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Agnieszka Adamska Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland

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Vitalii Ulychnyi Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland

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Katarzyna Siewko Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland

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Anna Popławska-Kita Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland

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Małgorzata Szelachowska Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland

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Marcin Adamski Faculty of Computer Science, Bialystok University of Technology, Białystok, Poland

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Angelika Buczyńska Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland

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Adam Jacek Krętowski Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland
Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland

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Cardiovascular risk factors could be present in mild adrenal autonomous cortisol secretion (MACS). However, the most frequent cardiovascular risk factors in MACS have not been established. The aim of the presseent study was to analyse the difference in cardiovascular risk factors in patients with MACS in comparison to those with non-functioning adrenal tumour (NFAT). A total of 295 patients with adrenal incidentaloma were included in this retrospective study. We divided our group into those who showed suppression in 1 mg overnight dexamethasone suppression test (DST) (NFAT) (serum cortisol level ≤1.8 μg/dL) and those who did not show suppression in the DST (MACS) (serum concentration of cortisol > 1.8 μg/dL and ≤5 μg/dL). In the studied groups, we analysed the presence of cardiovascular risk factors, such as obesity, prediabetes, type 2 diabetes mellitus (T2DM), hypertension, hyperlipidaemia, chronic kidney disease and cardiovascular events. In our study, 18.9% of patients were defined as MACS. Importantly, T2DM was diagnosed in 41% of MACS vs 23% of NFAT (P < 0.01) and higher frequency of occurrence of hyperlipidaemia in NFAT (72.4%) vs MACS (53.6%) (P = 0.01) was observed. We did not observed differences in the frequency of obesity, hypertension, chronic kidney disease, prediabetes, atrial fibrillation, stroke, ST and non-ST elevation myocardial infarction and coronary angioplasty between patients with MACS and NFAT (all P > 0.05; respectively). In MACS, T2DM is more prevalent than in NFAT; hyperlipidaemia is more prevalent in NFAT. Accordingly, no differences were found in the incidence of obesity, hypertension, prediabetes, chronic kidney disease between studied groups as well as cardiovascular events.

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Richard W Carroll Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand

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Brian Corley Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand
Department of Medicine, University of Otago, Wellington, New Zealand

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Joe Feltham Department of Radiology, Wellington Regional Hospital, New Zealand

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Patricia Whitfield Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand
Department of Medicine, University of Otago, Wellington, New Zealand

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William Park University of Otago, Wellington, New Zealand

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Rowena Howard Diabetes and Endocrinology Service, Hutt Hospital, New Zealand

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Melissa Yssel Department of Biochemistry & Endocrinology, Awanui Labs, New Zealand

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Ian Phillips Department of Biochemistry, Awanui Labs, Dunedin, New Zealand

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Simon Harper Department of Surgery & Anaesethesia, University of Otago, Wellington, New Zealand
Department of General Surgery, Wellington Regional Hospital, New Zealand

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Jun Yang Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria, Australia
Department of Medicine, Monash University, Clayton, Victoria, Australia

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Objective

The assessment of primary aldosteronism incorporates adrenal vein sampling (AVS) to lateralize aldosterone excess. Current adrenal vein sampling protocols rely on concurrent cortisol measurements to assess successful cannulation and lateralization and may be inaccurate in the setting of autonomous cortisol secretion. We aimed to compare the measurement of plasma cortisol and metanephrine concentrations to assess cannulation and lateralization during AVS.

Design

This is a diagnostic accuracy study in a tertiary referral endocrinology department.

Methods

Forty-one consecutive patients with confirmed primary aldosteronism undergoing AVS (49 procedures) were included. None had cortisol autonomy. The use of plasma metanephrine-based ratios were compared with standard cortisol-based ratios to assess cannulation and lateralization during ACTH-stimulated AVS.

