Screening and diagnosis of primary aldosteronism. Consensus document of all the Spanish Societies involved in the management of primary aldosteronism.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension (HT), and is associated with a higher cardiometabolic risk than essential HT. However, PA remains underdiagnosed, probably due to several difficulties clinicians usually find in performing its diagnosis and subtype classification. The aim of this consensus is to provide practical recommendations focused on the prevalence and the diagnosis of PA and the clinical implications of aldosterone excess, from a multidisciplinary perspective, in a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology, Spanish Association of Surgeons (AEC).

Renin as a Biomarker to Guide Medical Treatment in Primary Aldosteronism Patients. Findings from the SPAIN-ALDO Registry.

INTRODUCTION: Primary aldosteronism (PA) is associated with several cardiometabolic comorbidities. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy has been reported to reduce the cardiometabolic risk. However, the cardiovascular benefit could depend on plasma renin levels in patients on MRA. AIM: To compare the development of cardiovascular, renal and metabolic complications between medically treated patients with PA and those who underwent adrenalectomy, taking the renin status during MRA treatment into account. METHODS: A multicenter retrospective study (SPAIN-ALDO Register) of patients with PA treated at 35 Spanish tertiary hospitals. Patients on MRA were divided into two groups based on renin suppression (n = 90) or non-suppression (n = 70). Both groups were also compared to unilateral PA patients (n = 275) who achieved biochemical cure with adrenalectomy. RESULTS: Adrenalectomized patients were younger, had higher plasma aldosterone concentration, and lower potassium levels than MRA group. Patients on MRA had similar baseline characteristics when stratified into treatment groups with suppressed and unsuppressed renin. 97 (55.1%) of 176 patients without comorbidities at diagnosis, developed at least one comorbidity during follow-up (median 12 months vs. 12.5 months' follow-up after starting MRA and surgery, respectively). Surgery group had a lower risk of developing new cardiovascular events (HR 0.40 [95% CI 0.18-0.90]) than MRA group. Surgical treatment improved glycemic and blood pressure control, increased serum potassium levels, and required fewer antihypertensive drugs than medical treatment. However, there were no differences in the cardiometabolic profile or the incidence of new comorbidities between the groups with suppressed and unsuppressed renin levels (HR 0.95 [95% CI 0.52-1.73]). CONCLUSION: Cardiovascular, renal, and metabolic events were comparable in MRA patients with unsuppressed and suppressed renin. Effective surgical treatment of PA was associated with a decreased incidence of new cardiovascular events when compared to MRA therapy.

Epidemiology and diagnosis of primary aldosteronism. What have we learned from the SPAIN-ALDO registry?

PURPOSE: To summarize the available data on the prevalence, clinical repercussion, and diagnosis of primary aldosteronism (PA) and to discuss the SPAIN-ALDO registry's findings, which is the largest PA patient registry in Spain. METHODS: A comprehensive review of the literature focused on the prevalence, clinical presentation and diagnosis of PA was performed. RESULTS: PA is the most common cause of secondary arterial hypertension. In addition, PA patients have a higher cardio-metabolic risk than patients with essential arterial hypertension matched by age, sex, and blood pressure levels. However, despite its high prevalence and associated metabolic and cardiovascular complications, PA remains largely under-recognized, with less than 2% of people in at-risk populations ever tested. The diagnostic investigation is a multistep process, including screening, confirmatory testing, and subtype differentiation of unilateral from bilateral PA forms. Data from the SPAIN-ALDO registry have shed light on the cardiometabolic impact of PA and about the limitations in the PA diagnosis of these patients in Spain. CONCLUSIONS: The most common cause of secondary hypertension is PA. One of the most challenging aspects of the diagnosis is the differentiation between unilateral and bilateral PA because adrenal venous sampling is a difficult procedure that should be performed in experienced centers. Data from the SPAIN-ALDO registry have provided important information on the nationwide management of this pathology.

Is adrenal venous sampling always necessary to differentiate between unilateral and bilateral primary aldosteronism? Lesson from the SPAIN-ALDO register.

