scholarly journals SUN-LB96 Basal Contralateral Aldosterone Suppression Is Rare in Lateralized Primary Aldosteronism and Can Be Useful in Predicting Surgical Outcome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Marie-Josée Desrochers ◽  
Matthieu St-Jean ◽  
El Ghorayeb Nada ◽  
Isabelle Bourdeau ◽  
Benny So ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Surgical Outcome ◽  
Clinical Cure ◽  
Suppression Ratio ◽  
Postoperative Outcome ◽  
Roc Curves ◽  
Zona Glomerulosa ◽  
Unilateral Adrenalectomy ◽  
Biochemical Cure ◽  
Surgical Cure

Abstract Background: Adrenal venous sampling (AVS) is performed to distinguish between unilateral or bilateral source of aldosterone in primary aldosteronism (PA). Unilateral aldosteronomas should lead to suppression of renin and contralateral (CL) aldosterone secretion, assessed by the CL suppression ratio. We recently found that CL aldosterone suppression was relatively rare using the ratio of basal aldosterone concentration of the opposite adrenal vein/periphery (AOPP/AP) in contrast to the traditional cortisol-corrected aldosterone ratio ((A/C)OPP(A/C)P). Pathology studies showed frequent zona glomerulosa (ZG) hyperplasia adjacent to a dominant aldosteronoma, which could also indicate probable ZG hyperplasia in the CL adrenal. The ratio of basal CL suppression could be a usefull parameter to predict cure following unilateral adrenalectomy (UA), but controversy remains in the literature. Objectives: 1. To evaluate the prevalence of basal CL suppression using the AOPP/AP ratio as compared to the (A/C)OPP/(A/C)P ratio at previously established cut-offs. 2. To determine the best cut-off to predict clinical and biochemical surgical cure in two Canadian referral centers. 3. To compare the accuracy of the AOPP/AP ratio to the basal lateralization ratio (LR) and the post-ACTH LR in predicting the surgical outcome. Methods: 330 patients with PA and successful bilateral simultaneous basal and post-ACTH stimulated AVS (selectivity index >2 basally and >5 post-ACTH) were included; 124 patients found to be lateralized underwent UA. The follow-up data were evaluated for clinical and biochemical cure at 3 and 12 months using the PASO criteria. Results: Using AOPP/AP and (A/C)OPP/(A/C)P at the cut-off of 1, the prevalence of CL suppression is 6% and 45%, respectively. The median CL suppression ratio is 2.3 (1.3-5.1) in lateralized cases of PA using AOPP/AP. Using ROC curves, the AOPP/AP ratio is associated with clinical cure at 3 and 12 months and biochemical cure at 12 months. (A/C)OPP/(A/C)P is associated with biochemical cure only. The cut-offs for AOPP/AP offering the best sensitivity and specificity for clinical and biochemical cures at 12 months are 2.15 (Se 63% and Sp 71%) and 6.15 (Se 84% and Sp 77%), respectively. Basal LR and post-ACTH LR are associated with clinical cure but only the post-ACTH LR is associated with biochemical cure. Conclusions: Basal CL suppression defined by the AOPP/AP ratio is rare and incomplete compared to the traditional (A/C)OPP/(A/C)P ratio in lateralized cases of PA. This may reflect the frequent micronodular hyperplasia adjacent to dominant aldosteronomas and possibly in the CL adrenal. Basal CL aldosterone suppression may predict clinical postoperative outcome, but with modest accuracy.

scholarly journals Basal contralateral aldosterone suppression is rare in lateralized primary aldosteronism

2020 ◽  
Vol 183 (4) ◽  
pp. 399-409
Author(s):  
Marie-Josée Desrochers ◽  
Matthieu St-Jean ◽  
Nada El Ghorayeb ◽  
Isabelle Bourdeau ◽  
Benny So ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Surgical Outcomes ◽  
Clinical Cure ◽  
Postoperative Outcome ◽  
Roc Curves ◽  
Aldosterone Secretion ◽  
Contralateral Suppression ◽  
Biochemical Cure ◽  
Surgical Cure ◽  
Lateralization Index

