Renin Aldosterone Research Articles

KFRE for predicting ESRD risk in CKD 3-4 patients

Objective: The Kidney Failure Risk Equation (KFRE) is a useful tool for predicting chronic kidney disease (CKD) progression to end-stage renalkidney disease (ESRD). It has been validated in various countries populations. This study aimed to evaluate the prognostic significance of the KFRE model in a Turkish CKD cohort. Materials and Methods: In a prior retrospective study at a single center, the 4-variable KFRE model's accuracy in predicting end-stage renal disease (ESRD) progression was assessed. Among 246 stage 3 or 4 CKD individuals, two-year risk predictions categorized participants into low-intermediate (<20%) and high (≥20%) risk groups. Results: The model showed a sensitivity of 48.9% (95% confidence interval [CI] 34.08–63.94) and a specificity of 89.45% (95% CI 84.32–93.35) in predicting kidney failure progression in the Turkish population with stage 3–4 CKD. The area under the receiver operating characteristic curve was 0.69 (95% CI 0.60–0.79, p = 0.0001). Albuminuria, glomerular filtration rate, and renin–aldosterone system blockage were independently associated with kidney failure progression according to the Cox regression analysis. Conclusion: The findings of this study have demonstrated that the Kidney Failure Risk Equation (KFRE) model shows potential utility in predicting the progression of stage 3–4 chronic kidney disease (CKD) toward the critical stage of end-stage renal disease (ESRD) for the Turkish population.

Unmasking the Silent Menace: A Case Report of Aldosterone-Secreting Adrenal Cortical Adenoma

Background: Adrenal cortical adenoma with aldosterone hypersecretion, the most prevalent cause of secondary hypertension, represents a significant subset of adrenal tumors with distinct clinical implications. Clinical Description: A 30-year-old female presented with generalized body pain for two years and multiple episodes of sudden onset progressive weakness of the upper and lower limbs. Management: The diagnosis was confirmed by serum aldosterone and plasma renin activity and a laparoscopic right adrenalectomy was performed. The histopathology of the removed specimen helped to rule out adrenal cortical carcinoma Conclusion: A prompt diagnosis and surgical management improves the quality of life for patients with such rare diseases.

Hyperaldosteronism Screening and Findings From a Large Diverse Population With Resistant Hypertension Within an Integrated Health System.

Hyperaldosteronism (HA) is a common cause of secondary hypertension and may contribute to resistant hypertension (RH). The authors sought to determine and characterize HA screening, positivity rates, and mineralocorticoid receptor antagonist (MRA) use among patients with RH. A cross-sectional study was performed within Kaiser Permanente Southern California (7/1/2012-6/30/2017). Using contemporary criteria, RH was defined as blood pressure uncontrolled (≥ 130/80) on ≥ 3 medications or requiring ≥ 4 antihypertensive medications. The primary outcome was screening rate for HA defined as any aldosterone and plasma renin activity measurement. Secondary outcomes were HA screen positive rates and MRA use among all patients with RH. Multivariable logistic regression analysis was used to estimate odds ratio (with 95% confidence intervals) for factors associated with HA screening and for patients that screened positive. Among 102,480 patients identified as RH, 1977 (1.9%) were screened for HA and 727 (36.8%) screened positive for HA. MRA use was 6.5% among all patients with RH (22.5% among screened, 31.2% among screened positive). Black race, potassium < 4, bicarbonate > 29, chronic kidney disease, obstructive sleep apnea, and systolic blood pressure were associated with HA screening, but only Black race (1.55 [1.20-2.01]), potassium (1.82 [1.48-2.24]), bicarbonate levels (1.39 [1.10-1.75]), and diastolic blood pressure (1.15 [1.03-1.29]) were associated with positive screenings. The authors' findings demonstrate low screening rates for HA among patients with difficult-to-control hypertension yet a high positivity rate among those screened. Factors associated with screening did not always correlate with screening positive. Screening and targeted use of MRA may lead to improved blood pressure control and outcomes among patients with RH.

ASSOCIATION BETWEEN VITAMIN D LEVEL AND ESSENTIAL HYPERTENSION

Introduction: There is relationship between vitamin D deficiency and hypertension (HTN). The mechanism causing the development of HTN, the Renin Aldosterone Angiotensin System, was discovered to be strongly inhibited by vitamin D. This study was piloted to assess the role of vitamin D deficiency in the development of essential hypertension (EH). Methods: A total of 50 patients with EH and 50 healthy participants participated in this study. Every participant was subjected to clinical history, physical examination, and other necessary blood testing, electrocardiography, and echocardiography. Results: There was a significant decrease in vitamin D in hypertensive group (20.25±3.28 ng/mL) than normotensive group (38.33±6.89 ng/mL). Vitamin D level was moderately negative correlated with systolic blood pressure (BP) (r – 0.43, p – 0.001), strong negative correlation with diastolic BP (r – 0.76, p&lt;0.001), strong negative correlation with intimal thickness (r – 0.67, p&lt;0.001), and moderate negative correlation with ventricular mass (r – 0.48, p&lt;0.001). Intimal thickness and ventricular mass were significantly higher in patients with EH with low vitamin D than those with normal vitamin D levels. Conclusion: There is a strong inverse relationship between serum vitamin D and HTN. Vitamin D deficiency levels are considered an additional risk factor for cardiovascular morbidity and mortality.

