Double somatic mutations in CTNNB1 and GNA11 in an aldosterone-producing adenoma.

Double somatic mutations in CTNNB1 and GNA11/Q have recently been identified in a small subset of aldosterone-producing adenomas (APAs). As a possible pathogenesis of APA due to these mutations, an association with pregnancy, menopause, or puberty has been proposed. However, because of its rarity, characteristics of APA with these mutations have not been well characterized. A 46-year-old Japanese woman presented with hypertension and hypokalemia. She had two pregnancies in the past but had no history of pregnancy-induced hypertension. She had regular menstrual cycle at presentation and was diagnosed as having primary aldosteronism after endocrinologic examinations. Computed tomography revealed a 2 cm right adrenal mass. Adrenal venous sampling demonstrated excess aldosterone production from the right adrenal gland. She underwent right laparoscopic adrenalectomy. The resected right adrenal tumor was histologically diagnosed as adrenocortical adenoma and subsequent immunohistochemistry (IHC) revealed diffuse immunoreactivity of aldosterone synthase (CYP11B2) and visinin like 1, a marker of the zona glomerulosa (ZG), whereas 11ß-hydroxylase, a steroidogenic enzyme for cortisol biosynthesis, was mostly negative. CYP11B2 IHC-guided targeted next-generation sequencing identified somatic CTNNB1 (p.D32Y) and GNA11 (p.Q209H) mutations. Immunofluorescence staining of the tumor also revealed the presence of activated ß-catenin, consistent with features of the normal ZG. The expression patterns of steroidogenic enzymes and related proteins indicated ZG features of the tumor cells. PA was clinically and biochemically cured after surgery. In conclusion, our study indicated that CTNNB1 and GNA11-mutated APA has characteristics of the ZG. The disease could occur in adults with no clear association with pregnancy or menopause.

Cushing's Syndrome in Pregnancy Secondary to Adrenocortical Adenoma: A Case Series and Review.

PURPOSE: To present a case series of Cushing's syndrome (CS) during pregnancy caused by adrenocortical adenomas, highlighting clinical features, hormonal assessments and outcomes. METHODS: We describe five pregnant women with CS, detailing clinical presentations and laboratory findings. RESULTS: Common clinical features included a full moon face, buffalo back and severe hypertension. Elevated blood cortisol levels with circadian rhythm disruption and suppressed adrenocorticotrophic hormone (ACTH) levels were observed. Imaging revealed unilateral adrenal tumours. Two cases underwent laparoscopic adrenalectomies during the second trimester, while three had postpartum surgery. All required hormone replacement therapy, with postoperative pathological confirmation of adrenocortical adenomas. CONCLUSION: Diagnosis of CS during pregnancy is challenging due to overlapping features with normal pregnancy: elevated blood cortisol levels and abnormal diurnal rhythm of blood cortisol, suppressed aid diagnosis. Treatment should be individualised due to a lack of explicit optimum therapeutic approaches. Laparoscopic adrenalectomy may be an optimal choice, along with multidisciplinary management including hormone replacement therapy.

The improvement of postoperative blood pressure and associated factors in patients with hormone-negative adrenal adenoma and hypertension.

OBJECTIVE: To investigate the effect of adrenal surgery on blood pressure (BP) improvements in patients with hormone-negative adrenal adenoma (HNA) concomitant with hypertension and analyze associated prognostic factors. METHODS: We retrospectively reviewed the clinical data of patients with HNA and hypertension and patients with aldosterone-producing adenoma (APA) and hypertension who underwent adrenal surgery at our center between 2019 and 2022. Hypertension outcomes were evaluated in all patients and subjects were divided into three groups according to follow-up BP and the administration of anti-hypertensive agents: a clinical curation group, an improvement group, and a no-improvement group. Logistic regression analysis was performed to predict factors associated with clinical curation in patients with HNA post-surgery. RESULTS: Of the 182 patients with HNA, clinical curation was achieved in 58 patients (31.9%), improvement in 72 (39.5%), and no improvement in 52 (28.6%). The clinical curation, improvement and no improvement rates in patients with APA were 64.8% (n = 118), 15.9% (n = 29), and 19.2% (n = 35). Multivariate logistic regression analysis indicated that a duration of hypertension ≤6 years and a plasma aldosterone level >160 pg/ml were both independent factors for the clinical curation of hypertension in patients with HNA after adrenal surgery. CONCLUSION: Adrenal surgery can cure or improve hypertension in most patients with HNA, especially in a short duration of hypertension and high plasma levels of aldosterone.

