Endogenous Cushing syndrome (CS) is a rare disorder resulting from chronic exposure to excessive concentrations of cortisol. It is likely underdiagnosed because many clinical signs and symptoms are non-specific and overlap with those of common conditions. Furthermore, biochemical testing to diagnose CS can be complex and challenging, especially in milder cases. CS is characterized by excessive daily cortisol production, but it is also associated with a disrupted circadian rhythm of cortisol secretion. Traditional cortisol monitoring techniques rely on single-time-point measurements or a cumulation of measurements, which are unable to capture the complete daily rhythm of cortisol fluctuations. Currently, the utility of assessing individual patients' cortisol circadian rhythm during diagnosis and treatment of CS is not well characterized. In this review, we will discuss how cortisol is measured in clinical practice and the potential benefit of measurement and normalization of the cortisol circadian rhythm.

A 19-year-old woman presented with severe hypertension, hypokalemia, and clinical signs of Cushing syndrome (CS). Computed tomography imaging revealed a large left adrenal mass encasing a major vessel, a left renal lesion, a right ovarian teratoma, and multiple pulmonary micronodules. 18F-fluorodeoxyglucose positron emission tomography (18-FDG-PET) showed hypermetabolism in the adrenal mass, lung nodules, and teratoma. Biochemical work-up confirmed adrenocorticotropin-independent CS and elevated adrenal androgens, consistent with metastatic, unresectable adrenocortical carcinoma. The patient was started on mitotane and metyrapone, followed by 8 cycles of etoposide-doxorubicin-cisplatin plus mitotane. Despite treatment, the disease progressed. Adrenal biopsy revealed high tumor-infiltrating lymphocytes, low tumor mutation burden, low programmed death-ligand 1 expression, and microsatellite stability. Germline testing identified a TP53 pathogenic variant, confirming Li-Fraumeni syndrome. A single dose of pembrolizumab was administered as salvage therapy but led to grade 3 immune-related hepatitis and prolonged hospitalization, requiring cessation of both pembrolizumab and mitotane. Remarkably, a follow-up scan 3 months later showed 60% regression of the adrenal mass, stable renal and ovarian lesions, and resolution of lung nodules. The patient underwent complete surgical resection, achieving full remission. More than 1 year later, she remains disease free.

OBJECTIVE:Primary aldosteronism (PA) is a common cause of hypertension in young women. However, there is a paucity of data regarding its impact during pregnancy. The primary objective of this study was to describe the occurrence of hypertensive disorders of pregnancy (HDP) in PA. DESIGN:This retrospective cohort study compared outcomes in pregnancies according to PA status. PATIENTS:Pregnancies occurred between 2011 and 2022 at the Centre Hospitalier Universitaire de Sherbrooke. All selected pregnancies were screened for PA with an aldosterone-to-renin ratio (ARR) within a 5-year period. Pregnancies with more than two fetuses and with other endocrinopathies were excluded. MEASUREMENTS:To ascertain PA diagnosis, ARR measurements were conducted, followed by a confirmatory test if abnormal. RESULTS:Among 226 studied pregnancies, 15 (6.6%) were diagnosed with PA. In the PA group, pre-eclampsia was diagnosed in 46.7% of pregnancies (vs. 30.8%, p = 0.252), while gestational hypertension was diagnosed in 0.0% of pregnancies (vs. 16.6%, p = 0.136). Post-partum HDP occurred in 40.0% of pregnancies with PA (vs 19.4%, p = 0.093). Additionally, 40.0% and 13.3% of pregnancies with PA respectively required intravenous antihypertensive treatment (vs. 24.2%, p = 0.216) and intensive care admission (vs. 3.3%, p = 0.113). CONCLUSIONS:A trend towards an increased incidence of postpartum and severe pre-eclampsia was noted in the PA group.