FRI121 Markers Of Primary Aldosteronism In An Indigenous Australian Birth Cohort

Abstract Disclosure: E. Ng: None. S. Gwini: None. M. Stowasser: None. M.J. Young: None. P.J. Fuller: None. G.R. Singh: None. J. Yang: None. Primary aldosteronism (PA) is the most common endocrine cause of hypertension and a highly modifiable risk factor for cardiovascular disease (CVD). In PA, excess production of aldosterone leads to downregulation of renin and an elevated aldosterone-to-renin ratio (ARR). There are no data on aldosterone and renin profiles in Indigenous Australians despite their high rates of hypertension and CVD. Hence, we evaluated the prevalence of an abnormal ARR and the relationship between aldosterone, renin, ARR, and blood pressure (BP) in participants of the Aboriginal Birth Cohort (ABC) compared to age-matched non-Indigenous participants of the Top End Cohort (TEC). The ABC is the largest and longest running cohort of Aboriginal people in Australasia who have comprehensive health checks every 5-7 years with an overall aim of relating early life events to later health. Participants of the ABC were located in both urban and remote regions of the Northern Territory while the TEC was entirely urban. These results represent data collected between 2019 to 2021, when both cohorts were 32-35 years of age. Aldosterone and renin levels were measured by immunoassay. There were 255 participants in the ABC (205 remote, 50 urban) and 76 in the TEC. Aldosterone levels were similar while renin was lowest in TEC (7.5 mU/L) compared to the urban ABC (12.4 mU/L) (p=0.035) and remote ABC (29.3 mU/L) (p&amp;lt;0.001). Within the ABC, renin was lower in the urban cohort compared to the remote cohort (p&amp;lt;0.001). Median ARR was lowest in the remote ABC (10 pmol/LmU/L) compared to the urban ABC and TEC (ARR 28 and 43 pmol/LmU/L, respectively, p&amp;lt;0.001 when each compared to remote ABC, p=0.057 for urban ABC compared to TEC). There was a high prevalence of abnormal ARR (&amp;gt;70 pmol/L:mU/L) in both the urban ABC and TEC (26% and 28%, respectively), compared to only 3% in the remote ABC. The lower prevalence of ARR &amp;gt; 70 in the latter may be due to cryoactivation falsely elevating renin as transport on ice was required for samples from the remote ABC but not for urban ABC or TEC. Male sex, waist circumference and BMI were significantly positively associated with SBP and DBP in all cohorts while the ARR was positively associated with SBP in the TEC, but not in the ABC. This is the first study to examine aldosterone and renin in indigenous Australians. The finding of an abnormal ARR in over a quarter of the urban ABC and TEC suggests that the prevalence of PA is likely high and independent of indigenous status. The effect of cryoactivation on samples from remote regions may have masked abnormal ARR and a potential relationship between ARR and SBP, in contrast to the TEC where ARR was associated with increasing SBP. The data suggest that Indigenous Australians would benefit from adequate access to PA testing using accepted standards. Further evaluation with appropriate sample handling is warranted to appreciate the true prevalence of PA in this population. Presentation: Friday, June 16, 2023

FRI138 Diagnostic Accuracy Of Plasma Renin Activity Measured By Radioimmunoassay And LC-MS/MS For The Screening Of Primary Aldosteronism

Abstract Disclosure: A. Hong: None. J. Yoon: None. J. Park: None. W. Choi: None. H. Kim: None. H. Kang: None. Background: Plasma aldosteronism (PA) is screened based on the levels of aldosterone-to-renin ratio (ARR) and/or plasma aldosterone concentration. However, false positive cases are often observed due to low levels of plasma renin activity (PRA). Here, we aimed to compare diagnostic accuracy of PRA measured by radioimmunoassay (RIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the screening of PA. Materials and Methods: We retrospectively included 67 patients in whom PRA was measured using both RIA and LC-MS/MS due to adrenal incidentaloma or suspected secondary hypertension in a tertiary referral center. Patients with ARR≥20 underwent saline infusion test (SIT) and/or captopril challenge test (CCT) for the confirmation of PA. Results: The mean PRA was 3.1±7.5 ng/mL/hr by RIA and 3.0±6.3 ng/mL/hr by LC-MS/MS (P=0.284). The mean ARR was 53.7±137.4 by RIA and 41.2±129.9 by LC-MS/MS. The correlation coefficient between RIA and LC-MS/MS was 0.992 in patients with ARR&amp;lt;20 (n=38) (P&amp;lt;0.001) and 0.595 in patients with ARR ≥20 (n=29) (P=0.001). In patients who underwent confirmative test (CCT or SIT), false-positivity rate was 77.8% (7/9) based on RIA and 66.7% (6/9) based on LC-MS/MS. Conclusion: PRA measured using LC-MS/MS showed a significant positive correlation with PRA using RIA, particularly at ARR&amp;lt;20. ARR calculated by both methods for PRA revealed similar false-positives. Further studies are needed to validate diagnostic accuracy between the two methods of PRA for PA screening. Presentation: Friday, June 16, 2023

THU589 Positivity Rates Of Screening Criteria For Primary Aldosteronism: A Cohort Comparison Study

Abstract Disclosure: M. Marcelli: None. A. Panov: None. C. Bi: None. J.W. Funder: None. M.J. McPhaul: None. Current screening for primary aldosteronism (PA) relies on a single blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to establish an aldosterone-to-renin ratio (ARR). However, ARR cutoff levels vary between expert centers. Many studies have demonstrated that PAC may not represent a patient’s actual aldosterone status, suggesting the possible fallibility of the ARR. To investigate this possibility, we compared the positivity rates of 2 indicators of probable PA—ARR&amp;gt;28.9 and suppressed renin (PRA&amp;lt;1 ng/ml/hr)—in a cohort of 38,507 paired PAC and PRA samples. For each indicator, we also assessed positivity rates by self-reported sex (20578 [53.5%] women, 17882 [46.5%] men). Of the cohort, 1623 (4.2%) tested positive for possible PA based on an ARR of 28.9; 19551 (50.8%) tested positive for suppressed renin. Among the latter group, 2585 (6.7%) had PAC&amp;gt;15 ng/dL, 8465 (22%) between 5-15 ng/dL, and 8501 (22.1%) &amp;lt; 5 ng/dL. A recent algorithm suggested by Vaidya (1) defines the first of these groups as overtly positive screening and the second, intermediate group as positive screening, for a total positivity rate of 28.7%. Given the suppressed renin, there are probably a handful of positive PA cases, even in the 22.1 % group with PAC&amp;lt;5 ng/dL. A second finding was that rates of probable PA differed by sex. These differences were minor for the ARR criterion (4.3% of women vs. 4.1% of men tested positive) but major for the suppressed renin criterion with PAC&amp;gt;15 ng/dL (5.7% of women vs. 7.9% of men tested positive) and 5-15 ng/dL (23.6% of women vs. 20.2 of men tested positive). Florid PA was the only condition where more males than females tested positive, a finding deserving further expert consideration and study. In comparing two indicators of probable PA, the ARR criterion yielded a lower positivity rate than the suppressed renin criterion, suggesting that most PA cases may remain undetected if using AAR as a screening test.Reference: (1) JCEM 2020;105:3771 Presentation: Thursday, June 15, 2023

FRI190 Catching A Chimera: A Case Of Suspected Glucocorticoid Remediable Aldosteronism

