Because aldosterone plays an essential role in electrolytes balance and blood pressure control, primary aldosteronism is considered a cardiorenal disease. However, patients’ lived experiences and over 50,000 published studies attest of deleterious effects far beyond the heart, vasculature, and kidneys.

The Primary Aldosteronism Foundation maintains a database of salient publications with emphasis on commonly studied topics as well as signs, symptoms, and comorbidities associated with excess aldosterone and frequently experienced by patients. New articles and topics of interest are added as they become public.

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Autonomous cortisol secretion (ACS) has a relatively high prevalence in patients with primary aldosteronism (PA). There is still a lack of relevant studies to analyze the influence of ACS on diagnosing and managing PA. The objective of the study was to evaluate the influence of ACS on image–adrenal venous sampling (AVS) correlation and the postoperative results. This was a retrospective study using the Taiwan Primary Aldosteronism Investigation database from July 2017 to April 2020, with 327 PA patients enrolled. A total of 246 patients were included in the image–AVS analysis. Patients who had undergone unilateral adrenalectomy and a 12-month follow-up were included in the postoperative analysis. Sixty-five patients (26.4%) had ACS. The image–AVS discordance rate was higher in the ACS group compared to the non-ACS group (75.4% (n = 49) vs 56.4% (n = 102); odds ratio (OR) = 2.37 (CI: 1.26–4.48); P = 0.007). The complete biochemical success rate was higher in the non-ACS group than that in the ACS group (98.1% (n = 51) vs 64.3% (n = 9); OR = 28.333 (CI: 2.954–271.779); P = 0.001). In logistic regression analysis, ACS was the only factor associated with lower biochemical success (OR = 0.035 (CI: 0.004–0.339), P = 0.004). PA patients with ACS have higher image–AVS discordance rate and worse biochemical outcomes after surgery. ACS was the only negative predictor of postoperative biochemical outcomes. Further studies and novel biomarkers for AVS are crucial for obtaining better postoperative outcomes in PA patients with ACS.

Authors: Kuang Hung, Bo-Ching Lee, Po-Ting Chen, Kao-Lang Liu, Chin-Chen C
Keywords: autonomous cortisol secretion
DOI Number: 10.1530/EC-23-0121
Publication Year: 2023


Connshing syndrome is a rare disease characterized by mixed overproduction of mineralocorticoids and glucocorticoids from adrenal adenoma. We will describe a clinical case that illustrates a rare combination of aldosterone-cortisol co-secreting formation of the left adrenal gland against a background of bilateral macronodular adrenal hyperplasia, and the role of diagnostic methods in determining appropriate tactics for patient treatment. In January 2022, 49-year-old male was admitted to the Endocrinology Research Centre with complaints of increased blood pressure of 220/110 mm Hg, despite multicomponent antihypertensive therapy. According to the hormonal profile, primary hyperaldosteronism was confirmed (aldosterone 2770 pmol/l was increased, renin 0.5 mU/l, and hypokalemia was 2.71 mmol/l against a background of discontinuation of drugs that affect the renin-angiotensin system). ACTH-independent hypercortisolism was confirmed (cortisol in saliva in the evening was 60.33 nmol/l, dexamethasone suppression test was negative (cortisol was 238.8 nmol/l in the morning), ACTH in the morning was 4.88 pg/ml). Once spironolactone (250 mg per day) was introduced in addition to moxonidine (0.6 mg per day), nifedipine (90 mg per day), doxazosin (6 mg per day), the patient’s blood pressure and potassium was stabilized. As a result of MSCT of the abdominal cavity, the formation 30×35×41 mm in the left adrenal gland and the formation is 32×18×17 mm in the right adrenal gland were observed. The density was 17 HU in the native phase in the left adrenal gland, the absolute washout coefficient was 93%, the density was 9 HU in the native phase in the right adrenal gland, the absolute washout coefficient was 72%. To lateralize the side of aldosterone hyperproduction, adrenal vein sampling was performed. Unilateral hyperproduction of aldosterone on the left was confirmed (selectivity coefficient on the left was 27.5, on the right was 4.2 (both more than 3.0). The lateralizing gradient on the left was 2.8 (more than 2.0). Taking into account hypercortisolemia, a calculation was carried out on plasma normetanephrine levels. Laparoscopic left-sided adrenalectomy was performed in August of 2022. After surgical treatment, spironolactone was discontinued, but the patient was forced to take multicomponent antihypertensive therapy due to nephropathy (C3bA3) and a long history of arterial hypertension due to untimely treatment. Primary hyperaldosteronism is associated with increased cardiovascular risk, and hypercortisolism increases the risk of developing diabetes mellitus and osteoporosis. This case demonstrates the consequences of a late diagnosis of the mixed overproduction of mineralocorticoids and glucocorticoids caused by adrenal adenoma.

