Context
Primary aldosteronism (PA) is known to increase vertebral fracture (VF), although the detailed mechanism remains to be elucidated. We hypothesized that the PA subtype is associated with VF.
...Objective
To evaluate whether unilateral PA is associated with the prevalence of VF.
Design
This was a retrospective cross‐sectional study in a single referral centre.
Patients
We identified 210 hypertensive patients whose clinical data were available for case‐detection results. One hundred and fifty‐two patients were diagnosed with PA using captopril challenge tests.
Measurements
We measured the prevalence of VF, according to PA subtype.
Results
One hundred thirteen patients with PA were subtype classified by adrenal vein sampling. Of these, 37 patients had unilateral PA, 76 patients had bilateral PA, 58 patients had non‐PA; 39 patients with PA were not subtype‐classified. Patients with PA had a higher prevalence of VF (29%, 44/152) than those with non‐PA (12%, 7/58; P = .011). Moreover, unilateral PA had a higher prevalence of VF (46%, 17/37) than bilateral PA (20%, 15/76; P = .021). There was no significant difference in the prevalence of VF between bilateral PA and non‐PA. Unilateral PA was an independent risk factor for VF after adjusting for age and sex (OR: 3.16, 95% confidence interval: 1.12‐8.92; P = .017). Among patients with unilateral PA, serum cortisol concentrations after 1‐mg dexamethasone suppression test were higher in those with VF (1.32 ± 0.67 g/dL) than those without (0.96 ± 0.33 g/dL; P = .048).
Conclusions
Unilateral PA is an independent risk factor for VF.
Objective
The clinical practice guideline for primary aldosteronism (PA) places a high value on confirmatory tests to sparing patients with false‐positive results in case detection from undergoing ...adrenal venous sampling (AVS). However, it is unclear whether multiple types of confirmatory tests are more useful than a single type. To evaluate whether the machine‐learned combination of two confirmatory tests is more useful in predicting subtypes of PA than each test alone.
Design
A retrospective cross‐sectional study in referral centres.
Patients
This study included 615 patients with PA randomly assigned to the training and test data sets. The participants underwent saline infusion test (SIT) and captopril challenge test (CCT) and were subtyped by AVS (unilateral, n = 99; bilateral, n = 516).
Measurements
The area under the curve (AUC) and clinical usefulness using decision curve analysis for the subtype prediction in the test data set.
Results
The AUCs for the combination of SIT and CCT, SIT alone and CCT alone were 0.850, 0.813 and 0.786, respectively, with no significant differences between them. The AUC for the baseline clinical characteristics alone was 0.872, whereas the AUCs for these combined with SIT, combined with CCT and combined with both SIT and CCT were 0.868, 0.854 and 0.855, respectively, with no significant improvement in AUC. The additional clinical usefulness of the second confirmatory test was unremarkable on decision curve analysis.
Conclusions
Our data suggest that patients with positive case detection undergo one confirmatory test to determine the indication for AVS.
Primary aldosteronism (PA) is associated with an increased risk of cardiometabolic diseases, especially in unilateral subtype. Despite its high prevalence, the case detection rate of PA is limited, ...partly because of no clinical models available in general practice to identify patients highly suspicious of unilateral subtype of PA, who should be referred to specialized centers. The aim of this retrospective cross-sectional study was to develop a predictive model for subtype diagnosis of PA based on machine learning methods using clinical data available in general practice. Overall, 91 patients with unilateral and 138 patients with bilateral PA were randomly assigned to the training and test cohorts. Four supervised machine learning classifiers; logistic regression, support vector machines, random forests (RF), and gradient boosting decision trees, were used to develop predictive models from 21 clinical variables. The accuracy and the area under the receiver operating characteristic curve (AUC) for predicting of subtype diagnosis of PA in the test cohort were compared among the optimized classifiers. Of the four classifiers, the accuracy and AUC were highest in RF, with 95.7% and 0.990, respectively. Serum potassium, plasma aldosterone, and serum sodium levels were highlighted as important variables in this model. For feature-selected RF with the three variables, the accuracy and AUC were 89.1% and 0.950, respectively. With an independent external PA cohort, we confirmed a similar accuracy for feature-selected RF (accuracy: 85.1%). Machine learning models developed using blood test can help predict subtype diagnosis of PA in general practice.
