Cortisol Cosecretion Research Articles

Primary Bilateral Macronodular Adrenal Hyperplasia: A Case Series from a Tertiary Hospital

Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare etiology of Cushing’s syndrome characterized by the presence of multiple adrenal macronodules and variable levels of cortisol excess. Its pathogenesis is complex, involving mechanisms such as aberrant hormone receptors, adrenal paracrine ACTH production, and genetic germline pathogenic variants. However, management is not well established. Methods: This was a retrospective, observational study. We evaluated patients with PBMAH at our tertiary center. We aimed to describe the clinical, hormonal, and radiological characteristics; treatment approaches; and outcomes. Results: Twenty patients were included in this study. Patients had a mean age at diagnosis of PBMAH of 56.1 ± 11.1 years, and 10 patients (50.0%) were females. Most cases were initially investigated for adrenal incidentalomas. Median 8:00 a.m. serum cortisol after 1 mg dexamethasone overnight suppression test was 223.5 (73.1–698.6) nmol/L (8.11 [2.65–25.3] µg/dL), late-night salivary cortisol was 1.48 (0.765–3.21) times the upper limit of normal (ULN), and 24 h-UFC was 1.61 (0.42–3.64) times the ULN. One patient presented with the co-secretion of cortisol and aldosterone. Mean total adrenal size was 98.5 ± 25.6 mm, and the largest nodule size was 32.1 ± 9.09 mm. In six (31.6%) patients, the largest nodule had an attenuation higher than 10 HU. Germline pathogenic variants in ARMC5 were found in four (50.0%) of the eight tested patients who underwent genetic testing. Treatment strategies varied, with unilateral adrenalectomy often successfully controlling hypercortisolism in five (83.3%) of 6 patients with modest excess cortisol secretion. For mild autonomous cortisol secretion, active surveillance of comorbidities and appropriate treatment were not associated with progression of cortisol secretion after a median follow-up of 34.0 (10.5–83.0) months. Conclusion: This study underscores the need for personalized management strategies and identifies areas for future research to optimize the care of patients with PBMAH.

7109 "My Stomach hurts": A Rare Case of Adrenal Cortical Carcinoma

Abstract Disclosure: R.C. Attah: None. I. Sirisena: None. Pheochromocytoma/Paragangliomas are rare neurogenic tumors that arise from chromaffin cells present in the adrenal medulla or extra-adrenal paraganglia, these cells produce catecholamines. Typically, these tumors are discovered as incidentalomas. They can be hereditary as seen in genetic syndromes like multiple endocrine neoplasia type 2A or 2B, neurofibromatosis type 1 or Von Hippel Lindau syndrome but can occur sporadically. Patients typically present with hormonal hypersecretion signs or symptoms like abdominal pain, episodic headaches, sweating, hypertension and tachycardia, but some patients are asymptomatic. Patient is a 37-year-old female with past medical history of hypertension, type 2 diabetes mellitus and fatty liver who presented to the ED with abdominal pain for a few weeks. On arrival, her vitals were BP 205/124, HR 102, RR 14 and SpO2 100% on room air. CT abdomen was obtained which showed a 7.6 x 4.7 x 5.7 cm mass replacing left adrenal gland with small left retroperitoneal hemorrhage worrisome for adrenal cortical carcinoma, metastatic disease or pheochromocytoma. Hormonal workup revealed elevated 24-hr urine cortisol 124.2mcg (ref 4.0-50.0mcg/24h), normal aldosterone/renin ratio 10.63ng/dL (ref <30ng/dl), failed low dose dexamethasone suppression test with post-dex AM cortisol 7.20ug/dL (ref <1.8ug/dL), slightly elevated serum total catecholamine 1256pg/mL (242-1125 pg/mL), norepinephrine 1155pg/mL (ref 217-1109 pg/mL), total metanephrine and normetanephrine 341pg/mL (reg <205 pg/mL), normetanephrine 244.1 (ref <210.1pg/mL), elevated 24-hr urine normetanephrine 700ug/L (ref 131-612ug/L), metanephrine 136ug/L (ref 36-209ug/L) and DHEA-s level 285ug/dl (ref 23-266ug/dL). Due to elevation in cortisol, adrenal cortical carcinoma was suspected as these tumors are frequently associated with cortisol secretion. However, pheochromocytoma with co-secretion of ACTH could not be excluded. She was started on doxazosin for alpha blockade and eventually started on beta blockade with Metoprolol. She underwent a left adrenalectomy and was started on steroid taper post-op due to concern of cortisol co-secretion. Surgical pathology was positive for Left adrenal malignant pheochromocytoma and ganglioneuroma. Genetic panel was negative with no mutation identified in the 54 gene Hereditary paraganglioma-pheochromocytoma panel. This patient had a large adrenal tumor (>4cm mass) but mildly elevated catecholamines which could have led to misdiagnosis as her catecholamine levels were less than 2-3x ULN which is unusual for pheochromocytomas. Roughly 25% of people with pheochromocytoma are undiagnosed throughout their lifespan. This condition can be life-threatening, hence early diagnosis and intervention can be lifesaving. Prognosis of malignant pheochromocytoma is dependent on tumor size, presence of SDHB gene mutation or visceral metastases. Presentation: 6/1/2024

