Aldosterone Research Articles

Disclosure: F. Abdo: None. L. Sayyed Kassem: None.Pancreatic neuroendocrine tumors (pNETs) are rare, and vasoactive intestinal peptide-secreting tumors (VIPomas) are among the least common functional subtypes. We present the case of a 75-year-old male with a background of prolactinoma on cabergoline therapy who developed progressively worsening diarrhea over two years. His symptoms, initially attributed to irritable bowel syndrome with diarrhea (IBS-D) and recurrent infections, escalated to multiple hospitalizations for refractory nausea, vomiting, diarrhea, and severe electrolyte disturbances, culminating in hypovolemic shock and requiring intensive care unit (ICU) management. Testing confirmed that the diarrhea was secretory in nature. During hospitalization, capsule endoscopy revealed mucosal inflammation and ulcerations without bleeding. Workup demonstrated markedly elevated chromogranin A (2,853 ng/mL), mildly elevated plasma VIP (85.7 pg/mL, repeated: 22.9, ULN 58.8), and fasting gastrin levels peaking at 1,875 pg/mL while on high doses of proton pump inhibitors (PPI). 24-hour urinary 5-HIAA and thyroid-stimulating hormone (TSH) were within normal limits. PET Cu-64 dotatate imaging showed a somatostatin receptor-avid lesion near the pancreatic head and multiple areas of increased uptake in the pancreas. Endoscopic ultrasound (EUS) with fine-needle aspiration confirmed a low-grade, well-differentiated pNET. Given the finding of pancreatic NET and prolactinoma, the patient was evaluated for MEN1including parathyroid hormone (PTH) and calcitonin levels, both within normal limits. Genetic testing for MEN1 returned negative. The patient was started on monthly long-acting octreotide with resolution of diarrhea and improvement in electrolytes; however, he was readmitted for hypokalemia and hypomagnesemia despite continued absence of diarrhea. Further testing ruled out mineralocorticoid excess. He underwent distal pancreatectomy, lymph node dissection, and cholecystectomy. Pathology confirmed a 3 cm pancreatic head mass with low-grade pNET (Ki-67 <3%) staining negative for VIP and positive for synaptophysin, CD56, CDX2, and MOC-31. An additional 0.8 cm focus in the posterior pancreatic body and a positive lymph node were identified as well. Octreotide was discontinued postoperatively without recurrence of diarrhea and with marked reduction of chromogranin A to 483 ng/ml while on PPI 1 month postoperatively. This case highlights the diagnostic complexity of functional neuroendocrine tumors presenting with chronic secretory diarrhea Despite negative immunostaining for VIP, the combination of his clinical presentation, biochemical testing, imaging and surgical pathology point to a functional pNET. Whether this represents a case of VIPoma with episodic secretion and therefore only mildly elevated VIP levels, or a pNET secreting a non-evaluated gastrointestinal peptide, is unclear.Presentation: Sunday, July 13, 2025

