ResearchPad - adrenal---hypertension https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[MON-208 Age-Dependent Progression of Renal Dysfunction After Adrenalectomy for Aldosterone-Producing Adenomas in Japan]]> https://www.researchpad.co/article/elastic_article_8761 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.

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<![CDATA[MON-213 Cardiac Damage and Related Risk Factors in Patients with Primary Aldosteronism]]> https://www.researchpad.co/article/elastic_article_8730 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

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<![CDATA[MON-219 Prevalence and Incidence of Fractures in Patients with Adrenal Adenomas: A Population-Based Study of 1003 Patients]]> https://www.researchpad.co/article/elastic_article_7072 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.

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<![CDATA[MON-202 Germline SDHB Exon 1 Deletion Is Associated with Absence of <sup>131</sup>I-metaiodobenzylguanidine (MIBG) Uptake in Malignant Paragangliomas]]> https://www.researchpad.co/article/elastic_article_6999 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.

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<![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]]> https://www.researchpad.co/article/elastic_article_6748 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.

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<![CDATA[MON-206 Diagnosis of Non-Functional Masses in Adrenal Gland Topography - Experience of a Tertiary Health Center]]> https://www.researchpad.co/article/elastic_article_6579 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.

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<![CDATA[MON-221 Seated Saline Suppression Testing Is Comparable to Captopril Challenge Test for the Diagnosis of Primary Aldosteronism: A Prospective Study]]> https://www.researchpad.co/article/elastic_article_6539 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.

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<![CDATA[MON-205 Effectiveness of Pre-Op α-Blockade on Intra-Op Blood Pressure Control in Patients with Pheochromocytoma]]> https://www.researchpad.co/article/elastic_article_6472 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.

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<![CDATA[MON-198 Cosyntropin Stimulation on Adrenal Venous Sampling Obscure Surgically Curable Primary Aldosteronism]]> https://www.researchpad.co/article/elastic_article_6261 Context: While it has been shown that ACTH stimulation during adrenal venous sampling (AVS) for primary aldosteronism (PA) leads to correct lateralization, others showed opposite results. Whether to use ACTH stimulation during AVS for the subtype diagnosis of PA remains unsolved. Objectives: Our purpose of this study is to evaluate the clinical implications of ACTH stimulation during AVS in terms of surgical outcomes. Design and settings: Among JRAS cohort, we allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to 3 groups: basal lateralization index (LI)≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n=245); basal LI <2 with ACTH-stimulated LI ≥4 (n=15); basal LI≥2 with ACTH-stimulated LI <4 (U to Bilateral (B) group, n=54). We compared surgical outcomes among the groups. Results: Compared with the U to U group, the U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as a pathological finding. All patients in the U to Bgroup with clinical and biochemical benefits however had adrenal adenoma as a pathological finding and could be well differentiated from those with poor surgical outcome via basal LI, but not ACTH-stimulated LI. A receiver operating characteristic curve analysis demonstrated that the cut-off value of 8.3 showed the specificity of 84% for the prediction of good surgical outcome in U to B group.These results were similar even when we defined each group based on a cut-off value of 4 for basal LI. Although, the basal plasma aldosterone concentration (PAC) in the adrenal veins on both dominant and non-dominant sides among patients with better surgical outcome in the U to B group were not significantly different from those in the U to U group, there was a significant difference in the ACTH-stimulated PAC on the dominant side. Conclusions: We demonstrated novel findings showing that patients in the U to B group were shown to be comprised of 2 groups with good and poor surgical outcomes, and basal LI was useful in identifying PA patients with good surgical outcome in U to B group. The low expression level of MC2R receptor on aldosterone-producing adenoma (APA) might be the explanation of the weak response in aldosterone level in a proportion of surgically curable APA cases. These findings point to the important fact that ACTH stimulation on AVS obscure surgically curable cases of PA.

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<![CDATA[MON-220 Real World Performance of Urinary and Plasma Metanephrine Assays in Diagnosing Phaeochromocytoma/Paraganglioma]]> https://www.researchpad.co/article/elastic_article_6205 Introduction:

Diagnosis of pheochromocytoma/paraganglioma (PPGL) can be challenging. Plasma metanephrines have highest sensitivity (96-99%) yet lowest specificity (85%)1 whereas 24-hour urinary metanephrines have 87.5% sensitivity and 99.7% specificity. Diagnostic accuracy depends on factors such as patient positioning and medications, questioning its potential value in a hospital setting.