NT-proBNP levels in patients with primary hyperaldosteronism and autonomous cortisol cosecretion.

Patients with primary aldosteronism (PA) have higher cardiac comorbidities including more pronounced left ventricular hypertrophy than patients with essential hypertension. Autonomous cortisol cosecretion (ACS) is a common subtype in PA associated with a worse metabolic profile. Autonomous cortisol cosecretion may affect myocardial parameters and result in a worse cardiac outcome compared to patients with PA and without ACS. Three hundred and sixty-seven patients with PA undergoing 1 mg dexamethasone suppression test (DST) and echocardiography at baseline from 2 centers of the German Conn's Registry were included. Follow-up for up to 3.8 years was available in 192 patients. Patients with PA and ACS had higher NT-proBNP levels at baseline compared to patients with PA without ACS (114 vs 75.6 pg/mL, P = .02), but showed no difference in echocardiography values. NT-proBNP levels showed a significant positive correlation (r = 0.141, P = .011) with cortisol levels after DST at baseline. In response to therapy of PA, NT-proBNP levels decreased, but remained significantly higher in patients with ACS compared to patients without ACS. At follow-up, left ventricle end-diastolic dimension (LVEDD) decreased significantly only in patients without ACS. Left atrial diameter (LAD) decreased significantly in patients without ACS and in female patients with ACS but not in male patients. Left ventricular mass index (LVMI) significantly improved in female patients without ACS but remained unchanged in female patients with ACS as well as in male patients at follow-up. In patients with PA, concomitant ACS is associated with a worse cardiac profile and only partial recovery even years after initiation of targeted PA therapy.

Diagnosis and Management of Adrenocortical Carcinoma with co-secretion of Cortisol and Aldosterone

Adrenocortical carcinoma (ACC) accounts for 0.05-2% of all malignant tumors. Forty-five percent of ACCs with secretory function have excess glucocorticoids alone and only less than 1% secrete aldosterone. This is a case of a 44-year-old Filipino female with hypertension and a 12-year-history of an incidentaloma of the left adrenal gland, with recent-onset complaints of increasing abdominal girth, purple striae, amenorrhea, moon facies and a dorsocervical fat pad. Laboratory findings revealed low potassium levels, non-suppressed cortisol on dexamethasone test suggesting Cushing’s syndrome and elevated aldosterone-renin ratio and plasma aldosterone concentration pointing to primary hyperaldosteronism. A computed tomography scan revealed a left-sided adrenal mass measuring approximately 23 cm in largest diameter suggestive of carcinoma without metastasis or lymph node involvement. Complete resection via open adrenalectomy was performed and histopathologic assessment revealed Adrenocortical Carcinoma with Weiss score of 4. The Ki-67 proliferative index was found to be >20%. Radiotherapy was done as an adjuvant treatment. Although rare, co-secretion of cortisol and aldosterone can occur in functional tumors of adrenocortical carcinoma. Malignancy should always be considered in patients who present with a history of a unilateral adrenal mass and/ or in those with signs and symptoms of adrenal hormone excess. Thus, a proper assessment derived from a thorough medical history, physical examination and laboratory work-up is warranted in patients with an adrenal mass to ascertain the diagnosis and provide adequate management.