Results

There was strong agreement between a cortisol selectivity index (SI) ≥5.0 and an adrenal vein (AV) to peripheral vein (PV) plasma metanephrine ratio (AVmet–PVmet) of ≥12.0 to indicate successful cannulation of the AV (n = 117, sensitivity 98%, specificity 89%, positive predictive value (PPV) 95%, negative predictive value (NPV) 94%). There was strong agreement between the standard cortisol-based SI and an AV plasma metanephrine-to-normetanephrine ratio (AVmet–AVnormet) of ≥2.0 to indicate successful cannulation (n = 117, sensitivity 93%, specificity 86%, PPV 94%, NPV 84%). There was strong agreement between the cortisol- or metanephrine-derived lateralization index (LI) > 4.0 for determining lateralization (n = 26, sensitivity 100%, specificity 94.1%, PPV 91.6%, NPV 100%).

Conclusions

Ratios incorporating plasma metanephrines provide comparable outcomes to standard cortisol-based measurements for interpretation of AVS. Further studies are required to assess the use of metanephrine-derived ratios in the context of confirmed cortisol autonomy.

Significance statement

Primary aldosteronism is a common cause of secondary hypertension, and adrenal vein sampling remains the gold standard test to assess lateralization. Cortisol-derived ratios to assess cannulation and lateralization may be affected by concurrent cortisol dysfunction, which is not uncommon in the context of primary aldosteronism. Our study showed comparable outcomes when using accepted cortisol-derived or metanephrine-derived ratios to determine cannulation and lateralization during adrenal vein sampling. Further research is required to validate these findings and to assess the use of metanephrine-derived ratios in the context of confirmed concurrent cortisol dysfunction.

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Tomaž Kocjan Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

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Gaj Vidmar Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
University Rehabilitation Institute, Ljubljana, Slovenia
FAMNIT, University of Primorska, Koper, Slovenia

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Peter Popović Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia

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Milenko Stanković Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia

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The 20-point clinical prediction SPACE score, the aldosterone-to-lowest potassium ratio (APR), aldosterone concentration (AC) and the AC relative reduction rate after saline infusion test (SIT) have recently been proposed for primary aldosteronism (PA) subtyping prior to adrenal vein sampling (AVS). To validate those claims, we performed a retrospective cross-sectional study that included all patients at our center who had positive SIT to confirm PA and were diagnosed with either bilateral disease (BPA) according to AVS or with lateralized disease (LPA) if biochemically cured after adrenalectomy from November 2004 to the end of 2019. Final diagnoses were used to evaluate the diagnostic performance of proposed clinical prediction tools. Our cohort included 144 patients (40 females), aged 32–72 years (mean 54 years); 59 with LPA and 85 with BPA. The originally suggested SPACE score ≤8 and SPACE score >16 rules yielded about 80% positive predictive value (PPV) for BPA and LPA, respectively. Multivariate analyses with the predictors constituting the SPACE score highlighted post-SIT AC as the most important predictor of PA subtype for our cohort. APR-based tool of <5 for BPA and >15 for LPA yielded about 75% PPV for LPA and BPA. The proposed post-SIT AC <8.79 ng/dL criterion yielded 41% sensitivity and 90% specificity, while the relative post-SIT AC reduction rate of >33.8% criterion yielded 80% sensitivity and 51% specificity for BPA prediction. The application of any of the validated clinical prediction tools to our cohort did not predict the PA subtype with the high diagnostic performance originally reported.

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Paola Parra Ramírez Endocrinology & Nutrition Department, La Paz University Hospital, Madrid, Spain

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Patricia Martín Rojas-Marcos Endocrinology & Nutrition Department, La Paz University Hospital, Madrid, Spain

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Miguel Paja Fano Endocrinology & Nutrition Department, Hospital Universitario de Basurto, Bilbao, Spain
Medicine Department, Basque Country University, Bilbao, Spain

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Marga González Boillos Endocrinology & Nutrition Department, Hospital Universitario de Castellón, Castellón, Spain

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Eider Pascual-Corrales Endocrinology & Nutrition Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain

