bims-adreca 2024-04-07 papers

bims-adreca

Biomed News

on Adrenal calcium

Issue of 2024–04–07
thirteen papers selected by
Bakhta Fedlaoui, INSERM

Feasibility of primary aldosteronism diagnosis in initial evaluation without medication withdrawal or confirmatory tests.
Moderate salt restriction in primary aldosteronism improves bone metabolism through attenuation of urinary calcium and phosphate losses.
Mineralocorticoid receptor antagonists in kidney transplantation.
Zona glomerulosa derived Klotho modulates aldosterone synthase expression in young female mice.
Dysfunction of the Renin-Angiotensin-Aldosterone System in Human Septic Shock.
The effect of different treatment strategies on glycolipid metabolism disorders and cardiovascular events in primary aldosteronism.
Familial Hyperaldosteronism: an ENDO ERN Clinical Practice Guideline.
Development of a machine learning-based model for predicting individual responses to antihypertensive treatments.
Therapeutic role of yoga in hypertension.
Dietary Sodium and Blood Pressure-Reply.
Dietary Sodium and Blood Pressure.
Endocrine, cardiac and neuropsychological aspects of adult congenital adrenal hyperplasia.
Epinephrine also acts on beta cells and insulin secretion.

Endocrine. 2024 Apr 03.

Feasibility of primary aldosteronism diagnosis in initial evaluation without medication withdrawal or confirmatory tests.

Jorge Gabriel Ruiz-Sánchez, Álvaro Fernández Sánchez, Diego Meneses.

   PURPOSE: Primary aldosteronism (PA), a frequent cause of hypertension, is highly associated with cardiovascular risk and mortality. PA diagnosis is often difficult due to the need to discontinue antihypertensive medication interfering with the renin-angiotensin-aldosterone system (I-RAAS). Our objective was to ascertain diagnosis of PA through biochemical assessments during screening while maintaining I-RAAS medications.
METHODS: Hypertensive patients assessed for PA were involved. Patients were grouped according to the use of I-RAAS drugs during screening and the presence of PA. The diagnostic accuracy of the aldosterone-to-renin ratio (ARR), and other biochemical features were evaluated.
RESULTS: 265 patients included, 122/265 with PA, and 192/265 were on I-RAAS therapy. The area under ROC curve (AUROC) of ARR for PA in patients without I-RAAS was 0.769 (95%CI: 0.66-0.877), and was 0.877 (95%CI: 0.828-0.926) in those with I-RAAS drugs. Sensitivity, specificity, positive predictive value, and negative predictive value (PPV) of cut-off of ARR > 50 were: 76%, 81%, 77.5%, and 79.6%. ARR > 50 plus hypokalemia had a PPV of 92.6% for PA. AUROC values of ARR evaluated in each group of antihypertensive drugs were >0.850 in all cases.
CONCLUSIONS: ARR during I-RAAS therapy demonstrates reliability and accuracy for PA diagnosis. An ARR > 50 combined with hypokalemia while on I-RAAS medication could be considered indicative of PA diagnosis.

Keywords:  Hyperaldosteronism management; Hypertension; Primary aldosteronism; Secondary hypertension

DOI:  https://doi.org/10.1007/s12020-024-03798-0
Eur J Endocrinol. 2024 Mar 30. 190(4): K47-K52

Moderate salt restriction in primary aldosteronism improves bone metabolism through attenuation of urinary calcium and phosphate losses.

Holger Schneider, Denise Brüdgam, Hanna F Nowotny, Ralf Schmidmaier, Martin Reincke, Christian Adolf.

  Accumulating evidence links osteoporosis and dietary salt consumption. Primary aldosteronism (PA) is a model disease with increased dietary salt intake and constitutes an independent risk factor for osteoporosis. We, thus, assessed whether a short-term moderate reduction in salt intake in PA results in detectable osteoanabolic effects. Forty-one patients with PA on stable mineralocorticoid receptor antagonist therapy were subjected to a 12-week salt restriction. Serum and urinary electrolytes, markers of bone turnover, and a 15 steroids plasma profile were registered. After 12 weeks, urinary calcium and phosphate decreased, while plasma testosterone, serum phosphate, and bone alkaline phosphatase (BAP) all increased significantly. Longitudinal changes in BAP were independently correlated with changes in serum phosphate, parathyroid hormone, and urinary calcium in multivariate analysis. Salt restriction in PA limits urinary calcium and phosphate losses and may confer favorable osteoanabolic effects. Our findings suggest that salt restriction should be considered in patients with PA to improve bone health.