Rare Coexistence of Aldosterone-producing Adrenocortical Adenoma Confirmed by an Immunohistochemical Analysis of Steroidogenic Enzymes with Adrenal Ectopic Thyroid Tissue: A Case Report and Literature Review.

A 56-year-old man presented with a history of hypertension; clinically, the patient had primary aldosteronism (PA) and a 4-cm left adrenal tumor. The left adrenal glands, resected by adrenalectomy, also contained ectopic thyroid tissue (ETT). An immunohistochemical analysis of steroid-converting enzymes revealed an aldosterone-producing adenoma (APA). Among 19 previously reported cases of adrenal ETT, 4 had adrenal hormonal abnormalities, all of which were PA. This is the first case of adrenal ETT coexisting with APA, confirmed by steroid-converting enzyme expression. Further analyses using cumulative case data are required to clarify the correlation between adrenal ETT and APA.

Cardiovascular Risk Markers in Adults With Adrenal Incidentaloma and Mild Autonomous Cortisol Secretion.

CONTEXT: Many adrenal adenomas exhibit mild autonomous cortisol secretion (MACS). Although MACS is associated with increased cardiovascular mortality, the underlying mechanisms are not fully defined. OBJECTIVE: To investigate mechanisms that may link MACS and cardiovascular mortality in adults with adrenal adenoma. DESIGN: Cross-sectional study. PATIENTS: Twenty adults with adrenal adenoma and MACS and 20 controls with nonfunctioning adrenal adenoma. METHODS: Reactive hyperemia index (RHI) was measured by peripheral artery tonometry and 24-hour ambulatory blood pressure monitoring (24h AMBP) was performed. Indices of insulin secretion and sensitivity were estimated by measuring glucose and insulin fasting and following a mixed meal. MAIN OUTCOME MEASURE: The primary outcome was the difference in RHI between participants with MACS vs nonfunctioning adrenal adenoma. RESULTS: The average cortisol after 1-mg dexamethasone and urinary free cortisol were higher in patients with MACS. There was no significant difference in fasting RHI (2.0 [interquartile range (IQR) 1.6-2.4] vs 2.0 [IQR 1.7-2.2, P = .72), but postprandial RHI was higher in patients with MACS (2.2 [1.8-2.7] vs 1.8 [1.5-2.2], P = .04). 24-hour ambulatory blood pressure monitoring and Matsuda index were not significantly different in the groups. Fasting glucose and glucose area under the curve after the mixed meal were higher and insulinogenic index was lower in participants with MACS. CONCLUSION: Adults with adrenal adenoma and MACS do not have fasting endothelial dysfunction and postprandial endothelial function may be better. These patients have fasting and postprandial hyperglycemia with lower insulin secretion, which may underlie the association between MACS and increased cardiovascular mortality.

Postoperative ACTH-stimulated aldosterone predicts biochemical outcome in primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is the most common surgically curable cause of hypertension. Unilateral aldosterone-producing adenoma can be treated with adrenalectomy. Clinical and biochemical outcomes are assessed 6-12 months after adrenalectomy according to primary aldosteronism surgical outcome (PASO) consensus criteria. Earlier prediction of biochemical remission would be desirable as it could reduce cumbersome follow-up visits. We hypothesized that postoperative adrenocorticotropic hormone (ACTH) stimulated plasma aldosterone concentrations (PAC) measured shortly after adrenalectomy can predict PASO outcomes. DESIGN: Retrospective cohort study. METHODS: We analyzed 100 patients of the German Conn's registry who underwent adrenalectomy and postoperative ACTH stimulation tests within the first week after adrenalectomy. Six to twelve months after adrenalectomy we assessed clinical and biochemical outcomes according to PASO criteria. Serum cortisol and PAC were measured by immunoassay at baseline and 30 min after the intravenous ACTH infusion. We used receiver operating characteristics (ROC) curve analysis and matched the parameters to PASO outcomes. RESULTS: Eighty-one percent of patients had complete, 13% partial, and 6% absent biochemical remission. Complete clinical remission was observed in 28%. For a cut-off of 58.5 pg/mL, stimulated PAC could predict partial/absent biochemical remission with a high sensitivity (95%) and reasonable specificity (74%). Stimulated PAC's area under the curve (AUC) (0.89; confidence interval (CI) 0.82-0.96) was significantly higher than other investigated parameters. CONCLUSIONS: Low postoperative ACTH stimulated PAC was predictive of biochemical remission. If confirmed, this approach could reduce follow-up visits to assess biochemical outcome.