PURPOSE: To evaluate whether the clinical, biochemical and radiological features of patients with primary aldosteronism (PA) can predict both main subtypes of PA. METHODS: A retrospective multicenter study of PA patients followed in 27 Spanish tertiary hospitals (SPAIN-ALDO Register). Only patients with confirmed unilateral or bilateral PA based on adrenal venous sampling (AVS) and/or postsurgical biochemical cure after adrenalectomy were included. Supervised regression techniques were used for model development. RESULTS: 328 patients [270 unilateral PA (UPA), 58 bilateral PA (BPA)] were included. The area under the curve (AUC) for aldosterone/potassium ratio and aldosterone responses following saline infusion test were 0.602 [95%CI 0.520 to 0.684] and 0.574 [95% CI 0.446-0.701], respectively, to differentiate UPA from BPA. The AUC was 0.825 [95% 0.764-0.886] when the prediction model with seven parameters - comorbidities (dyslipidemia, cerebrovascular disease, sleep apnea syndrome [SAS]), systolic blood pressure (SBP), plasma aldosterone levels (PAC), hypokalemia and unilateral adrenal nodule >1 cm and normal contralateral adrenal gland on CT/MRI - was used. In patients without comorbidities, hypokalemia, SBP > 160 mmHg, PAC > 40 ng/dL, and unilateral adrenal lesions were associated with a likelihood of having a UPA of 98.5%. The chance of BPA was higher in individuals with comorbidities, SBP < 140 mmHg, normokalemia, low PAC levels, and no adrenal tumors on the CT/MRI (91.5%). CONCLUSION: A combination of high PAC, SBP > 160 mmHg, low serum potassium, a unilateral adrenal nodule>1 cm and no comorbidities could predict a UPA with a 98.5% accuracy.

Adrenal Incidentalomas and Other Endocrine-Related Adenomas: How Much Does Cortisol Secretion Matter?

Background: Adrenal incidentalomas (AI) are frequent findings in clinical practice. About 40% of AIs are associated with hypercortisolism of variable severity. Although mild autonomous cortisol secretion (MACS) has been associated with the impaired clinical outcome of several diseases, its effect on the development of benign neoplasms is unknown. Aim: To compare the prevalence of adenomas (thyroid, parathyroid, pituitary and other locations) in patients with nonfunctioning AIs (NFAIs) and MACS. Methods: A multicenter, retrospective study of patients with AIs evaluated in four tertiary hospitals was performed. Results: A total of 923 patients were included. Most patients were male (53.6%), with a mean age at diagnosis of 62.4 ± 11.13 years; 21.7% presented with bilateral AIs. MACS was observed in 29.9% (n = 276) of patients, while 69.9% (n = 647) were NFAIs. Adenomas in locations other than the adrenal gland were observed in 36% of the studied population, with a similar distribution in patients with MACS and NFAIs (33% vs. 32%; p > 0.05). There were no statistically significant differences in the prevalence of pituitary, thyroid, parathyroid or other endocrine-related adenomas between both groups, but the prevalence of metabolic comorbidities and mortality was increased in patients with MACS, specifically in patients with thyroid and other endocrine-related adenomas (p < 0.05). Conclusions: Adenomas in locations other than the adrenal glands occur in one third of patients with AIs. Mild autonomous hypercortisolism does not affect the prevalence of other endocrine-related adenomas but is associated with increased metabolic comorbidities and mortality, especially in patients with thyroid adenomas and adenomas in other locations.

Diagnostic Accuracy of Adrenal Iodine-131 6-Beta-Iodomethyl-19-Norcholesterol Scintigraphy for the Subtyping of Primary Aldosteronism.