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Ana García-Cano Biochemistry Department, Hospital Universitario Ramón y Cajal, Madrid, Spain

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Jorge Gabriel Ruiz-Sanchez Endocrinology & Nutrition Department, Hospital Fundación Jiménez Díaz, Madrid, Spain

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Almudena Vicente Endocrinology & Nutrition Department, Complejo Universitario de Toledo, Toledo, Spain

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Emilia Gómez-Hoyos Endocrinology & Nutrition Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

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Rui Ferreira Endocrinology & Nutrition Department, Hospital Universitario de La Princesa, Madrid, Spain

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Iñigo García Sanz General & Digestive Surgery Department, Hospital Universitario de La Princesa, Madrid, Spain

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Mònica Recasens Endocrinology & Nutrition Department, Hospital Josep Trueta, Servei d’Endocrinologia, Girona, Spain

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Begoña Pla Peris Endocrinology & Nutrition Department, Hospital Universitario de Castellón, Castellón, Spain

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Rebeca Barahona San Millan Endocrinology & Nutrition Department, Hospital Josep Trueta, Servei d’Endocrinologia, Girona, Spain

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María José Picón César Endocrinology & Nutrition Department, Complejo Hospitalario Málaga (Hospital Virgen de la Victoria), IBIMA Malaga, Malaga, Spain
CIBEROBN, Madrid, Spain

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Patricia Díaz Guardiola Endocrinology & Nutrition Department, Hospital Universitario Infanta Sofía, Madrid, Spain

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Juan Jesús García González Endocrinology & Nutrition Department, Hospital Universitario Virgen de la Macarena, Sevilla, Spain

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Carolina Perdomo Endocrinology & Nutrition Department, Clínica Universidad de Navarra, Pamplona, Spain

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Laura Manjón Endocrinology & Nutrition Department, Hospital Universitario Central de Asturias, Oviedo, Spain
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain

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Rogelio García-Centeno Endocrinology & Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Juan Carlos Percovich Endocrinology & Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Ángel Rebollo Román Endocrinology & Nutrition Department, Hospital Reina Sofía, Córdoba, Spain

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Paola Gracia Gimeno Endocrinology & Nutrition Department, Hospital Royo Villanova, Zaragoza, Spain

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Cristina Robles Lázaro Endocrinology & Nutrition Department, Hospital Universitario de Salamanca, Salamanca, Spain

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Manuel Morales Biochemistry and Molecular Genetics Department-CDB, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain

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Felicia Hanzu Endocrinology & Nutrition Department, Hospital Clinic, Barcelona, Spain

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Marta Araujo-Castro Endocrinology & Nutrition Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain
University of Alcalá, Madrid, Spain

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Objective

To compare the presentation and evolution of primary aldosteronism (PA) in the elderly (≥65 years) and young patients (<65 years).

Methods

A retrospective multicenter study was performed in 20 Spanish hospitals of PA patients in follow-up between 2018 and 2021.

Results

Three hundred fifty-two patients with PA <65 years and 88 patients ≥65 years were included. Older PA patients had a two-fold higher prevalence of type 2 diabetes, dyslipidemia, and cerebrovascular disease, but these differences disappeared after adjusting for hypertension duration. At diagnosis, diastolic blood pressure was lower than in young patients (83.3 ± 11.54 vs 91.6 ± 14.46 mmHg, P < 0.0001). No differences in the rate of overall correct cannulation (56.5% vs 42.3%, P = 0.206) or the diagnosis of unilaterality (76.9% vs 62.5%, P = 0.325) in the adrenal venous sampling (AVS) was observed between the elderly and young groups. However, there was a lower proportion of PA patients who underwent adrenalectomy in the elderly group than in the younger group (22.7% (n  = 20) vs 37.5% (n  = 132), P = 0.009). Nevertheless, no differences in the rate of postsurgical biochemical (100% (n  = 14) vs 92.8% (n  = 90), P = 0.299) and hypertension cure (38.6% (n  = 51) vs 25.0% (n  = 5), P = 0.239) were observed between both groups.