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

Disclosure: N. Chamorro-Pareja: None. M.E. Manning: None. M.S. Haines: BioAge - Scientific Advisory Board. K.K. Miller: Amgen - Received study medication and investigator-initiated research grants, Bristol-Myers Squibb - Equity, General Electric - Equity, Boston Scientific - Equity, Becton Dickinson - Equity.Abiraterone, an androgen-production inhibitor, was FDA-approved in 2011 to treat metastatic prostate cancer. By inhibiting 17α-hydroxylase and C17,20-lyase, it also decreases cortisol production. Although prednisone 5-10 mg daily is routinely prescribed to prevent mineralocorticoid excess and concomitantly serves as glucocorticoid replacement therapy, adrenal insufficiency as a complication of this treatment may be under-recognized, resulting in underutilization of stress dose steroids during acute illness in this group of patients particularly prone to medical crises. Objective: To characterize the clinical presentation of patients receiving abiraterone who underwent cortisol testing and to evaluate the risk of adrenal insufficiency in this group. Methods: The Mass General Brigham Research Patient Database Registry was used to search patient medical records from January 1, 2014 to July 31, 2024. “Definite” adrenal insufficiency was defined as an outpatient AM serum cortisol <3 ug/dL (before 10AM) or a peak serum cortisol <15 ug/dL on a cosyntropin stimulation test (CST). Probable adrenal insufficiency was defined as an inpatient AM serum cortisol <3 µg/dL or outpatient AM serum cortisol 3-5 µg/dL. The medical records of these patients, including provider encounters, laboratory results, and medication records were reviewed. Results: Out of >4000 patients who received abiraterone, only 171 (4%) underwent cortisol testing of any kind. Among these, 23 (13%) met criteria for adrenal insufficiency, and 14 (8%) met the criteria for probable adrenal insufficiency. In patients with definite adrenal insufficiency, median age was 74 years (IQR 70-82), and 87% were White. Testing was prompted by symptoms in 83% of patients, with the most common being fatigue (57%), anorexia/weight loss (35%), and orthostatic hypotension/dizziness (39%). The median AM cortisol was 2.5 µg/dL (IQR 0.8-3.9) and the median peak cortisol on CST was 5.1 µg/dL (IQR 2.6-9.1). Forty-three percent (n=10) received stress dose steroids or sick day dosing after diagnosis of adrenal insufficiency. Conclusion: Despite the known effect of abiraterone on cortisol synthesis, fewer than 5% of patients treated with this medication underwent cortisol testing, yet nearly 15% of those tested met criteria for adrenal insufficiency. The true incidence of adrenal insufficiency in this population remains uncertain. However, our findings underscore the importance of maintaining a high clinical suspicion for adrenal insufficiency in patients on abiraterone. Educating patients about this complication and ensuring timely administration of stress dose steroids during acute illness are critical. Further studies are warranted to clarify the incidence and optimal management strategies for adrenal insufficiency in this setting.Presentation: Monday, July 14, 2025

Abstract Disclosure: A. Tapia-Castillo: None. J.A. Pérez: None. P. Carrión: None. R. Baudrand: None. T. Uslar: None. M. Hernández: None. R. Pinilla: None. A. Martinez: None. C.E. Fardella: None. C.A. Carvajal: None. The nonclassic apparent mineralocorticoid excess (NCAME) is a prevalent endocrine disorder affecting 7% of the population. Characterized by reduced activity of the 11β-hydroxysteroid dehydrogenase type 2 enzyme (11βHSD2), disrupting the balance between cortisol and cortisone, potentially influencing other redox reactions (11-OH &amp;gt;11-Keto) crucial for steroid metabolism. Since endogenous (adrenal and gonadal) and exogenous steroids could be influenced by sex, identification of a sex-specific steroidomic profiles in NCAME, would provide valuable insights associated to the pathophysiologic mechanisms associated to NCAME. Objective: To identify a sex-differentiated steroid profile in subjects with NCAME. Subjects: A cross-sectional study was conducted in a cohort of 41 subjects classified as having NCAME (F/E &amp;gt; 4.1 ug/dl; E &amp;lt; 2.1 ug/dl) and controls. Clinical variables (blood pressure (BP), BMI, % fat, age) and biochemical variables (renin activity (PRA), sodium (Na) and potassium (K) excretion, urinary albumin, and NGAL) were determined. Women using oral contraceptives were excluded. The cohort was dichotomized by sex. Methods: An analysis of 21 steroids was performed using mass spectrometry (UPLC-Q-TOF/MS). Statistical analysis was performed using the Mann-Whitney T-test with Prism v9. Results: 21 subjects with NCAME were identified, of whom 14 were women and 7 were men. No difference in age or percentage of fat was observed between the groups. In women with NCAME, we observed lower PRA (1.4 ± 0.7 vs 1.7 ± 0.4 ng/ml/h; p&amp;lt;0.05), urinary Na/K ratio (2.6 ± 1.2 vs 3.0 ± 0.9; p&amp;lt;0.05), and higher urinary albumin (12.6 ± 6.7 vs 6.0 ± 4.6 mg/24h; p=0.02) and potassium excretion (52 ± 19 vs 32 ± 12 mEq/24h; p=0.02) than in control women. Their steroid profile showed lower levels of cortisone (1.6 ± 0.4 vs 2.5 ± 0.4 ug/dl; p&amp;lt;0.0001), increased 11-hydroxyandrosterone (2.2 ± 0.2 vs 1.9 ± 0.2; p=0.003), and decreased 17-hydroxypregnenolone sulfate (15.5 ± 7.3 vs 25.7 ± 6.0; p=0.002) and 11-oxo-androsterone glucuronide (7.6 ± 2.0 vs 10.5 ± 3.5; p=0.04) than controls.In men with NCAME, we observed higher levels of NGAL (145.8 ± 64 vs 86.6 ± 31 ng/ml; p=0.03), and their steroid profile showed higher levels of cortisol (14.7 ± 4.4 vs 11.1 ± 4.9 ug/dl; p&amp;lt;0.05) and F/E ratio (7.3 ± 2.7 vs 4.4 ± 1.3; p=0.01), and decreased 6β-hydroxycortisol (4.6 ± 1.7 vs 11.0 ± 4.2; p=0.01). Conclusion: This study provides novel insights into the sex-dependent biochemical and steroidomic signatures of NCAME. The identification of 11-hydroxyandrosterone as a key player in female NCAME suggests that this metabolite could act as an endogenous inhibitor and could modulate the activity of the 11βHSD2 enzyme, support the development of innovative biomarkers and personalized interventions for NCAME. Presentation: Monday, July 14, 2025