OBJECTIVE:Severity classifications are essential for many diseases to prioritize patient management tasks such as diagnosis, treatment, and follow-up. Primary aldosteronism (PA), a common cause of secondary hypertension, lacks a standardized severity scale despite generally requiring invasive diagnostics like adrenal venous sampling (AVS). This study aimed to develop a global expert consensus-based classification for PA severity to improve clinical decision-making. METHODS:A panel of 45 international experts from 40 centers across four continents used the Delphi method to create a consensus severity classification for PA. This classification was then applied retrospectively to 2593 PA patients from 26 centers to assess its association with the disease subtype. RESULTS:After four rounds, the Primary Aldosteronism Severity Classification (PASC), which integrates biochemical and clinical parameters including serum potassium, blood pressure, and basal plasma aldosterone concentration, was established. Primary Aldosteronism Severity Classification classifies PA into mild (3 and 4 points), moderate (5-7 points), and severe (8 and 9 points). Among the cohort from 26 centers, 13.9%, 63.0%, and 23.1% were classified as mild, moderate, and severe, respectively, aligning with lateralized subtype prevalence rates of 14.7%, 44.6%, and 72.6%. CONCLUSION:Primary Aldosteronism Severity Classification is a newly developed simplified, semi-quantitative classification of PA severity. The correlation between PASC and lateralized PA subtype supports its potential to provide graded recommendations of AVS prior to surgical indication in each patient.

Disclosure: S.R. Chacko: None. C.A. Villavicencio Torres: None. K. Yu: None. S.G. Waguespack: None. L. Lu: None. Z. Belaya: None. T. Bandgar: None. A. Sada: None. O. Ragnarsson: None. B. Altieri: None. A. Newman: None. P. Vibhatavata: None. M. Tóth: None. E.V. Varlamov: None. C. Badiu: None. A. Paissan: None. M. St-Jean: None. H. Falhammar: None. N. Imamudeen: None. L. Haberbosch: None. M. Bobrowicz: None. A. Tabarin: None. R. Shah: None. M.R. Gadelha: None. A. Peersen: None. W.F. Young: None. J. Kaplan: None. J. Varghese: None. M.A. Habra: None. O. Golounina: None. G.A. Melnichenko: None. A.R. Lila: None. C. Yamichannaiah: None. I. Bancos: None. Context: Cushing syndrome (CS) due to ectopic ACTH secretion (EAS) is a rare condition, associated with severe hypercortisolism and consequent morbidity and mortality. Its varied and often emergent presentation make diagnosis and treatment challenging. Objectives: 1.Characterize clinical and biochemical presentation of EAS. 2.Describe the scope of hypercortisolism-related complications, overall and CS-specific mortality. 3.Identify factors associated with CS-specific mortality. Methods: We conducted a multicenter retrospective cohort study in patients with EAS at 37 centers. Outcomes were clinical/biochemical severity scores, complications, overall and CS-specific mortality. Results: In 1053 patients [median age at diagnosis 52 years (IQR 37-64), 57% women], metastatic disease was present at diagnosis in 585 (56%). The most common sources of EAS were bronchial neuroendocrine neoplasm (NEN) (304, 29%), pancreatic NEN (114, 11%) and small cell lung carcinoma (114, 11%), with the source of EAS being occult in 192 (18%). Clinical and biochemical severity scores were severe in 475 (45%) and 873 patients (92%) respectively. Hypokalemia was present in 819 patients (78%) in the year prior to diagnosis. Of 342 patients (32%) who had IPSS, 301 (88%) suggested an ectopic source, 7 (2%) a pituitary source, and 23 (7%) were non-diagnostic. Of 595 patients who had both functional and cross-sectional imaging, discordant findings were seen in 122 (21%), concordant lesion was seen on both in 326 (55%), and no lesion in 147 (25%). Of those with discordant results, cross-sectional imaging was accurate in 66 (54%) and functional imaging in 56 (46%).Management included medical therapy alone in 237 (23%), surgical excision of the source of EAS in 158 (15%), bilateral adrenalectomy in 77 (7%) and multimodal therapies in 498 patients (47%). Complications within 5 years after diagnosis included hospitalization related to CS or its therapy in 351 (33%), infection in 337 (32%), thromboembolic event in 102 (10%), cardiovascular event in 83 (8%) and cerebrovascular event in 27 (3%). During a median follow-up of 35 months (IQR 20-122) from CS diagnosis, death occurred in 462 patients (44%), with the cause of death related to CS in 149 (14%). CS-specific mortality was higher in metastatic compared with non-metastatic disease (19% vs. 7%, P<0.001). On multivariable analysis of age, sex, clinical and biochemical severity, older age (HR 1.03, 95% CI: 1.02-1.04) and lower clinical severity score (HR 0.97, 95% CI: 0.94-0.99), were associated with higher CS-specific mortality. Conclusion: Our interim analysis, the largest worldwide, found that most patients with EAS had severe hypercortisolism and hypokalemia. Metastatic disease was present in 56%, and the source of EAS was occult in 18%. CS-related death occurred in 14%, emphasizing the need for urgent management. Presentation: Monday, July 14, 2025