Methods:

The audit was performed in a hospital which caters to a population of 400,000. Data was collected retrospectively on patients who had a request for plasma or urine metanephrines from March 2018 – September 2018.

Results:

A total of 85 patient order requests (58% male, 42% female) were reviewed; only 2 patients were ultimately diagnosed with a pheochromocytoma.

The mean age of patients was 48 years. The most common indication for requests was hypertension (64 patients).

Locations of order requests included 42% from outpatient clinics, 32% inpatient requests, 18% from Ambulatory Care, 6% by A&E and 2% by GP. Of the 27 (32%) inpatient requests, 10 had positive results: 1 diagnosed with primary aldosteronism, 1 with hypercortisolism and the others had no definite diagnosis. 8/10 patients with positive results did not have a repeat test.

Focusing on plasma metanephrines, 52% plasma metanephrines samples were negative, 22% were positive and 26% were not processed due to laboratory error. From the 19 positive plasma metanephrines, adrenal adenoma was present in 7 patients (from this group, 1 was referred for surgery with confirmed diagnosis of pheochromocytoma), 1 patient’s MIBG scan was negative and 1 diagnosis of stress-related raised metanephrines was made. The remaining 10 patients did not undergo an adrenal scan.

9 out of 18 cases with positive urine metanephrines had an adrenal adenoma. In 7/9, plasma metanephrines were positive, the remaining 2 had negative plasma metanephrines.

34 cases with initial negative test still had another urine/plasma metanephrines performed with similar negative result. Furthermore <50% of the positive urine or plasma metanephrines were referred to and reviewed by the Endocrine team.

Discussion:

This audit highlights the potential pitfalls of investigating PPGL with plasma and urinary metanephrines, and in fact raises the question of its accuracy as an inpatient diagnostic tool as none of the positive inpatient tests resulted in a diagnosis of PPGL. Inappropriate urine and plasma metanephrines requests cause financial burden and patient anxiety. Even with outpatient requests, few positive results led to a PPGL diagnosis. Patient selection and conditions of testing must be more rigorously scrutinised and threshold for positive result must be raised for specificity of the test to be improved in ‘real world’ conditions.

References:

1. Lenders JW al. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002.

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<![CDATA[MON-199 Targeting Pheochromocytoma/Paraganglioma with Polyamine Inhibitors]]> https://www.researchpad.co/article/elastic_article_6081 Background: Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors that are mostly benign. Metastatic disease occurs in about 10% of cases, and for these patients no effective therapies are available. Patients with mutations in the succinate dehydrogenase subunit B (SDHB) gene tend to have metastatic disease with very little treatment options. To find a new treatment strategy, we utilized a metabolomics approach to identify unique metabolic pathways. A metabolomic analysis was performed on human hPheo1 cells and shRNA SDHB knockdown hPheo1 (hPheo1 SDHB KD) cells. Additional analysis of 50 human fresh frozen PCC/PGL samples was conducted. Since the polyamine pathway surfaced in the metabolomics analysis, we hypothesized that treatment with polyamine inhibitors would be an effective option for aggressive PCC/PGL tumors. In vitro studies using N1,N11-diethylnorspermine (DENSPM) and N1,N12- diethylspermine (DESPM) treatments were carried out. DENSPM efficacy was assessed in xenograft models. Results: Components of the polyamine pathway were elevated in hPheo1 SDHB KD cells compared to wild-type cells. A similar observation was noted in SDHx PCC/PGLs tumor tissues compared to their SDHB wild-type counterparts. Specifically, spermidine, and spermine were significantly elevated in SDHx-mutated PCC/PGLs, with a similar trend in hPheo1 SDHB KD cells. Polyamine pathway inhibitors DENSPM and DESPM effectively inhibited growth of hPheo1 cells in vitro as well in mouse xenografts. Conclusions: This study demonstrates overactive polyamine pathway in PCC/PGL with SDHB mutations. Treatment with polyamine inhibitors significantly inhibited hPheo1 cell growth and led to growth inhibition in xenograft mouse models treated with DENSPM. These studies strongly implicate the polyamine pathway in PCC/PGL pathophysiology and provide new foundation for exploring the role for polyamine analogue inhibitors in treating metastatic PCC/PGL.