Abstract Disclosure: W. Thi: None. P. Mikkilineni: None. ACTH producing extra-pituitary tumors are rarely reported and account for about 5-20% of Cushing’s syndrome cases. They exhibit diverse clinical courses, which are particularly challenging to manage. Diagnosis requires clinical suspicion, supported by biochemical tests and imaging findings. A multidisciplinary approach is recommended to address both hypercortisolism and underlying neoplasms. A 44-year-old White male with recently diagnosed small cell lung cancer, on chemotherapy (carboplatin and etoposide) and anti-PDL-1 Ab (atezolizumab), presented with proximal muscle weakness, easy bruising, uncontrolled hyperglycemia, and hypertension. He has known metastases to the liver, bone, and adrenal glands. Labs showed leukocytosis, anemia, mildly elevated ALT, hypokalemic alkalosis with HbA1c 9.1%. Further work-up showed elevated random serum cortisol 119.6mcg/dL at 7 pm, repeat 8 am cortisol levels were 71 and 81.2mcg/dL (3.7-19.4mcg/dL) on 2 separate days with ACTH 139pg/mL (7.2-63.3pg/mL). Markedly elevated 24-hour urine free cortisol 11009.2mcg/24h (5-64mcg/24h), and non-suppressed serum cortisol following the 8 mg dexamethasone suppression test. MRI brain did not reveal any pituitary lesions. He was initially started on ketoconazole 200mg TID for 3 days, then switched to osilodrostat 1mg BID due to concerns of hepatotoxicity from the combined use of ketoconazole and anti-PDL-1, as well as his treatment with voriconazole for invasive aspergillosis. Aldactone was initiated for the excess mineralocorticoid effect of Cushing’s. Type 2 diabetes was managed with basal bolus insulin. His antihypertensive and insulin doses significantly reduced, and he no longer required potassium supplements. After 1 week of treatment, his serum cortisol improved to 52.9mcg/dL, further decreasing to 11.3mcg/dL, and 24-hour urine cortisol down to 102mcg/24h after 2 weeks. He was discharged on osilodrostat 1mg QD, educated on adrenal insufficiency symptoms, given PO hydrocortisone tablets, with a plan to monitor 24-hour urine free cortisol biweekly for dose titration. Unfortunately, he was readmitted for septic shock and passed away shortly after his family chose to pursue comfort care. Ectopic secretion of ACTH, primarily caused by small cell lung cancer (45%), has a higher incidence of hypokalemic alkalosis compared to other causes. While bilateral adrenalectomy may improve survival, medical treatment is crucial for alleviating major clinical symptoms and comorbidities such as hyperglycemia, bleeding, thromboembolism, depression, and opportunistic infections. A once-daily potent steroidogenesis inhibitor, osilodrostat, with a titration regimen, normalizes cortisol levels in ectopic Cushing’s. Transient hypocortisolism may occur, but can be managed with hydrocortisone replacement. Patients and caregivers must be educated about possible adrenal insufficiency. Presentation: Monday, July 14, 2025