Abstract Disclosure: A. Khan: None. B. Ramchandani: None. H.B. Aftab: None. Introduction: Familial hyperaldosteronism type 1 (FH-I), also known as glucocorticoid remediable aldosteronism (GRA) is responsible for 1% of cases of primary aldosteronism (PA). It is caused by a chimeric fusion of the CYP11B2 and CYP11B1 genes resulting in ACTH-sensitive aldosterone production. We describe a case of suspected GRA and outline the diagnosis of this rare condition. Case. A 52-year-old female with history of type 2 diabetes mellitus, obesity, sleep apnea, SVT with ablation presented with long-standing history of resistant hypertension (HTN). HTN was diagnosed in her late twenties. She was previously trialed on eight different classes of antihypertensive medications excluding mineralocorticoid antagonists or potassium-sparing diuretics but HTN remained uncontrolled. Current regimen included hydralazine, nebivolol, and furosemide. Her sister had HTN diagnosed in her forties, a nephew with HTN diagnosed in his early twenties and mother with HTN with unclear age of diagnosis. Her systolic and diastolic BP averaged 150 mmHg and 90 mmHg, respectively, on both home and clinic monitoring. Physical examination was significant for mild cushingoid appearance. Screening tests for pheochromocytoma and hypercortisolism were normal. Plasma aldosterone concentration (PAC) was noted to be at 14.4 ng/dl (&amp;lt;39.2) with a plasma renin activity (PRA) of &amp;lt;0.6 ng/mL/h (2.9 - 10.8), with aldosterone to renin ratio (ARR) of 24. Repeat testing showed PAC of 15.1 ng/dl, PRA&amp;lt;0.6 ng/ml/hr (ARR: 25.1) with potassium of 3.3 mmol/L (3.5 -5.1). PAC levels remained unsuppressed above 10 ng/dL following four-hour, seated, 2 L IV saline suppression test with serum potassium of 3.5 mmol/L. CT abdomen showed normal appearance of the adrenal glands. Given early age of onset of HTN and strong family history, 3-day dexamethasone test was performed using 1 mg oral dexamethasone every 12 hours following which PAC suppressed to &amp;lt;1 ng/dl. Patient was started on spironolactone 25 mg twice daily and at the time of writing is awaiting genetic testing to confirm the diagnosis of GRA. Discussion: GRA is a rare subtype of PA which has an increased risk of cardiovascular and cerebrovascular complications. Our case highlights the importance of screening for GRA in patients who have a personal and/or family history of early onset HTN who have screened positive for PA. Genetic testing for chimeric CYP11B1/B2 gene is the confirmatory step of diagnosis, however, a 3-day dexamethasone suppression test can be used to screen for GRA with a high sensitivity. Elevated levels of urine 18-hydroxycortisol and 18-oxocortisol are also noted but these are not widely available tests. Treatment of GRA is with medical management only; since surgical intervention is not required; proper diagnosis can also save the patient from unnecessary and invasive tests such as adrenal vein sampling. Presentation: Friday, June 16, 2023

THU474 Primary Hyperaldosteronism As A Cause Of PTH Elevation After Parathyroid Surgery

Abstract Disclosure: W. Thi: None. A. Rao: None. Background: Primary hyperaldosteronism can cause hypercalciuria, parathyroid hormone (PTH) elevation due to secondary hyperparathyroidism, and reduce bone mineral density. Screening for primary hyperaldosteronism can be done with serum aldosterone-renin ratio (ARR). We report a case of recurrent hyperparathyroidism after parathyroid surgery. Workup identified primary hyperaldosteronism as the cause of recurrent hyperparathyroidism. Treatment with spironolactone normalized PTH levels. Case Presentation: A 59-year-old African-American female in the Columbia VA Health Care System presented with hypertension, hypokalemia, bone density loss, and elevated PTH with normal calcium, one year after resection of a right inferior parathyroid adenoma to treat primary hyperparathyroidism. The patient had uncontrolled hypertension with hypokalemia while on losartan and amlodipine. Serum calcium was 9.4mg/dl(8.4-10.2mg/dl), PTH 89.4 pg/ml(29.2-79.9pg/ml), albumin 3.8g/dl(3.5-5G/dl), vitamin D 34 ng/ml(&amp;gt;28.9ng/ml), aldosterone 9ng/dl(&amp;lt;/=28ng/dl), plasma renin activity 0.28ng/ml/h(0.25-5.82ng/ml/h), ARR 32. Treatment of the patient with potassium supplements corrected the hypokalemia to 3.7mmol/L (5-5.1mm/l), and ARR was 94 with aldosterone 17 ng/dl and PRA 0.18 ng/ml/h and 24-hour urine calcium 304mg/24h(35-250mg/24h). Based on the laboratory values, and the absence of adrenal nodules during a CT scan, a diagnosis of primary hyperaldosteronism due to idiopathic hyperplasia of the adrenal was made. Spironolactone was started and PTH levels dropped down to 64.8pg/ml and serum calcium remained normal 5 months after treatment was initiated. Discussion: Primary Hyperaldosteronism causes extravascular fluid volume expansion with a reduction in proximal tubular sodium and calcium reabsorption. Increased calcium and sodium delivery to distal segments of the nephron leads to sodium reabsorption by mineralocorticoids without reabsorbing calcium, resulting in hypocalcemia with concomitant secondary hyperparathyroidism. Bone loss results from direct mineralocorticoid receptor-mediated effects of aldosterone on osteoblasts and osteoclasts and indirectly from high PTH levels to promote bone resorption. Treatment of primary hyperaldosteronism can reverse bone loss and reduce fracture risk rate within 18-36 months. This case suggests that primary hyperaldosteronism be considered a cause of secondary hyperparathyroidism and successfully treated with mineralocorticoid receptor antagonists. Presentation: Thursday, June 15, 2023

THU607 Improving Screening For Primary Aldosteronism Among People With Apparent Treatment Resistant Hypertension