PURPOSE: To evaluate the diagnostic accuracy of the 131I-6ß-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy for the subtyping diagnosis of primary aldosteronism (PA), considering as gold standard for the diagnosis of unilateral PA (UPA), either the results of the adrenal venous sampling (AVS) or the outcome after adrenalectomy. METHODS: A retrospective multicenter study was performed on PA patients from 14 Spanish tertiary hospitals who underwent NP-59 scintigraphy with an available subtyping diagnosis. Patients were classified as UPA if biochemical cure was achieved after adrenalectomy or/and if an AVS lateralization index > 4 with ACTH stimulation or >2 without ACTH stimulation was observed. Patients were classified as having bilateral PA (BPA) if the AVS lateralization index was ≤4 with ACTH or ≤2 without ACTH stimulation or if there was evidence of bilateral adrenal nodules >1 cm in each adrenal gland detected by CT/MRI. RESULTS: A total of 86 patients with PA were included (70.9% (n = 61) with UPA and 29.1% (n = 25) with BPA). Based on the NP-59 scintigraphy results, 16 patients showed normal suppressed adrenal gland uptake, and in the other 70 cases, PA was considered unilateral in 49 patients (70%) and bilateral in 21 (30%). Based on 59-scintigraphy results, 10.4% of the patients with unilateral uptake had BPA, and 27.3% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the NP-59 scintigraphy for PA subtyping was 0.812 [0.707-0.916]. Based on the results of the CT/MRI and NP-59 scintigraphy, only 6.7% of the patients with unilateral uptake had BPA, and 24% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the model combining CT/MRI and 59-scintigraphy results for subtyping PA was 0.869 [0.782-0.957]. CONCLUSION: The results of NP-59 scintigraphy in association with the information provided by the CT/MRI may be useful for PA subtyping. However, their diagnostic accuracy is only moderate. Therefore, it should be considered a second-line diagnostic tool when AVS is not an option.

Effect of Obesity on Clinical Characteristics of Primary Aldosteronism Patients at Diagnosis and Postsurgical Response.

CONTEXT: Patients with obesity have an overactivated renin-angiotensin-aldosterone system (RAAS) that is associated with essential hypertension. However, the influence of obesity in primary aldosteronism (PA) is unknown. OBJECTIVE: We analyzed the effect of obesity on the characteristics of PA, and the association between obesity and RAAS components. METHODS: A retrospective study was conducted of the Spanish PA Registry (SPAIN-ALDO Registry), which included patients with PA seen at 20 tertiary centers between 2018 and 2022. Differences between patients with and without obesity were analyzed. RESULTS: A total of 415 patients were included; 189 (45.5%) with obesity. Median age was 55 years (range, 47.3-65.2 years) and 240 (58.4%) were male. Compared to those without obesity, patients with obesity had higher rates of diabetes mellitus, chronic kidney disease, obstructive apnea syndrome, left ventricular hypertrophy, prior cardiovascular events, higher means of systolic blood pressure, and required more antihypertensive drugs. Patients with PA and obesity also had higher values of serum glucose, glycated hemoglobin A1c, creatinine, uric acid, and triglycerides, and lower levels of high-density lipoprotein cholesterol. Levels of blood aldosterone (PAC) and renin were similar between patients with and without obesity. Body mass index was not correlated with PAC nor renin. The rates of adrenal lesions on imaging studies, as well as the rates of unilateral disease assessed by adrenal vein sampling or I-6ß-iodomethyl-19-norcholesterol scintigraphy, were similar between groups. CONCLUSION: Obesity in PA patients involves a worse cardiometabolic profile, and need for more antihypertensive drugs but similar PAC and renin levels, and rates of adrenal lesions and lateral disease than patients without obesity. However, obesity implicates a lower rate of hypertension cure after adrenalectomy.

Autonomous cortisol secretion in patients with primary aldosteronism: prevalence and implications on cardiometabolic profile and on surgical outcomes.

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.

Genetic Study in Pheochromocytoma: Is It Possible to Stratify the Risk of Hereditary Pheochromocytoma?

