Objective: Prediction models have been developed to predict either unilateral or bilateral primary aldosteronism, and these have not been validated externally. We aimed to develop a simplified score to predict both subtypes and validate this externally. Methods: Our development cohort was taken from 165 patients who underwent adrenal vein sampling (AVS) in two Asian tertiary centres. Unilateral disease was determined using both AVS and postoperative outcome. Multivariable analysis was used to construct prediction models. We validated our tool in a European cohort of 97 patients enrolled in the SPARTACUS trial who underwent AVS. Previously published prediction models were also tested in our cohorts. Results: Backward stepwise logistic regression analysis yielded a final tool using baseline aldosterone-to-lowest-potassium ratio (APR, ng/dl/mmol/l), with an area under receiver-operating characteristic curve of 0.80 (95% CI 0.70–0.89). In the Asian development cohort, probability of bilateral disease was 90.0% (with APR <5) and probability of unilateral disease was 91.4% (with APR >15). Similar results were seen in the European validation cohort. Combining both cohorts, probability of bilateral disease was 76.7% (with APR <5), and probability for unilateral was 91.7% (with APR >15). Other models had similar predictive ability but required more variables, and were less sensitive for identifying bilateral PA. Conclusion: The novel aldosterone-to-lowest-potassium ratio is a convenient score to guide clinicians and patients of various ethnicities on the probability of primary aldosteronism subtype. Using APR to identify patients more likely to benefit from AVS may be a cost-effective strategy to manage this common condition.

ContextStudies find surgery superior to medications in the treatment of primary aldosteronism (PA). It would be ideal to compare surgical and medical therapy in patients with unilateral PA only, who have the option between these treatment modalities. However, this is challenging as most patients with unilateral PA on adrenal vein sampling (AVS) undergo surgery.ObjectiveTo compare outcomes of surgery and medications in patients with confirmed or likely unilateral PA.DesignRetrospective cohort study of 274 patients with PA managed at two referral centres from 2000 to 2019.Patients154 patients identified with unilateral PA using AVS and a validated clinical prediction model were treated with surgical (n = 86) or medical (n = 68) therapy.MeasurementsPrimary outcome was a composite incident cardiovascular event comprising acute myocardial infarction, coronary revascularization, stroke, atrial fibrillation or congestive cardiac failure. Secondary outcomes were clinical and biochemical control.ResultsCardiovascular outcomes were comparable, with the surgery group having an adjusted hazard ratio of 0.93 (95% CI: 0.32–2.67), p = .89. Both treatments improved clinical and biochemical control, but surgery resulted in better systolic blood pressure, 133.0 ± 11.7 mmHg versus 137.9 ± 14.6 mmHg, p = .02, and lower defined daily dosages of antihypertensive medications, 1.0 (IQR 0.0–2.0) versus 2.6 (IQR 0.8–4.3), p < .001. In addition, 12 of 86 patients in the surgery group failed medical therapy before opting for surgery.ConclusionIn patients with unilateral PA who can tolerate medications, medical therapy improves clinical and biochemical control, and may offer similar cardiovascular protection. However, surgery reduces pill burden, may cure hypertension and is recommended for unilateral PA.

Background: In patients with primary aldosteronism (PA), long-term cardiovascular and mortality outcomes after adrenalectomy versus mineralocorticoid receptor antagonist (MRA) have not been compared yet. We aim to compare the clinical outcomes of these patients after treatment. Design and Methods: A systematic review and meta-analysis was conducted by searching PubMed, Cochrane library, and Embase from no start date restriction to Dec 18, 2021. Our composite primary outcomes were long-term all-cause mortality and/or major adverse cardiovascular events (MACE), including coronary artery disease (CAD), stroke, arrhythmia, and congestive heart failure. We adopted the random-effects model and performed subgroup analyses, meta-regression, and trial sequential analysis (TSA). Results: A total of 9 studies with 8,473 adult patients with PA (≥18 years) were enrolled. Lower incidence of composite primary outcomes was observed in the adrenalectomy group (odds ratio (OR): 0.46 [95% CI, 0.38-0.56], P < 0.001). We found lower incidence of all-cause mortality (OR: 0.33 [95% CI, 0.15-0.73], P = 0.006) and MACE (OR: 0.55, [95% CI, 0.40-0.74], P = 0.0001) in the adrenalectomy group. The incidence of CAD (OR: 0.33 [95% CI, 0.15-0.75], P = 0.008), arrhythmias (OR: 0.46 [95% CI, 0.27-0.81], P = 0.007), and congestive heart failure (OR: 0.52 [95% CI, 0.33-0.81], P = 0.004) were also lower in adrenalectomy group. The meta regression showed patient’s age may attenuate the benefits of adrenalectomy on composite primary outcomes (coefficient: 1.084 [95% CI, 1.005-1.169], P = 0.036). TSA demonstrated that the accrued sample size as well as effect size were sufficiently large to draw a solid conclusion, and the advantage of adrenalectomy over MRA was constant with the chronological sequence. Conclusions: In conclusion, adrenalectomy could be preferred over MRA for patients with PA in reducing the risk of all-cause mortality and/or MACE and should be considered as the treatment of choice. That patients with PA could get less benefit from adrenalectomy as they age warrants further investigation.