Abstract Disclosure: K. Zekarias: None. K. Tessier: None. J. Kohlenberg: None. Introduction: The screening rate for primary aldosteronism (PA) is low among people with resistant hypertension. People with PA experience significantly more cardiovascular complications than those with primary hypertension and an equivalent degree of blood pressure control1. Therefore, identification of people with PA for early-directed therapy is crucial. Objective: We aimed to improve the screening rate for PA among people with apparent treatment resistant hypertension (aTRH), defined as blood pressure &amp;gt;140/90 despite the concurrent use of three antihypertensive drug classes or any person with hypertension on &amp;gt;4 antihypertensive medications. Methods: Using an electronic medical record (EMR) best practice alert (BPA), we implemented a quality improvement (QI) program from 9/17/2022-3/16/2023. We included adults ≥18 years of age with aTRH, who were identified using ICD codes, the last three blood pressure measurements and the antihypertensive medication list. During office visits with nephrologists, cardiologists, endocrinologists, family medicine physicians, and internists, a BPA notified providers if the person with aTRH had not been previously screened for PA with plasma aldosterone and plasma renin activity. The alert defined aTRH, suggested that screening be performed regardless of active medications, and contained an order set for plasma aldosterone, plasma renin activity, and plasma potassium. Furthermore, the BPA suggested referral to an endocrinologist if the patient fulfilled criteria for positive case detection for PA, defined as plasma renin activity &amp;lt; 1 ng/mL/hour and plasma aldosterone concentration (PAC) &amp;gt; 10 ng/dL or the plasma aldosterone to renin ratio (ARR) &amp;gt; 30 with PAC &amp;gt; 10. We compared the PA screening rate after the implementation of the BPA to the PA screening rate over the 1 year prior to the BPA implementation (9/16/2021-9/16/2022). Results: Plasma aldosterone lab orders were placed for 3.4% (179/5,261) of people with aTRH post-BPA implementation compared to 1.9% (211/10,944) pre-BPA implementation (p&amp;lt;0.01). Positive case detection for PA occurred in 25% (38/152) of people screened post -BPA implementation compared to 27% (47/173) pre-BPA implementation (p=0.66). People with aTRH who were younger (p&amp;lt;0.01) were more likely to be screened for PA pre-BPA implementation and this did not change post-implementation. Conclusion: Implementation of a QI program employing a BPA with an embedded order set in the EMR improved the screening rate for PA among adults with aTRH. Reference 1. Monticone S, D'Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, Mulatero P. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018 Jan; 6 (1):41-50. Presentation: Thursday, June 15, 2023

THU518 Ectopic Cushing Syndrome In A Case Of Ewing Sarcoma

Abstract Disclosure: M. Fasen: None. S.E. Mayson: None. Background: Ewing sarcoma (ES) is a rare and aggressive neoplasm occurring in bone and soft tissue in children to young adults. It is part of a spectrum of neoplastic diseases known as the ES family of tumors that display varying degrees of neuroendocrine features. Ectopic Cushing’s syndrome (ECS) is also a rare but severe condition associated with unregulated ACTH or CRH secretion by neuroendocrine tumors (NETs) that can cause severe hypercortisolism. The most common tumors associated with ECS include small cell lung carcinoma, bronchial carcinoid and medullary carcinoma of the thyroid gland. Sarcomas causing ECS are extremely rare with only a handful of cases reported in the literature, mostly in children. Herein we detail what we believe to be the first reported case of ECS occurring in an adult male patient with ES. Clinical Case: A 23-year-old man with ES metastatic to pancreas, liver and bone was admitted to the hospital with acute on chronic back pain and lower extremity weakness, and subsequently diagnosed with cord compression and neutropenia from chemotherapy. New onset hypertension and refractory hypokalemia were observed prompting endocrinology consultation. Physical examination revealed facial fullness, central obesity and wide violaceous striae on his abdomen and axillae. Biochemical evaluation demonstrated blood glucose consistently over 300 mg/dL, serum potassium 2.5 mmol/L, renin 0.9 ng/ml/hr (0.2-1.6 ng/ml/hr), aldosterone renin ratio &amp;lt; 3.3, morning cortisol 73 ug/dL (4-22 ug/dL), and ACTH 1020 pg/mL (72-63 pg/mL). A 1 mg overnight dexamethasone suppression test yielded a serum cortisol of 90 ug/dL and 24-hour urine free cortisol was 6388 ug/d (&amp;lt;60 ug/d). MRI brain demonstrated a normal pituitary gland, and FDG PET-CT showed new areas of uptake in bone concerning for metastatic progression and new bilateral adrenal enlargement without nodularity. High dose dexamethasone suppression testing was deferred in the context of rapid neuropsychiatric deterioration characterized by somnolence and psychosis. The decision was made to treat immediately with spironolactone and ketoconazole, as well as insulin for hyperglycemia management. His mental status, blood pressure, serum potassium, glucose and cortisol improved following the initiation and titration of medical therapy. He was discharged home with addition of metyrapone and hospice support. Two months later the patient succumbed to his illness. Conclusion: The severity of hypercortisolism is a negative predictor of survival and prompt control should be the main therapeutic goal along with prevention of cortisol-induced complications in patients with ECS. ACTH and CRH immunostaining of the patient’s ES histopathology slides is pending. Presentation: Thursday, June 15, 2023

THU590 Screening Of Primary Aldosteronism With Low-threshold Criteria In An Outpatient Clinic Setting

Abstract Disclosure: M.S. Myint: None. A. Szafran-Swietlik: None. Introduction: Primary aldosteronism (PA) is an underdiagnosed cause of hypertension due to a remarkedly low testing rate. We hypothesized that a lower threshold should be set for testing PA. Hence, we tested for PA in patients with moderate hypertension and compared it to the group that met the Endocrine Society (ES) guideline. Methods: This is a prospective cohort pilot study. Inclusion criteria included hypertension plus any one of the following: (i) age &amp;lt; 40, (ii) use of ≥ 3 antihypertensives, (iii) sleep apnea, (iv) presence of adrenal incidentaloma, (v) hypokalemia, (vi) heart failure without meeting other criteria and (vii) use of 2 antihypertensives without meeting other criteria. Patients were divided into the Standard Group (SG) and the Low-threshold Group (LG). Patients in the SG met one of the standard criteria based on ES guideline (i.e., criteria i through v). Those in the LG met one of our low-threshold criteria vi or vii. Patients were included regardless of their hypertension control. Due to limitations, we did not include 2 criteria: 1) family history of PA and 2) family history of hypertension or stroke before age 40. Patients taking spironolactone were excluded from the study. Patients were pre-screened by chart review. Plasma aldosterone concentration (AC) and plasma renin activity (RA) were ordered during the encounter with the selected patients. The results were followed at their subsequent visits. Those who had a positive plasma aldosterone renin ratio (ARR) of &amp;gt;20 were either marked as “Confirmed Cases” (CC) if they did not require a confirmatory test or marked as “Oral Salt Loading” (OSL) if they required a confirmatory test. Data were analyzed using descriptive study. Results: 793 patients were pre-screened. 149 out of 793 patients met our inclusion criteria. AC and RA were ordered for 105 (70.4%) out of 149 patients. 63 (66.2%) out of 105 patients did the test but 42 patients did not. Among the 63 patients who did the test, 45 fit into the Standard Group. 7 out of 45 patients had positive ARR (15% of SG; 11% of those who did the test) among which 3 were CC and 4 were OSL. In this group, age &amp;lt;40 (n=6), use of ≥3 antihypertensives (n=24), sleep apnea (n=15), adrenal incidentaloma (n=12), and hypokalemia/ borderline hypokalemia (n=6). In the subgroup of the patients taking ≥ 3 antihypertensives, 5 out of 24 patients had positive ARR (11% of SG; 7.9% of those who did the test) among which 3 were CC and 2 were OSL. 18 out of 63 patients fit into our Low-threshold Group. 5 out of 18 patients had positive ARR (27.7% of LG; 7.9% of those who did the test) among which 2 were CC and 3 were OSL. Conclusion: In our study, both the Standard Group (SG) and the Low-threshold group (LG) had a significant number of positive ARR. More research is needed to investigate the prevalence of PA among patients with hypertension regardless of the grade and control of hypertension. A low threshold guideline might improve the rate of testing for PA. Presentation: Thursday, June 15, 2023

