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Primary Aldosteronism in Elderly Patients: evaluation of Aldosterone renin ratio cut-off value in different groups of age and immunohistochemical adrenocortical variations with age
Get PDFLa diagnosi di iperaldosteronismo primario (PA) è comune, ma solitamente sottovalutata nei pazienti anziani in cui il già elevato rischio assoluto di eventi cardiovascolari, in particolare la fibrillazione atriale, può essere ulteriormente peggiorato dal PA.
Prima parte del progetto.
Il rapporto aldosterone/renina (ARR) è attualmente considerato il test di screening più affidabile e disponibile per la diagnosi di PA, tuttavia, la minore accuratezza dell'ARR con l'aumentare dell'età ha rappresentato una sfida cruciale per lo screening della PA tra la popolazione anziana.
Per chiarire i potenziali effetti dell'età sullo screening del PA, pazienti da due dataset (dataset 1 e dataset 2), con diagnosi finale di PA e non-PA, reclutati in modo prospettico, e da un terzo dataset risultato dalla fusione dei primi due (dataset 3), sono stati suddivisi in quattro gruppi di età. Abbiamo valutato se l'ARR basale potesse essere impostato su un valore soglia più elevato nei pazienti più anziani fornendo un guadagno diagnostico. Il risultato è stato che un valore soglia di ARR di 57,44 ng/mIU per la prima e la terza coorte di pazienti, e di 45,56 ng/mIU per la seconda, in pazienti di età superiore ai 70 anni, corrisponde ad un maggiore valore predittivo positivo e maggiore diagnostic odds ratio; questo determina una riduzione in modo esponenziale del tasso di falsi positivi con una specificità diagnostica maggiore per valori di ARR superiori al valore soglia indicato, nei pazienti sopra i 70 anni di età.
Questi risultati indicano che un valore soglia di ARR più elevato nei pazienti di età superiore ai 70 anni, può semplificare l'iter diagnostico, con conseguente risparmio di risorse e spesa medica, offrendo la possibilità di una diagnosi più accurata e la giusta terapia (medica o chirurgica) per un miglior controllo della pressione arteriosa.
Seconda parte del progetto.
Sia l'invecchiamento che la secrezione inappropriata di aldosterone aumentano il rischio di sviluppare malattie cardiovascolari; tuttavia, l'influenza dell'invecchiamento sugli aspetti anatomopatologici e immunoistochimici della corticale surrenalica sono ancora non ben definiti.
La relazione tra età, variabili biochimiche ed espressione dell'aldosterone sintetasi surrenalica (CYP11B2) è stata valutata in 40 surreni di pazienti affetti da PA surrenalectomizzati. Eseguita l’analisi immunoistochimica, sono stati analizzati i focolai anomali di cellule che esprimono CYP11B2, chiamati cluster di cellule produttrici di aldosterone (APCC), nella zona glomerulosa (ZG) della corticale surrenalica. I nostri risultati hanno mostrato una correlazione positiva tra concentrazione plasmatica di aldosterone (PAC), ARR ed età.
La nostra piccola coorte di pazienti affetti da PA non ha confermato una diminuzione età-dipendente della normale espressione del CYP11B2 della zona glomerulosa e un aumento dell'espressione del cluster di cellule produttrici di aldosterone. L’obiettivo futuro è di focalizzare la nostra ricerca sul ruolo delle APCC nell'invecchiamento in diversi gruppi clinici e biochimici di pazienti affetti da PA in una più ampia coorte di pazienti.Primary aldosteronism (PA) is common, but usually overlooked in the old patients in whom the already high absolute risk of cardiovascular events, particularly atrial fibrillation, can be further increased by PA.
First part of the project.
Background: Aldosterone/renin ratio (ARR) is currently regarded as the most reliable and available screening test for PA, however, the falling accuracy of ARR with increasing age has posed crucial challenge for PA screening among aged population.
Methods, patients and results: To clarify potential effects of age on screening of PA, subjects from two datasets, prospectively recruited (dataset 1 and dataset 2) and from a third merged dataset (dataset 3), with PA and non-PA final diagnosis, were subdivided into four age groups. We assessed whether the basal ARR could be set to a higher cut-off value in older patients furnishing a diagnostic gain. We found that a higher ARR cut-off value of 57.44 ng/mIU for cohort 1 and merged cohort of patients and of 45.56 ng/mIU for cohort 2, in patients older than 70 years old, showed a higher positive likelihood and diagnostic odds ratio, hence the false-positive rate fell exponentially, and, conversely, the specificity increased with rising ARR values in oldest patients.
Conclusions: These results indicate that a higher ARR cut-off value in patients older than 70, can simplify the diagnostic workup, resulting in saving of money and resources, offering the chance of diagnosis and the right therapy (medical or surgical) for a better control of blood pressure (BP).
Second part of the project.
Background: Both aging and inappropriate secretion of aldosterone increase the risk for developing cardiovascular disease; however, the influence of aging on aldosterone secretion and pathology is not well understood.