Abstract Background and Aims Abiraterone is a hormonal antagonist that inhibits CYP17 used in advanced prostate cancer. Due to its mechanism of action, it diverts steroidogenesis toward aldosterone synthesis, causing secondary hyperaldosteronism (hypertension, hypokalemia, hypernatremia and volume overload). The aim of this study is to determine the incidence of renal events (RE), associated risk factors for RE, and the association of RE with mortality in a series of patients with advanced prostate cancer treated with abiraterone. Method A single-center retrospective study including patients with advanced prostate cancer who initiated abiraterone from 1/1/2013 to 31/7/2024, follow-up until 31/12/2024. Renal event defined by: new-onset or worsening hypertension (HTN), acute kidney injury (AKI), electrolyte imbalance (hypokalemia or hypernatremia) and/or volume overload (defined by clinical criteria or initiation/increased diuretic treatment). Results 79 patients, mean age 76.05 ± 9.50 years; 70.90% had castration-resistant prostate cancer (CRPC) and 89.87% had metastatic disease (M). At baseline, 21.5% presented known CKD (estimated glomerular filtration rate &amp;lt;60 ml/min/1.73 m²), 21.52% had an AKI prior to abiraterone initiation, 55.7% had HTN and 22.78% were on diuretics. Mean follow-up: 17 months (11.25–27.25 months). At the end of follow-up, 63.29% presented RE (30.38% AKI, 25.52% de novo HTN, 36.71% electrolyte imbalance and 16.45% volume overload). In 4% of cases, RE led to abiraterone discontinuation. Patients who presented RE showed no significant difference in age, baseline CKD, HTN, diabetes or sodium/potassium values compared to those without RE. However, M and prior AKI were significantly more common in patient with RE (M: 98% vs 75.86%, P = 0.0017; previous AKI: 30% vs 6.89%, P = 0.0110). Multivariate analysis showed that HTN and M were a risk factor for RE (HTN: 3.33; 95% CI 1.091–10.206, P = 0.0347; M: 13.3, 95% CI 1.418–124.444, P = 0.0235). Among patients with AKI (24/79), 33.3% presented KDIGO-AKI stage 2 and 25% stage 3, at a mean time of 18 months (7.25–43 months) after starting abiraterone. No patients required dialysis. Following AKI episode, 50% developed CKD. Patients with AKI had an increased bCr (1 mg/dl vs 0.8 mg/dl, P = 0.027) and presented more frequently HTN (75% vs 43.64%, P = 0.0230). Multivariate analysis showed that HTN was a risk factor for AKI during the abiraterone treatment (OR 3.946; 95% CI 1.127–13.818, P = 0.0318). Electrolyte imbalance occurred in 36.71% patients at a mean of 10.5 months (4–27 months) after starting abiraterone. Hypokalemia (31.65%) was more common than hypernatremia (11.39%), with mild cases predominating. The mean potassium and sodium levels were 3.2 mmol/L (3.00–3.3 mmol/L) and 145.5 mmol/L (145–148 mmol/L), respectively. New-onset or worsening HTN appeared in 25.52% patients at a mean of 10 months (2–32.5months) after starting abiraterone. 16.45% patients had volume overload at a mean of 16 months (4.5–37 months) after starting abiraterone; all required diuretic adjustment, but no cases of acute pulmonary edema were reported. At the end of follow-up, 18.99% of patients died at a mean of 13 months (9–29 months) after starting abiraterone. CRPC and AKI were associated with mortality (CRPC: 93.3% vs 64.1%, P = 0.0310; AKI 60% vs 23.44%, P = 0.041). Multivariant analysis including age, CRPC, M, AKI and RE showed that AKI was a risk of factor for mortality (OR 6.35; 95% CI 1.152–34.957, P = 0.0338). Conclusion In a cohort of patients with advanced prostate cancer treated with abiraterone, 63.29% had RE. HTN and metastatic cancer were risk factor for RE. AKI episode occurred in 30.38% patients during treatment and HTN was a risk factor for presenting it. Electrolyte imbalance was usually mild and occurred in 36.71% patients. HTN occurred in 25.52% patients, and volume overload in 16.45% patients. 18.99% abiraterone-treated patients died at the end of follow-up; developing AKI during the treatment increased the risk of death by 6.3 times. Thus, these data highlight the importance of monitoring renal function, electrolytes and blood pressure during the follow-up in patients treated with abiraterone.