BACKGROUND:Primary aldosteronism (PA) is a common treatable cause of hypertension. When caused by unilateral adrenal disease, it is potentially curable by adrenalectomy. However, specialized tests and other factors may delay definitive treatment. We assessed the time to adrenalectomy (TTA) for patients worldwide. METHODS:We conducted an international, multicentre retrospective study involving 39 centres from 15 countries to determine the total time taken from the first presentation to adrenalectomy and the intervals between each stage (screening, confirmatory, subtyping, and adrenalectomy). We included patients with PA who underwent adrenalectomy from January 1, 2018, to October 30, 2022. Post-adrenalectomy outcomes were evaluated using the Primary Aldosteronism Surgery Outcome criteria. We performed multivariable quantile and linear regression to identify characteristics associated with longer TTA. RESULTS:We included 861 patients, mean age 49.3 ± 11.1 years, and 44.5% were women. Overall median TTA was 13.5 months, IQR: 6.6-24.5. Median intervals were 0.1 months (screening), 1.0 months (confirmatory), 4.1 months (subtyping), and 4.3 months (adrenalectomy). On multivariable analysis, median TTA was increased by 5.4 months for each additional adrenal vein sampling (AVS) procedure. Other factors associated with longer TTA included adrenalectomy post-COVID-19, younger age, and additional screening tests. Compared with countries with routine AVS, those without AVS had a shorter TTA (6.1 vs 15.1 months, P < .001), but greater likelihood of absent/partial biochemical success post-adrenalectomy (27.4% vs 12.4%, P < .001). CONCLUSION:Primary aldosteronism management is time-consuming worldwide, especially for subtyping tests and adrenalectomy. While omitting AVS reduces overall time, patients are less likely to achieve biochemical cure post-adrenalectomy.

Disclosure: D. Oprea: None. A. Groleau: None. D. Laura: None. F. Lefrançois: None. M. Malick: None. A. Côté: None. M. Roy-Lacroix: None. M. Mahone: None. M. St-Jean: None. N. Sauvé: None. Background and Purpose: Primary aldosteronism (PA) is a frequent cause of secondary hypertension in young adults. However, to this day, there is still limited data regarding its prevalence and impact during pregnancy. Methods: The prospective phase of the H.A.P.P.I. project consisted of a bicentric cohort study, which was conducted between 2022 and 2024 in Quebec, Canada. All patients diagnosed with hypertensive disorders of pregnancy (HDP) who delivered in one of two university centers were eligible and were recruited during their post-partum follow-up to be screened for PA with an aldosterone/renin ratio (ARR). Additional confirmatory testing was performed if positive screening, according to local reference values. Patients with other endocrinopathies or secondary aldosteronism were excluded. Our primary objective was to determine PA prevalence among patients who experienced any subtype of HDP. Results: Among 240 included patients, 232 patients have completed their ARR screening. Preliminary results have shown positive screening in 18.1 % (n = 42) of patients, of which additional testing confirmed 18 (7.8%) PA diagnoses. Additional testing is pending for 24 patients. 44.4% (n = 8/18) of patients with confirmed PA were of African descent, as opposed to 10.0% in patients with negative PA screening (p < 0.001). Hypokalemia prevalence was not different between patients with positive PA screening and the ones with negative screening (antepartum: 14.3% (n = 3/21) vs. 13.0%, p = 1.00; post-partum: 7.1% (n = 2/28) vs. 8.3%, p = 1.00). 61.9% of patients with positive PA screening (n = 26/42) required labor induction because of HDP occurrence, compared to 49.5% of patients with negative PA screening (p = 0.173). Pre-eclampsia (54.8% (n = 23/42)) was the most frequent type of HDP in patients with positive PA screening, compared to chronic (19.1% (n = 8/42)) and gestational hypertension (40.5% (n = 17/42)). There was no difference between antepartum preeclampsia (72.9%, vs 75.6%, p = 1.00), postpartum preeclampsia (26.1%, vs. 24.4%, p = 1.00), and preeclampsia with adverse conditions (42.9%, vs. 41.6%, p = 1.00) compared to patients with negative ARR screening. Conclusion: So far, an estimated PA prevalence of 7.8% was described in patients recently diagnosed with HDP, who presented mainly as antepartum preeclampsia. Final results will be presented at the conference. Keywords: Primary Hyperaldosteronism, Aldosterone, Hypertension, Pregnancy-Induced, Pregnancy, Pregnant Women, Pregnancy Outcome. Presentation: Sunday, July 13, 2025