Aldosterone:metanephrine ratio better predicts laterality in patients with primary aldosteronism and mild autonomous cortisol co-secretion than aldosterone:cortisol ratio

Aldosterone:metanephrine ratio better predicts laterality in patients with primary aldosteronism and mild autonomous cortisol co-secretion than aldosterone:cortisol ratio

PREVALENCE AND OUTCOME OF PRIMARY ALDOSTERONISM IN PBMAH: A SINGLE CENTER STUDY AND A SYSTEMATIC REVIEW OF THE LITERATURE

Objective: Primary bilateral macronodular adrenocortical hyperplasia (PBMAH), characterized by benign adrenocortical macronodules and variable levels of cortisol excess, can also lead to an excess of mineralocorticoids, although there is only anecdotal evidence. To assess the prevalence and characteristics of primary aldosteronism (PA) in patients with PBMAH. Design and method: We conducted a systematic review according to the PRISMA guidelines. We reviewed single case reports and case series of patients with PBMAH and PA in Pubmed, Embase and Cochrane from database inception to December 2023. PBMAH was defined radiologically as at least 1 bilateral adrenal nodule of at least 10 mm. Findings were compared to patients with PBMAH without PA derived from LMU Hospital and literature. Results: 1018 articles were screened, and 36 articles were assessed for eligibility. We identified 18 articles (8 single case reports and 10 case series), resulting in 68 cases with PBMAH with PA. Of those, 12 had cosecretion of cortisol. The prevalence of PA in PBMAH, in six studies (166 patients), ranged from 2-44%. The median age at diagnosis was 51.5 (47.5-56.2). The majority of patients with PBMAH and PA were male compared to patients with PBMAH without PA (59% vs 39%, p= 0.0295). At baseline, the mean arterial pressure was 112 mmHg (113-133) and the median duration of hypertension was 108 months (48-135). The serum aldosterone concentration and plasma renin activity were 253 ng/l (159-436) and 0.23 ng/ml/h (0.16-0.44), respectively. Adrenal nodules were smaller in patients with PBMAH with PA compared to patients with PBMAH without PA (22 vs 30 mm, p=0.0498). Treatment modality was reported in 30 cases: 28 patients underwent adrenalectomy (two bilateral, two subtotal, and 24 unilateral) and two received mineralocorticoid receptor antagonists (MRA). In comparison, fewer patients with PBMAH without PA underwent adrenalectomy (54/106, p=0.0005). Conclusions: PA in PBMAH appears to be more frequent than previously thought. Multicenter studies will help to clarify the association between these conditions and the most appropriate treatment modality.

The influence of cortisol co-secretion on clinical characteristics and postoperative outcomes in unilateral primary aldosteronism.

The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically. To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population. Retrospective cohort study. We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion. UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery. UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.

Effect of mild cortisol cosecretion on body composition and metabolic parameters in patients with primary hyperaldosteronism.

To investigate the effects of simultaneous cortisol cosecretion (CCS) on body composition in computed tomography(CT)-imaging and metabolic parameters in patients with primary aldosteronism (PA) with the objective of facilitating early detection. Retrospective cohort study. Forty-sevenpatients with PA and CCS confirmed by 1-mg dexamethasone suppression test (DST) with a cutoff of ≥1.8 µg/dL were compared with PA patients with excluded CCS(non-CCS, n = 47) matched by age and sex. Segmentation of the fat compartments and muscle area at the third lumbar region was performed on non-contrast-enhanced CT images with dedicated segmentation software. Additionally, liver, spleen, pancreas and muscle attenuation were compared between the two groups. Mean cortisol after DST was 1.2 µg/dL (33.1 nmol/L) in the non-CCS group and 3.2 µg/dL (88.3 nmol/L) in the CCS group with mild autonomous cortisol excess (MACE). No difference in total, visceral and subcutaneous fat volumes was observed between the CCS and non-CCS group (p = .7, .6 and .8, respectively). However, a multivariable regression analysis revealed a significant correlation between total serum cholesterol and results of serum cortisol after 1-mg DST (p = .026). Classification of the patients based on visible lesion on CT and PA-lateralization via adrenal venous samplingalso did not show any significant differences in body composition. MACE in PA patients does not translate into body composition changes on CT-imaging. Therefore, early detection of concurrent CCS in PA is currently only attainable through biochemical tests. Further investigation of the long-term clinical adverse effects of MACE in PA is necessary.