Comprehensive adrenal steroid profiling during frog metamorphosis.

Apparent mineralocorticoid excess is an extraordinarily rare autosomal recessive disorder, with less than 100 cases reported to date. This monogenic disorder, due to dysfunction of the 11-beta-hydroxysteroid type 2 enzyme, is characterized by severe hypertension and hydroelectrolytic disorders. The initial suspicion and diagnosis of this disease are crucial for targeted treatment, thereby improving the prognosis of these patients and minimizing complications.

Glucocorticoid Resistance Syndrome: A Systematic Review of the Genotypes, Phenotypes, and Their Relationships.

Premises: Gestational hypertension and preeclampsia, affecting 6-8% of pregnancies, typically resolve postpartum. However, persistent hypertension after delivery poses a unique challenge. Description: This case report focuses on a 35-year-old woman with a one-year history of hypertension, initially exhibiting normal aldosterone/renin ratio. During pregnancy, she received alpha-methyldopa with limited effectiveness. Emergency cesarean section at 36 weeks was necessitated by uncontrolled hypertension. Postpartum, the patient experienced headaches and muscle cramps, with a mean ABPM24h of 140/100 mmHg on nifedipine and alpha-methyldopa. Further evaluation revealed elevated plasma aldosterone (31.7 ng/dl), suppressed renin (0.9 IUI/ml), an elevated aldosterone-to-renin ratio (35.22), and low serum potassium (2.4 mEq/l). Adrenal imaging identified a 1 cm left adrenal nodule suggestive of adenoma. Effective blood pressure and potassium control were achieved with spironolactone, and the patient is slated for adrenal venous sampling to subtype primary aldosteronism (PA).Conclusions: PA, a significant cause of secondary hypertension, affects less than 1% of pregnant women, often resulting from idiopathic bilateral adrenal hyperplasia or aldosterone-producing adenoma. This case underscores the rarity of PA in pregnancy, with fewer than 40 cases reported in the literature. Given the pivotal role of the renin–angiotensin–aldosterone system in maternal and fetal well-being during pregnancy, early PA diagnosis is imperative to mitigate severe complications associated with gestosis.

Accurate measurement of plasma aldosterone (ALD) and renin is important in primary aldosteronism screening and diagnosis. The high variability of ALD and renin due to salt intake, age, and sex, as well as the lack of immunoassay standardization necessitates the establishment of region-, age-, sex- and assay-specific reference intervals (RIs). This study established RIs for ALD and renin using novel sandwich chemiluminescent immunoassays. ALD and renin were measured on a fully automated chemiluminescence platform (Maglumi X8, Snibe, China). The analytic performances were estimated following CLSI guidelines. A total of 2,281 healthy participants from Beijing, Jiangsu, Henan, Gansu and Guangdong were recruited. Total imprecision were 1.42-5.09 % for ALD and 1.07-4.11 % for renin. The maximum dilution rates were 50×and 10× for ALD and renin. Interferences of 22 and six interferents for ALD and renin were acceptable. The sandwich ALD immunoassay results highly correlated with LC-MS/MS (r=0.994). The RI of ALD was partitioned based on salt intake, with central 95 % RIs for males of 16.9-185 ng/L (46.8-513 pmol/L) in Guangdong and 26.5-242 ng/L (73.5-671 pmol/L) in other four regions. Females showed an age-dependent decline in ALD levels (RIs in Guangdong: 26.9-442 ng/L [74.6-1,226 pmol/L, 18-40 years], 32.4-326 ng/L [89.9-904 pmol/L, 41-60 years], 21.2-199 ng/L [58.8-552 pmol/L, >60 years], whereas males exhibited no significant change. Renin RIs: females: 3.43-89.2 mU/L (18-40 years), 0.92-67.1 mU/L (41-60 years), 0.66-55 mU/L (>60 years); males: 2.23-95.1 mU/L (≤60 years), 1.71-68.9 mU/L (>60 years). This is the first study to establish accurate ALD and renin RIs for sandwich immunoassays. Region-, age- and sex-specific RIs were recommended, which will enhance the accuracy of clinical screening and diagnosis of primary aldosteronism.