Abstract Disclosure: L. Branchaud-Croisetière: None. J. Castilloux: None. E. Turcotte: None. A. Bégin: None. M. St-Jean: Advisory Board Member; Self; GlaxoSmithKline, HRA Pharmaceuticals. Research Investigator; Self; AstraZeneca, Novo Nordisk, Spruce Biosciences. Speaker; Self; GlaxoSmithKline, Recordati Rare Diseases. In advanced ACC, limited effective treatment options are available beyond mitotane and cytotoxic chemotherapy. PD-L1 blockade has shown promising results in small numbers of advanced ACC. In ACC, the reported partial response rate to pembrolizumab is around 25%.[1] Only one case of a significant partial response to a single dose of Pembrolizumab as salvage therapy for metastatic ACC was previously published.[1] In April 2023, a 19-year-old woman presented with severe hypertension, hypokalemia and clinical signs of Cushing syndrome (CS). Thoraco-abdominal scan revealed a left-sided cluster of confluent adrenal masses (7.3 x 14.4 x 11.4 cm), a left cortical renal lesion (2.8x2x2.1cm), a right ovarian teratoma (7.9 x 7.8x7.9 cm) and at least 25 pulmonary micronodules. FDG-PET SCAN revealed a significant hypermetabolism of the left adrenal lesions (SUV 18.6), ovarian teratoma (SUV 5.5) and pulmonary micronodules (SUV 1.1-2). Cortisol and androgens secretion was confirmed biochemically. Initially, she was not candidate for a debulking surgery because the tumor was surrounding the aorta, and mesenteric arteries. Hypertension and hypokalemia were treated with spironolactone, amlodipine, amiloride and irbesartan. Cushing syndrome was treated with metyrapone. In April 2023, Etoposide-Doxorubicine-Cisplatin (EDP) was administered in combination with Mitotane (max: 8g/day). After 6 cycles of EDP-M the disease regressed slightly but was considered stable based on RECIST criteria. After 8 cycles, the follow-up imaging showed a progression of the adrenal lesion (9.2x18.2cm) but stable pulmonary micronodules. A biopsy of the adrenal lesion, for therapeutic purpose, revealed microsatellite stability (MSS). The patient refused germinal genetic testing. It was decided in multidisciplinary tumor board to try Pembrolizumab. In December 2023, she received one cycle of Pembrolizumab (140mg), but the treatment was complicated by grade 4 immune-mediated hepatitis. A few weeks following Pembrolizumab she completely normalized her blood pressure and hypokalemia despite cessation of all her anti-hypertensive drugs. Pembrolizumab and Mitotane were stopped and hepatitis completely resolved after two months of Mycophenolate Mofetil and ongoing decreasing dose of prednisone. In March 2024, CT scan showed a 60% regression of the adrenal mass (4.1 x 7.2 cm), stability of the renal lesion and ovarian teratoma and complete resolution of the pulmonary micronodules. We suspect an ongoing effect of immunotherapy and Mitotane, since Mitotane levels were still in the therapeutic range (15.1 mg/L) six weeks following cessation. Mitotane was resumed in March 2024. The patient will potentially have a resection of the left adrenal lesion in the next month. This is second published case of a significant response to Pembrolizumab as second-line therapy for advanced ACC. [1] Raj Net al. J Clin Oncol. 2020 Presentation: 6/1/2024

Context: Renin-angiotensin-aldosterone system (RAAS) activation is closely linked to obesity; however, the sex-specific associations between RAAS activity and body composition among individuals without obesity are not well understood. Objective: To investigate the associations of aldosterone and renin with body composition according to sex in the general population. Design: Population-based cohort study. Setting: Qu & eacute;bec (Canada). Participants: Adults aged 40 to 69 years enrolled in CARTaGENE between 2009 and 2010 (N = 3687). Exposures: Plasma aldosterone and renin concentrations. Main Outcome: Measures Body composition assessed via anthropometrics (waist circumference and waist-to-hip ratio), bioelectrical impedance (lean body mass, fat mass, and muscle mass), and cardiac magnetic resonance imaging (epicardial and pericardial adipose tissue volumes). Results: The mean (SD) age and body mass index were 55 (8) years and 27.3 (4.8) kg/m(2), respectively. Among males, higher aldosterone and renin were associated with increased waist circumference, increased waist-to-hip ratio, increased fat mass, decreased lean body mass, and decreased muscle mass (P < .05). Aldosterone (P = .02), but not renin (P = .43), was associated with increased ectopic cardiac adiposity in males. In contrast, higher renin (P < .05), but not aldosterone (P >= .05), was associated with increased waist circumference, increased waist-to-hip ratio, and increased cardiac adiposity in females. Among females, higher renin and aldosterone were associated with increased fat mass (P < .05) but were not associated with lean body mass or muscle mass (P >= .05). All aforementioned associations were independent of body weight. Conclusion: Independent of body weight, increased RAAS activity is associated with unfavorable differences in body composition; however, the strength and pattern of association varies by sex.