THU591 HyperAldosteronism In Pregnancy Predicted Impacts (H.A.P.P.I.): A Retrospective Cohort Study

Abstract Disclosure: D. Oprea: None. F. Lefrançois: None. A.C. Côté: None. M. Roy-Lacroix: None. M. St-Jean: None. N. Sauvé: None. Introduction: Hypertensive disorders of pregnancy (HDP) are increasing worldwide and are associated with a high rate of maternal and fetal morbidity and mortality. Primary aldosteronism (PA) is a frequent and reversible cause of secondary hypertension in young non-pregnant women (18%) (1). Until now, no studies have detailed the prevalence, nor the outcomes associated with PA during pregnancy. Research Question: In HDP, are cases of PA associated with different impacts on maternal-fetal health compared to pregnant women without PA? Methods: This retrospective cohort study compared 252 pregnancies according to their PA status. We included pregnancies that were followed at the Centre Hospitalier Universitaire de Sherbrooke (CHUS) between 2011 and 2022, and who had had an aldosterone/renin ratio (ARR) screening for PA, in a five-year period before or after the analyzed pregnancy. Monofetal and twin pregnancies were included. Concomitant diagnoses of pheochromocytoma, hyperthyroidism or Cushing syndrome were excluded. The primary objective of this study was to describe the occurrence of HDP in women with PA. Secondary objectives were to describe maternal, fetal and neonatal outcomes and compare them according to PA status. Results: Among 252 pregnancies, 15 were diagnosed with a PA (concerning 12 women). Our preliminary analysis showed a greater prevalence of advanced maternal age (53.3% vs 24.5, p = 0.028) and Afro-American ethnicity (60.0 % vs 10.1%, p &amp;lt; 0.001) in the PA group, in addition to a tendency towards class I obesity (40.0% vs 13.1%, p = 0.166) in this group. There were no differences in terms of prevalence of chronic hypertension (26.7% vs 25.7 %, p = 0.936), delivery mode and overall fetal morbidity and mortality. Although not statistically significant, preeclamspia tended to be more frequent (40.0% vs 27.0%, p = 0.276) and gestational hypertension less frequent (0.0 % vs 16.0%, p = 0.092) during pregnancy in the PA group. 40.1% (vs 19.0%, p = 0.052) of PA-associated HDP were diagnosed in post-partum (including 33.4 % of preeclampsia in this group) and required intravenous hypertensive treatment (40.0% vs 23.2%, p = 0.209). Also, 13.3% of pregnancies in the PA group (vs. 3.0 %, p = 0.093) required hospitalization at the intensive care unit (ICU). All cases of PA were diagnosed within 5 years pre-conception or post-partum. Conclusion: Pregnancies with PA diagnosis within a five-year period tended to present more frequently with HDP as preeclampsia, especially in the post-partum period, and often required more intensive antihypertensive treatment and ICU hospitalization. The upcoming second prospective phase of this study will better assess the prevalence of PA in pregnant women experiencing HDP. Reference: (1) Alam S. et al., Clin Endocrinol, June 2021;94(6):895903. Presentation: Thursday, June 15, 2023

THU594 Outcome Data From Fabulas: A Feasibility Study Of Radiofrequency Endoscopic Ablation, With Ultrasound Guidance, As A Non-surgical, Adrenal Sparing Treatment For Aldosterone Producing Adenomas

Abstract Disclosure: G. Argentesi: None. X. Wu: None. A. Ney: None. E. Goodchild: None. K. Laycock: None. Y. Lee: None. R. Senanayake: None. J. MacFarlane: None. E. Ng: None. J. Kearney: None. A. Palma: None. I. Munteanu: None. J. Salsbury: None. E.D. Benu: None. P. Ebano: None. P. Wilson: None. E.M. Godfrey: None. G. Goodchild: None. J. Bestwick: None. M. Gurnell: None. H. Cheow: None. S.P. Pereira: None. W. Drake: None. M.J. Brown: None. Introduction: Primary aldosteronism (PA) is potentially curable if due to a unilateral aldosterone producing adenoma (APA), but complete clinical success after adrenalectomy is the exception. Selective radiofrequency ablation (RFA) of the APA, if safe, would lower the bar for intervention, but there are concerns about catecholamine crises, peri-adrenal catastrophes, and ablation of non-functional adenomas. Endoscopic ultrasound (EUS)-guided RFA of left-side APAs is an attractive alternative in which proximity to the stomach enables multiple, short, precise burns as the catheter is steered around the APA. Aims and Methods: We conducted a 3-centre feasibility study to determine the safety of EUS-RFA as an adrenal sparing treatment, and assess likely efficacy. The APA was visualised as increased uptake of 11C-metomidate (MTO) in a post-dexamethasone PET CT (1). Initial recruitment was limited to patients in whom surgery was contra-indicated (co-morbidities, ambiguous estimation of unilateral PA). α-and ß blockade were introduced 2 weeks prior to RFA, performed under general anaesthesia or deep sedation. Metanephrines were measured before and during RFA. Following diagnostic fine-needle aspiration (FNA), a 5-10 mm19G StarmedTM ablation probe was introduced into the APA. The primary outcome was safety, pre-specified as absence of perforation, haemorrhage, or infarction of major organs on a CT scan performed within 24-48 hours of RFA. Secondary outcomes, at 6 months post-RFA, were PASO criteria for biochemical/clinical success, changes in aldosterone/renin ratio (ARR), BP and drug doses, and in the MTO uptake on repeat scan. Results: 28 patients (21 male), age 57.9 ± 10.23, were studied. 7 patients had 2 ablations. None of the pre-specified serious adverse events occurred. Metanephrines rose in only one patient, given ephedrine and metaraminol. 2 further patients had RFA-related events which delayed discharge but rapidly resolved. 14 patients achieved complete biochemical success and 3 partial. 4 patients achieved complete clinical success and 4 partial. ARR fell from median 3975 (IQR 2090-7475) to 880 (369-2670), p&amp;lt;0.001. BP was unchanged, but on less treatment: number of antihypertensives and defined daily dose fell from 2.9 (95% CI 2.4-3.3) to 2 (1.5-2) and from 4.9 (3.6 -6.2) to 2.7 (1.7-3.6) respectively. In 6 patients, MTO uptake into the APA was reduced to &amp;lt;50% of adjacent adrenal (indicating complete ablation) whilst the latter was unchanged or minimally reduced in all patients (i.e. preserved function). APA diameter was reduced in 21/28 patients. In 13/28 FNA samples analysed to date, all were positive for CYP11B2 (8/13 strongly and 5/13 weakly positive). Conclusion: EUS-guided trans-gastric RFA is a safe alternative to adrenalectomy for the treatment of left-sided APAs. RFA is now being compared with surgery in a RCT of 110 patients with PA. 1. Wu et al. Nat Med 29:190-202, 2023. Presentation: Thursday, June 15, 2023