Bartter syndrome is an uncommon autosomal recessive renal tubular condition that is usually diagnosed in childhood; there are few reports of adult-onset cases and even fewer that are correctly diagnosed. We present a 48-year-old woman with no co-morbidities who was seen with generalized weakness, fatigue, carpopedal spasms and tingling in both hands, muscle cramps, and frequent urination. Clinical assessment showed a positive Trousseaus sign, and laboratory tests established hypokalemia, metabolic alkalosis, hyper reninism, hypocalcemia and hypercalciuria with renal biopsy showing juxtaglomerular hyperplasia. The patient was treated with intravenous potassium and calcium supplementation, ACE inhibitors, NSAIDS, followed by oral therapy, dietary counseling. She stayed asymptomatic on follow-up. Adult-onset Bartter syndrome is a rare clinical phenomenon that must be kept in mind in the differential diagnosis of unexplained metabolic alkalosis and hypokalemia, particularly in normotensive individuals. Timely diagnosis and proper treatment may result in outstanding outcomes. This case highlights the significance of recognizing late-onset variants and distinguishing them from other tubulopathies like Gitelman syndrome.

Chronic kidney disease (CKD) is a significant global health issue, and effective treatments are limited. Xiaoyu Xiezhuo Decoction (XYXZD), a traditional Chinese medicine, has shown potential in modulating the gut-kidney axis and related signaling pathways. This study investigates the effects of XYXZD in alleviating tubulointerstitial fibrosis (TIF) in a unilateral ureteral obstruction (UUO) rat model by targeting the aldosterone (ALD)/mineralocorticoid receptor (MR)/serum- and glucocorticoid-inducible kinase-1 (SGK-1) signaling pathway and exploring the role of butyrate. UUO rats were divided into four groups: control, UUO model, XYXZD treatment, and irbesartan treatment. Renal function was assessed by measuring serum creatinine (Scr), blood urea nitrogen (BUN), and ALD levels. Fibrosis markers, including alpha-smooth muscle actin (α-SMA) and Collagen Type III (COL-III), as well as signaling molecules such as phosphorylated SGK-1 (p-SGK-1) and phosphorylated nuclear factor kappa B (p-NF-κB), were analyzed by Western blot and immunohistochemistry. Gut microbiota composition was evaluated using 16S ribosomal DNA (rDNA) sequencing, and the role of butyrate was examined via oral gavage treatment. XYXZD significantly improved renal function, reduced fibrosis, and restored gut microbiota balance by increasing butyrate-producing bacteria. XYXZD also reduced serum ALD levels and inhibited SGK-1 phosphorylation, suggesting modulation of the ALD/MR signaling pathway. Furthermore, butyrate treatment reduced MR nuclear translocation, supporting its role in the therapeutic effects of XYXZD. XYXZD alleviates renal injury in UUO rats by modulating the gut-kidney axis, particularly through the ALD/MR/SGK-1 signaling pathway, with butyrate playing a critical role. These findings highlight a promising approach for CKD treatment by targeting gut microbiota and enhancing butyrate production.