Abstract Disclosure: B. Brochu: None. Y. Collin: None. R. Temmar: None. F. Bernier: None. K. Dandurand: None. M. St-Jean: None. M. Massicotte: None. Background: Composite pheochromocytoma-ganglioneuroma is a rare tumor combining features of both pheochromocytoma/paraganglioma (PPGL) and neurogenic tumors. Cosecretion of vasoactive intestinal peptide (VIP) is even less common and highlights the diverse secretory potential of these tumors. Clinical Case: An 80-year-old woman presented with severe chronic diarrhea that had been progressively worsening over the past 10 years. The diarrhea was associated with chronic hyponatremia between 128 and 132 mmol/L. She also had mild hypertension, with a mean blood pressure of 145/90 mm Hg. An abdominal CT scan revealed a right adrenal mass of 68 mm x 44 mm x 50 mm with a density of 19 HU without contrast. A 24-hour urinary collection demonstrated normetanephrines (NM) levels at 3.5 times the upper limit of normal. A 68Ga-DOTATATE PET/CT demonstrated significant uptake only in the adrenal mass. Because of the ongoing severe diarrhea, that is unusual in the context of NM secreting PPGL, serum VIP level was measured and came back at nearly three times the upper limit of normal. A provisional diagnosis of pheochromocytoma with VIP and catecholamines cosecretion was made and surgical resection by laparotomy was performed without complication. Pathology demonstrated a composite tumor combining a pheochromocytoma and a ganglioneuroma, with a Pheochromocytoma of the Adrenal gland Scaled Score (PASS) score of 3. Tumor immunohistochemical staining was positive for VIP in both pheochromocytoma and ganglioneuroma cells. After surgery, diarrhea and hyponatremia resolved and blood pressure normalized. Conclusion: This is one of the very rare cases described in the current literature of a composite pheochromocytoma coproducing catecholamines and VIP. While the two tumors might have developed synchronously, the finding of VIP secretion in the pheochromocytoma and the ganglioneuroma suggest that both tumors might originate from the same cell. Presentation: 6/1/2024

Abstract Disclosure: C. Ter Li Min: None. K. Xuan Han: None. M. Araujo-Castro: None. E. Gkaniatsa: None. M. Reincke: None. T. Viet Tran: None. H. Tran: None. M. Stowasser: None. M.A. Grytaas: None. A. Turcu: None. J. Matrozova: None. N. Sukor: None. T. Kocjan: None. R. Baudrand: None. M. Tsuiki: None. M. Murakami: None. J. Yang: None. T. Katabami: None. M. Naruse: None. M. St-Jean: None. F. Ceccato: None. T. Puar Hai Kiat: None. Background: Primary aldosteronism (PA) is a common cause of hypertension. Patients with unilateral PA can be cured by adrenalectomy. However, the time required to undergo specialised tests like adrenal vein sampling (AVS), and laparoscopic adrenalectomy may delay management. We assessed the current time-to-adrenalectomy (TTA) for patients with PA worldwide. Methods: We conducted an international, multi-center retrospective study involving 37 centers from 15 countries to determine the total time from first presentation to adrenalectomy, and each interval: screening (first presentation to first screening test), confirmatory, subtyping, and adrenalectomy. We included all patients with PA who underwent adrenalectomy from 1st January 2018 to 30th October 2022. After adrenalectomy, patients were evaluated using Primary Aldosteronism Surgery Outcome (PASO) consensus. Patient and center characteristics were compared at the 25th, 50th, and 75th percentiles of TTA using multivariable quantile regression. Multivariable linear regression was used to identify factors associated with longer intervals. Results: Among 708 included patients (mean age 49.2 years, 45.8% female), the overall median TTA was 14.0 months (IQR 7.1-25.2). The median intervals were 0.1 months (screening), 2.3 months (confirmatory), 4.2 months (subtyping), and 5.1 months (adrenalectomy). On multivariable analyses, patients with an additional screening test, an additional AVS, and who presented post-COVID-19 had a significantly longer TTA at the 75th percentile, by 3.2 months, 12.3 months, and 6.0 months respectively. Other factors that increased TTA were younger age, lower baseline diastolic blood pressure (BP) and more baseline BP medications. Factors associated with a longer screening interval included younger age, lower baseline potassium, and lower diastolic BP, while additional screening tests were associated with a longer confirmatory interval. Factors associated with a longer adrenalectomy interval were more baseline BP medications, additional confirmatory tests and additional AVS. Patients who presented post-COVID-19 were associated with longer time at all intervals. Compared to centers that routinely perform AVS, centers without AVS had shorter TTA (6.1 vs 16.5 months, P<0.001), similar PASO clinical outcome, but poorer PASO biochemical outcome, with complete, partial and absent biochemical success seen in 66.4%, 11.9%, 21.6% vs 86.8%, 3.7%, 9.5%, P<0.001, respectively. Conclusion: Based on real-world data from patients with PA managed in five continents, most patients required more than one year from first specialist presentation to adrenalectomy. The longest intervals are time required to undergo AVS and adrenalectomy. While omitting AVS may reduce the TTA, this is associated with poorer biochemical outcome. The COVID-19 pandemic contributed to delayed healthcare delivery worldwide. Presentation: 6/1/2024