FRI125 Recurrence Of Primary Aldosteronism Long-Term After Adrenalectomy For Aldosterone-Producing Adenoma With KCNJ5 Gene Mutation: A Two-Cases Report

Abstract Disclosure: K. Aiga: None. M. Kometani: None. D. Aono: None. S. Karashima: None. T. Yoneda: None. Primary aldosteronism (PA) is a major cause of secondary hypertension. PA is known to have higher prevalence of cerebral or cardiovascular complications, indicating the importance of early detection and treatment for PA. PA is caused by autonomous secretion of aldosterone in the adrenal glands. PA is characterized by high plasma aldosterone concentration, low plasma renin activity and hypokalemia. PA is classified into unilateral PA (aldosterone-producing adenoma [APA] or unilateral hyperplasia) and bilateral PA (bilateral adrenal hyperplasia). PA with aldosterone excess in bilateral adrenal glands is defined as bilateral PA. On the other hand, PA with aldosterone excess in unilateral adrenal gland is defined as unilateral PA. Strategies for PA treatment depends on the subtype of PA. Medication by mineralocorticoid receptor antagonists is a common treatment for bilateral PA. Adrenalectomy is the most efficient treatment for unilateral PA. In general, patients tend to maintain normal serum potassium level and blood pressure after adrenalectomy, and recurrence of PA is extremely rare. Recently, mutation in the gene named KCNJ5 was found to derive APA. Herein, we report two cases of PA recurrence more than 10 years after surgical treatment for APA. Somatic mutation in KCNJ5 was detected in the first occurrence of PA in both cases. First case, a 52-year-old woman was examined for hypertension 22 years after total adrenalectomy of the right adrenal gland. Recurrent PA was diagnosed based on high aldosterone-renin-ratio (ARR), identification of left adrenal gland tumor by computed tomography (CT), and a confirmatory test. Second case, a 65-year-old man was examined for hypertension 17 years after total adrenalectomy of the left adrenal gland. He had maintained his blood pressure using medication since the onset of hypertension 4 years after the surgery. A year later, a high ARR was observed. PA recurrence was determined by a right adrenal gland tumor noted on CT and a confirmatory test. Tissues of the adrenal gland were obtained from adrenalectomy in both cases. Histopathological analysis revealed presence of one adenoma in the first case, while two adenomas were confirmed in the second case. Somatic mutation in KCNJ5 gene was detected in both cases. To date, there are no specific guidelines established for the management of recurrent PA. Early detection is crucial for the prevention of severe cardiovascular diseases. Long-term follow-up is recommended after the treatment of PA. Presentation: Friday, June 16, 2023

FRI203 A Case Of Pseudoadrenal Tumor Mimicking Left Adrenal Pheochromocytoma

Abstract Disclosure: A. Tanabe: None. E. Sugito: None. H. Kajio: None. Approximately 50% of adrenal incidentalomas are non-functional cortical adenomas, and 25% are adrenocortical hormone-secreting adenomas and pheochromocytomas. Adrenocortical carcinomas, and pheochromocytomas which have malignant potential, need to be differentiated and removed even if the tumors are hormonally inactive. In addition to these adrenal origin tumors, anatomic structures and tumors that develop in tissues neighboring the adrenal glands (pseudoadrenal tumors) may be confused with primary adrenal tumors. The larger the tumor, the more difficult it is to determine continuity with the adrenal glands. Herein we report a patient with gastrointestinal stromal tumor (GIST) that mimicked a left adrenal pheochromocytoma. A 47-year-old man was diagnosed with a left adrenal incidentaloma at 40 years of age. The tumor had irregular margins and grew from 18 mm to 30 mm in maximum diameter over 7 years. The mass appeared to be in the tip of the lateral limb of the left adrenal gland and was located between the left adrenal gland and the posterior wall of the stomach. The patient had no abnormal findings other than general obesity. The blood pressure was 106/72 mmHg with antihypertensive agents. The plasma corticotropin and cortisol concentrations were normal and suppressed normally after a 1-mg overnight dexamethasone suppression test. The plasma aldosterone concentration and renin activity were increased with angiotensin receptor blocker and diuretic therapy. The 24-h urine fractionated metanephrines levels were at the upper limit of the reference range. Because the tumor showed unenhanced computed tomography (CT) attenuation of 40-50 Hounsfield units, hormonally-inactive adrenocortical carcinoma or pheochromocytoma had to be differentiated. I-123-metaiodobenylguanidine (I-123-MIBG) scintigraphy showed tumor avidity consistent with a pheochromocytoma. A laparoscopic left adrenalectomy was performed; however, no tumor was present in the resected specimen. Abdominal CT postoperatively showed that the tumor remained intact and appeared to connect to the posterior wall of the stomach. A laparotomy was performed and the tumor was removed. The tumor was localized to the intraperitoneal space and isolated from the posterior wall of the stomach. The pathological diagnosis was a GIST. Although it has been reported that I-123-MIBG may accumulate in tumors other than neuroendocrine tumors, reports on GISTs are rare. Lessons learned from our case include the importance of clinicians need to be aware of the limitations of diagnostic imaging studies in diagnosing non-functioning adrenal incidentalomas, which require a pathologic analysis for the final diagnosis. Moreover, clinicians need to provide patients with sufficient informed consent when deciding on treatment strategies. Presentation: Friday, June 16, 2023