Diabetes mellitus is associated with an increased risk of falls, which increases the incidence of osteoporotic fractures and accordingly decreases quality of life. However, the association between ...fall risk and diabetic complications is not completely understood. Therefore, the aim of this study was to examine the association between fall risk and osteoporotic fractures in patients with type 2 diabetes mellitus (T2DM). We enrolled 194 Japanese patients with T2DM and assessed their fall risk using a brief interview form that included five items covering physical and social aspects of functioning and environmental factors. We examined the associations between fall risk and the presence of diabetic complications, such as neuropathy, retinopathy, nephropathy, cardiovascular disease, cerebrovascular disease, peripheral artery disease (PAD), and osteoporotic fractures (including any fracture and vertebral fractures only). In the multivariate logistic regression analysis, a longer history of T2DM, the presence of neuropathy and PAD, and a history of any fractures were significantly and positively associated with the risk of falls. On the other hand, a lower body mass index, the presence of neuropathy, and the risk of falls were independently and positively associated with the risk of any fracture. When fractures were limited to vertebral fractures only, the association with the risk of falls remained significant. We found that the risk of falls and osteoporotic fractures were associated in patients with T2DM and that a brief screening test of the risk of falls was useful for assessing the risk of osteoporotic fractures.
In the first case, a 60-year-old man who was using continuous subcutaneous insulin infusion (CSII), developed recurrent hypoglycemia due to insulin antibodies. This is the first report of such a case ...using CSII. In the second case, a 70-year-old man was follow-up case who developed hypoglycemia while using human insulin. In both cases, the hypoglycemia subsided after switching to multiple daily insulin injection and/or insulin preparation. The results of Scatchard analyses of the two cases were similar to those of cases of insulin autoimmune syndrome (IAS) that improved after recovery from hypoglycemia.The clinical characteristics and Scatchard analysis data were essentially the same as those for IAS, except for the presence of insulin administration.
Unilateral subtype of primary aldosteronism (PA) is a common surgically curable form of endocrine hypertension. However, more than half of the patients with PA who undergo unilateral adrenalectomy ...suffer from persistent hypertension, which may discourage those with PA from undergoing adrenalectomy even when appropriate. The aim of this retrospective cross-sectional study was to develop machine learning-based models for predicting postoperative hypertensive remission using preoperative predictors that are readily available in routine clinical practice. A total of 107 patients with PA who achieved complete biochemical success after adrenalectomy were included and randomly assigned to the training and test datasets. Predictive models of complete clinical success were developed using supervised machine learning algorithms. Of 107 patients, 40 achieved complete clinical success after adrenalectomy in both datasets. Six clinical features associated with complete clinical success (duration of hypertension, defined daily dose (DDD) of antihypertensive medication, plasma aldosterone concentration (PAC), sex, body mass index (BMI), and age) were selected based on predictive performance in the machine learning-based model. The predictive accuracy and area under the curve (AUC) for the developed model in the test dataset were 77.3% and 0.884 (95% confidence interval: 0.737-1.000), respectively. In an independent external cohort, the performance of the predictive model was found to be comparable with an accuracy of 80.4% and AUC of 0.867 (95% confidence interval: 0.763-0.971). The duration of hypertension, DDD of antihypertensive medication, PAC, and BMI were non-linearly related to the prediction of complete clinical success. The developed predictive model may be useful in assessing the benefit of unilateral adrenalectomy and in selecting surgical treatment and antihypertensive medication for patients with PA in clinical practice.
Context
The success rate of cannulation of the right adrenal vein is limited. The aldosterone gradient within the same adrenal vein branch is specific for aldosterone‐producing adenoma.
Objective
...This study was performed to investigate whether the absolute aldosterone gradient within the left adrenal vein (left‐AV absolute aldosterone gradient) indicates unilateral excess aldosterone.
Design and setting
A retrospective cross‐sectional study in a single referral centre.
Patients and methods
In total, 123 consecutive patients with primary aldosteronism who had successful adrenal vein sampling (AVS) data were examined. The left‐AV absolute aldosterone gradient was considered significant when a gradient of >4:1 in the aldosterone‐to‐cortisol ratio between the common trunk vein and central vein was found.
Main outcome measure
The prevalence of the unilateral subtype in patients with a significant left‐AV absolute aldosterone gradient.
Results
The prevalence of the unilateral subtype was higher in patients with than without a significant left‐AV absolute aldosterone gradient (88.2% 15/17 vs 21.7% 23/106, P < .001). Of 60 patients with spontaneous hypokalemia, left unilateral disease on computed tomography, or both, a significant left‐AV absolute aldosterone gradient was present only in patients with the unilateral subtype on AVS (42.9% 15/35), but not in those with the bilateral subtype (0.0% 0/25). These data were validated in an external cohort.
Conclusion
The presence of a significant left‐AV absolute aldosterone gradient can be used to diagnose the left unilateral subtype of primary aldosteronism on AVS in patients with spontaneous hypokalemia, left unilateral disease on computed tomography or both.
