiary hospital who underwent surgical treatment for masses in adrenal gland topography between 2006 and 2018. All patients had hormonal evaluations, according to the European and American Societies of Endocrinology guidelines. Two expert radiologists reviewed all images. Forty-six patients were included in the study, and the surgical specimens were analyzed by the same experienced pathologist. Patients with confirmed adrenocortical carcinoma (ACC) were excluded from this cohort. Results: Thirty-two (69.6%) patients were female. The median age was 49.5 years old (range 18-82yo). Abdominal or lumbar pain was the most frequent reason for medical investigation (43.5%). Adrenal incidentalomas represented 38.4% of the cohort. None of these patients had any clinical signs of adrenal hyperfunction, nor hormonal alteration. Twenty-four patients (52.17%) presented a mass on the left side, and only two cases presented bilateral adrenal masses. The median size was 8.6cm (1.3-18cm). The mean of Hounsfield Units (HU) on a non-contrasted CT was 25HU (0-50HU). Several etiologies were found: 8 cases (18%) of ganglioneuroma; 6 cases (13,5%) of adrenal cysts; 4 cases (9%) of leiomyosarcoma and adrenal hemorrhage; 3 cases (6.5%) of infectious disease; 2 cases (4.5%) of lymphangioma, schwannoma, and sarcoma. We also found single cases of renal cell carcinoma, poorly differentiated small cell neuroendocrine carcinoma, hepatocellular carcinoma, high grade dedifferentiated liposarcoma, epithelioid neoplasia, epithelial neoplasia with neuroendocrine differentiation, malignant peripheral nerve sheath tumor of the adrenal gland, poorly differentiated neuroblastoma, high grade lymphoma, myelolipoma, acute splenitis, arteriovenous malformation, and prostate cancer metastasis. Discussion and Conclusion: Ganglioneuroma was the most frequent diagnosis in adrenal incidentalomas in our cohort. In general, these conventional radiological exams could not differentiate lesions originated in the adrenal glands from lesions of other origins. In this large cohort, we could identify non-adrenal origin in approximately 45% of the patients with masses in the adrenal topography.

<![CDATA[SAT-550 Changes in Albuminuria Precede Dietary Sodium-Dependent Changes in BP During Aging - a Longitudinal Study]]> Background: Hypertension (HT) is a well-established independent risk factor for adverse cardiovascular and renal (CVR) outcomes and a high salt (HS) diet is the main cause for high blood pressure (BP). Despite extensive research focusing on HT, surprisingly there are no longitudinal studies assessing the long-term effects of HS. Aims: This study aimed (1) to evaluate the timing of onset for changes in CVR health during long-term sodium loading and (2) to assess whether salt restriction can prevent these effects.

Methods: C57BL/6 mice were randomized to HS, moderate (NS) or low (LS) salt diet and followed longitudinally for 50 weeks (wks). BP, urinary albumin/creatinine ratio (AC), plasma aldosterone (PA) and renin activity (PRA) were assessed monthly. At the end of the study, renal artery resistance and left ventricular (LV) parameters were measured by ultrasound and echocardiogram. Renal AT1 expression (Western Blot) and activity (IHQ) were quantified.

Results: At the beginning of the study, there were no differences in BP and AC between the three dietary groups. Relative to wk 1, BP (mmHg) in the HS group was higher in wk 21 (131±1.7 vs. 115±3.0, p= 0.05). Sodium restriction delayed this increase: SBP was higher in wk 41 in the NS group compared to the wk 1 (128±3.4 vs. 115±6.4, p= 0.05) but did not reach significance in the LS group until the end of the study. Similarly, relative to wk 1, AC (µg/mg) only in the HS group reached significantly higher levels in wk 17 (44±4.2, p<0.05). Again, sodium restriction delayed the occurrence of renal damage. AC reached significance in wks 25 and 41 for NS and LS (35±1.1 and 42±2.6 respectively, p<0.05 vs. baseline). Interestingly, the changes in AC always preceded the changes in BP, irrespective of diet. PA and PRA were appropriately activated by dietary salt restriction and suppressed by aging. The aging-induced suppression appeared stronger for PA than for PRA in the HS group only. Long-term sodium loading (HS) induced increased renal resistance, which was prevented in the LS but not in the NS group. Relative to HS, the LV mass index and cardiac output were lower in the NS and LS groups (p<0.05). LV volume indices and ejection fraction did not differ between groups. Renal AT1 protein expression and activation status (IHQ) were decreased in the sodium restricted group. Conclusions: Our study showed that long-term exposure to HS induced a progressive increase in BP and AC in mice. Importantly, these changes were delayed by long-term reduction in sodium intake. Interestingly, changes in AC preceded those in BP, irrespective of diet. Cardiac parameters suggest a sodium-induced eccentric cardiac hypertrophy in the older age, which was prevented by sodium restriction. One possible mechanism behind these effects is the overactivation of the AT1 receptor pathway.

<![CDATA[MON-221 Seated Saline Suppression Testing Is Comparable to Captopril Challenge Test for the Diagnosis of Primary Aldosteronism: A Prospective Study]]> Abstract:

Objective: Saline suppression testing (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) is reported to be superior to recumbent SST (RSST). Whether SSST is better than CCT remains unclear. Therefore we conducted a prospective study to compare the diagnostic accuracy of SSST and CCT.

Methods: Hypertensive patients with high risk of PA were consecutively included. Patients with aldosterone-renin ratio≥1.0 ng•dl-1/μIU•ml-1 were asked to complete SSST, CCT and fludrocortisone suppression test (FST). Using FST as the reference standard (plasma aldosterone concentration [PAC] post-FST ≥6.0 ng•dl-1), area under the receiver-operator characteristic curves (AUC), sensitivity and specificity of SSST and CCT were calculated, and multiple regression analyses were conducted to identify potential factors for false diagnosis.