Apparent mineralocorticoid excess (AME) is a rare genetic disorder caused by reduced activity of the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme. It is characterized by hypertension, hypokalemia, and low levels of renin and aldosterone. This study presents the case of a 2-year-old female patient who exhibited abdominal distension, hypertension, recurrent hypokalemia with metabolic alkalosis, failure to thrive, polyuria, and features of rickets. Furthermore, the patient presented with nephrocalcinosis and enlarged kidneys with a normal renal Doppler study. The genetic analysis revealed a homozygous mutation in the HSD11B2 gene, confirming the diagnosis of AME. The treatment with amiloride and spironolactone resulted in normalized urine output, stabilized blood pressure, and balanced electrolyte levels. This case emphasizes the importance of considering AME in pediatric patients presenting with unexplained refractory hypertension associated with hypokalemia and nephrocalcinosis, and it underscores the crucial role of genetic testing in diagnosis and management.

Benign and rare renal juxtaglomerular cell tumor produces renin, leading to secondary hyperaldosteronism. Typical clinical features include hypertension, elevated renin activity, hyperaldosteronism, and hypokalemia. Herein, we present a unique and enlightening case of juxtaglomerular cell tumor with hypertension, with normal renin activity and potassium levels. A 39-year-old Sri Lankan man with a personal history of uncontrollable hypertension was admitted to our hospital for a right renal mass on ultrasound. Dynamic contrast-enhanced computed tomography and magnetic resonance imaging showed a 20-mm mass in the cortex of the right kidney. The preoperative diagnosis was nonclear cell renal cell carcinoma on the basis of both radiological findings, but a 10-mm mass was also found in the bilateral adrenal gland. Although plasma renin activity was normal while plasma aldosterone concentration was elevated at the upright position, primary aldosteronism (plasma aldosterone concentration/plasma renin activity ratio above 200) was not present. Partial nephrectomy of the tumor led to remission of hypertension and hyperaldosteronism. The patient was diagnosed with juxtaglomerular cell tumor on the basis of immunohistological findings. We coincidentally conducted the hormonal tests owing to the small adrenal mass. Hormonal testing should be conducted in patients with both uncontrollable or juvenile hypertension and renal masses and, regardless of plasma renin activity, the preoperative diagnosis of juxtaglomerular cell tumor should not be ruled out in such patients.

Introduction: Chronic kidney disease (CKD) is a common, often late-diagnosed and progressive condition associated with increased morbidity and mortality, mainly due to elevated cardiovascular risk. Diabetes is the one of the leading causes of CKD. Due to the significant role that excessive mineralocorticoid receptor (MR) activation plays in the development of diabetic kidney disease (DKD), new therapies that target this pathway, are being investigated. Finerenone is a non-steroidal selective antagonist that reduces inflammation and fibrosis by blocking MR overactivity in the kidneys, heart, and blood vessels. Materials and Methods: This review is based on a comprehensive analysis of studies on the use of finerenone in patients with CKD and type 2 diabetes (T2D). Additionally, this article explores the potential applications of finerenone. The review was developed using a PubMed database and ClinicalTrials.gov. Results: The results of the FIDELIO-DKD and FIGARO-DKD trials, as well as the FIDELITY pooled analysis, showed that finerenone significantly improved renal and cardiovascular outcomes. They also showed that although hyperkalemia is a major adverse effect of finerenone treatment, the therapy is safe with appropiate monitoring and dose adjustment. In addition, its possible beneficial effects are in non-diabetic CKD, heart failure with preserved (HFpEF) and mildly reduced (HFmrEF) ejection fraction, advanced of CKD with lower estimated glomerular filtration rate (eGFR), and diabetic retinopathy. Conclusion: Clinical studies have confirmed that finerenone is a valuable addition to nephroprotective and cardioprotective strategies in the management of CKD associated with T2D, as reflected in latest clinical guidelines. Its safety profile is generally acceptable. Ongoing clinical trials will help clarify whether the approved indications for finerenone can be extended to non-diabetic CKD or additional clinical settings.