Context: Unilateral aldosteronomas should suppress renin and contralateral aldosterone secretion. Complete aldosterone suppression in contralateral adrenal vein sample (AVS) could predict surgical outcomes. Objectives: To retrospectively evaluate the prevalence of basal contralateral suppression using Aldosterone (A)contralateral(CL)/Aperipheral(P) as compared to (A/Cortisol(C)CL)/(A/C)P ratio in primary aldosteronism (PA) patients studied in two Canadian centers. To determine the best cut-off to predict clinical and biochemical surgical cure. To compare the accuracy of ACL/AP to the basal and post-ACTH lateralization index (LI) in predicting surgical cure. Methods: In total, 330 patients with PA and successful AVS were included; 124 lateralizing patients underwent surgery. Clinical and biochemical cure at 3 and 12 months were evaluated using the PASO criteria. Results: Using ACL/AP and (A/C)CL/(A/C)P at the cut-off of 1, the prevalence of contralateral suppression was 6 and 45%, respectively. Using ROC curves, the ACL/AP ratio is associated with clinical cure at 3 and 12 months and biochemical cure at 12 months. (A/C)CL/(A/C)P is associated with biochemical cure only. The cut-offs for ACL/AP offering the best sensitivity (Se) and specificity (Sp) for clinical and biochemical cures at 12 months are 2.15 (Se: 63% and Sp: 71%) and 6.15 (Se: 84% and Sp: 77%), respectively. Basal LI and post-ACTH LI are associated with clinical cure but only the post-ACTH LI is associated with biochemical cure. Conclusions: In lateralized PA, basal contralateral suppression defined by ACL/AP is rare and incomplete compared to the (A/C)CL/(A/C)P ratio and is associated with clinical and biochemical postoperative outcome, but with modest accuracy.

scholarly journals Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism

2021 ◽  
Vol 28 (1) ◽  
pp. 1-13
Author(s):  
Marcela Rassi-Cruz ◽  
Andrea G Maria ◽  
Fabio R Faucz ◽  
Edra London ◽  
Leticia A P Vilela ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Early Onset ◽  
Zona Glomerulosa ◽  
Unilateral Adrenalectomy ◽  
Transfected Cells ◽  
Functional Studies ◽  
Protein Levels ◽  
Whole Exome ◽  
Hyperplastic Tissue ◽  
Bilateral Adrenal Hyperplasia

Abstract Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, ‘sporadic’ bilateral adrenal hyperplasia (BAH) is the most frequent cause of PA and remains without genetic etiology in most cases. Our aim was to investigate new genetic defects associated with BAH and PA. We performed whole-exome sequencing (paired blood and adrenal tissue) in six patients with PA caused by BAH that underwent unilateral adrenalectomy. Additionally, we conducted functional studies in adrenal hyperplastic tissue and transfected cells to confirm the pathogenicity of the identified genetic variants. Rare germline variants in phosphodiesterase 2A (PDE2A) and 3B (PDE3B) genes were identified in three patients. The PDE2A heterozygous variant (p.Ile629Val) was identified in a patient with BAH and early-onset HT at 13 years of age. Two PDE3B heterozygous variants (p.Arg217Gln and p.Gly392Val) were identified in patients with BAH and HT diagnosed at 18 and 33 years of age, respectively. A strong PDE2A staining was found in all cases of BAH in zona glomerulosa and/or micronodules (that were also positive for CYP11B2). PKA activity in frozen tissue was significantly higher in BAH from patients harboring PDE2A and PDE3B variants. PDE2A and PDE3B variants significantly reduced protein expression in mutant transfected cells compared to WT. Interestingly, PDE2A and PDE3B variants increased SGK1 and SCNN1G/ENaCg at mRNA or protein levels. In conclusion, PDE2A and PDE3B variants were associated with PA caused by BAH. These novel genetic findings expand the spectrum of genetic etiologies of PA.

scholarly journals Does Contralateral Suppression at Adrenal Venous Sampling Predict Outcome Following Unilateral Adrenalectomy for Primary Aldosteronism? A Retrospective Study

2015 ◽  
Vol 100 (4) ◽  
pp. 1477-1484 ◽  
Author(s):  
Martin J. Wolley ◽  
Richard D. Gordon ◽  
Ashraf H. Ahmed ◽  
Michael Stowasser
Keyword(s):  
Retrospective Study ◽  
Primary Aldosteronism ◽  
Median Number ◽  
Antihypertensive Medications ◽  
Unaffected Side ◽  
Unilateral Adrenalectomy ◽  
Contralateral Suppression ◽  
Biochemical Cure ◽  
Lateralization Index