THU587 High Prevalence Of Primary Aldosteronism Diagnosis In Patients With Papillary Thyroid Cancer And Hypertension: A Cross-sectional Case-control Study

Abstract Disclosure: A.W. Maciel: None. T. Freitas: None. D.L. Danilovic: None. G.F. Fagundes: None. F. Freitas-Castro: None. L. Santana: None. A. Guimaraes: None. A. Pio-Abreu: None. J. V. Silveira: None. F. Consolim-Colombo: None. L. Bortolotto: None. M.C. Fragoso: None. A. Latronico: None. L. Drager: None. B.B. Mendonca: None. A.O. Hoff: None. M.Q. Almeida: None. Introduction: Aldosterone excess can cause oxidative stress leading to DNA damage in vitro and in vivo. Single case reports demonstrated a coincidence of primary aldosteronism (PA) with different malignancies. A higher prevalence of thyroid nodules and non-toxic multinodular goiter was described in patients with PA compared to those with essential hypertension (HT). A single study showed an association between PA and papillary thyroid cancer (PTC), but without a paired control group. Objective: To assess PA prevalence in a transversal cohort of patients with PTC and HT compared to a paired control group with HT. Methods: In this cross-sectional case-control study, PA was investigated in all patients with PTC and HT (n= 114), regardless of HT severity, under active surveillance at a cancer institute from 2019 to 2022. The control group included 228 (2:1) age-, sex- and body mass index (BMI)-matched individuals from a retrospective cohort of HT previously investigated for PA from 2011 to 2022. Serum aldosterone and plasma direct renin concentrations were measured by a chemiluminescent immunoassay. A positive PA screening was defined by aldosterone ≥10 ng/dL and aldosterone to renin ratio ≥2 ng/dL/μUI/mL. Results: Age, sex and BMI were not statistically different between PTC and control groups, respectively (age 59.8 ± 12 vs. 58.9 ± 12.3 yrs, p= 0.67; 79% vs. 81% women, p= 0.67; BMI 30.7 ± 5.8 vs. 30.8 ± 6.5 Kg/m2, p= 0.98). PA was diagnosed in 35 out of 114 PTC patients with HT. The prevalence of PA in the PTC group (30.5%, confidence interval (IC) 22.6%-40.1%) was significantly higher when compared to the paired control group with HT (11.84%, CI 8.08%-16.93%; p&amp;lt; 0.0001). Although PA prevalence was higher in the PTC group, only 20.2% had stage 3/resistant HT (vs. 38% in the control group, p= 0.003). The number of anti-hypertensive medications was lower in the PTC group compared to controls (2 drugs, 1 to 3 vs. 4 drugs, 3 to 5, respectively; p&amp;lt; 0.001). When analyzing only PA patients in both groups, frequency of stage 3/resistant HT and number of medications were lower in the PTC group (p&amp;lt; 0.001 and p&amp;lt; 0.001, respectively). Although HT was more severe in PA patients without PTC, aldosterone and renin levels were not different in PA patients from PTC and control groups, respectively (p= 0.15 and p= 0.34). Conclusion: PA prevalence was strikingly high among patients with PTC and HT, supporting the recommendation of PA screening in this patient group, regardless of HT severity. Presentation: Thursday, June 15, 2023

FRI271 A Case Of Autoimmune Polyglandular Syndrome Type 2 Presenting With Cardiac Symptoms

Abstract Disclosure: J. Lin: None. C. Lee: None. A.R. Crawford: None. C. Taub: None. Autoimmune polyglandular syndrome type 2 (APS 2) is characterized by the combination of autoimmune adrenal insufficiency with autoimmune primary hypothyroidism, and/or type 1 diabetes mellitus, as well as other autoimmune conditions. The estimated prevalence is reported to be 1.4-4.5 cases per 100,000 persons. Presenting symptoms are often nonspecific, leading to delayed diagnosis; however, manifestations can sometimes become rapidly life-threatening. Cardiac symptoms, rare but clinically significant, can be the first presentation for APS 2. 34 year old male with history of asthma presents with nausea and chest pain, found to have pericarditis that was complicated by pericardial tamponade and cardiogenic shock requiring emergent pericardiocentesis and mechanical support with veno-arterial extracorporeal membrane oxygenation. Stress dose steroids were given due to concern for fulminant myocarditis. His condition improved with glucocorticoid treatment, but the etiology of his acute decompensation was unclear. He completed the prednisone taper before discharge and was started on amiodarone for atrial flutter. He presented with recurrent symptoms a week later. Cardiac MRI showed pericarditis without myocarditis. PET scan showed pericardial inflammation without evidence of malignancy or vasculitis. Broad infectious workup including viral studies was negative. An extensive biochemical workup showed low serum aldosterone and high renin activity while on prednisone. Autoimmune workup was positive for 21-hydroxylase antibody, thyroid peroxidase antibody, and homozygous for celiac HLA DQ8, suggestive of APS 2. Patient was started on levothyroxine for subclinical hypothyroidism with TSH &amp;gt;20. Interleukin blockade with anakinra was initiated, and patient was discharged with 25mg of daily prednisone pending insurance authorization for anakinra. A month later, patient re-presented with pericarditis. Patient received stress dose steroids, and was started on fludrocortisone. Levothyroxine was stopped because of amiodarone induced thyrotoxicosis. Patient was discharged on a prednisone taper regimen, and anakinra was approved a month later. Few case reports have described the association between APS 2 with pericardial tamponade. In healthy patients presenting with unexplained pericarditis, autoimmunity should be considered as a differential diagnosis as it can rapidly become life-threatening requiring urgent intervention. It is important to recognize for these patients, they are at risk for recurrent pericarditis and cardiac tamponade. Presentation: Friday, June 16, 2023