Objective To assess the usefulness of the upright posture stimulation test (UPT) in the confirmation of primary aldosteronism (PA) in patients in whom saline tests (ST) were inconclusive. Methods One hundred eighty-seven adult patients with possible PA were retrospectively included and compared to 25 control subjects. Blood samples were obtained after a 1-hour supine posture and during 2 hours of ambulation. An increase in plasma aldosterone concentration (PAC) >= 50% with a suppressed renin (<= 10.1 ng/L; <= 1 ng/mL/hour) and a cortisol increase <= 50% were considered abnormal. Results PA patients had higher basal PAC and lower basal direct renin concentration (DRC) (P < .0001) and a higher maximal PAC (P = .0025) and lower maximal DRC (DRCmax) (P < .0001) during UPT compared to controls. PA was confirmed in 145 patients (77.5%), based on either oral/IV ST or UPT. DRCmax <= 12 ng/L during UPT was a predictor of PA (receiver operating characteristic curve sensitivity 93.8%, specificity 88%), and 95.6% of PA patients increased PAC >= 50% on UPT (median 222.2%), while renin remained suppressed. All 41 PA patients with false-negative IV ST (PAC < 162 pmol/L) and 88.9% with borderline response (162-240 pmol/L) had a DRCmax <= 12, while, respectively, 97.6% and 100% increased aldosterone by >= 50%. Similar responses to UPT were found in lateralized (28/63) and bilateral PA source (35/63). PA diagnosis increased from 23.6% to 88.8% using UPT results instead of IV ST and were confirmed at pathology and clinical outcome after adrenalectomy (n = 22). Conclusion UPT can be useful to confirm PA, particularly in patients with suspected false-negative ST.