Authors: Evgeniia Kolpakova, Arina Krainyaya, Alla Tskaeva, Marina Yukina, Nadezhda Platonova, Ekaterina Troshina
Keywords: Connshing syndrome
DOI Number: 10.1530/endoabs.90.EP91
Publication Year: 2023


Connshing syndrome (CoSh) (adrenal-related synchronous aldosterone (A) and cortisol (C) excess) represents a distinct entity among PA (primary hyperaldosteronisms) named by W. Arlt et al. in 2017, but the condition has been studied for more than 4 decades. Within the last few years, this is one of the most dynamic topics in hormonally active adrenal lesions due to massive advances in steroids metabolomics, molecular genetics from CYP11B1/B2 immunostaining to genes constellations, as well as newly designated pathological categories according to the 2022 WHO classification. In gross, PA causes 4-10% of all high blood pressure (HBP) cases, and 20% of resistant HBP; subclinical Cushing syndrome (SCS) is identified in one-third of adrenal incidentalomas (AI), while CoSh accounts for 20-30% to 77% of PA subjects, depending on the tests used to confirm autonomous C secretion (ACS). The clinical picture overlaps with PA, hypercortisolemia being mild. ACS is suspected in PA if a more severe glucose and cardiovascular profile is identified, or there are larger tumours, ACS being an independent factor risk for kidney damage, and probably also for depression/anxiety and osteoporotic fractures. It seems that one-third of the PA-ACS group harbours mutations of C-related lines like PRKACA and GNAS. A novel approach means we should perform CYP11B2/CYP11B1 immunostaining; sometimes negative aldosteronoma for CYP11B1 is surrounded by micronodules or cell clusters with positive CYP11B1 to sustain the C excess. Pitfalls of hormonal assessments in CoSh include the index of suspicion (check for ACS in PA patients) and the interpretation of A/C ratio during adrenal venous sample. Laparoscopic adrenalectomy is the treatment of choice. Post-operative clinical remission rate is lower in CoSh than PA. The risk of clinically manifested adrenal insufficiency is low, but a synthetic ACTH stimulating testing might help to avoid unnecessary exposure to glucocorticoids therapy. Finally, postponing the choice of surgery may impair the outcome, having noted that long-term therapy with mineralocorticoids receptors antagonists might not act against excessive amounts of C. Awareness of CoSh improves management and overall prognosis.

Authors: Mara Carsote
Keywords: connshing syndrome, cushing syndrome
DOI Number: 10.3390/diagnostics12112772
Publication Year: 2022


Dietary sodium recommendations are debated partly due to variable blood pressure (BP) response to sodium intake. Furthermore, the BP effect of dietary sodium among individuals taking antihypertensive medications is understudied.  The objective of the study was to examine the distribution of within-individual BP response to dietary sodium, the difference in BP between individuals allocated to consume a high- or low-sodium diet first, and whether these varied according to baseline BP and antihypertensive medication use. The study involved prospectively allocated diet order with crossover in community-based participants enrolled between April 2021 and February 2023 in 2 US cities. A total of 213 individuals aged 50 to 75 years, including those with normotension (25%), controlled hypertension (20%), uncontrolled hypertension (31%), and untreated hypertension (25%), attended a baseline visit while consuming their usual diet, then completed 1-week high- and low-sodium diets. Among the 213 participants who completed both high- and low-sodium diet visits, the median age was 61 years, 65% were female and 64% were Black. While consuming usual, high-sodium, and low-sodium diets, participants’ median systolic BP measures were 125, 126, and 119 mm Hg, respectively. The median within-individual change in mean arterial pressure between high- and low-sodium diets was 4 mm Hg (IQR, 0-8 mm Hg; P < .001), which did not significantly differ by hypertension status. Compared with the high-sodium diet, the low-sodium diet induced a decline in mean arterial pressure in 73.4% of individuals. The commonly used threshold of a 5 mm Hg or greater decline in mean arterial pressure between a high-sodium and a low-sodium diet classified 46% of individuals as “salt sensitive.” At the end of the first dietary intervention week, the mean systolic BP difference between individuals allocated to a high-sodium vs a low-sodium diet was 8 mm Hg (95% CI, 4-11 mm Hg; P < .001), which was mostly similar across subgroups of age, sex, race, hypertension, baseline BP, diabetes, and body mass index. Adverse events were mild, reported by 9.9% and 8.0% of individuals while consuming the high- and low-sodium diets, respectively. Dietary sodium reduction significantly lowered BP in the majority of middle-aged to elderly adults. The decline in BP from a high- to low-sodium diet was independent of hypertension status and antihypertensive medication use, was generally consistent across subgroups, and did not result in excess adverse events.