FRI157 Systematic Germline Genetic Analysis In A Cohort Of Adults With Primary Aldosteronism And Hypertension Onset ≤35 yo : Low Yield Of Genetic Pathogenic Variants

Abstract Disclosure: S. Parisien-La Salle: None. D. Nadine: None. Z. El-Haffaf: None. A. Lacroix: None. I. Bourdeau: None. Introduction: Primary aldosteronism (PA) is a common but underdiagnosed cause of hypertension. Although most cases are sporadic, up to 5% of patients have a familial form of PA. Current guidelines recommend germline genetic analysis in patients who present PA &amp;lt; 20 yo or have a family history of PA. As PA is underdiagnosed, we hypothesized that some patients with PA do not undergo germline genetic screening since familial history of PA is unrecognized. Objective: To evaluate the yield of systematic germline genetic analysis for familial PA in patients with PA, hypertension detection ≤ 35 yo and a family history of hypertension. Methods: From 2012-2022, patients diagnosed with PA (positive ARR and confirmatory testing), hypertension onset ≤ 35 yo and a family history of hypertension were offered genetic counselling for germline screening for known familial causes of PA. After informed consent, patients underwent germline analysis for the chimeric gene CYP11B2/CYP11B1 (Ruhr University Bochum, Germany) and a multigene panel including KCNJ5, CACNA1D, CACNA1H and CLCN2 genes (Fulgent, CA). Results: Twenty-five patients consented for genetic analysis. Thirteen patients (52%) were female. In regards to ethnic origin, 52% were French Canadians, 24% African-Americans and the other 24% was split between Asian, European and Middle Eastern descent. The mean age at diagnosis of hypertension was 28.3 yo and 39.7 yo at PA diagnosis. At PA diagnosis, 91.3% (21/23) had previous hypokalemia and 12% (3/25) a cortisol co-secretion (1 mg dexamethasone test&amp;gt; 50 nmol/L). Approximately 13% were on one hypertension drug, 30% on two, 26% on three, 26% on four and 5% were on five medications. Comobordities included: 8% atrial fibrillation, 20% obstructive sleep apnea and 4% coronary heart disease. All patients had a family history of hypertension, 5 patients (20%) had a family history of stroke, and 1 patient (4%) had a family history of PA. Of the patients who had already undergone adrenal vein sampling (n=22), 68.2% (15/22) underwent an adrenalectomy for lateralised aldosterone secretion and 31.8% (7/22) were treated with medical therapy for bilateral disease. None of the 24 patients who underwent testing for glucocorticoid-remediable aldosteronism were found to have the chimeric gene CYP11B2/CYP11B1. Twenty-three patients underwent the multigene panel and no pathogenic variants were identified. However, 4/23 (17,4%) patients carried a variant of unknown significance (VUS) in CACNA1H or CLCN2 genes (CACNA1H c.1315C&amp;gt;T(p.Arg439Cys),CACNA1H c.3868G&amp;gt;A(p.Val1290Ile),CACNA1H c.1939G&amp;gt;A (p.Gly647Ser), CLCN2 c.2402C&amp;gt;T, (p.Thr801Ile)). Conclusion: Systematic germline genetic testing for familial PA in this cohort of patients with PA, hypertension diagnosis ≤ 35 yo and a family history of hypertension did not yield positive results. Although PA is an underdiagnosed disease, familial forms remain very rare. Presentation: Friday, June 16, 2023

Autonomous cortisol secretion in patients with primary aldosteronism: prevalence and implications on cardiometabolic profile and on surgical outcomes.

The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 µg/dL (confirmed ACS if >5 µg/dL and possible ACS if 1.8-5 µg/dL) in the absence of specific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS-PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS-PA and PA-only patients was similar, except for older age and larger tumor size of the adrenal lesion in the ACS-PA group. When comparing the ACS-PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64-22.32)) and cardiovascular events (OR 5.0 (2.29-11.07)) was higher in ACS-PA patients than in ACS patients. The coexistence of ACS in patients with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS-PA and PA-only groups. Co-secretion of cortisol and aldosterone affects almost one-third of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS-PA and PA-only are similar.