Keywords:  aldosterone; alkaline phosphatase; calcium excretion; sodium

DOI:  https://doi.org/10.1093/ejendo/lvae020
Eur J Clin Invest. 2024 Apr 05. e14206

Mineralocorticoid receptor antagonists in kidney transplantation.

Mehmet Kanbay, Sidar Copur, Berk Mizrak, Francesca Mallamaci, Carmine Zoccali.

   BACKGROUND: The fundamental role of the renin-angiotensin-aldosterone system in the pathophysiology of chronic kidney disease, congestive heart failure, hypertension and proteinuria is well established in pre-clinical and clinical studies. Mineralocorticoid receptor antagonists are among the primary options for renin-angiotensin-aldosterone system blockage, along with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.
METHODS: In this narrative review, we aim to evaluate the efficiency and safety of mineralocorticoid receptor antagonists in kidney transplant recipients, including the potential underlying pathophysiology.
RESULTS: The efficiency and safety of mineralocorticoid receptor antagonists in managing chronic kidney disease and proteinuria, either non-nephrotic or nephrotic range, have been demonstrated among nontransplanted patients, though studies investigating the role of mineralocorticoid receptor antagonists among kidney transplant recipients are scarce. Nevertheless, promising results have been reported in pre-clinical and clinical studies among kidney transplant recipients regarding the role of mineralocorticoid receptor antagonists in terms of ischaemia-reperfusion injury, proteinuria, or calcineurin inhibitor-mediated nephrotoxicity without considerable adverse events such as hypotension, hyperkalaemia or worsening renal functions.
CONCLUSION: Even though initial results regarding the role of mineralocorticoid receptor antagonist therapy for kidney transplant recipients are promising, there is clear need for large-scale randomized clinical trials with long-term follow-up data.

Keywords:  chronic kidney disease; kidney transplantation; mineralocorticoid receptor antagonists; proteinuria; renin‐angiotensin‐aldosterone system

DOI:  https://doi.org/10.1111/eci.14206
Endocrinology. 2024 Apr 04. pii: bqae040. [Epub ahead of print]

Zona glomerulosa derived Klotho modulates aldosterone synthase expression in young female mice.

Arezoo Daryadel, Cong Tang, Ye Xie, Mirko Peitzsch, Viktoria Fisi, Constanze Hantel, Dominique Loffing-Cueni, David T Breault, David Penton, Johannes Loffing, Felix Beuschlein.

  Klotho plays a critical role in the regulation of ion and fluid homeostasis. A previous study reported that haplo-insufficiency of Klotho in mice results in increased aldosterone synthase (CYP11B2) expression, elevated plasma aldosterone and high blood pressure. This phenotype was presumed to be the result of diminished Klotho expression in zona glomerulosa (zG) cells of the adrenal cortex, however systemic effects on adrenal aldosterone production could not be ruled out. To examine whether Klotho expressed in the zG is indeed a critical regulator of aldosterone synthesis, we generated a tamoxifen-inducible, zG-specific mouse model of Klotho deficiency by crossing Klotho-flox mice with Cyp11b2-CreERT mice (zG-Kl-KO). Tamoxifen-treated Cyp11b2-CreERT animals (zG-Cre) served as controls. Rosa26-mTmG reporter mice were used for Cre-dependent lineage-marking. Two weeks after tamoxifen induction, the specificity of the zG-Cre line was verified using immunofluorescence analysis to show that GFP expression was restricted to the zG. RNA in situ hybridization revealed a 65% down-regulation of Klotho mRNA expression in the zG of zG-Kl-KO female mice at 12-weeks of age compared to control mice. Despite this significant decrease, zG-Kl-KO mice exhibited no difference in plasma aldosterone levels. However, adrenal CYP11B2 expression and the CYP11B2 promotor regulatory transcription factors, NGFIB and Nurr1, were enhanced. Together with in vitro experiments, these results suggest that zG-derived Klotho modulates Cyp11b2 but does not evoke a systemic phenotype in young adult mice on a normal diet. Further studies are required to investigate the role of adrenal Klotho on aldosterone synthesis in aged animals.