Context: In primary aldosteronism (PA), adrenal vein sampling (AVS) distinguishes unilateral and bilateral disease by comparison of aldosterone/cortisol (A/F) ratios. There is controversy about the criteria for interpretation, however, and in particular it is not clear whether contralateral suppression (CS) (defined as A/Fadrenal ≤ A/Fperipheral on the unaffected side) is important. We therefore performed a retrospective study to determine whether CS in surgically treated unilateral PA was associated with blood pressure (BP) and biochemical outcomes. Setting and Design: Patients who underwent unilateral adrenalectomy for PA after successful AVS were included if the lateralization index (A/Fdominant:A/Fnondominant) was ≥2. Cases were reviewed at 6 to 24 months follow-up for outcomes with respect to the presence and degree of CS. Results: Sixty-six of 80 patients had CS. Baseline characteristics were similar. At postoperative follow-up, those with CS had lower systolic BP (SBP) (128 mm Hg vs 144 mm Hg, P = .001), a greater proportion with cure or improvement of hypertension (96% vs 64%, P = .0034), a greater proportion with biochemical cure of PA on fludrocortisone suppression testing (43 of 49 [88%] vs 4 of 9 [44%], P = .002) and were taking a lower median number of antihypertensive medications (0 vs 1.5, P = .0032). In a multivariate model, the degree of CS and preoperative SBP were both significantly correlated with postoperative SBP, but the lateralization index, sex, and age were not. Conclusion: In this study, the presence of CS correlated with good BP and biochemical outcomes from surgery. This finding suggests that CS should be a factor in deciding whether to offer surgery for treatment of PA.

scholarly journals Analysis of Unilateral Adrenal Hyperplasia with Primary Aldosteronism from the Aspect of Messenger Ribonucleic Acid Expression for Steroidogenic Enzymes: A Comparative Study with Adrenal Cortices Adhering to Aldosterone-Producing Adenoma

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 999-1006 ◽  
Author(s):  
Kazuto Shigematsu ◽  
Kioko Kawai ◽  
Junji Irie ◽  
Hideki Sakai ◽  
Osamu Nakashima ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Zona Glomerulosa ◽  
Adrenal Hyperplasia ◽  
Steroidogenic Enzymes ◽  
Unilateral Adrenalectomy ◽  
Messenger Ribonucleic Acid ◽  
Unilateral Adrenal Hyperplasia ◽  
Aldosterone Production ◽  
Long Term Follow Up ◽  
Aldosterone Producing Adenoma

Unilateral adrenal hyperplasia with primary aldosteronism is very rare and shows similar endocrine features to aldosterone-producing adenoma and bilateral adrenal hyperplasia. In this study, the mRNA expression of steroidogenic enzymes in unilateral adrenal hyperplasia was examined by in situ hybridization. We found subcapsular micronodules composed of spironolactone body-containing cells, which showed intense expression for 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, 18-hydroxylase, and 21-hydroxylase but not 17α-hydroxylase, indicating aldosterone production. This expression pattern was the same as that in unilateral multiple adrenocortical micronodules, reported recently. Additionally, it was noted that a nodule with active aldosterone production was closely adjacent to one showing intense 17α-hydroxylase expression. In the adrenal cortices adhering to aldosterone-producing adenoma, the majority of hyperplastic zona glomerulosa and hyperplastic nodules demonstrated a decreased steroidogenic activity. However, minute nodules indicative of active aldosterone production were found at high frequency. These results suggest that the subcapsular micronodules observed might be the root of aldosterone-producing adenoma. Furthermore, we emphasize the need for long-term follow-up after unilateral adrenalectomy or enucleation of the adenoma because of the possibility that buds with autonomous aldosterone production may still be present in the contralateral or remaining adrenal tissue.

scholarly journals Treatment of Unilateral PA by Adrenalectomy: Potential Reasons for Incomplete Biochemical Cure

2018 ◽  
Vol 127 (02/03) ◽  
pp. 100-108 ◽  
Author(s):  
Yuhong Yang ◽  
Martin Reincke ◽  
Tracy Williams
Keyword(s):  
Primary Aldosteronism ◽  
Clinical Success ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Unilateral Adrenalectomy ◽  
Cerebrovascular Events ◽  
Medication Dosage ◽  
Aldosterone Production ◽  
Clinical Benefits ◽  
Biochemical Cure