[Comparison of coagulation function between adrenocorticotropic hormone independent Cushing syndrome and nonfunctional adrenal adenoma and its influence factors].

OBJECTIVE: To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS). METHODS: In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups. RESULTS: In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05). CONCLUSION: ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.

Adrenal cortical adenoma arising in the setting of renal-adrenal fusion: a case report and review of the literature.

BACKGROUND: Renal-adrenal fusion is a rare entity resulting from incomplete encapsulation of the adrenal gland and kidney. Only 18 cases have been reported in English literature to date. CASE PRESENTATION: Our patient is a 77-year-old African American female who presented with a systolic blood pressure of 200 mmHg. Computed tomography showed an enhancing 9 × 6 cm mass anterior and medial to the left kidney. The patient underwent a left adrenalectomy with partial nephrectomy. Gross and histologic examinations revealed an adrenal cortical adenoma and renal-adrenal fusion. CONCLUSION: Renal-adrenal fusion may pose a diagnostic challenge, particularly when there is a concurrent adrenal adenoma. It is important to be aware of this uncommon anomaly to avoid misdiagnosis and overtreatment.

Bilateral co-secretory lesions presenting with coexisting Cushing syndrome and primary aldosteronism: a case report.

BACKGROUND: There is an increasing number of cases of aldosterone- and cortisol-producing adenomas (A/CPAs) reported in the context of primary aldosteronism (PA). Most of these patients have PA complicated with subclinical Cushing's syndrome; cases of apparent Cushing's syndrome (CS) complicated with aldosteronism are less reported. However, Co-secretory tumors were present in the right adrenal gland, a cortisol-secreting adenoma and an aldosterone-producing nodule (APN) were present in the left adrenal gland, and aldosterone-producing micronodules (APMs) were present in both adrenal glands, which has not been reported. Here, we report such a case, offering profound insight into the diversity of clinical and pathological features of this disease. CASE PRESENTATION: The case was a 45-year-old female from the adrenal disease diagnosis and treatment centre in West China Hospital of Sichuan University. The patient presented with hypertension, moon-shaped face, central obesity, fat accumulation on the back of the neck, disappearance of cortisol circadian rhythm, ACTH < 5 ng/L, failed elevated cortisol inhibition by dexamethasone, orthostatic aldosterone/renin activity > 30 (ng/dL)/(ng/mL/h), and plasma aldosterone concentration > 10 ng/dL after saline infusion testing. Based on the above, she was diagnosed with non-ACTH-dependent CS complicated with PA. Adrenal vein sampling showed no lateralization for cortisol and aldosterone secretion in the bilateral adrenal glands. The left adrenocortical adenoma was removed by robot-assisted laparoscopic resection. However, hypertension, fatigue and weight gain were not alleviated after surgery; additionally, purple striae appeared in the lower abdomen, groin area and inner thigh, accompanied by systemic joint pain. One month later, the right adrenocortical adenoma was also removed. CYP11B1 were expressed in the bilateral adrenocortical adenomas, and CYP11B2 was also expressed in the right adrenocortical adenomas. APN existed in the left adrenal gland and APMs in the adrenal cortex adjacent to bilateral adrenocortical adenomas. After another surgery, her serum cortisol and plasma aldosterone returned to normal ranges, except for slightly higher ACTH. CONCLUSIONS: This case suggests that it is necessary to assess the presence of PA, even in CS with apparent symptoms. As patients with CS and PA may have more complicated adrenal lesions, more data are required for diagnosis.