Keywords:  CYP11B2; Cre-lox system; Klotho; aldosterone; zona glomerulosa

DOI:  https://doi.org/10.1210/endocr/bqae040
Peptides. 2024 Mar 29. pii: S0196-9781(24)00054-8. [Epub ahead of print] 171201

Dysfunction of the Renin-Angiotensin-Aldosterone System in Human Septic Shock.

Christopher L Schaich, Daniel E Leisman, Marcia B Goldberg, Micheal R Filbin, Ashish K Khanna, Mark C Chappell.

Sepsis and septic shock are global healthcare problems associated with mortality rates of up to 40% despite optimal standard-of-care therapy and constitute the primary cause of death in intensive care units worldwide. Circulating biomarkers of septic shock severity may represent a clinically relevant approach to individualize those patients at risk for worse outcomes early in the course of the disease, which may facilitate early and more precise interventions to improve the clinical course. However, currently used septic shock biomarkers, including lactate, may be non-specific and have variable impact on prognosis and/or disease management. Activation of the renin-angiotensin-aldosterone system (RAAS) is likely an early event in septic shock, and studies suggest that an elevated level of renin, the early and committed step in the RAAS cascade, is a better predictor of worse outcomes in septic shock, including mortality, than the current standard-of-care measure of lactate. Despite a robust increase in renin, other elements of the RAAS, including endogenous levels of Ang II, may fail to sufficiently increase to maintain blood pressure, tissue perfusion, and protective immune responses in septic shock patients. We review the current clinical literature regarding the dysfunction of the RAAS in septic shock and potential therapeutic approaches to improve clinical outcomes.

DOI: https://doi.org/10.1016/j.peptides.2024.171201
Hypertens Res. 2024 Apr 02.

The effect of different treatment strategies on glycolipid metabolism disorders and cardiovascular events in primary aldosteronism.

Shiting Zhou, Jing Liu, Zhuo Li, Mingfeng Yang, Ruohe Sha, Ruike Yan, Xinxin Wang, Yanli Cao.

  Recent studies have explored the association between primary aldosteronism and cardiovascular disease incidence. The association between specific primary aldosteronism treatments and differential improvement in cardiovascular event rates is yet to be established. This study was designed to compare the relative effects of spironolactone therapy and surgical intervention on cardiovascular outcomes among primary aldosteronism patients. This retrospective observational study included 853 primary aldosteronism patients from the First Affiliated Hospital of China Medical University between 2014 and 2022. Patients who had completed abdominal computed tomography (CT) examinations with similar metabolic characteristics and 6-month follow-up analyses were included in this study. These patients were separated into a surgical treatment group (n = 33) and a spironolactone treatment group (n = 51). Demographic data, biochemical analysis results, liver/spleen (L/S) X-ray attenuation ratio, hospitalization frequency, and cardiovascular events were compared between the two groups. The spironolactone group demonstrated significantly improved metabolic characteristics compared to the surgical group, shown by lower BMI, blood pressure, total cholesterol (TC), insulin resistance index (IRI), and reduced non-alcoholic fatty liver disease prevalence. Metabolic parameters did not differ significantly within the surgical treatment group when comparing pre- and postoperative values. The incidence of cardiovascular events was lower in the spironolactone group compared to the surgery group (23/33 vs. 20/51, P < 0.001) despite higher hospitalization rates(37/31 vs. 61/53, P < 0.001). In patients with primary aldosteronism, spironolactone treatment is more effective than surgical intervention in remediating abnormal lipid and glucose metabolism while improving cardiovascular outcomes. Chinese clinical trial registry registration number: ChiCTR2300074574.