AbstractThe importance of an early diagnosis and appropriate management of patients with primary aldosteronism (PA) has become increasingly clear because of the adverse impact of the disorder on cardiovascular and cerebrovascular events and target organ damage. Adrenalectomy potentially cures patients with unilateral PA resulting in normalisation of blood pressure or significant clinical improvements in the majority of patients. Different criteria have been used to evaluate outcomes of unilateral adrenalectomy. Clinical remission (cure of hypertension) is observed in 6% to 86% of patients and clinical benefits from surgery are seen in the majority. Several factors have been identified that predict clinical success after surgery such as age, sex, anti-hypertensive medication dosage and known duration of hypertension. Biochemical remission of PA after unilateral adrenalectomy, characterised by the resolution of hyperaldosteronism and correction of pre-surgical hypokalaemia, is observed in 67% to 100% of patients with unilateral PA. In only a small proportion of patients, adrenalectomy fails to resolve hyperaldosteronism and inappropriate aldosterone production persists after surgery. In this review we discuss the potential reasons for failing to cure hyperaldosteronism after unilateral adrenalectomy for unilateral primary aldosteronism.

scholarly journals Re-Evaluating Absent Clinical Success After Adrenalectomy in Unilateral Primary Aldosteronism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A298-A298
Author(s):  
Troy Puar ◽  
Yvonne Chan ◽  
Lih-Ming Loh ◽  
Roger Foo ◽  
Peng Chin Kek
Keyword(s):  
Diabetes Mellitus ◽  
Primary Aldosteronism ◽  
Clinical Success ◽  
Significant Proportion ◽  
Antihypertensive Medications ◽  
Unilateral Adrenalectomy ◽  
Recommended Treatment ◽  
Post Surgery ◽  
Biochemical Cure

Abstract Introduction: Adrenalectomy cures unilateral primary aldosteronism (PA), and improves or cures hypertension. However, a significant proportion of patients are classified with absent clinical success post-surgery, suggesting that surgery was ineffective. Methods: We assessed all patients 6–12 months after unilateral adrenalectomy for clinical outcomes using Primary Aldosteronism Surgical Outcomes (PASO), AVIS-2 and CONNsortium criteria. We estimated blood pressure (BP) changes after adjustment for changes in defined daily dosages (DDD) of antihypertensive medications. Finally, patients were reassessed using PASO at their most recent clinical visit. Results: 104 patients with unilateral PA underwent adrenalectomy at two tertiary centres from 2000–2019. 24 (23%), 31(30%) and 54 (52%) patients were classified with absent clinical success using PASO, AVIS-2 and CONNsortium criteria respectively. Amongst 24 patients with absent clinical success using PASO criteria, 10 had complete biochemical cure, 3 partial, 2 absent, and 9 had resolution of hypokalemia. On multivariate analysis, absent clinical success was associated with presence of hyperlipidemia, diabetes mellitus and lower DDD at baseline. After adjustment for changes in DDD, 7 of 24 patients showed BP improvement ≥20/10mmHg. After follow-up of mean 5.6 years, 12 of 24 patients showed partial or complete clinical success when reassessed using PASO criteria. Only 6 of 104 (5.8%) patients failed to show any clinical improvement after surgery. Conclusions: Although some patients may be classified with absent clinical success post-surgery, majority demonstrate evidence of clinical benefit. Unilateral adrenalectomy remains the recommended treatment option for patients with unilateral PA.

scholarly journals SUN-195 Bilateral Aldosterone-Producing Adenomas: A New Subtype of Bilateral Primary Aldosteronism?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ana Alice Wolf Maciel ◽  
Thaís Castanheira de Freitas ◽  
Marcelo L Balancin ◽  
Felipe L Ledesma ◽  
Tatiana S Goldbaum ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Urinary Free Cortisol ◽  
Zona Glomerulosa ◽  
R Ratio ◽  
Basal Cortisol ◽  
Endocrine Hypertension ◽  
Free Cortisol ◽  
Biochemical Cure ◽  
Bilateral Adrenal Hyperplasia ◽  
The Right