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<![CDATA[MON-211 Prevalence, Characteristics and Outcomes of Primary Aldosteronism in Newly Diagnosed Hypertensives in China (Pa China)]]> https://www.researchpad.co/article/elastic_article_6078 Abstract

Background 44.7% adults in China have hypertension but the prevalence of primary aldosteronism (PA) in Chinese hypertensives is unknown. Objective We prospectively investigated the prevalence of PA in newly diagnosed hypertensives and tested the hypothesis that these PA patients have less severe cardiovascular complications and better outcomes when compared to those diagnosed after established (or prolonged) hypertension. Method In a community health center, consecutive hypertensive patients with an aldosterone-renin ratio≥2 (ng∙dL−1/mIU∙L−1) and plasma aldosterone concentration >10ng/dL underwent captopril challenge test and/or saline infusion test for confirmation. Adrenal CT scan and adrenal vein sampling were used for subtyping. PA patients were followed up for one year and clinical outcomes were compared with PA patients from an established hypertensive cohort. Results 1020 newly diagnosed hypertensive patients were screened over 16 months. Forty were diagnosed with PA, 948 with non-PA, resulting in a prevalence of 4.0%. Thirty-two patients were diagnosed as “possible PA” due to positive screening but failure to complete the confirmatory test. Compared to non-PA, PA patients more frequently displayed microalbuminuria (P=0.031), but the incidence of cardiovascular events was not different (P=0.927). For patients treated with surgery, complete clinical success rate was 85.7%, 28% higher than that of PA patients diagnosed after prolonged hypertension. For patients treated with medication, blood pressure control rate was 79.3%, 30% higher than that of PA patients diagnosed after prolonged hypertension. Conclusions The prevalence of PA in patients with newly diagnosed hypertension in China was at least 4.0%. PA screening in newly diagnosed hypertensive patients can lead to better clinical outcomes.

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<![CDATA[MON-207 Validating and Optimizing the Guideline Criterion for Skipping Confirmatory Tests of Primary Aldosteronism]]> https://www.researchpad.co/article/Nd2e780fe-dac2-4814-8fec-3dc3ddc7908f Abstract

Background: Confirmatory tests of primary aldosteronism (PA), including saline infusion test (SIT), captopril challenge test (CCT) and fludrocortisone suppression test (FST), are recommended by the Endocrine Society Clinical Practice Guideline. In order to simplifying diagnostic process, a criterion for skipping confirmatory tests was established by the guideline, while the evidence is lacking.

Objective: To validate and optimize the guideline criterion for skipping confirmatory tests.

Design: Prospective diagnostic study.

Setting: Chongqing, China.

Measurements: A total of 501 patients with high risk of PA were retrospectively enrolled. All of them completed at least two confirmatory tests (CCT, SIT, and FST). The guideline criterion is: history of spontaneous hypokalemia, plasma renin concentration (PRC) below detection levels and plasma aldosterone (PAC)>20ng/dl (550pmol/L). An optimized criterion (history of spontaneous hypokalemia, PRC <2.5 uIU/ml and PAC>20 ng/dl) was established based on the guideline criterion. Parameters such as sensitivity, specificity and area under the receiver-operator characteristic curves (AUC) were calculated to compare the diagnostic value of these two criteria.

Results: Using SIT, CCT and FST (cutoffs: PAC post-SIT 10 ng·dl-1; PAC post-CCT 11 ng·dl-1; PAC post-FST 6 ng·dl-1) for PA diagnosis, the specificity of the guideline criterion was 1.00 (0.98–1.00), 1.00(0.98–1.00) and 1.00(0.97–1.00) respectively, while the sensitivity was 0.12 (0.09–0.17), 0.12(0.08–0.16) and 0.09(0.06–0.12) respectively. Compared to the guideline criterion, the sensitivity of the optimized criterion was significantly improved [SIT: 0.42 (0.36–0.49); CCT: 0.41 (0.35–0.48); FST: 0.30 (0.25–0.34), all the P values < 0.001 when compared to the guideline criterion]. However, the specificity of the optimized criterion was similar to the guideline criterion (all the P values>0.05).

Limitation: This study was carried out in a single center.

Conclusions: The guideline criterion shows high specificity but low sensitivity for direct diagnosis of PA. The optimized criterion has greatly improved the sensitivity and may be more suitable for skipping confirmatory tests of PA.