INTRODUCTION: It is estimated that 30-40% of patients with apparently sporadic pheochromocytomas (PHEOs) have an inherited predisposition syndrome. The aim of our study was to develop a predictive model of hereditary PHEO based on the clinical, hormonal, and radiological features present at the diagnosis of patients with PHEOs. METHODS: A retrospective multicenter cohort study of patients with PHEOs with available genetic study from 18 tertiary hospitals. Clinical, biochemical, and radiological features were used to build a multivariate logistic regression model. The estimation of all possible equations was used to select the model with the best diagnostic accuracy (lower Akaike index). RESULTS: A total of 245 patients were included: 169 (69.0%) patients with sporadic PHEOs and 76 (31%) with hereditary PHEOs. The parsimonious predictive model with the highest diagnostic accuracy for the prediction of hereditary PHEO combined the variables age, non-cardiovascular disease, urinary norepinephrine levels, and tumor size. The area under the ROC curve of this model was 0.800 (0.705-0.887). Based on the predictive model, the probability of hereditary PHEO in patients older than 60 years with cardiovascular disease, high levels of urinary norepinephrine and unilateral PHEOs >60 mm was <2%. And if the age was above 80 years, lower than 1%. The probability of sporadic PHEO linearly increased with age (MH Test for linear Trend: χ2 (1) = 30.05; p < 0.001). CONCLUSION: In certain populations such as old patients with cardiovascular disease, with high levels of urinary norepinephrine and large tumors in which the probability of hereditary PHEO is very low, genetic testing could be avoided in the absence of specific suspicion.

First survey on the diagnosis and treatment of primary aldosteronism by Spanish Endocrinology and Nutrition specialists.

OBJECTIVE: To evaluate the indication and the resources for the screening/diagnosis of primary aldosteronism (PA) in Endocrinology units in Spain. MATERIAL AND METHODS: An anonymous 2-phase (2020/2021) online survey was conducted by the AdrenoSEEN group among SEEN members with data about screening, confirmation tests, availability of catheterisation and the treatment of PA. RESULTS: Eighty-eight (88) specialists completed the survey. Plasma aldosterone concentration and plasma renin activity were available at all centres; urinary aldosterone was available in 55% of them. The most frequent indications for determining the aldosterone/renin ratio (ARR) were adrenal incidentaloma (82.6%), hypertension with hypokalaemia (82.6%), hypertension in patients <40 years (79.1%) and a family history of PA (77.9%). 61% and 18% of the respondents used an ARR cut-off value of PA of ≥30 and 20ng/dl per ng/mL/, respectively. The intravenous saline loading test was the most commonly used confirmatory test (66.3%), followed by the captopril challenge test (24.4%), with the 25mg dose used more than the 50mg dose (65% versus 35%). 67.4% of the participants confirmed the availability of adrenal vein catheterization (AVC). 41% of this subgroup perform it with a continuous infusion versus 30.5% with an ACTH (1-24) bolus, whereas 70.3% employ sequential adrenal vein catheterization. 48% of the participants reported an AVC success <50%. Total laparoscopic adrenalectomy was the treatment of choice (90.6%), performed by specialists in General and Digestive Surgery specialising in endocrinological pathology. CONCLUSION: PA screening and diagnostic tests are extensively available to Spanish endocrinologists. However, there is a major variability in their use and in the cut-off points of the diagnostic methods. The AVS procedure remains poorly standardised and is far from delivering optimal performance. Greater standardisation in the study and diagnosis of PA is called for.

Nonfunctioning adrenal incidentalomas with cortisol post-dexamethasone suppression test >0.9 µg/dL have a higher prevalence of cardiovascular disease than those with values ≤0.9 µg/dL.