FRI165 BIUXX

Abstract Disclosure: A. Haider: None. M. Sadiq: None. J. Shakesprere: None. G.K. Sidhu: None. Background: Syndrome of inappropriate anti-diuretic hormone (ADH) secretion (SIADH) is characterized by inappropriate ADH secretion causing hyponatremia due to free water retention. Plasma volume expansion leads to renin inhibition by the renal juxtaglomerular complex, resulting in decreased aldosterone secretion with inappropriate natriuresis. However, when autonomous renin-independent aldosterone production is present, natriuresis can be suppressed, causing normal sodium levels despite inappropriately high ADH. Case: 58-year-old male with history of resistant hypertension &amp; bipolar disorder on Oxcarbazepine presented with dizziness, lightheadedness, and severe hypokalemia (2.7 mmol/L, n 3.5-5.0 mmol/L). CT Adrenals revealed an incidental 1.2 cm left-sided adrenal adenoma [HU 6, 40% washout]. Serum aldosterone and plasma renin activity (PRA) were obtained in the supine position via LC/MS/MS assay; concurrent serum K+ was 3.4 mmol/L. Spironolactone was started and titrated to 50 mg BID for blood pressure control due to high suspicion of hyperaldosteronism. The patient was continued on Oxcarbazepine 900 mg BID. A 3 mg Dexamethasone suppression test showed suppressed morning cortisol (1.0 μg/dL, n &amp;lt;1.8 μg/dL). Urine catecholamines and metanephrines were obtained and normal. 3-4 days after starting Spironolactone, the patient developed severe subacute hyponatremia (119 mmol/L, n 135-145 mmol/L) from an admission level of 137 mmol/L. No active renal or GI losses, diuretic use, or untreated hypothyroidism were documented. Serum osmolality was low (262 mOsm/kg, n 275-295 mOsm/kg) with urine osmolality of 357 mOsm/kg (n 50-1200 mOsm/kg) and urine sodium of 92 mEq/L (n &amp;gt;20 mEq/L). Serum aldosterone and PRA levels returned with normal aldosterone (7 ng/dL, n 2-9 ng/dL) but suppressed PRA (0.07 ng/mL/hr, n 0.7-3.3 ng/mL/hr) and elevated aldosterone-renin ratio (100 ng/dL per ng/mL/hr, n ≤ 30 ng/dL per ng/mL/hr). As renin was very low despite mild hypokalemia and active Losartan use at the time of testing, these findings were suggestive of primary aldosteronism. In-hospital 24-hour urine aldosterone collection showed urine aldosterone of 29.3 mcg/24 h (n 5-19 mcg/24 h) with urine sodium of 93 mmol/ 24 h (n 40-220 mmol/24 h). Oxcarbazepine was subsequently tapered off; Spironolactone was intermittently held until complete discontinuation. Fluid restriction and oral salt repletion were started and the patient’s sodium ultimately normalized. Outpatient saline suppression testing and adrenal vein sampling were scheduled. Conclusion: Oxcarbazepine was likely causing high ADH release but co-occurring untreated hyperaldosteronism inhibited natriuresis. Use of Spironolactone unmasked natriuresis by blocking aldosterone activity on the intercalated cells of the renal nephron. Stopping Oxcarbazepine ultimately resulted in hyponatremia resolution. Presentation Date: Friday, June 16, 2023

FRI355 Hypokalemia-induced Nephrogenic Diabetes Insipidus In A Patient With Medullary Thyroid Carcinoma And Paraneoplastic Cushing’s Syndrome

Abstract Disclosure: S. Jhawar: None. S. Jumani: None. Y. Sterrett: None. H. Elenius: None. P. Veeraraghavan: None. C. Ryan: None. J. Del Rivero: None. S.M. Sadowski: None. N. Nilubol: None. J.G. Verbalis: None. L.K. Nieman: None. E. Globa: None. M.S. Zemskova: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Nephrogenic diabetes insipidus (NDI) is commonly associated with the use of medications such as lithium, antibiotics, and chemotherapeutic agents or with renal disorders. Rarely, NDI can be a manifestation of paraneoplastic conditions. We describe a case of NDI caused by severe hypokalemia in a patient with metastatic medullary thyroid cancer (MTC) and paraneoplastic Cushing’s syndrome (CS). Clinical Case: A 47-year-old male with sporadic, metastatic MTC (RET M918T pathogenic variant) was referred to our institution for further management. The patient had florid metastases to the liver, lungs, and skeleton, with a calcitonin of 158,535 pg/mL [normal (NL): &amp;lt;14.3], and a CEA of 3,634 pg/mL (NL: 0.8-3.4), but surprisingly, without an intrathyroidal primary tumor. Vandetanib and octreotide were previously trialed but discontinued due to financial constraints. The patient had diarrhea, but no other symptoms. Physical exam revealed cervical lymphadenopathy, facial plethora, dorsocervical fat pad, and a single purple stria on the chest. Further work up revealed markedly elevated 24-hr urine free cortisol (12,460 mcg/24hr; NL: 35-45), ACTH 116 pg/mL (normal 5.0-46.0), and an undetectable serum aldosterone and plasma renin activity, raising suspicion for paraneoplastic ectopic-CS. Immunostaining of the MTC biopsy specimen showed ACTH positivity. During the inpatient admission, polyuria of &amp;gt;3L/day was noted on two consecutive 24-hour urine measurements. Laboratory investigations revealed hypernatremia (serum sodium: 147 mmol/L; NL: 136-145), elevated serum osmolality (303 mOsm/Kg; NL: 278-298), and a low urine osmolality (215 mOsm/kg; NL: 300-900), thus establishing the diagnosis of DI. A simultaneous, elevated plasma copeptin (36.3 pmol/L; NL: &amp;lt;13.1) further suggested NDI. Also noted was severe hypokalemia (serum potassium: 1.7 mmol/L; NL: 3.5-5.1), with normal serum magnesium and calcium. A thorough review of patient’s medication list did not reveal any culprit drug for hypokalemia or NDI. Hypokalemia was managed with aggressive oral and intravenous potassium repletion. A bilateral adrenalectomy was performed to treat the ectopic-CS, which improved the hypokalemia and resolved the NDI. Three months later, the patient unfortunately died due to progression of MTC. Conclusion: Severe hypokalemia causes autophagic degradation of aquaporin-2 channels in the renal tubules and is an under-recognized cause of NDI. Profound hypercortisolism in ectopic-CS may result in cortisol-mediated overactivation of mineralocorticoid receptors that can cause renal potassium loss leading to NDI. Only 0.6% of MTCs are associated with ectopic-CS (PMID: 16029131). Our report highlights hypokalemia-induced NDI as a manifestation of paraneoplastic CS resulting from MTC. Presentation: Friday, June 16, 2023