High Plasma 18β-Glycyrrhetinic Acid Levels Are Associated With More Intensive Antihypertensive Treatment, Resistant Hypertension and Apparent Mineralocorticoid Excess in Patients With Type 2 Diabetes.

INTRODUCTIONFamilial glucocorticoid resistance syndrome (FGRS) is a rare condition leading to compensatory ACTH hypersecretion and excess adrenal steroid production. Patients often present with mineralocorticoid and androgen excess but without features of Cushing’s syndrome. CASEA 17-year-old, male, Malay was referred for recurrent episodes of acute paralysis secondary to hypokalaemia and concomitant hypertension since the age of 7 years. Investigations showed persistent hypokalaemia with metabolic alkalosis. Clinically, he was not dysmorphic, taller for his age, increased skin pigmentation and was in pubertal with testicular volume of 6 ml and stretched penile length of 7 cm. Laboratory investigations showed a very marked increase in random serum cortisol of more than 2000 with elevated ACTH level. Luteinizing hormone-releasing hormone (LHRH) test confirmed a diagnosis of peripheral precocious puberty. Adrenal ultrasound did not show any suspicion of malignancy. He was started on oral dexamethasone and anti-hypertensive. He showed some improvement clinically and biochemically with no further history of paralysis and improvement in serum cortisol and potassium levels. This patient presentation is consistent with FGRS where impaired cortisol signaling leads to compensatory increase in ACTH causing excess mineralocorticoid and sex hormones. Management focuses on reducing ACTH stimulation using high-dose dexamethasone and addressing complications such as hypertension and electrolyte imbalances. CONCLUSIONCareful evaluation of a child presenting with unexplained hypertension, hypokalaemia and hyperpigmentation is very important. Early diagnosis is crucial for appropriate management and genetic counselling.

INTRODUCTION/BACKGROUNDGlucocorticoid resistance syndrome (GRS) is a rare condition characterized by biochemical hypercortisolism without the typical clinical manifestations of Cushing’s syndrome. Patients with GRS exhibit elevated serum cortisol, increased 24-hour urinary free cortisol, normal to elevated ACTH, non-suppressed low-dose dexamethasone-suppression test results and preserved circadian rhythm, which are findings that help distinguish it from Cushing’s disease. It is associated with various mutations in the NR3C1 gene, which encodes the glucocorticoid receptor. Clinical presentations can vary from being asymptomatic to exhibiting features of mineralocorticoid or androgen excess such as hypertension with hypokalemia or hyperandrogenism. CASEA 51-year-old female with type 2 diabetes mellitus, hypertension, and dyslipidemia presented with bilateral lower limb edema and intermittent facial flushing. Her BMI was within normal range, and her blood pressure and blood glucose were well-controlled. Notably, she had persistent hypokalemia and elevated cortisol levels. MRI of the pituitary revealed a partial empty sella with a suspected right-sided pituitary adenoma. Her bone mineral density was also normal. Inferior petrosal sinus sampling confirmed ACTH-dependent hypercortisolism. However, in the absence of clinical features of Cushing’s syndrome, diagnosis of GRS was made. She was started on dexamethasone, leading to significant reduction in cortisol levels over nine months. However, her condition was complicated by recurrent infections, soft tissue abscesses, and a newly diagnosed systemic lupus erythematosus (SLE) with concomitant lupus nephritis. Frequent steroid adjustments were necessary to manage autoimmune flares, which, in turn, increased her risk for opportunistic infections, culminating in severe Pneumocystis jirovecii pneumonia. CONCLUSIONThis case illustrates the diagnostic and therapeutic challenges of managing GRS, particularly when complicated by autoimmune disease and infection risk. While dexamethasone is effective in suppressing the HPA axis in GRS due to its glucocorticoid receptor affinity and mineralocorticoid-sparing properties, its use in patients with concurrent immunosuppressive conditions like SLE requires careful balance to avoid immunosuppression-related complications. Individualized steroid management is crucial to optimize outcomes and minimize adverse events.

The follow up of 3 patients with apparent mineralocorticoid excess after 32 years