Impact of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas.

The purpose of this study was to evaluate the effects of administration of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas (NFA). Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were measured to assess vascular function in 22 patients with NFA who had hypertension and/or diabetes mellitus (DM) and 272 patients without adrenal incidentalomas who had hypertension and/or DM (control patients with hypertension and/or DM). FMD and NID were measured in the morning before and after administration of 1 mg of dexamethasone at 2300 h in 18 patients with NFA. There were no significant differences in FMD and NID between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM (3.4 ± 2.8% vs. 2.9 ± 1.9% and 11.5 ± 5.7% vs. 11.4 ± 4.3%, P = 0.46, and P = 0.99, respectively). There were no significant differences in vascular function between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM even after adjustment for cardiovascular risk factors. Overnight 1 mg dexamethasone increased FMD from 2.4 ± 1.9% to 5.3 ± 3.2% (P < 0.01) and increased NID from 12.1 ± 4.2% to 14.0 ± 2.8% (P < 0.01) in patients with NFA. The overnight 1 mg dexamethasone suppression test does not impair FMD and NID in patients with NFA. Decreases in circulating levels of cortisol may improve vascular function.Clinical Trial Registration: This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000039512).

Primary aldosteronism 2.0: an update for clinicians on diagnosis and treatment.

Primary aldosteronism (PA), characterized by inappropriately high concentrations of the adrenal-derived hormone aldosterone, is the most common endocrine cause of arterial hypertension. As compared with individuals with essential hypertension, patients with PA have a significantly increased cardiovascular risk that cannot be fully reversed by common antihypertensive treatment because of blood pressure-independent deleterious effects of aldosterone. Measurement of the aldosterone to renin ratio (ARR), reflecting the degree of aldosterone excess, is the classic screening test for PA, but thresholds for an elevated ARR vary substantially and are arbitrary, as there exists a wide disease continuum that spans from preclinical stages to overt PA. Treatment approaches for PA with either mineralocorticoid receptor antagonists for bilateral disease or unilateral adrenalectomy for aldosterone-producing adenomas (APA) are highly effective to mitigate the excess cardiovascular risk associated with PA. Subtype classification according to the dichotomous concept of unilateral PA, mainly due to APAs, vs bilateral PA, mainly due to bilateral adrenal hyperplasia, has been recently challenged by advances in the pathophysiologic understanding and therapeutic spectrum of PA. The implementation of current PA guidelines into clinical routine is extremely poor, as reflected by the fact that most patients suffering from PA remain undiagnosed and probably untreated. Pragmatic approaches are required to address this public health problem. In this review, we present an up­to­date overview on the clinical significance, diagnosis, and treatment of PA, with the aim to provide guidance for clinicians regarding the management of this disease, paying particular attention to its feasible implementation into daily clinical routine.

Prolonged postoperative hypoaldosteronism related to hyperkalemia in patients with aldosterone-producing adenoma.

Hyperkalemia is developed in a part of patients with aldosterone-producing adenoma (APA) after adrenalectomy, suspected to be due to the insufficiency of aldosterone secretion. The purpose of this study is to determine the frequency and characteristics of prolonged postoperative hypoaldosteronism (PPHA) using chemiluminescent enzyme immunoassay (CLEIA). We studied 58 patients with APA with long time after adrenalectomy and whose PAC was measured using a CLEIA kit. The PAC value measured using CLEIA was significantly lower than that of using RIA between two consecutive visits before and after the shift of measuring method of PAC (median [interquantile range], 123.0 [99.8-164.0] vs. 39.5 [15.8-64.2] pg/mL, p < 0.01). PAC was below the minimum limit of quantification (4.0 pg/mL) of the CLEIA kit at least once in nine patients (15.5%) who had PPHA. The PPHA group were older (mean ± standard deviation, 61.3 ± 8.5 vs. 50.5 ± 10.1 years, p < 0.01) and had lower eGFR (60.3 ± 14.0 vs. 82.3 ± 22.8 mL/min/1.73 m2, p < 0.01) than the non-PPHA group. The frequency of postoperative hyperkalemia (maximum serum potassium >5.5 mEq/L) was higher in the PPHA group than in the non-PPHA group (55.6% vs. 8.2%, p < 0.01). In conclusion, a few patients with APA long time after adrenalectomy had unmeasurable PAC using CLEIA. PPHA is likely to develop in patients with APA after adrenalectomy who are older and have impaired renal function. Additionally, PPHA is related to the occurrence of postoperative hyperkalemia.