'Pseudo-failure' of adrenal vein sampling due to cortisol co-secretion by KCNJ5-mutant adenoma, and prediction of complete clinical success by urine hybrid steroid assay

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Primary Aldosteronism and Cortisol Cosecretion in a Patient with Adrenal Adenoma

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Prevalence of Cortisol Cosecretion in Patients With Primary Aldosteronism: Role of Metanephrine in Adrenal Vein Sampling.

Adrenal venous sampling (AVS) is the gold standard procedure for subtype diagnosis in patients with primary aldosteronism (PA). Cortisol is usually adopted for the normalization of aldosterone levels in peripheral and adrenal samples. However, asymmetrical cortisol secretion can potentially affect the lateralization index, leading to subtype misdiagnosis. We aimed to assess the prevalence of asymmetrical cortisol secretion in patients undergoing AVS and whether variations in adrenal vein cortisol might influence AVS interpretations. We then evaluated the use of metanephrines for the normalization of aldosterone levels for lateralization index. We retrospectively included 101 patients with PA who underwent AVS: 49 patients underwent unstimulated AVS, while 52 patients underwent both unstimulated and cosyntropin-stimulated AVS. Eighty-eight patients had bilateral successful AVS according to metanephrine ratio. We assessed the prevalence of asymmetrical cortisol secretion through the cortisol to metanephrine (C/M) lateralization index (LI). We then evaluated whether the use of aldosterone to metanephrine (A/M) LI can improve the diagnostic accuracy of AVS compared with aldosterone to cortisol (A/C) LI. Asymmetrical cortisol secretion is present in 18% of patients with PA. Diagnosis with A/M LI and A/C LI is discordant in 14% of patients: 9% had a diagnosis of unilateral PA with A/M LI instead of bilateral PA with A/C LI and 5% had a diagnosis of bilateral PA with A/M LI instead of unilateral PA. The assessment of metanephrine levels in AVS is useful for the determination of selectivity and lateralization, allowing an accurate diagnosis, especially in patients with asymmetrical cortisol secretion.

PSAT017 A Case of Aldosterone- and Cortisol Co-secreting Adrenal Corticol Neoplasm with Lipomatous and Myeiolipomatous Metaplasia

Abstract Background Adrenal lipomatous tumors are uncommon fatty tumors of theadrenal glands with myelolipoma being the most common histologic feature.Adrenal myelolipoma is a benign adrenal cortical neoplasm composed of fat andmyeloid tissue, commonly diagnosed if fat composition of tumor is more than 50% on cross-sectional imaging studies. The myelolipomatous metaplasia is asecondary degenerative change in primary adrenal tumor, usually seen in benignadrenocortical adenomas and rarely in adrenocortical carcinomas and corticalneoplasms of uncertain malignant potential. Adrenocortical neoplasms areclassified as benign or malignant based on modified Weiss score, when the criteriaare not clear, the tumor is classified as a neoplasm of uncertain malignant lesion.As adrenal lipomatous tumors are usually benign and non-functional, patients withthese tumors often do not undergo hormonal evaluation. Clinical Case A 58-year-old female with a history of hypertension diagnosed atage 35 years, on five antihypertensive agents and a history of intermittentspontaneous hypokalemia, was found to have a 6 cm left adrenal myelolipoma onnon-contrast computed tomography of the abdomen performed when she presentedfor left flank pain due to nephrolithiasis. The biochemical evaluation showedpotassium of 2.8 meq/l, plasma aldosterone of 65.9 ng/dl with plasma renin activityof 0.1 ng/ml/hr. An overnight 1 mg dexamethasone suppression test showed nonsuppressible serum cortisol of 10.8 μg/dl. DHEAS, and ACTH were measured at24.5 μg/dl and &amp;lt;5 pg/ml, respectively. Left adrenalectomy was performed and onthe following day, morning serum cortisol was 2.3 μg/dl with aldosterone of 6.2ng/dl and plasma renin activity of 4.2 ng/ml/hr. Expectedly patient beganexperiencing nausea, and postural dizziness. Patient systolic blood pressure was inlow100 mmHg. Thus, hydrocortisone therapy was initiated. Immediatelypostoperatively and thereafter, her blood pressure was controlled with noantihypertensive agent, and morning cortisol measured without hydrocortisone for∼36 h remained low at 1.2 μg/dL. Pathology showed adrenal cortical neoplasm ofuncertain malignant potential with associated lipomatous and myelolipomatousmetaplasia without atypical mitoses, or lymphovascular invasion, or necrosis, orcapsular invasion, with negative surgical margins. Although mitotic activity in thetumor is lacking, the tumor was designated uncertain malignant potential due to thelarge size (7 cm), and lack of clear cells &amp;lt; 25% according to modified Weiss score. Conclusion We report a rare case of aldosterone and cortisol co-secreting adrenalcortical neoplasm of uncertain malignant potential with lipomatous andmyelolipomatous metaplasia. While the majority of cases of myelolipoma arebenign and non-functioning, this case emphasizes the importance of looking forsymptoms and signs pointing to adrenal hyperfunction, thorough hormonal andmorphologic evaluation and, definitive treatment is curative unilateraladrenalectomy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