PURPOSE: To analyze the differences in the cardiometabolic profile in patients with nonfunctioning adrenal incidentalomas (NFAI) with post-dexamethasone suppression test (DST) cortisol ≤1.4 µg/dL (NFAI ≤ 1.4) and those with post-DST cortisol >1.4 µg/dL (NFAI > 1.4) and between NFAI with post-DST cortisol ≤0.9 µg/dL (NFAI ≤ 0.9) and those with levels >0.9 µg/dL (NFAI > 0.9). METHODS: Multicenter retrospective observational study of patients with NFAIs. NFAI was defined as an adrenal incidentaloma with negative hormonal study (including metanephrines, post-DST cortisol ≤1.8 µg/dL and aldosterone/renin ratio when screening was indicated). Autonomous cortisol secretion (ACS) development was defined as an NFAIs in which post-DST serum cortisol >1.8 µg/dL were evidenced during hormonal follow-up evaluation. RESULTS: A total of 593 NFAI were included. Based on the 1.4 µg/dL threshold in the DST, most of the NFAI were classified as NFAI ≤ 1.4 (74.5%). Patients in the NFAI > 1.4 group were older than those in the NFAI ≤ 1.4 group, but there was no difference in the cardiometabolic profile after adjusting for age. A total of 69.5% of the patients had DST > 0.9 µg/dl. They were older and had a higher prevalence of cardiovascular disease than NFAI ≤ 0.9, even after adjusting by age (adjusted OR = 2.23 [1.10-4.53]). Patients in the NFAI > 1.4 group developed ACS more commonly than the NFAI ≤ 1.4 group (23.5% vs. 7.44%, P < 0.001). However, when the threshold of 0.9 µg/dL was considered, no difference was found between NFAI ≤ 0.9 and NFAI > 0.9 (P = 0.126). CONCLUSION: The threshold of 1.4 µg/dL in the DST is useful to predict which patients with NFAI had a higher risk of ACS development during follow-up; and the threshold of 0.9 µg/dL to identify those patients with NFAI with a higher cardiovascular risk.

Glycemic disorders in patients with pheochromocytomas and sympathetic paragangliomas.

The objective of our study was to determine the prevalence of glycemic disorders (diabetes mellitus and prediabetes) in patients with pheochromocytomas and sympathetic paragangliomas (PPGLs) and identify risk factors for their development and the likelihood of their resolution after surgery. A multicentric retrospective study of patients with PPGLs submitted to surgery between 2000 and 2021 in 17 Spanish hospitals was performed. Diabetes-specific data were collected at diagnosis, in the immediate- and long-term postsurgical follow-up. A total of 229 patients with PPGLs were included (218 with pheochromocytomas and 11 with sympathetic paragangliomas). Before surgery, glycemic disorders were diagnosed in 35.4% of the patients (n = 81): 54 with diabetes and 27 with prediabetes. The variables independently associated with a higher risk of glycemic disorders were sporadic PPGL (odds ratio (OR) = 3.26 (1.14-9.36)) and hypertension (OR = 3.14 (1.09-9.01)). A significant decrease in fasting plasma glucose and HbA1c levels was observed after surgery, in the short-term and long-term follow-up (P < 0.001). After a median follow-up of 48.5 months (range 3.3-168.9), after surgery, 52% of diabetic and 68% of prediabetic patients experienced a complete resolution. Lower body mass index (BMI) (P = 0.001), lower glucose levels (P = 0.047) and shorter duration of diabetes prior to surgery (P = 0.021) were associated with a higher probability of diabetes resolution. In conclusion, glycemic disorders in patients with PPGLs are present in more than a third of them at diagnosis. Sporadic PPGLs and hypertension are risk factors for their development. More than 50% of cases experience a complete resolution of the glycemic disorder after resection of the PPGLs.

Predictive model of hypertension resolution after adrenalectomy in primary aldosteronism: the SPAIN-ALDO score.

PURPOSE: To develop a predictive model of hypertension resolution after adrenalectomy in patients with primary aldosteronism (PA), based on their presurgical characteristics. METHODS: A retrospective multicenter study of PA patients in follow-up in 20 Spanish tertiary hospitals between 2018 and 2021 was performed (SPAIN-ALDO Register). Clinical response postadrenalectomy was classified according to the primary aldosteronism surgical outcome (PASO) consensus criteria. The predictive model was developed using a multivariate logistic regression model with the estimation of all possible equations. RESULTS: A total of 146 patients (54.8% females; mean age of 51.5 ± 10.9 years) with PA who underwent unilateral adrenalectomy were included. After a mean follow-up of 29.1 ±â€Š30.43 months after surgery, hypertension cure was obtained in 37.7% ( n  = 55) of the patients. The predictive model with the highest diagnostic accuracy to predict hypertension cure combined the variables female sex, use of two or fewer antihypertensive medications, hypertension grade 1, without type 2 diabetes and nonobesity. The area under the receiver operating characteristic curve of this model was 0.841 [0.769-0.914]. Based on this model, the group of patients with a higher probability of cure (80.4%) were those without type 2 diabetes, BMI <30 kg/m 2 , female sex, hypertension grade 1 and who use two or fewer antihypertensives. Our predictive model offered a slightly higher diagnostic accuracy than Wachtel's (area under the curve [AUC]: 0.809), Utsumi's (AUC: 0.804) and Zarnegar's (AUC: 0.796) models and was similar than the Burello's (AUC: 0.833) model. CONCLUSION: Female sex, use of two or fewer antihypertensive medications, hypertension grade 1, no type 2 diabetes and nonobesity may predict hypertension cure after adrenalectomy in patients with PA. Our score provides a potential tool to guide preoperative patient counseling.