Abstract Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). PA subtypes include aldosterone-producing adenomas (APA) and bilateral adrenal hyperplasia. To date, few PA patients with bilateral adenomas have been reported, but only one case was well characterized by anatomopathological analysis and clinical outcome after adrenal sparing surgery (1). Clinical case: A 53-year-old woman was referred to investigate resistant HT and hypokalemia. (3.0 mEq/L). PA screening revealed aldosterone (A) of 37.9 ng/dL, renin (R) < 1.6 (4.4-46.1 mUI/L), A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis: seated saline infusion test (A= 83.3 ng/dL) and intravenous furosemide test (R= 3.1 mUI/L; positive test <13 mUI/L). Hypercortisolism investigation revealed a non-suppressible cortisol after an overnight 1 mg low-dose dexamethasone suppression [cortisol (C)= 2.9 μg/dL and dexamethasone= 701 (˃130 ng/dL)], and normal urinary free cortisol, midnight salivary cortisol, plasma DHEAS and ACTH levels. Computed tomography demonstrated bilateral adrenal nodules without adrenal thickening: 3.5 cm right nodule (pre-contrast density of 7UH density; absolute wash-out of 71%) and 2.5 cm left nodule (pre-contrast density of 8UH density; absolute wash-out of 78%). Sequential adrenal venous (AV) sampling (AVS) under continuous cosyntropin infusion showed a lateralization index of 3.4 (bilateral disease <4). Then, the patient underwent right adrenalectomy and left nodulectomy. In the postoperative period, she presented normalization of K+ levels and complete HT remission. She remained under hydrocortisone replacement for 2 months. After 2 months, biochemical evaluation revealed normal basal cortisol levels (13.3 µg/dL) and biochemical cure of PA (A= 3.1 ng/dL and R= 15.3 mUI/L). Currently, she doesn’t have symptoms of adrenal insufficiency after discontinuation of hydrocortisone. Anatomopathological analysis showed bilateral adenomas (Weiss score of 0) in both sides without adjacent hyperplasia. CYP11B2 immunohistochemistry displayed a strong staining in 50% of cells in the right adenoma and in 30% of cells in the left adenoma. Few aldosterone-producing cell clusters (APCC) were identified in the right zona glomerulosa, which is a frequent finding in normal adrenals. Conclusion: We herein described a very rare case of PA caused by bilateral-producing adenomas, confirmed by AVS and CYP11B2 staining after adrenal sparing surgery.

Neurophysiological seizure-onset predictors of epilepsy surgery outcome: a multivariable analysis

2020 ◽  
Vol 133 (6) ◽  
pp. 1863-1872 ◽  
Author(s):  
Hideaki Tanaka ◽  
Jean Gotman ◽  
Hui Ming Khoo ◽  
André Olivier ◽  
Jeffery Hall ◽  
...  
Keyword(s):  
Surgical Outcome ◽  
Focal Epilepsy ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Postoperative Outcome ◽  
Seizure Onset ◽  
Resective Surgery ◽  
Scalp Eeg ◽  
Surgery Outcome ◽  
Intracerebral Eeg

OBJECTIVEThe authors sought to determine which neurophysiological seizure-onset features seen during scalp electroencephalography (EEG) and intracerebral EEG (iEEG) monitoring are predictors of postoperative outcome in a large series of patients with drug-resistant focal epilepsy who underwent resective surgery.METHODSThe authors retrospectively analyzed the records of 75 consecutive patients with focal epilepsy, who first underwent scalp EEG and then iEEG (stereo-EEG) for presurgical assessment and who went on to undergo resective surgery between 2004 and 2015. To determine the independent prognostic factors from the neurophysiological scalp EEG and iEEG seizure-onset information, univariate and standard multivariable logistic regression analyses were used. Since scalp EEG and iEEG data were recorded at different times, the authors matched scalp seizures with intracerebral seizures for each patient using strict criteria.RESULTSA total of 3057 seizures were assessed. Forty-eight percent (36/75) of patients had a favorable outcome (Engel class I–II) after a minimum follow-up of at least 1 year. According to univariate analysis, a localized scalp EEG seizure onset (p < 0.001), a multilobar intracerebral seizure-onset zone (SOZ) (p < 0.001), and an extended SOZ (p = 0.001) were significantly associated with surgical outcome. According to multivariable analysis, the following two independent factors were found: 1) the ability of scalp EEG to localize the seizure onset was a predictor of a favorable postoperative outcome (OR 6.073, 95% CI 2.011–18.339, p = 0.001), and 2) a multilobar SOZ was a predictor of an unfavorable outcome (OR 0.076, 95% CI 0.009–0.663, p = 0.020).CONCLUSIONSThe study findings show that localization at scalp seizure onset and a multilobar SOZ were strong predictors of surgical outcome. These predictors can help to select the better candidates for resective surgery.

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