A 24-year-old Chinese woman with Graves' disease presented with myositis two months after treatment with carbimazole. The patient's myositis resolved with hydration and cessation of carbimazole. No other causes of myositis were found, and a change in the medication to propylthiouracil was uneventful. Review of the literature suggests a possible genetic susceptibility, as the majority of reported cases are Asian in origin, similiar to patients who present with thyrotoxic periodic paralysis. Changing the antithyroid drugs (ATDs) administered, decreasing the dose of pre-existing ATDs in the treatment regimen or addition of levothyroxine has been shown to result in clinical improvement of this complication. These observations suggest various mechanisms of carbimazoleinduced myositis in the treatment of Graves' disease, including the direct effect of ATDs on myocytes, immune-related responses secondary to ATDs and rapid decrements in thyroid hormone, with ensuing myositis.

u,v , for the PA CURE investigators à Objective: Adrenal vein sampling (AVS) is recommended to subtype primary aldosteronism, but it is technically challenging. We compared 11 C-Metomidate-PET-computed tomography (PET-CT) and AVS for subtyping of primary aldosteronism.Methods: Patients with confirmed primary aldosteronism underwent both AVS and 11 C-Metomidate PET-CT (postdexamethasone). All results were reviewed at a multidisciplinary meeting to decide on final subtype diagnosis. Primary outcome was accuracy of PET versus AVS to diagnosis of unilateral primary aldosteronism based on post-surgical biochemical cure. Secondary outcome was accuracy of both tests to final subtype diagnosis.Results: All 25 patients recruited underwent PET and successful AVS (100%). Final diagnosis was unilateral in 22 patients, bilateral in two and indeterminate in one due to discordant lateralization. Twenty patients with unilateral primary aldosteronism underwent surgery, with 100% complete biochemical success, and 75% complete/partial clinical success. For the primary outcome, sensitivity of PET was 80% [95% confidence interval (95% CI): 56.3-94.3] and AVS was 75% (95% CI: 50.9-91.3). For the secondary outcome, sensitivity and specificity of PET was 81.9% (95% CI: 59.7-94.8) and 100% (95% CI: 15.8-100), and AVS was 68.2% (95% CI: 45.1-86.1) and 100% (95% CI: 15.8-100), respectively. Twelve out of 20 (60%) patients had both PET and AVS lateralization, four (20%) PET-only, three (15%) AVS-only, while one patient did not lateralize on PET or AVS. Post-surgery outcomes did not differ between patients identified by either test. Conclusion:In our pilot study, 11 C-Metomidate PET-CT performed comparably to AVS, and this should be validated in larger studies. PET identified patients with unilateral primary aldosteronism missed on AVS, and these tests could be used together to identify more patients with unilateral primary aldosteronism.

Head and neck paragangliomas that are exclusively or predominantly dopamine-secreting are rare. Surgery and/or radiotherapy are modalities for locoregional tumoral control. Little is known about the efficacy of radiotherapy for biochemical control in such tumors. We report a 62-year-old Chinese man with bilateral carotid body tumors which were exclusively dopamine secreting. The left-sided tumor invaded the skull base and encased the left carotid artery. Surgery was not performed due to high risk of morbidity and mortality. The patient received external beam radiotherapy to bilateral neck regions. Progressive decline and eventual normalization of urinary dopamine excretion was seen together with a slight reduction in tumor size. This is the first report demonstrating the efficacy of radiotherapy for both biochemical and locoregional control of functioning carotid body paragangliomas.

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Introduction: New-onset diabetes after transplantation (NODAT) is an increasingly recognised metabolic complication of kidney transplantation that is associated with increased morbidity and mortality. This study aimed to determine the incidence of NODAT and identify risk factors for development of NODAT among kidney allograft recipients in a single centre. Materials and Methods: We retrospectively reviewed all kidney allograft recipients in our centre between 1998 and 2007. NODAT were determined using criteria as per American Diabetes Association guidelines. Logistic regression analyses were performed to identify predictors of NODAT. Results: Among 388 patients included in the analysis, NODAT was reported in 94 patients (24.2%) after a median follow-up time of 52.1 months. The cumulative incidence of NODAT was 15.8%, 22.8% and 24.5% at 1, 3, and 5 years following transplantation. Seven clinical factors were independent predictors of NODAT: older age, HLA B13 and B15 phenotypes, use of sirolimus, acute rejections, higher pre-transplant and post-transplant (day 1) plasma glucose levels. Patients with NODAT had poorer outcomes in both graft and patient survival. Conclusion: Our study demonstrates a significant risk and burden of NODAT in an Asian transplant population. Risk stratification and aggressive monitoring of blood glucose early post-transplantation is necessary to identify high-risk patients so that appropriate tailoring of immunosuppression and early institution of lifestyle modifications can be implemented. Key words: Diabetes mellitus, Immunosuppression, Kidney transplantation, Metabolic complication, Sirolimus