Adrenal venous sampling in primary aldosteronism: Experience of a Spanish multicentric study (Results from the SPAIN-ALDO Register).

OBJECTIVE: The aim of this study was to evaluate the rate of adrenal venous sampling (AVS) performance in patients with primary aldosteronism (PA), the main reasons for its non-performance, and the success and complications rate of this procedure in Spain. Moreover, the concordance between CT/MRI and AVS for PA subtyping was evaluated. METHODS: A retrospective multicenter study of PA patient follow-up in 20 Spanish tertiary hospitals between 2018-2021 was performed (SPAIN-ALDO Register). RESULTS: Of the 440 patients with PA included in the study, 153 underwent AVS (34.8%). The main reasons for not performing AVS were: patient rejection to the procedure, low catheterization rate in the center and unilateral disease based on CT/MRI. The overall success rate was 44.4% (the left adrenal vein was properly canulated in 77.8% and the right adrenal vein in 48.4%). Only 3 patients experienced minor complications. In the 45 patients with unilateral disease according to AVS, CT/MRI indicated bilateral disease or normal adrenal glands in 17. In the 23 patients with bilateral disease, CT/MRI indicated unilateral disease in 14. However, no significant differences were observed in biochemical response (P = 0.051) and hypertension resolution (P = 0.150) between patients who underwent surgery based on CT/MRI results and those who underwent surgery based on AVS results. CONCLUSION: In our setting, AVS is still an underused technique in patients with PA. The low experience and success rate in AVS partially justify these results. More training for providers and patients needs to be done to include appropriate well performed AVS in the diagnosis algorithm of PA.

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

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.

Diagnóstico del hiperaldosteronismo primario / Diagnosis of primary hyperaldosteronism

El hiperaldosteronismo primario (HAP) es la forma más frecuente de hipertensión arterial secundaria, y se asocia a un mayor riesgo cardiometabólico que el observado en pacientes con HTA esencial. Por tanto, es preceptivo mantener un alto índice de sospecha clínica para HAP. Si se confirma un cociente aldosterona/renina elevado se deben realizar pruebas de confirmación, habitualmente una prueba de sobrecarga salina intravenosa o de captopril, salvo en pacientes con HAP franco, con hipopotasemia espontánea, aldosterona plasmática > 20 ng/dL y renina suprimida, en los que no sería estrictamente necesario este paso para confirmar el diagnóstico de HAP. El último paso en el diagnóstico del HAP es el estudio de localización, siendo la tomografía axial computarizada (TC) de suprarrenales la prueba inicial de elección, y el cateterismo de venas adrenales (CVA), la prueba definitiva de localización en la mayor parte de los casos. En esta revisión se resumen los datos sobre el diagnóstico del HAP, desde el cribado al estudio de confirmación y de localización. (AU)

Primary aldosteronism (PA) is the most common cause of secondary arterial hypertension. Moreover, it is associated with a higher cardio-metabolic risk than the observed in patients with essential arterial hypertension (EHT). Therefore, a high index of clinical suspicion for PA is mandatory. If an elevated aldosterone/renin ratio is confirmed, confirmatory tests should be performed, with the exception in those patients with florid PA, with, with spontaneous hypokalaemia, plasma aldosterone > 20 ng/dL and suppressed renin, in whom this step would not be strictly necessary. Intravenous saline infusion test or captopril test are the commonly used confirmatory tests. The last step in the diagnosis of PA is the localization study, being the computerized axial tomography (CT) of the adrenal glands the initial test of choice, and adrenal venous sampling (AVS), the definitive localization test in most cases. This review summarizes the available data about the diagnosis of PA, from screening to confirmatory study and localization. (AU)

Evolution of the cardiometabolic profile of primary hyperaldosteronism patients treated with adrenalectomy and with mineralocorticoid receptor antagonists: results from the SPAIN-ALDO Registry.