Case series: Primary aldosteronism diagnosed despite normal screening investigations: A report of three cases.

RATIONALE: Since the introduction of the aldosterone-to-renin ratio (ARR) as a screening tool for primary aldosteronism (PA), there has been a marked increase in the reported prevalence of this condition among hypertensive, even normotensive, subjects. PATIENT CONCERNS: But ARR as a spot blood draw for estimating a patient's aldosterone secretory status is influenced by many factors. DIAGNOSES: Here, we describe a series of patients with biochemically confirmed PA, whose diagnosis was delayed by the initial ARR assessment with non-suppressed renin. INTERVENTIONS: Patient 1 had a history of resistant hypertension for many years and had a negative initial screening for secondary hypertension (including ARR). At the reevaluation, ARR was close to cutoff still with normal renin after strict and extended drug washout, and the further workup for PA demonstrated a unilateral aldosterone producing adenoma that was surgically removed, with subsequent complete biochemical remission and partial clinical success. Patient 2 was diagnosed with idiopathic hyperaldosteronism combined with obstructive sleep apnea syndrome, which could increase renin resulting in a negative ARR, and finally got a better treatment effect with PA-specific spironolactone, as well as continuous positive airway pressure. Patient 3 with hypokalemia as the main presentation was finally diagnosed with PA after excluding other diseases, and proceeded to laparoscopic adrenalectomy and histologically confirmed an aldosterone producing adenoma. Postoperatively, patient 3 achieved complete biochemical success without any medicine. OUTCOMES: The clinical status of all three patients was effectively managed, resulting in either complete resolution or notable improvement of their respective conditions. LESSONS: After rigorous standardized diagnostic evaluation, there are still many reasons for ARR negative in PA, but they all basically occur in the background of normal or normal-high renin without suppression. A negative screening test result should be repeated and analyzed carefully if this is not consistent with the clinical picture. If, despite a repeatedly negative ARR, clinical suspicion remains high, we recommend consideration of further evaluation, including confirmatory tests and adrenal venous blood sampling (AVS) or even 68Ga-pentixafor PET/CT to better confirm the diagnosis and improve patient outcomes.

[Comparison the characteristics of serum adrenocortical hormone profile in patients with adrenal cortical carcinoma and adrenal coritcal adenoma].

Objective: To compare the characteristics of serum adrenocortical hormone profiles detected by liquid chromatography tandem mass spectrometry in patients with adrenal cortical carcinoma and adrenal adenoma. Methods: A total of 23 patients with adrenal cortical carcinoma and 119 patients with adrenal cortical adenoma/hyperplasia who visited the Department of Endocrinology and/or the Department of Urology of Peking University First Hospital from January 2018 to June 2022 were analyzed retrospectively. The imaging characteristics and serum adrenal cortical hormone profiles detected by liquid chromatography tandem mass spectrometry were analyzed retrospectively. The independent related factors of adrenal cortical carcinoma were screened by univariate analysis and multivariate logistic regression analysis. Results: The age of patients with adrenal cortical carcinoma was 46 (35, 57) years, and 15 (65.2%) were female; The age of adrenal cortical adenoma patients was 49 (40, 58) years old, and 80 (67.2%) were female. There was no significant difference in age and gender between the two groups (all P values>0.05). The maximum tumor diameter M (Q1, Q3) of patients with adrenocortical carcinoma was 7.05 (5.45, 9.78) cm, which was larger than that of patients with adrenocortical adenoma [2.1 (1.6, 3.0) cm] (P<0.001). Compared with patients with adrenal adenoma, the androstenedione (AD) of patients with adrenal cortical carcinoma [4.056 9 (1.619 5, 7.907 9) nmol/L vs 1.517 5 (0.935 1, 2.582 1) nmol/L (P<0.001)] was significantly increased; 11-ketotestosterone/11-ketoandrostenedione [0.034 3 (0.020 6, 0.079 2) vs 0.041 0 (0.028 6, 0.061 5) (P=0.089)] and 11-ketoandrostenedione/11-hydroxyandrostenedione [0.013 0 (0.006 4, 0.086 7) vs 0.063 0 (0.018 2, 0.162 5) (P=0.042)] were significantly decreased. Multivariate analysis found that AD, the largest diameter of the tumor, 11-ketotestosterone/11-ketoandrostenedione and 11-ketoandrostenedione/11-hydroxyandrostenedi-one were related factors for adrenal cortical carcinoma, with OR values (95%CI) of 1.841 (1.093-3.100), 5.130 (2.332-11.285), 0.381 (0.167-0.867) and 0.000 (0.000-0.014), respectively, all P values <0.05. Conclusions: The larger diameter of adrenal cortical tumor and the higher the level of androstenedione are independent risk factors for adrenal cortical carcinoma. The reduction conversion of 11-hydroxyandrostenedione to 11-ketoandrostenedione and 11-ketoandrostenedione to 11-ketotestosterone were independently associated with adrenal cortical carcinoma.