Abstract Disclosure: N. Younes: None. M. St-Jean: None. M. Desrochers: None. I. Bourdeau: None. A. Lacroix: None. Objectives: Renin-independent aldosterone excess characterizes primary aldosteronism (PA). We have previously shown that PA is frequently regulated by aberrant stimuli, including the upright posture stimulation test (UPT), in which plasma aldosterone concentrations (PAC) increase in a renin-independent manner. In this study, we further examined the usefulness of UPT in diagnosing PA. Methods: We conducted a retrospective analysis of the medical records of 187 adult patients who underwent an UPT as part of their evaluation for possible PA and 25 control subjects, in 2 referral university centers between January 2011 and December 2021. UPT was conducted in an ambulatory setting, mostly in patients with potential false negative or borderline results of oral/IV saline confirmation tests. UPT was performed in a fasting state, early morning, 72 hours off beta-blockers, ACE, or ARBS. Patients were in a supine posture for 1 hour, followed by ambulation for 2 hours. Blood samples were collected for PAC, renin, and cortisol, at baseline and at 30 minutes intervals during ambulation. An abnormal response was defined as a ≥50% rise in PAC with a suppressed renin (≤10.1 ng/L or ≤1 ng/mL/h) and a cortisol increase ≤50%. Results: Median age of patients was 55.0 [IQR (46.0; 63.0)], 52.4% were female. 93.6% were taking at least one antihypertensive medication and 32% had hypokalemia. 43.5% did not have adrenal nodules at imaging. 76.5% (n=143) were diagnosed with PA, based on either IV/oral sodium load or UPT. When compared to controls, PA patients had higher basal PAC and lower basal renin levels (p<.0001) and achieved a higher maximal PAC and lower maximal renin (renin max) in response to posture [median PAC (IQR): 802.0 pmol/L (569.0, 1244.0) in PA v/s 624.0 pmol/L (500.0, 736.0) in controls, p=0.0081 and median renin 5.0 ng/L [IQR (3.0, 8.0)] in PA v/s 27.5 ng/L in controls (19.0, 46.0); p<.0001]. Renin max ≤10.1 had the best sensitivity and specificity for predicting PA (90% and 92%, respectively). 95.3% of PA patients increased PAC by at least 50% on UPT (median increase 363%), while renin remained suppressed. All 42 PA patients with a false negative (PAC ≤162 pmol/L) on IV saline test had a renin max ≤10.1 during UPT and 97.6% increased aldosterone by at least 50%. 84% of PA patients with a borderline response (162-240 pmol/L) on IV saline test, had a renin max ≤10.1 and all patients increased aldosterone by at least 50%. 42 patients underwent adrenal vein sampling: 50% had lateralized PA (potassium was lower than in bilateral PA, p=0.003). However, the aldosterone and renin response to UPT did not significantly differ between the two subtypes of PA. Conclusion: A renin-independent aldosterone increase during UPT can be used to confirm PA diagnosis, which was particularly useful in patients with false negative saline loading tests. Renin-independent PAC response to UPT occurred equally in lateralized and bilateral PA. Presentation: Friday, June 16, 2023

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 < 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

Objective Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized. Design In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated. Results We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers. Conclusions Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA.

Abstract Disclosure: L. Branchaud-Croisetière: None. M. St-Jean: Speaker; Self; Recordati rare disease, GlaxoSmithKline. Stock Owner; Self; Spruce bioscience. Cushing syndrome (CS) is caused by PBMAH in <2% of cases. Treatment is mostly surgical with unilateral or bilateral adrenalectomy, but in some cases, identification of aberrant receptors can allow the use of targeted medical therapies. Only a few cases of adrenal CS associated with an aberrant LH/hCG receptors that were treated with GnRH agonist were described. In December 2020, we saw a 72-year-old woman for bilateral adrenal nodules and an ACTH independent hypercortisolism. Her past medical history includes depression, insomnia, and osteoporosis with multiples fragility fractures. She was taking citalopram, calcium, vitamin D and alendronate was added in 2021. In the follow-up she developed dyslipidemia and hypertension. There were no sign of CS on physical examination. In 2020, a non-contrast thoracic scan was done and showed a right adrenal nodule of 3x1,4 cm and a left adrenal nodule of 3 x 2 cm both with densities < 10 HU and no atrophy of the adrenal limbs. In August 2021, a FDG PET scan showed an SUV of 3,4 on the right side and 3,7 on the left side. Morning cortisol after 1 mg DST (done twice) were 122 and 133 nmol/L (N <50). Aldosterone to renin ratio and 17-OHP were normal. In September 2020, a 4 mg IV dexamethasone suppression test was done and cortisol was 189 nmol/L at 9h am on day 2. Between 2020 and 2021, ACTH (3 values) were between 1,3-1,7 pmol/L (N 0-10 pmol/L) and DHEAS (3 values) between 1-1,6 (N 0,95-11,67 mol/L). 24h UFC (7 values) varied from 280,6 to 600,6 nmol/d (N 153-789 nmol/d). LNSC (8 values) were normal <2 to 3 nmol/L (N <5) except for one value at 6 nmol/L. In February 2022, systematic research for aberrant receptors was done. The cortisol have showed an ACTH-independent increased of 242% following 100 mcg IV of LHRH. There was also a significant ACTH-independent increase after 10 IU of vasopressin (+ 66%) and 10 mg of maxeran PO (+ 98%). There was no significant increase in cortisol after stimulation with glucagon 1mg IV and the upright posture test. We couldn’t obtain cortisol measures after stimulation with cortrosyn and the mixed-meal test because of issues with samples. Treatment with Leuprolide 3,75mg IM monthly was started in April 2022 and the dose was increased to 7,5 mg in August 2022 because of partial response observed initially. There was a response with an increase in ACTH from <1,1 to 2,6 pmol/L until December 2022. Since January 2023, ACTH (3 values) have decreased between 1,8-2 pmol/L. In January 2023, the morning cortisol after 1 mg DST was 104 nmol/L and 24h UFC were 161 and 306 nmol/d and two LNSC were <2 nmol/L. However, with the recent decrease in ACTH, we suspect an escape to Leuprolide. In summary, this is a rare case of MACS due to PBMAH expressing aberrant LH receptors with initial response to Leuprolide. We are waiting for the results of genetic testing. The patient could eventually benefit from a left unilateral adrenalectomy if escape from medical treatment is confirmed. Presentation: Thursday, June 15, 2023