LBODP024 Successful Adrenal Vein Sampling Using Dexamethasone Premedication In Patients With Iodine Contrast Media Allergy

Abstract Background Preparation of patients with iodine contrast media (ICM) allergy who require adrenal vein sampling (AVS) to establish source of aldosterone excess in confirmed primary aldosteronism (PA) is controversial. Usual premedication with high dose prednisone can interfere with cortisol determinations, possibly altering the aldosterone-to-cortisol ratios for the identification of lateralized aldosterone excess. Objective Evaluate the efficacy and safety of premedication with high dose dexamethasone to perform AVS in patients with ICM. Methods 177 consecutive patients with confirmed PA who underwent bilateral simultaneous basal and post ACTH bolus AVS at our center between January 2010 and December 2020 were retrospectively analyzed for reported ICM allergy. A total of 7 patients (4%) with history of allergic reactions to ICM were premedicated with three doses of 7.5 mg dexamethasone rather than the usual 50 mg of prednisone. Results No breakthrough allergic reactions were reported in the 7 patients. The mean age at the time of AVS procedure was 55.1 ± 16.8 years. Patients had been hypertensive for a mean of 6.7 ± 5.9 years. The mean systolic blood pressure on the day of the procedure was 137.4 ± 4.2 mmHg and the mean diastolic blood pressure 77.1 ± 12.9 mmHg. Most patients had at least 2 anti-hypertensive medications in their drug regimen prior to AVS procedure, none being mineralocorticoid receptor antagonists. Dexamethasone suppression effect on AVS: All basal peripheral cortisol levels were suppressed, &amp;lt; 50 nmol/L, confirming lack of meaningful cortisol co-secretion. The basal and post-ACTH selectivity index were respectively &amp;gt;2 and &amp;gt; 5 bilaterally in all patients, confirming adequate cannulation of both adrenal veins. Basal peripheral plasma aldosterone concentration (PAC) was also reduced by dexamethasone administration by an average of 66 ± 30% in comparison with PAC measured before AVS. Despite basal suppression, PAC increased following ACTH bolus injection with an average rise of 698.8 ± 644.5% from baseline. AVS results: Four patients had lateralized (A/C ratio &amp;gt; 2 basally and &amp;gt;4 post ACTH), while three had bilateral source according to AVS results. Follow up data for a mean of 58 ± 41.4 months was available for 6 patients. In the three patients who underwent unilateraladrenalectomy for lateralized source, basal and post-ACTH lateralization ratios were concordant. All 3 patients had contralateral suppression, confirmed adrenocortical adenoma at histopathology and clinical (n=3) (normal blood pressure without medication) and/or biochemical cure (n=2) (direct renin concentration &amp;gt; 10 ng/dL) at follow up. Conclusion AVS using dexamethasone premedication is safe and accurate for diagnosing source of aldosterone excess in patients with PA and ICM allergy. Presentation: No date and time listed

Influence of cortisol cosecretion on non-ACTH-stimulated adrenal venous sampling in primary aldosteronism: a retrospective cohort study.