Keywords:  Adrenal surgery; Cardiovascular events; Non-alcoholic fatty liver; Primary aldosteronism; Spironolactone

DOI:  https://doi.org/10.1038/s41440-024-01648-0
Eur J Endocrinol. 2024 Apr 04. pii: lvae041. [Epub ahead of print]

Familial Hyperaldosteronism: an ENDO ERN Clinical Practice Guideline.

Paolo Mulatero, Ute I Scholl, Carlos E Fardella, Evangelia Charmandari, Andrzej Januszewicz, Martin Reincke, Celso E Gomez-Sanchez, Michael Stowasser, Olaf M Dekkers.

We describe herein the European Reference Network on Rare Endocrine Conditions (Endo-ERN)- clinical practice guideline on diagnosis and management of familial forms of hyperaldosteronism. The guideline panel consisted of 10 experts in primary aldosteronism, endocrine hypertension, pediatric endocrinology and cardiology as well as a methodologist. A systematic literature search was conducted, and because of the rarity of the condition, most recommendations were based on expert opinion and small patient series. The guideline includes a brief description of the genetics and molecular pathophysiology associated with each condition, the patients to be screened and how to screen. Diagnostic and treatment approaches for patients with genetically determined diagnosis are presented. The recommendations apply to patients with genetically proven familial hyperaldosteronism and not to families with more than one case of PA without demonstration of a responsible pathogenic variant.

DOI: https://doi.org/10.1093/ejendo/lvae041
Nutr Metab Cardiovasc Dis. 2024 Mar 04. pii: S0939-4753(24)00086-3. [Epub ahead of print]

Development of a machine learning-based model for predicting individual responses to antihypertensive treatments.

Jiayi Yi, Lili Wang, Jiali Song, Yanchen Liu, Jiamin Liu, Haibo Zhang, Jiapeng Lu, Xin Zheng.

   BACKGROUND AND AIMS: Personalized antihypertensive drug selection is essential for optimizing hypertension management. The study aimed to develop a machine learning (ML) model to predict individual blood pressure (BP) responses to different antihypertensive medications.
METHODS AND RESULTS: We used data from a pragmatic, cluster-randomized trial on hypertension management in China. Each patient's multiple visit records were included, and two consecutive visits were paired as the index and subsequent visits. The least absolute shrinkage and selection operator method was used to select index visit variables for predicting subsequent BP. The dataset was randomly divided into training and test sets in a 7:3 ratio. Model performance was evaluated using mean absolute error (MAE) and R-square in the test set. A total of 19,013 hypertension management visit records (6282 patients) were included. The mean age of the study population was 63.9 years, and 2657 (42.3%) were females. A total of 12 phenotypical features (age, sex, smoking within seven days, body mass index, waist circumference, index visit systolic BP, diastolic BP, heart rate, comorbidities of diabetes, dyslipidemia, coronary heart disease, and stroke), together with currently taking any prescribed antihypertensive medication regimens and visits time interval were selected to build the model. The Extreme Gradient Boost model performed best among all candidate algorithms, with an MAE of 8.57 mmHg and an R2 = 0.28 in the test set.
CONCLUSION: The ML techniques exhibit significant potential for predicting individual responses to antihypertensive treatments, thereby aiding clinicians in achieving optimal BP control safely and efficiently.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT03636334. Registered July 3, 2018, https://clinicaltrials.gov/study/NCT03636334.

Keywords:  Antihypertensive medication; Blood pressure; Machine learning; Predictive model

DOI:  https://doi.org/10.1016/j.numecd.2024.02.014
World J Methodol. 2024 Mar 20. 14(1): 90127

Therapeutic role of yoga in hypertension.

Anjali Mangesh Joshi, Arkiath Veettil Raveendran, Muruganathan Arumugam.

  Systemic hypertension is an established risk factor for coronary artery disease and cerebrovascular accident and control of blood pressure reduces the risk of a major cardiovascular event. Both non-pharmacological and pharmacological treatment options are available to treat hypertension. Yoga, recently received more attention as a treatment modality for various lifestyle disorders, even though practiced in India since ancient times. In this review, we are analyzing the role of yoga in the treatment of systemic hypertension.