Feasibility of single-port laparoscopic partial adrenalectomy with selective adrenal venous sampling and high-resolution ultrasound for unilateral aldosterone-producing adenomas.

BACKGROUND: The surgical and endocrinological outcomes of single-port laparoscopic partial adrenalectomy for patients with aldosterone-producing adenomas are unknown. Precise diagnosis of intra-adrenal aldosterone activity and a precise surgical procedure may improve outcomes. In this study, we aimed to determine the surgical and endocrinological outcomes of single-port laparoscopic partial adrenalectomy with preoperative segmental selective adrenal venous sampling and intraoperative high-resolution laparoscopic ultrasound in patients with unilateral aldosterone-producing adenomas. We identified 53 patients with partial adrenalectomy and 29 patients with laparoscopic total adrenalectomy. Single-port surgery was performed for 37 and 19 patients, respectively. METHODS: A single-center, retrospective cohort study. All patients with unilateral aldosterone-producing adenomas diagnosed by selective adrenal venous sampling and treated surgically between January 2012 and February 2015 were included. Follow-up with biochemical and clinical assessments was set at 1 year after surgery for short-term outcomes and was performed every 3 months after surgery. RESULTS: We identified 53 patients with partial adrenalectomy and 29 patients with laparoscopic total adrenalectomy. Single-port surgery was performed for 37 and 19 patients, respectively. Single-port surgery was associated with shorter operative and laparoscopic times (odds ratio, 0.14; 95% confidence interval, 0.039-0.49; P = .002 and odds ratio, 0.13; 95% confidence interval, 0.032-0.57; P = .006, respectively). All single-port and multi-port partial adrenalectomy cases showed complete short-term (median 1 year) biochemical success, and 92.9% (26 of 28 patients) who underwent single-port partial adrenalectomy and 100% (13 of 13 patients) who underwent multi-port partial adrenalectomy showed complete long-term (median 5.5 years) biochemical success. No complications were observed with single-port adrenalectomy. CONCLUSION: Single-port partial adrenalectomy is feasible after selective adrenal venous sampling for unilateral aldosterone-producing adenomas, with shorter operative and laparoscopic times and a high rate of complete biochemical success.

Unique Case of Cardiomyopathy Secondary to Adrenal Adenoma (Primary-Aldosteronism).