Results: A total of 183 patients diagnosed as PA and 48 as essential hypertension completed the study. Using PAC post-SSST and PAC post-CCT to confirm PA, SSST and CCT had comparable AUCs (AUCSSST 0.83 [0.78,0.88] vs. AUCCCT 0.86 [0.81,0.90], P=0.308). Setting PAC post-SSST and post-CCT at 8.5 ng•dl-1 and 11 ng•dl-1, respectively, the sensitivity and specificity of SSST [0.71 (95%CI 0.64 to 0.77) and 0.82(0.68,0.90)] and CCT [0.73(0.66,0.79) and 0.80(0.66,0.89)] were not significantly different. In the multiple regression analyses, 1SD increment of sodium intake resulted in 40% lower risk of false diagnosis in SSST.

Conclusions: SSST and CCT have comparable diagnostic accuracy. Insufficient sodium intake decreases the diagnostic efficiency of SSST but not CCT. Since the CCT is simpler and cheaper, it is preferable to the SSST.

<![CDATA[SAT-549 Identification of Somatic Mutations in CLCN2 as a Cause of Aldosterone-Producing Adenomas]]> Background: Primary aldosteronism (PA) results from both unilateral and bilateral adrenal disease. Unilateral disease is most often caused by aldosterone-producing adenomas (APAs). We recently identified aldosterone-driver somatic mutations in approximately 90% of APAs using an aldosterone synthase (CYP11B2) immunohistochemistry (IHC)-guided DNA sequencing approach. In the present study, we analyzed DNA from APA samples found to be mutation negative. Methods: Formalin-fixed paraffin-embedded tissue samples from PA patients who underwent adrenalectomy were studied. Genomic DNA was isolated from 118 APAs (identified by CYP11B2 IHC). Next generation sequencing (NGS) was performed to identify known aldosterone-driver mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D. APA DNA that was mutation negative and the adjacent normal adrenal tissue DNA were subjected to Whole Exome Sequencing (WES). Results: Targeted NGS and WES detected two variants in the voltage-gated chloride channel ClC-2 (encoded by CLCN2), which were confirmed by Sanger sequencing. One of the CLCN2 mutations (p.Gly24Asp) was identical to that previously found to cause germline early-onset PA. The second CLCN2 mutation, which would affect the same region of the protein, was an unreported PA mutation (p.Met22fs). The presence of these variants in two tumors suggests that CLCN2 mutations as a cause of APAs are rare with an approximate prevalence of 1.7% (2/118 APAs). Conclusion: In this study, we identified somatic mutations in CLCN2, in two of 118 APAs. Germline variants in this gene have previously been shown to cause of familial hyperaldosteronism type II and the current findings indicate that similar mutations cause a small proportion of APAs. These findings also indicate that WES of CYP11B2-guided mutation negative APAs can help determine rarer genetic causes of sporadic PA.

<![CDATA[MON-205 Effectiveness of Pre-Op α-Blockade on Intra-Op Blood Pressure Control in Patients with Pheochromocytoma]]> Pheochromocytoma are rare tumors arising from catecholamine producing chromaffin tissue. Surgical manipulation of pheochromocytoma inevitably leads to supraphysiologic levels of circulating catecholamines. Such manipulation has the potential to lead to an intra-operative hypertensive crisis, cardiac arrhythmia, myocardial infarction, or pulmonary edema. When inadequately primed pre-operatively, a patient exposed to such surges may experience life-threatening consequences.

Phenoxybenzamine is a non-competitive, non-selective α 1 and α 2 receptor antagonist that prevents blood pressure liability during surgical resection of pheochromocytoma. Previous literature has suggested that phenoxybenzamine affords more pronounced peri-operative systolic blood pressure control as compared to selective alpha-blockers. This superior control potentially is at the cost of postoperative hypotension owing to the irreversible nature of phenoxybenzamine.1

Our study compares the effects of pre-operative phenoxybenzamine on perioperative outcomes at a single tertiary medical center from 2004 to 2019. The cumulative pre-operative phenoxybenzamine dose was compared to the maximum intra-operative blood pressure, need for IV blood pressure lowering medications, duration of vasopressor need, volume replacement need, duration of time in the OR, duration of hospital stay, and pre-operative catecholamine levels. We speculate that increased phenoxybenzamine exposure will result in reduced peak intra-operative blood pressure and need for IV blood pressure lowering medications but may increase the need for post-resection intra-operative vasopressors and post-resection volume replacement.

After IRB approval, (ID #00031606), we performed a data warehouse query for the ICD 9 and 10 codes of “pheochromocytoma” and “paraganglioma”. Patients who did not have confirmed pheochromocytoma on pathology were excluded. Data was collected retrospectively on 30 patients who underwent adrenalectomy for pheochromocytoma. 14 charts were excluded due to incomplete intra-operative anesthetic documentation.

Our results suggest that there is no significant correlation between peak intra-operative MAP and cumulative phenoxybenzamine exposure. The cumulative dose of pre-operative phenoxybenzamine did not correlate with the number of anti-hypertensive medications used intra-operatively. An increased cumulative dose of pre-operative phenoxybenzamine was not associated with an increased duration of intra-operative vasopressor medications. Intra-operative volume replacement needs were surprisingly reduced with increased cumulative pre-operative phenoxybenzamine exposure.

1 P.A. van der Zee, A. de Boer. Pheochromocytoma: A review on preoperative treatment with phenoxybenzamine or doxazosin. The Netherlands Journal of Medicine. May 2014; Vol. 72 No 4, 190-201.