Cortisol measurements are essential for the interpretation of adrenal venous samplings (AVS) in primary aldosteronism (PA). Cortisol cosecretion may influence AVS indices. We aimed to investigate whether cortisol cosecretion affects non-adrenocorticotrophic hormone (ACTH)-stimulated AVS results. Retrospective cohort study at a tertiary referral center. We analyzed 278 PA patients who underwent non-ACTH-stimulated AVS and had undergone at least a 1-mg dexamethasone suppression test (DST). Subsets underwent additional late-night salivary cortisol (LSC) and/or 24-h urinary free cortisol (UFC) measurements. Patients were studied from 2013 to 2020 with follow-up data of 6 months following adrenalectomy or mineralocorticoid antagonist therapy initiation. We analyzed AVS parameters including adrenal vein aldosterone/cortisol ratios, selectivity, lateralization (LI) and contralateral suppression indices and post-operative ACTH-stimulation. We classified outcomes according to the primary aldosteronism surgical outcome (PASO) criteria. Among the patients, 18.9% had a pathological DST result (1.9-5 µg/dL: n = 44 (15.8%); >5 µg/dL: n = 8 (2.9%)). Comparison of AVS results stratified according to the 1-mg DST (≤1.8 vs >1.8 µg/dL: P = 0.499; ≤1.8 vs 1.8 ≤ 5 vs >5 µg/dL: P = 0.811) showed no difference. Lateralized cases with post DST serum cortisol values > 5 µg/dL had lower LI (≤1.8 µg/dL: 11.11 (5.36; 26.76) vs 1.9-5 µg/dL: 11.76 (4.9; 31.88) vs >5 µg/dL: 2.58 (1.67; 3.3); P = 0.008). PASO outcome was not different according to cortisol cosecretion. Marked cortisol cosecretion has the potential to influence non-ACTH-stimulated AVS results. While this could result in falsely classified lateralized cases as bilateral, further analysis of substitutes for cortisol are required to unmask effects on clinical outcome.

Hypocortisolemia following unilateral adrenalectomy

Abstract Objective Unilateral adrenalectomy (UA) is the best option for unilateral functioning and non-functioning adrenal adenomas, localized primary or metastatic carcinomas. Post-operative hypocortisolemia (HC) in Cushing Syndrome is well known, but several studies reported HC after UA for other indications. A systematic full endocrine investigation for all adrenal mass is not systematic and dexamethasone suppression test (DST) is not recommended in non-Cushing functioning tumours. Double secretion (autonomous cortisol co-secretion) is a rare phenomenon. The purpose of the study was to review incidence of postoperative HC in a tertiary centre. Methods Retrospective study (2012–2020) looking for hypocortisolemia after UA in patients operated for Cushing Syndrome and other endocrine tumours. Pre- and postoperative laboratory findings were reviewed in a total of 115 patients with UA. Patients receiving perioperative dexamethasone (DEX) for nausea and vomiting prophylaxis were included as well. Results UA (51 right and 64 left) were performed in 47 women and 68 men (mean age 53.5 y.), laparoscopically in 97 (84.3%, 3 converted). UA indications included: Cushing (8), autonomous cortisol secretion (10, in 2 with combined Conn), Conn syndrome (37), pheochromocytoma (24), non-functioning adenoma (10, adrenal carcinoma (3), adrenal metastasis (19) and other diagnosis (4). 18 patients had a preoperative DST (15.7%). Anaesthesia reports revealed that 53/115 patients received DEX. 51/115 patients had a control of postoperative cortisol level. Hypocortisolemia was observed overall in 28/51 patients, by excluding Cushing patients in 24/45, in 19/53 patients who received DEX and in 7/48 in those without DEX. Confusion comes when patients receiving DEX had normal postoperative cortisolemia. Conclusion The fact that some patients received DEX (ERAS pathway), complicated the interpretation of cortisol levels at postoperative day one (D1). DEX is known to supress the hypothalamic-pituitary-adrenal axis (HPA axis) at D1. Thus, claiming that hypocortisolemia is the result of cortisol co-secretion (adenoma with double secretion), also able to supress the HPA axis, is not possible in patients who received DEX. These results suggests 1) to fully investigate all hormone functions in case of adrenal mass and 2) not administrating DEX in patients undergoing UA, for adequately assessing the HPA axis function postoperatively.

Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021.

Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and mortality rates than essential hypertension. The Japan Endocrine Society (JES) has developed an updated guideline for PA, based on the evidence, especially from Japan. We should preferentially screen hypertensive patients with a high prevalence of PA with aldosterone to renin ratio ≥200 and plasma aldosterone concentrations (PAC) ≥60 pg/mL as a cut-off of positive results. While we should confirm excess aldosterone secretion by one positive confirmatory test, we could bypass patients with typical PA findings. Since PAC became lower due to a change in assay methods from radioimmunoassay to chemiluminescent enzyme immunoassay, borderline ranges were set for screening and confirmatory tests and provisionally designated as positive. We recommend individualized medicine for those in the borderline range for the next step. We recommend evaluating cortisol co-secretion in patients with adrenal macroadenomas. Although we recommend adrenal venous sampling for lateralization before adrenalectomy, we should carefully select patients rather than all patients, and we suggest bypassing in young patients with typical PA findings. A selectivity index ≥5 and a lateralization index >4 after adrenocorticotropic hormone stimulation defines successful catheterization and unilateral subtype diagnosis. We recommend adrenalectomy for unilateral PA and mineralocorticoid receptor antagonists for bilateral PA. Systematic as well as individualized clinical practice is always warranted. This JES guideline 2021 provides updated rational evidence and recommendations for the clinical practice of PA, leading to improved quality of the clinical practice of hypertension.

Adrenal Venous Sampling for Subtype Diagnosis of Primary Hyperaldosteronism.

Adrenal venous sampling (AVS) is the key procedure for lateralization of primary hyperaldosteronism (PA) before surgery. Identification of the adrenal veins using computed tomography (CT) and intraoperative cortisol assay facilitates the success of catheterization. Although administration of adrenocorticotropic hormone (ACTH) has benefits such as improving the success rate, some unilateral cases could be falsely diagnosed as bilateral. Selectivity index of 5 with ACTH stimulation to assess the selectivity of catheterization and lateralization index (LI) >4 with ACTH stimulation for unilateral diagnosis is used in many centers. Co-secretion of cortisol from the tumor potentially affects the lateralization by the LI. Patients aged <35 years with hypokalemia, marked aldosterone excess, and unilateral adrenal nodule on CT have a higher probability of unilateral disease. Patients with normokalemia, mild aldosterone excess, and no adrenal tumor on CT have a higher probability of bilateral disease. Although no methods have 100% specificity for subtype diagnosis that would allow bypassing AVS, prediction of the subtype should be considered when recommending AVS to patients. Methodological standardization and strict indication improve diagnostic quality of AVS. Development of non-invasive imaging and biochemical markers will drive a paradigm shift in the clinical practice of PA.

Apparent failed and discordant adrenal vein sampling: A potential confounding role of cortisol cosecretion?

Adrenal vein sampling (AVS) and computed tomography (CT) often show confusingly discordant lateralisation results in primary aldosteronism (PA). We tested a biochemical algorithm using AVS data to detect cortisol cosecretion as a potential explanation for discordant cases. Retrospective analysis from a large PA + AVS database. All patients with PA and AVS, 2005-2020. An algorithm using biochemical data from paired AVS + CT images was devised from physiological first principles and informed by data from unilateral, AVS-CT concordant patients. The algorithm involved calculations based upon the expectation that low cortisol levels exist in adrenal vein effluent opposite an aldosterone-and-cortisol-producing adrenal mass and may reverse lateralisation due to inflated aldosterone/cortisol ratios. The algorithm was applied to cases with discordant CT-AVS lateralisation to determine whether this might be a common or explanatory finding. Clinical and biochemical characteristics of identified cases were collected via chart review and compared to CT-AVS concordant cases to detect evidence of biological plausibility for cortisol cosecretion. From a total of 588 AVS cases, 141 AVS + CT pairs were clear unilateral PA cases, used to develop the three-step algorithm for AVS interpretation. Applied to 88 AVS + CT discordant pairs, the algorithm suggested possible cortisol cosecretion in 40%. Case review showed that the proposed cortisol cosecretors, as identified by the algorithm, had low/suppressed adrenocorticotropic hormone levels, larger average nodule sizeand lower plasma aldosterone. Pending external validation and outcome verification by surgery and tissue immunohistochemistry, cortisol cosecretion from aldosteronomas may be a common explanation for discordant CT-AVS results in PA.