Objective Glucose-lowering drug-induced hypoglycemia is a serious complication and there have been a few reports of seasonal variations in hypoglycemia in patients with type 2 diabetes. The aim of ...the present study was to examine the association between severe drug-induced hypoglycemia and seasonal variations, and to elucidate the contributing factors. Methods This retrospective, single center clinical study, analyzed the cases of 125 patients who required emergency hospitalization for severe drug-induced hypoglycemia between January 1, 2001 and December 31, 2014. The period from November to April was defined as the cold season. Results Severe hypoglycemia occurred more often in the cold season than in the warm season. In the cold season, 62 of 9,981 (0.6%) emergency department visits involved patients who required hospitalization for drug-induced hypoglycemia. In contrast, in the warm season, 27 of 8,649 (0.3%) visits involved patients who required hospitalization for drug-induced hypoglycemia (p=0.002). The proportion of patients treated with sulfonylurea (SU) in the cold season was higher than that in the warm season. Even the use of low-dose SU caused hypoglycemia in the cold season. In the SU-treated group, the proportion of patients with white blood cell and/or C-reactive protein elevation was higher in the cold season than in the warm season (p=0.04). Conclusion Severe glucose-lowering drug-induced hypoglycemia occured more frequently in the cold season than in the warm season, and was associated with an inflammatory state in patients treated with SU.
Pathological excess of fibroblast growth factor 23 (FGF23) causes mineral and bone disorders. However, the causality of FGF23 in the development of osteoporosis remains unknown. Whether FGF23 has ...systemic effects on cardiometabolic disorders beyond regulating mineral metabolism is also controversial. In this study, we investigated the causal effect of FGF23 on osteoporosis and cardiometabolic disorders using Mendelian randomization (MR) analysis. Summary statistics for single-nucleotide polymorphisms with traits of interest were obtained from the relevant genome-wide association studies. As a result, FGF23 was found to be inversely associated with femoral neck-BMD (odds ratio OR 0.682, 95% confidence interval CI 0.546–0.853, p = 8e-04) and heel estimated BMD (eBMD) (OR 0.898, 95%CI 0.820–0.985, p = 0.022) in the inverse-variance-weighted analysis, but not lumbar spine-BMD and fractures. The results were supported by the weighted-median analysis, and there was no evidence of pleiotropy in the MR-Egger analysis. FGF23 was associated with FN-BMD and eBMD after adjustment for estimated glomerular filtration rate, height, and body mass index in multivariable MR analysis. On the other hand, there was no association between FGF23 and cardiometabolic traits including cardio artery disease, brachial-ankle pulse wave velocity, intima-media thickness of carotid arteries, systolic and diastolic blood pressure, fasting glucose, high and low-density lipoprotein cholesterol, and triglycerides. Therefore, this MR study established that FGF23 was involved in bone loss and, in contrast, was not involved in cardiometabolic disorders. Our findings provide important insights into the role of FGF23 in the pathogenesis of osteoporosis and cardiometabolic disorders.
•Role of FGF23 in the development of osteoporosis remains unknown.•Whether FGF23 has systemic effects on cardiometabolic disorders is controversial.•Mendelian randomization (MR) analysis is able to infer causal association.•This MR study found that FGF23 was associated with bone loss.•In contrast, FGF23 was not associated with cardiometabolic disorders.
Abstract
Context
The current clinical guidelines suggest that confirmatory tests for primary aldosteronism (PA) may be excluded in some of patients who have elevated plasma aldosterone concentration ...(PAC) under plasma renin suppression. However, this has low-priority evidence and is under debate in use of serum potassium.
Objective
This study aimed to investigate an appropriate setting for sparing confirmatory tests in PA.
Design and Setting
A retrospective cross-sectional study in a single referral center.
Participants
This study included 327 patients who had hypertension under plasma renin suppression and underwent the captopril challenge test (CCT) between January 2007 and April 2019. CCT results were used to diagnose PA.
Main Outcome Measure
Diagnostic value of PAC and serum potassium in confirmation of PA.
Results
Of the studied patients, 252 of 327 (77%) were diagnosed with PA. All 61 patients with PAC > 30 ng/dL were diagnosed with PA. In patients with PAC between 20 and 30 ng/dL, 44 of 55 (80%) were diagnosed with PA, while all 26 with PAC between 20 to 30 ng/dL who had spontaneous hypokalemia were diagnosed with PA. The proportion of unilateral PA determined by adrenal vein sampling (AVS) was higher in patients who had PAC > 30 ng/dL or those with spontaneous hypokalemia who had PAC between 20 and 30 ng/dL than those who did not meet the criteria (76% vs. 17%, P < .001).
Conclusion
Confirmatory tests in PA could be spared in patients who have typical features of PA and these patients had a high probability of unilateral PA on AVS.
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