INTRODUCTION: To our knowledge this is the first & only case report in India wherein primary aldosteronism (adrenal adenoma) presented with cardiomyopathy (regressed post-surgery). MATERIALS: First reported case in India. RESULT: Herein August 2018 IPGMER-SSKM-Kolkata 29-year female presented with 1-month exertional dyspnoea, occasional chest pain, sweating, fainting. On examination (Pulsus-bisferiens, forceful-well sustained-double-kicking-apex, grade-3-ejection-systolic-murmur (left 3rd intercostal space) (murmur intensity increased by Valsalva & standing). Left-ventricular-hypertrophy by ECG (R(I)+S(III) 35 mm) & Echocardiography (LVO Tobstruction, RWMA, wall-hypokinesia, systolic-anterior-motion, asymmetric-septal-hypertrophy excluded). Cardiac-MRI confirmed cardiomyopathy (patchy late gadolinium enhancements). She refused endomyocardial biopsy (normal troponin & NT-pro-BNP). Uncontrolled hypertension (BP 190/150) despite maximum Prazosin20 & Clonidine 100 dosage, besides persistent hypokalemia (despite repeated Intravenous KCL). With raised 24 hour Urine K + 52 meq/day raised TTKG 17.5, high serum AR Ratio (87.65) high Aldosterone (44.7) (normal Plasma Renin Activity (PRA 0.5) normal Cortisol (12.1). 24 x 22 x 15 mm hypodense mixed enhancing mass Left Adrenal in Contrast CT abdomen. Spironolactone 50, Ramipril 5, Ramipril5 subsequently added. Following unilateral adrenalectomy (histopathology 4 x 4 x 1 cm benign adrenal cortical adenoma) (without pleomorphism nor necrosis). (BP finally controlled before discharge following week. Patients cardiac function improved over next 6-months (complete regression of LVH in ECG-Echo & LGE in cardiac-MRI). Patient been regularly followed (till October 2022) at AIIMS-kalyani. Well controlled Hypertension (only Amlodipine 2.5 mg) (normal K + level, still in remission, normal potassium & normal cardiac function). CONCLUSION: Prior in-vitro studies suggested possible aldosterone (excess) induced direct activation of mineralocorticoid receptors in (low-density/serum-free) ventricular myocytes (culture); also aldosterone increases mRNA for cardiac-ANF & alpha/beta-myosin heavy-chains (aldosterone also effects collagen deposition & fibroblast proliferation). All of these were clearly prevented by adding spironolactone. References Higuchi S, Ota H, Tezuka Y, et al. Aldosterone-induced cardiac damage in primary aldosteronism depends on its subtypes, Endocr Connect 2021;10(1):29-36. Petramala L, Concistrè A, Olmati F, et al. Cardiomyopathies and adrenal diseases. Int J Mol Sci 2020;21(14):5047.

Food-dependent Cushing's syndrome due to unilateral adrenocortical adenoma with cortisol secretion without ACTH elevation detected in peripheral blood by the CRH test: a case report.

We report an extremely rare case of a 61-year old woman with food-dependent Cushing's syndrome (FDC) due to unilateral adrenocortical adenoma (UAA) with cortisol (CORT) secretion without ACTH elevation detected in peripheral blood by the CRH test. She was on oral medications for hypertension and depression, and presented weight gain, general fatigue, muscle weakness, and hypokalemia. Despite the fact that the diurnal variation of ACTH was always suppressed, a diurnal variation in CORT was observed, in the form of low levels in the early morning and high levels in the afternoon. An increase in CORT was shown in a 75 g-oral glucose tolerance test (OGTT) and in a mixed meal tolerance test, but no change in CORT levels was seen in intravenous glucose tolerance tests. Elevated CORT levels were observed in response to intravenous injection of CRH, although ACTH levels were always below the measured sensitivity. Laparoscopic left adrenalectomy was performed, which resulted in postoperative improvement in potassium and ACTH levels and disappearance of the CORT secretory response in the OGTT. Clear expression of glucose-dependent insulinotropic polypeptide receptor (GIPR), CRH and CRH receptor 2 (CRHR2) were confirmed in the surgically-resected UAA specimen by molecular and immunohistochemical analyses, suggesting the involvement of not only GIPR, but also CRH and CRHR2 in FDC.

[Adrenalectomy for primary hyperaldosteronism : retrospective review of 57 patients in CHU of Liege]. / Surrénalectomie pour hyperaldostéronisme primaire : revue rétrospective de 57 cas au CHU de Liège.