Conclusion

Older patients with PA have a worse cardiometabolic profile than young patients with PA that it is related to a longer duration of hypertension. However, the results of the AVS, and adrenalectomy are similar in both groups. Therefore, the management of elderly patients with PA should be based not only on age, but rather on the overall medical, physical, social, and mental characteristics of the patients.

Open access
Marta Araujo-Castro Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain
University of Alcalá, Madrid, Spain

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Miguel Paja Fano Department of Endocrinology & Nutrition, OSI Bilbao-Basurto, Hospital Universitario de Basurton & Basque Country University, Medicine Department, Bilbao, Spain

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Begoña Pla Peris Department of Endocrinology & Nutrition, Hospital Universitario de Castellón, Castellón, Spain

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Marga González Boillos Department of Endocrinology & Nutrition, Hospital Universitario de Castellón, Castellón, Spain

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Eider Pascual-Corrales Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain

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Ana María García-Cano Department of Biochemistry, Hospital Universitario Ramón y Cajal, Madrid, Spain

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Paola Parra Ramírez Department of Endocrinology & Nutrition, Hospital Universitario La Paz Madrid, Spain

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Patricia Martín Rojas-Marcos Department of Endocrinology & Nutrition, Hospital Universitario La Paz Madrid, Spain

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Jorge Gabriel Ruiz-Sanchez Department of Endocrinology & Nutrition, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain

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Almudena Vicente Department of Endocrinology & Nutrition, Hospital Universitario de Toledo, Toledo, Spain

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Emilia Gómez-Hoyos Department of Endocrinology & Nutrition, Hospital Universitario de Valladolid, Valladolid, Spain

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Rui Ferreira Department of Endocrinology & Nutrition, Hospital Universitario Rey Juan Carlos, Madrid, Spain

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Iñigo García Sanz Department of General & Digestive Surgery, Hospital Universitario de La Princesa, Madrid, Spain

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Mónica Recasens Department of Endocrinology & Nutrition, Institut Català de la Salut Girona, Girona, Spain

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Rebeca Barahona San Millan Department of Endocrinology & Nutrition, Institut Català de la Salut Girona, Girona, Spain

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María José Picón César Department of Endocrinology & Nutrition, Hospital Universitario Virgen de la Victoria de Málaga, IBIMA Malaga, Spain CIBEROBN, Madrid, Spain

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Patricia Díaz Guardiola Department of Endocrinology & Nutrition, Hospital Universitario Infanta Sofía, Madrid, Spain

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Carolina Perdomo Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain

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Laura Manjón Department of Endocrinology & Nutrition, Hospital Universitario Central de Asturias & Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain

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Rogelio García-Centeno Department of Endocrinology & Nutrition, Hospital Universitario Gregorio Marañón, Madrid, Spain

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Juan Carlos Percovich Department of Endocrinology & Nutrition, Hospital Universitario Gregorio Marañón, Madrid, Spain

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Ángel Rebollo Román Department of Endocrinology & Nutrition, Hospital Reina Sofía, Córdoba, Spain

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Paola Gracia Gimeno Department of Endocrinology & Nutrition, Hospital Rollo Villanova, Zaragoza, Spain

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Cristina Robles Lázaro Department of Endocrinology & Nutrition, Complejo Universitario de Salamanca, Salamanca, Spain

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Manuel Morales Biochemistry and Molecular Genetics Department-CDB, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain

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María Calatayud Department of Endocrinology & Nutrition, Hospital Doce de Octubre, Madrid, Spain

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Simone Andree Furio Collao Department of Endocrinology & Nutrition, Hospital Doce de Octubre, Madrid, Spain

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Diego Meneses Department of Endocrinology & Nutrition, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain

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Miguel Antonio Sampedro Nuñez Department of Endocrinology & Nutrition, Hospital Universitario La Princesa, Madrid, Spain