Abstract Background Primary aldosteronism (PA) is associated with a high burden of cardiometabolic complications such as coronary heart disease, atrial fibrillation, left ventricular hypertrophy, stroke and chronic kidney disease. It is therefore essential to screen, confirm the diagnosis and then implement a targeted treatment, to lower the rate of these complications. According to the latest Endocrine Society guidelines for the management of PA, unilateral adrenalectomy is recommended when the secretion of aldosterone is mostly coming from one adrenal. If the secretion is bilateral or if the patient refuse surgery, medical treatment with mineralocorticoid receptor antagonist is indicated. Nevertheless, there are limited data comparing these two treatments on their impact on the number and dosage of anti-hypertensive drugs needed to control the disease. Objective The objective was to compare the impact of medical or surgical treatment on the antihypertensive defined daily dose (DDD) after 6 months of treatment in our cohort of PA patients followed at the CHUS. We've also evaluated the kalemia, blood pressure and renin after 6 and 12 months of treatment. Long term blood pressure control has also been evaluated. Methodology To answer this question, we conducted a single-center retrospective cohort study. Adults followed at CHUS between 2000 and 2021, with a confirmed diagnosis of PA and a follow-up of at least 6 months were included. Pregnancy was the only exclusion criteria. The primary outcome was the variation in the antihypertensiveDDD in patients medically treated compared to those surgically treated after 6 months. Results A total of 46 patients were included in our cohort, from which 28 were medically treated. Patients in the surgical group were younger, had a higher diastolic blood pressure and aldosterone/renin ratio. Among the 18 patients who underwent unilateral adrenalectomy, only 6 of them had a clearly lateralized secretion confirmed by adrenal veins sampling. At 6 months, the antihypertensive DDD variation was statistically significantly higher in the surgical group, with a decrease of 1.7 compared to a decrease of 0.6 in the medical group. Even after age, diastolic blood pressure and aldosterone/renin ratio adjustments, the difference between the 2 groups remains statistically significant, with a p value of 0. 033. Conclusion These results indicate that the surgical treatment of patient with primary aldosteronism leads to a greater DDD decrease at 6 months, even after adjusting for disease severity and despite the fact that the surgical group is not exclusively unilateral. However, the impact of disease control on long-term outcomes could not be assessed due to missing data. Presentation: No date and time listed

Endogenous Cushing's syndrome (CS) is rare during pregnancy, probably because hypercortisolism induces anovulation and infertility. To date, slightly above 200 cases have been reported in the literature. The most frequent etiology of CS diagnosed during gestation is from primary adrenal causes, namely adrenal adenomas and an entity called pregnancy-induced CS. The latter can be secondary to the aberrant adrenal expression of luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) in the adrenal lesions. Diagnosis of CS during pregnancy is extremely challenging, as a consequence of the physiologic hypercortisolism normally present during pregnancy. Assessment of excess cortisol production tests should be interpreted cautiously using adapted upper limits of normal criteria for pregnant patients and a high index of suspicion is required for diagnosis. Imaging is also limited due to high risk of radiation exposure with computed tomography and teratogenicity with contrast agents. The optimal treatment strategy is surgical resection of adrenal adenoma or pituitary adenoma, ideally before 24 weeks of gestation to reduce the risk of maternal and fetal complications. In mild cases, surgery can be postponed until after delivery and treatment should focus on controlling metabolic complications of hypercortisolism, such as hypertension and dysglycemia. Maternal and fetal outcomes of excess cortisol exposure, except fetal loss, are not readily improved by successful treatment of hypercortisolism.