Primary hyperaldosteronism is the most common cause of secondary hypertension. Diagnostic clarification is essential because surgery is the treatment of choice for patients with unilateral disease (aldosterone-producing adenoma and unilateral cortical hyperplasia). We report a series of 57 patients that had adrenalectomy for primary hyperaldosteronism between April 1994 to January 2022 by the endocrine surgery team of the University Hospital of Liege. Our aim is to evaluate the diagnostic performance of adrenal venous sampling in lateralizing aldosterone hypersecretion and to compare it with other imaging techniques. The study also reviews postoperative outcomes in terms of blood pressure values, kalemia and antihypertensive medications.

L'hyperaldostéronisme primaire est la cause la plus fréquente d'hypertension artérielle secondaire. La mise au point diagnostique est essentielle, car la chirurgie est le traitement de choix pour les patients souffrant d'une forme unilatérale de la maladie (adénome de Conn et hyperplasie corticale unilatérale). Nous rapportons une série de 57 patients opérés de surrénalectomie pour hyper-aldostéronisme primaire, d'avril 1994 à janvier 2022, par l'équipe de chirurgie endocrinienne du CHU de Liège. Notre objectif est d'évaluer la performance diagnostique du cathétérisme veineux surrénalien à latéraliser l'hypersécrétion d'aldostérone et de la comparer aux autres techniques d'imagerie. L'étude porte également sur les résultats post-opératoires en termes de valeurs de pression artérielle, de kaliémie et de réduction du traitement médicamenteux antihypertenseur.

Cardiovascular and metabolic characters of KCNJ5 somatic mutations in primary aldosteronism.

Background: Primary aldosteronism (PA) is the leading cause of curable endocrine hypertension, which is associated with a higher risk of cardiovascular and metabolic insults compared to essential hypertension. Aldosterone-producing adenoma (APA) is a major cause of PA, which can be treated with adrenalectomy. Somatic mutations are the main pathogenesis of aldosterone overproduction in APA, of which KCNJ5 somatic mutations are most common, especially in Asian countries. This article aimed to review the literature on the impacts of KCNJ5 somatic mutations on systemic organ damage. Evidence acquisition: PubMed literature research using keywords combination, including "aldosterone-producing adenoma," "somatic mutations," "KCNJ5," "organ damage," "cardiovascular," "diastolic function," "metabolic syndrome," "autonomous cortisol secretion," etc. Results: APA patients with KCNJ5 somatic mutations are generally younger, female, have higher aldosterone levels, lower potassium levels, larger tumor size, and higher hypertension cure rate after adrenalectomy. This review focuses on the cardiovascular and metabolic aspects of KCNJ5 somatic mutations in APA patients, including left ventricular remodeling and diastolic function, abdominal aortic thickness and calcification, arterial stiffness, metabolic syndrome, abdominal adipose tissue, and correlation with autonomous cortisol secretion. Furthermore, we discuss modalities to differentiate the types of mutations before surgery. Conclusion: KCNJ5 somatic mutations in patients with APA had higher left ventricular mass (LVM), more impaired diastolic function, thicker aortic wall, lower incidence of metabolic syndrome, and possibly a lower incidence of concurrent autonomous cortisol secretion, but better improvement in LVM, diastolic function, arterial stiffness, and aortic wall thickness after adrenalectomy compared to patients without KCNJ5 mutations.

HCG-responsive aldosteronoma with transient secretion during pregnancy confirmed through HCG-stimulated adrenal venous sampling.

Primary aldosteronism can be regulated by the ectopic expression of G-protein coupled receptors in aldosteronomas or bilateral hyperplasias. We report a rare case of a young woman in whom 2 pregnancies were complicated by pre-eclampsia and 1 miscarriage. The transient primary aldosteronism during pregnancies suggested the possibility of HCG stimulated aberrant adrenal expression of LHCG receptor in her adrenal tissues. This was supported by increased aldosterone and renin suppression during 5-day HCG stimulation test outside of pregnancy. Following a second 5-day HCG stimulation test, bilateral simultaneous adrenal vein sampling identified a lateralized source of aldosterone from an 8 mm right adrenal nodule. A right laparoscopic adrenalectomy resulted in clinical and biochemical cure and allowed a further uneventful pregnancy a few years later. This case illustrates the indication to investigate for potential primary aldosteronism in woman with transient hypertension during pregnancy.