Methods, patients and results: The relationship between age, biochemical variables and adrenal aldosterone synthase (CYP11B2) expression was evaluated in 40 adrenal glands from adrenalectomized PA patients. Following immunohistochemistry, abnormal foci of CYP11B2-expressing cells, called aldosterone-producing cell clusters (APCC), in the zona glomerulosa (ZG) of the adrenal cortical, were analyzed. Our results showed a positive correlation between plasma aldosterone concentration (PAC), ARR and age in this cohort of patient; APCC number and APCC total area (normalized for the total cortical area) were not age correlated. No correlation was found between direct renin concentration (DRC), PAC and number of APCC and APCC total area, but these two histopathological variables were negative correlated with ARR.
Conclusions: Our small cohort of PA patients didn’t confirm an age-dependent decrease of normal zona glomerulosa CYP11B2 expression and an increase of aldosterone-producing cell cluster expression too. Future researches will be focused on the role of APCCs through aging in different clinical and biochemical set of aldosterone producing adenoma (APA) patients from a bigger cohort of patients
Letter to editor on “Thirty‐six‐month results of laparoscopic‐based renal denervation plus unilateral laparoscopic adrenalectomy for the treatment of patients with resistant hypertension caused by unilateral aldosterone‐producing Adenoma”
No full textSurgical approaches in hereditary endocrine tumors
No full textEndocrine tumors of thyroid, adrenal and parathyroid glands may be due to germline and inheritable mutations in 5-30% of patients. Medullary Thyroid Carcinoma, Pheochromocytoma, Paraganglioma, and Familial Primary Hyperparathyroidism are the most frequent entity. Hereditary endocrine tumors usually have a suggestive familial history; they occur earlier than sporadic variants, are multifocal, and have increased recurrence rates. They may be present as isolated variant or associated to other neoplasms in a syndromic setting. Genetic diagnosis should be preferably available before surgery because specific and targeted operative management are needed to achieve the best chance of cure. This review was aimed to discuss the surgical approaches for some of the most frequent hereditary endocrine tumors of thyroid, adrenal and parathyroid glands, focusing on medullary thyroid carcinoma, Pheochromocytoma, Paraganglioma and hereditary primary hyperparathyroidism (pHPT). Hereditary Medullary Thyroid Carcinoma is caused by RET mutations, and may be associated to Pheochromocytomas in MEN 2 setting. Total thyroidectomy and at least central neck nodal dissection is required. The availability of genetic screening allows prophylactic or early surgery in asymptomatic patients, with subsequent definitive cure. Hereditary Pheochromocytomas may be present in several syndromes (MEN 2, VHL, NF1, Paraganglioma/Pheochromocytoma syndrome); it may involve both adrenals; in these cases, a cortical sparing adrenalectomy should be performed to avoid permanent hypocorticosurrenalism. Hereditary Primary Hyperparathyroidism may frequently occur associated to MEN 1, MEN 2A, MEN 4, Hyperparathyroidism-Jaw Tumor Syndrome; it may involve all the parathyroid glands, requiring subtotal parathyroidectomy or total parathyroidectomy plus autotransplantation. In some cases, a selective parathyroidectomy might be performed
Total adrenalectomy versus subtotal adrenalectomy for bilateral pheochromocytoma: meta-analysis
Get PDFBackground: Bilateral pheochromocytomas are rare and often heritable. Total adrenalectomy leads to a definitive oncological cure, with subsequent definitive hypocortisolism. Subtotal adrenalectomy is a possible alternative. The aim of this study was to assess the effects of total adrenalectomy and subtotal adrenalectomy on bilateral pheochromocytoma in terms of post-surgical rate of recurrence, metastatic disease, and steroid dependence. Methods: Systematic searches in the bibliographic databases PubMed, Embase, and Europe PMC were performed for 1945 to 1 June 2023. PRISMA guidelines were followed and the PICO strategy was applied to English-language studies comparing subtotal adrenalectomy with total adrenalectomy. A random-effects model was used to assess the different outcomes for studies with high heterogeneity. The Newcastle-Ottawa scale and the Risk Of Bias In Non-randomized Studies of Interventions ('ROBINS-I') tool were used to assess quality and risk of bias. Results: From a total of 12 909 studies, 1202 patients (from 10 retrospective studies) were eligible for the meta-analysis. In six studies, including 1176 patients, the recurrence rate after subtotal adrenalectomy and total adrenalectomy was 14.1 versus 2.6 per cent respectively (OR 4.91, 95 per cent c.i. 1.30 to 18.54; P = 0.020; I2 72 per cent). In nine studies, including 1124 patients, the rate of post-surgical steroid dependence was 93.3 versus 11.6 per cent after total adrenalectomy and subtotal adrenalectomy respectively (OR 0.003, 95 per cent c.i. 0.0003 to 0.03; P < 0.00001; I2 66 per cent). Based on two studies, including 719 patients, no differences were evident regarding the occurrence of post-surgery metastatic disease. Conclusion: Subtotal adrenalectomy leads to less post-surgical primary adrenal insufficiency, but leads to a higher postoperative recurrence rate. Future prospective randomized studies, with clear eligibility criteria, are needed to confirm these results
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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