Authors: Deepak K. Gupta, Cora E. Lewis, Krista A. Varady, Yan Ru Su, Meena S. Madhur, Daniel T. Lackland, Jared P. Reis, Thomas J. Wang, Donald M. Lloyd-Jones, Norrina B. Allen
Keywords: dietary sodium, salt
DOI Number: 10.1001/jama.2023.23651
Publication Year: 2023


Somatic variants in KCNJ5 are the most common cause of primary aldosteronism (PA). There are few patients with PA in whom the disease is caused by germline variants in the KCNJ5 potassium channel gene (familial hyperaldosteronism type III—FH-III). A 5-year-old patient who developed hypertension due to bilateral adrenocortical hyperplasia (BAH) causing PA had negative peripheral DNA testing for any known genetic causes of PA. He was treated medically with adequate control of his PA but by the third decade of his life, due to worsening renal function, he underwent bilateral adrenalectomy. Focused exome sequencing in multiple nodules of his BAH uncovered a “hot-spot” pathogenic KCNJ5 variant, while repeated Sanger sequencing showed no detectable DNA defects in peripheral blood and other tissues. However, whole exome, “deep” sequencing revealed that 0.23% of copies of germline DNA did in fact carry the same KCNJ5 variant that was present in the adrenocortical nodules, suggesting low level germline mosaicism for this PA-causing KCNJ5 defect. Thus, this patient represents a unique case of BAH due to a mosaic KCNJ5 defect. Undoubtedly, his milder PA compared with other known cases of FH-III, was due to his mosaicism. This case has a number of implications for the prognosis, treatment, and counseling of the many patients with PA due to BAH that are seen in hypertension clinics.

Authors: Andrea G Maria, Mari Suzuki, Annabel Berthon, Crystal Kamilaris, Andrew Demidowich, Justin Lack, Mihail Zilbermint, Fady Hannah-Shmouni, Fabio R Faucz, Constantine A Stratakis
Keywords: KCNJ5, germline mosaicism
DOI Number: 10.1093/ajh/hpz172
Publication Year: 2019


The purpose of the study was to evaluate whether the clinical, biochemical and radiological features of patients with primary aldosteronism (PA) can predict both main subtypes of PA. 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. 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%). 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.

Authors: Paola Parra Ramírez, Patricia Martín Rojas-Marcos, Miguel Paja Fano, Marga González Boillos, Begoña Pla Peris, Eider Pascual-Corrales, Ana María García Cano, Jorge Gabriel Ruiz-Sanchez, Almudena Vicente Delgado, Emilia Gómez Hoyos, Rui Ferreira, Iñigo García Sanz, Mònica Recasens Sala, Rebeca Barahona San Millan, María José Picón César, Patricia Díaz Guardiola, Carolina M Perdomo, Laura Manjón-Miguélez, Rogelio García Centeno, Juan Carlos Percovich, Ángel Rebollo Román, Paola Gracia Gimeno, Cristina Robles Lázaro, Manuel Morales-Ruiz, María Calatayud, Simone Andree Furio Collao, Diego Meneses, Miguel Antonio Sampedro Nuñez, Verónica Escudero Quesada, Elena Mena Ribas, Alicia Sanmartín Sánchez, Cesar Gonzalvo Diaz, Cristina Lamas, Raquel Guerrero-Vázquez, María Del Castillo Tous, Joaquín Serrano Gotarredona, Theodora Michalopoulou Alevras, Eva María Moya Mateo, Felicia A Hanzu, Marta Araujo-Castro
Keywords: subtype, adrenal venous sampling, AVS
DOI Number: 10.1007/s12020-023-03609-y
Publication Year: 2023