OBJECTIVE: To analyze the evolution of the cardiometabolic profile of patients with primary hyperaldosteronism (PA) after the treatment with surgery and with mineralocorticoid receptor antagonists (MRA). DESIGN: Retrospective multicentric study of patients with PA on follow-up in twelve Spanish centers between 2018 and 2020. RESULTS: 268 patients with PA treated by surgery (n = 100) or with MRA (n = 168) were included. At baseline, patients treated with surgery were more commonly women (54.6% vs 41.7%, P = 0.042), had a higher prevalence of hypokalemia (72.2% vs 58%, P = 0.022) and lower prevalence of obesity (37.4% vs 51.3%, P = 0.034) than patients treated with MRA. Adrenalectomy resulted in complete biochemical cure in 94.0% and clinical response in 83.0% (complete response in 41.0% and partial response in 42.0%). After a median follow-up of 23.6 (IQR 9.7-53.8) months, the reduction in blood pressure (BP) after treatment was similar between the group of surgery and MRA, but patients surgically treated reduced the number of antihypertensive pills for BP control more than those medically treated (∆antihypertensives: -1.3 ± 1.3 vs 0.0 ± 1.4, P < 0.0001) and experienced a higher increased in serum potassium levels (∆serum potassium: 0.9 ± 0.7 vs 0.6 ± 0.8mEq/ml, P = 0.003). However, no differences in the risk of the onset of new renal and cardiometabolic comorbidities was observed between the group of surgery and MRA (HR = 0.9 [0.5-1.5], P = 0.659). CONCLUSION: In patients with PA, MRA and surgery offer a similar short-term cardiovascular protection, but surgery improves biochemical control and reduces pill burden more commonly than MRA, and lead to hypertension cure or improvement in up to 83% of the patients.

Predictive model of pheochromocytoma based on the imaging features of the adrenal tumours.

The purpose of our study was to develop a predictive model to rule out pheochromocytoma among adrenal tumours, based on unenhanced computed tomography (CT) and/or magnetic resonance imaging (MRI) features. We performed a retrospective multicentre study of 1131 patients presenting with adrenal lesions including 163 subjects with histological confirmation of pheochromocytoma (PHEO), and 968 patients showing no clinical suspicion of pheochromocytoma in whom plasma and/or urinary metanephrines and/or catecholamines were within reference ranges (non-PHEO). We found that tumour size was significantly larger in PHEO than non-PHEO lesions (44.3 ± 33.2 versus 20.6 ± 9.2 mm respectively; P < 0.001). Mean unenhanced CT attenuation was higher in PHEO (52.4 ± 43.1 versus 4.7 ± 17.9HU; P < 0.001). High lipid content in CT was more frequent among non-PHEO (83.6% versus 3.8% respectively; P < 0.001); and this feature alone had 83.6% sensitivity and 96.2% specificity to rule out pheochromocytoma with an area under the receiver operating characteristics curve (AUC-ROC) of 0.899. The combination of high lipid content and tumour size improved the diagnostic accuracy (AUC-ROC 0.961, sensitivity 88.1% and specificity 92.3%). The probability of having a pheochromocytoma was 0.1% for adrenal lesions smaller than 20 mm showing high lipid content in CT. Ninety percent of non-PHEO presented loss of signal in the "out of phase" MRI sequence compared to 39.0% of PHEO (P < 0.001), but the specificity of this feature for the diagnosis of non-PHEO lesions low. In conclusion, our study suggests that sparing biochemical screening for pheochromocytoma might be reasonable in patients with adrenal lesions smaller than 20 mm showing high lipid content in the CT scan, if there are no typical signs and symptoms of pheochromocytoma.