Multifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study.

BACKGROUND: Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy. METHODS: We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue. RESULTS: The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein CACNA1D mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45-17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00-26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20-6.31]). CONCLUSIONS: Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.

ERAP1 Shows Distinct Regulatory Mechanisms on Blood Pressure Modulation Between Males and Females.

The authors have withdrawn their manuscript owing to editing error. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Desmopressin Stimulation Test in a Pregnant Patient with Cushing's Disease.

Objective: Hypothalamic-pituitary-adrenal axis stimulation during pregnancy complicates the investigation of Cushing's syndrome (CS). Our objective was to present the case of a pregnant patient with CS caused by a pituitary tumor in whom the desmopressin stimulation test helped in the diagnosis and led to appropriate management. Case Report: A 27-year-old woman with 9-week gestation presented with a 2-month history of proximal myopathy. She had high blood pressure, wide purplish striae, and a 1-year history of hypertension and dysglycemia. The 8 am cortisol level was 32.4 µg/dL (normal, 5-18 µg/dL), late-night salivary cortisol level was 0.7 µg/dL (11 pm, normal, <0.4 µg/dL), 24-hour urinary free cortisol levels were 237.6 µg/d (normal, 21.0-143.0 µg/d), and adrenocorticotropic hormone (ACTH) levels were 44.0 pg/mL (8 am, normal, 0-46.0 pg/mL). Nongadolinium-enhanced pituitary magnetic resonance imaging revealed no obvious lesion. The desmopressin stimulation test showed a 70% increase in ACTH levels from baseline after desmopressin administration. Pituitary magnetic resonance imaging with gadolinium revealed an 8 × 8 × 7-mm3 pituitary adenoma. Transsphenoidal surgery was performed, which revealed the presence of ACTH-positive tumor cells. After tumor removal, the patient carried on pregnancy uneventfully. Discussion: During pregnancy, ACTH levels may not be an accurate marker to help in the differential diagnosis of CS. Moreover, nongadolinium pituitary imaging might not detect small pituitary lesions. Conclusion: In the present case, the desmopressin stimulation test suggested the diagnosis of Cushing's disease, which subsequently led to successful treatment. This suggests that the desmopressin test serves as a useful test for diagnosing Cushing's disease in pregnant individuals.

Newly Discovered Abnormal Glucose Tolerance in Patients With Acute Myocardial Infarction and Cardiovascular Outcomes: A Meta-analysis.

BACKGROUND: The prevalence of unrecognized abnormal glucose tolerance (AGT) and the incidence of recurrent cardiovascular (CV) events in patients with acute myocardial infarction (MI) has not been systematically evaluated. PURPOSE: The purposes of this study were to define the prevalence of newly discovered AGT and examine the risk of recurrent major adverse cardiac events (MACE) and mortality in patients with acute MI. DATA SOURCES: Medline, Embase, Cochrane Library, and Google Scholar were searched for relevant articles. STUDY SELECTION: Inclusion criteria included prospective studies in patients with acute MI without known history of diabetes; AGT diagnosed using fasting plasma glucose, 2-h oral glucose tolerance test, or HbA1c; and incidence of MACE and/or all-cause mortality in newly discovered AGT. DATA EXTRACTION: Two investigators extracted the data. Pooled prevalence, incidence rate ratios, and hazard ratios (HRs) were calculated using random-effects models. DATA SYNTHESIS: In 19 studies (n = 41,509, median follow-up 3.1 years), prevalence of newly discovered AGT was 48.4% (95% CI 40.2-56.6). Prediabetes had a higher mortality risk than normal glucose tolerance (NGT) (HR 1.36 [95% CI 1.13-1.63], P < 0.001) and MACE (1.42 [1.20-1.68], P < 0.001). Newly diagnosed diabetes had higher mortality risk than NGT (1.74 [1.48-2.05], P < 0.001) and MACE (1.54 [1.23-1.93], P < 0.001). LIMITATIONS: This is not a meta-analysis of individual patient data. Time-to-event analysis and covariate-adjusted analysis cannot be conducted to examine heterogeneity reliably. Few studies reported CV death and heart failure hospitalizations. CONCLUSIONS: Patients with acute MI have a high prevalence of newly discovered AGT. Aggressive risk reduction strategies in this population, especially in those with prediabetes, are warranted.

Clinical Characteristics and Treatment Outcomes in Endogenous Cushing's Syndrome: A 15-Year Experience from Thailand.

The most common subtype of endogenous Cushing's syndrome (CS) is Cushing's disease (CD), with higher proportions of adrenal CS reported from Asia, compared to other continents. However, little was known about CS in this territory. This study was to investigate the distribution, clinical characteristics, and treatment outcomes of CS in a single tertiary hospital in Thailand. We performed a retrospective evaluation of 82 patients with endogenous CS during 2001-2015. The most common subtype was CD, followed by adrenal CS and ectopic ACTH syndrome (EAS), respectively. Weight gain was the most common presentation. Normal body mass index (BMI), Asian cutoff, was observed in 33% of patients. Specific features of CS (plethora, muscle weakness, bruising, and/or wide purplish striae) were documented in less than half of patients. The median age, adrenocorticotropic hormone (ACTH), and urinary free cortisol (UFC) concentrations were significantly different among 3 subtypes of CS and were highest among patients with EAS. An initial remission rate after transsphenoidal surgeries in CD was 62%, with higher rates in pituitary microadenomas compared to macroadenomas. All patients with unilateral adrenal disease achieved CS remission after adrenal surgeries. Patients with EAS achieved CS remission mostly from bilateral adrenalectomy. The highest mortality rate was observed in the EAS group. These findings were consistent with previous studies in Asia, with more proportions ACTH-independent CS.