Keywords:  Asana; Blood pressure; Hypertension; Meditation; Pranayama; Yoga

DOI:  https://doi.org/10.5662/wjm.v14.i1.90127
JAMA. 2024 04 02. 331(13): 1155-1156

Dietary Sodium and Blood Pressure-Reply.

Deepak K Gupta, Cora E Lewis, Norrina B Allen.

DOI: https://doi.org/10.1001/jama.2024.1910
JAMA. 2024 04 02. 331(13): 1154-1155

Dietary Sodium and Blood Pressure.

Thomas C Keyserling, Veeral M Saraiya, Alice S Ammerman.

DOI: https://doi.org/10.1001/jama.2024.1907
Clin Endocrinol (Oxf). 2024 Apr 04.

Endocrine, cardiac and neuropsychological aspects of adult congenital adrenal hyperplasia.

Lukas Ochsner Ridder, Camilla Mains Balle, Anne Skakkebæk, Marie Lind-Holst, Mette Mølby Nielsen, Pernille Hermann, Stinus Hansen, Dorte Guldbrand Nielsen, Sine Knorr, Niels Holmark Andersen, Mette Hansen Viuff, Agnethe Berglund, Claus Højbjerg Gravholt.

   OBJECTIVE: To investigate the metabolic, cardiovascular, and neuropsychological phenotype, quality of life (QoL), and hormonal regulation in individuals with congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired synthesis of cortisol in the adrenal cortex and, if untreated compensatory hyperandrogenism. CAH is associated with an increased cardiovascular and metabolic morbidity, possibly due to overtreatment with glucocorticoids, leading to weight gain, insulin resistance, and metabolic syndrome.
DESIGN, PARTICIPANTS, MEASUREMENTS: Thirty-seven individuals with CAH and 33 age- and sex-matched controls were evaluated at a single centre at Aarhus University Hospital with echocardiography, electrocardiogram, 24-h blood pressure, biochemistry, anthropometrics, and autism spectrum, anxiety, depression, personality, cognitive failures, and QoL were assessed using questionnaires.
RESULTS: CAH individuals had lower height than controls (170.5 vs. 182.9 cm in males and 160.2 vs. 170.1 cm in females, p < 0.01). Compared with female controls, females with CAH had higher haemoglobin (8.8 vs. 8.2 mmol/L, p = 0.003) and BMI (29.7 vs. 25.5 kg/m2, p = 0.006), reduced insulin sensitivity (HOMA-IR): 2.7 vs. 1.9, p = 0.018), prolonged E-wave deceleration time (193 vs. 174 cm, p = 0.015), and E/é ratios (5.4 vs. 4.5, p = 0.017), and lower self-reported QoL. Males with CAH had more cognitive complaints (p = 0.034) and higher autistic scores (19.9 vs. 14.9; p = 0.068) compared with male controls. More individuals with CAH than controls reported writing problems.
CONCLUSION: A sex-specific comorbidity profile is evident in CAH, with females presenting with decreased metabolic and overall self-reported health, whereas males with CAH presented with increased cognitive complaints and autistic traits.

Keywords:  cardiology; congenital adrenal hyperplasia; endocrinology; neuropsychology; quality of life

DOI:  https://doi.org/10.1111/cen.15055
World J Clin Cases. 2024 Mar 26. 12(9): 1712-1713

Epinephrine also acts on beta cells and insulin secretion.

Lina Zabuliene, Ioannis Ilias.

  In a recent review examining neurotransmitter modulation of insulin secretion, the significant impact of epinephrine was not addressed. Its primary action involves inhibiting insulin release via alpha-adrenergic receptors, thereby reducing the response to insulin secretion stimulators, through the activation of K+ channels and resulting in membrane hyperpolarization in beta cells.

Keywords:  Epinephrine; Glucose; Human; Insulin; Islets

DOI:  https://doi.org/10.12998/wjcc.v12.i9.1712