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Verónica Escudero Quesada Department of Nephrology, Hospital Universitario Doctor Peser, Valencia, Spain

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Elena Mena Ribas Department of Endocrinology & Nutrition, Hospital Universitario Son Espases, Islas Baleares, Spain

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Alicia Sanmartín Sánchez Department of Endocrinology & Nutrition, Hospital Universitario Son Espases, Islas Baleares, Spain

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Cesar Gonzalvo Diaz Department of Endocrinology & Nutrition, Hospital Universitario De Albacete, Albacete, Spain

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Cristina Lamas Department of Endocrinology & Nutrition, Hospital Universitario De Albacete, Albacete, Spain

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Raquel Guerrero-Vázquez Department of Endocrinology & Nutrition, Hospital Virgen de la Macarena, Sevilla, Spain

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María del Castillo Tous Department of Endocrinology & Nutrition, Hospital Virgen de la Macarena, Sevilla, Spain

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Joaquín Serrano Department of Endocrinology & Nutrition, Hospital General Universitario de Alicante, Alicante, Spain

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Theodora Michalopoulou Department of Endocrinology and Nutrition, Joan XXIII University Hospital, Tarragona, Spain

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Eva María Moya Mateo Internal Medicine, Hospital Infanta Leonor de Vallecas, Madrid, Spain

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Felicia Hanzu Department of Endocrinology & Nutrition, Hospital Clinic, IDIPAS, Barcelona, Spain

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Purpose

The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes.

Methods

This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 µg/dL (confirmed ACS if >5 µg/dL and possible ACS if 1.8–5 µg/dL) in the absence of specific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels.

Results

The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS–PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS–PA and PA-only patients was similar, except for older age and larger tumor size of the adrenal lesion in the ACS–PA group. When comparing the ACS–PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64–22.32)) and cardiovascular events (OR 5.0 (2.29–11.07)) was higher in ACS–PA patients than in ACS patients. The coexistence of ACS in patients with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS–PA and PA-only groups.

Conclusion

Co-secretion of cortisol and aldosterone affects almost one-third of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS–PA and PA-only are similar.

Open access
Sharmin Jahan Department of Medicine, Monash University, Melbourne, Victoria, Australia
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia
Department of Endocrinology and Metabolism, BSMMU, Dhaka, Bangladesh

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Jun Yang Department of Medicine, Monash University, Melbourne, Victoria, Australia
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia

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Jinbo Hu Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Qifu Li Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Peter J Fuller Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia

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Primary aldosteronism (PA) is the most common cause of endocrine hypertension and is often underdiagnosed. This condition is associated with increased cardiovascular morbidity and mortality in comparison to age and blood pressure matched individuals with essential hypertension (EH). The diagnostic pathway for PA consists of three phases: screening, confirmatory testing, and subtyping. The lack of specificity in the screening step, which relies on the aldosterone to renin ratio, necessitates confirmatory testing. The Endocrine Society’s clinical practice guideline suggests four confirmatory tests, including the fludrocortisone suppression test (FST), saline suppression test (SST), captopril challenge test (CCT), and oral sodium loading test (SLT). There is no universally accepted choice of confirmatory test, with practices varying among centers. The SST and FST are commonly used, but they can be resource-intensive, carry risks such as volume overload or hypokalemia, and are contraindicated in severe/uncontrolled HTN as well as in cardiac and renal impairment. In contrast, CCT is a safe and inexpensive alternative that can be performed in an outpatient setting and can be applied when other tests are contraindicated. Despite its simplicity and convenience, the variability in captopril dose, testing posture, and diagnostic threshold limit its widespread use. This narrative review evaluates the diagnostic accuracy of the CCT across different populations, addresses controversies in its usage, and proposes recommendations for its use in the diagnosis of PA. Furthermore, suggestions for future research aimed at promoting the wider utilization of the CCT as a simpler, safer, and more cost-effective diagnostic test are discussed.

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