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<![CDATA[MON-210 Role of Female Gender and Subcutaneous Fat in the Positive Association of Obesity with Idiopathic Hyperaldosteronism]]> https://www.researchpad.co/article/N007b2492-01e2-463a-a288-c81ddf44295d <![CDATA[MON-214 Biochemical Abnormalities in Endocrine Function Associated with Lutetium 177-DOTATATE Therapy in Metastatic Pheochromocytoma and Paraganglioma]]> https://www.researchpad.co/article/Ne3a3c30c-985c-40c7-8335-881c5725683b <![CDATA[MON-200 Clinical Characterizations of Aldosterone- and Cortisol-Producing Adrenal Tumors in Primary Aldosteronism]]> https://www.researchpad.co/article/Na4e013ec-db86-47fa-aa46-2032d4227342 <![CDATA[MON-204 Pheochromocytoma and Paraganglioma: An Emerging Cause of Secondary Osteoporosis]]> https://www.researchpad.co/article/N9bbf880b-8c47-45f6-83cf-45698fd1a0b6 <![CDATA[MON-196 A Single-Center Experience of Patients with Metastatic Pheochromocytoma/Paraganglioma Treated with 177Lu-DOTATATE]]> https://www.researchpad.co/article/N6664e8c5-66c2-432f-bdc4-5ecb6083559f 50% decrease) of chromogranin A was found in 1/6 patients and of catecholamines in 2/6 patients. No hematological or kidney toxicity grade 3–4 was registered.Median overall survival and median progression-free survival rate will be reported after the end of the study.To date, about 250 PPGL patients have been treated with PRRT. PRRT using 177Lu-DOTA-SSAs has shown promise for treatment of PPGLs with improvement of clinical symptoms and/or disease control in the setting of retrospective small case reports or case series. However, more well-designed prospective studies are required to confirm these findings. ]]> <![CDATA[MON-212 Genetic Spectrum Of A Canadian Cohort Of Sporadic Pheochromocytomas And Paragangliomas: Higher Prevalence Of Germline Mutations In PGL And NGS Assay With A Multigene Panel Increases The Mutation Rate]]> https://www.researchpad.co/article/N20835caa-9dec-43b8-91ed-37818cd1046b T (p.Arg133*) mutation was found in 12 out of the 13 SDHC mutations reflecting the presence of a funder effect in the French Canadian population. In the 11 mutated PHEOs, there were 3 MAX (27.3%), 3 VHL (27.3%), 2 RET (18.2%), 1 SDHB (9.1%), 1 NF1 (9.1%), 1 FH (9.1%) mutations.From 2015- 2019, we proposed NGS assay with the multigene panel to 12 patients (9 PHEOS and 3 PGLs) for whom the initial genetic test was negative. Novel germline mutations were found in 4 (33.3%) of these patients, representing 10.8% (4/37) of the mutation-carriers. Mutations were found in 2/9 PHEOs; a 28 yo female with bilateral PHEOs (MAX (deletion exon 1 and 2)) and a 33 yo male with malignant PHEO (MAX (c.3G>A)), and in 2/3 PGLs; a 31 yo woman with metastatic abdominal PGL (SDHA (c.985C>T) and a 59 yo woman with a thoracic PGL (SDHA (c.1432_1432 + 1del).Variants of uncertain significance (VUS) were identified in 7/60 PGLs (11.6%) and 5/75 PHEOs (6.7%) but the significance of these variants remains to be determined. Conclusion: In our cohort, the prevalence of germline mutations was of 44.3% in apparently sporadic PGLs and 14.7% in PHEOs. Genetic re-evaluation overtime using multigene sequencing by NGS assay in a subgroup of patients led to an increase of mutation rate in PHEOs and PGLs with the identification of germline MAX and SDHA mutations. ]]> <![CDATA[MON-195 Genetic Analysis and Clinical Characteristics of Hereditary Paraganglioma and Pheochromocytoma Syndrome in Korean Population]]> https://www.researchpad.co/article/N82a6ca15-4f4a-44dd-b145-b2f92c3b4b00 A (p.Gly417Glu), NF1 c.6215delA (p.His2072LeufsTer10), NF1 c.6777del (p.Gly2260fs), and SDHC exon 2-6 duplication. In conclusion, we report the prevalence of germline mutations in Korean PPGL patients, and the rate of hereditary PPGL is estimated to be as high as 62.1%. NGS is a good and accessible tool for genetic analysis in patients with PPGLs, and further research on molecular classification will lead to precision medicine. ]]>