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Obesity and the Diagnostic Accuracy for Primary Aldosteronism
Abstracts / Can J Diabetes 41 (2017) S22–S83
77 Cardiovascular Outcomes in Subclinical Cushing’s Syndrome versus Non-functioning Adrenal Adenoma: A Systematic Review JANE PARK, ALYSSA DE LUCA, HEIDI DUTTON, JANINE MALCOLM, MARY-ANNE DOYLE Ottawa, ON
S29
Conclusion: Obesity results in a nonlinear correlation with PAC, PRA, and ARR, which affects the accuracy of case detection for PA. Patients with a BMI ≥30 kg/m2 are less accurately identified as having PA if SST and/or 24-hour urinary aldosterone after oral sodium loading are used. 79 Weight Loss as an Initial Manifestation of Cushing’s Syndrome PARUL KHANNA*, TISHA JOY London, ON
Background: There is growing evidence that subclinical Cushing’s syndrome (SCS) is associated with increase prevalence of cardiovascular (CV) risk factors. It is, however, unclear if SCS is associated with increased CV outcomes compared with non-functioning adrenal adenomas (NFAA). The objectives of this study were to evaluate 1) CV outcomes and 2) CV risk factors in patients with SCS versus NFAA. Methods: A literature review was performed using EMBASE, Medline, Cochrane Library and reference lists within selected articles. The study protocol was registered with PROSPERO. Results: A literature search yielded 4 studies that met inclusion criteria. Studies varied on their definitions of SCS and CV outcomes. The prevalence of CV outcomes in SCS was>3 times greater than in patients with NFAA. Two longitudinal studies further demonstrated increased incidence of new CV events (SCS 20.5% vs NFAA 8.4%, p=0.04), CAD (SCS 18% vs NFAA 9%, p=0.03), stroke (13% vs 7%, p=0.03) and increased CV mortality in patients with SCS (SCS 22.6% vs 2.5%, p=0.02). Only 2/4 studies found that SCS was associated with higher prevalence of DM. There was no difference in HTN or dyslipidemia demonstrated in any study. Conclusion: There is significant heterogeneity among the few studies evaluating the association between SCS and CV outcomes. While these studies suggest an increased risk of CV outcomes in patients with SCS, many did not adjust for known confounders. Larger, high quality, prospective studies are needed to evaluate this association and to identify modifiable risk factors.
Background: Cushing’s syndrome is a disorder of hypercortisolism that is typically characterized by truncal weight gain, easy bruising, purple striae, glucose intolerance/diabetes, and hypertension. Ectopic secretion of adrenocorticotropin hormone (ACTH) from tumours is rare, accounting for 10% of cases of Cushing’s syndrome. Case: A 51 year-old man (BMI 18.3 kg/m2), non-smoker, presented with a history of weight loss in the setting of new-onset diabetes. Although his blood sugars improved with the use of insulin, he had ongoing weight loss. History of proximal muscle weakness and erectile dysfunction prompted further biochemical testing. In addition to secondary hypogonadism and hypothyroidism, he had an elevated ACTH level of 22.95 pmol/L with a 24 hour urine cortisol of 13184 (normal <346) nmol/d. Imaging documented a right upper lobe lung mass measuring 3.5cm×3.6cm and multiple metastatic lesions to the brain, pituitary and liver as well as bilateral adrenal enlargement. Histology confirmed the diagnosis of large cell neuroendocrine tumor with primary lung origin. Discussion: Although diabetes and Cushing’s syndrome are often associated with weight gain, weight loss rather than weight gain may occur in the setting of ectopic Cushing’s syndrome. This case therefore demonstrates the importance of keeping a broad differential for patients with ongoing weight loss.
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Obesity and the Diagnostic Accuracy for Primary Aldosteronism FADY HANNAH-SHMOUNI, AMIT TIROSH, CHARALAMPOS LYSSIKATOS, ELENA BELYAVSKAYA, MIHAIL ZILBERMINT, SMITA B. ABRAHAMMAYA, B. LODISH, CONSTANTINE A. STRATAKIS Bethesda, MD
Regional Variability in the Baseline Profile and Treatments of Patients with Type 2 Diabetes, Hypertension and Hypercholesterolemia in Canadian Routine Care: First Results from the CV-CARE Registry RONALD GOLDENBERG*,†, ALAN BELL†, WILL CHENG, MONIQUE GIGUERE†, JOHN S. SAMPALIS†, EMMANOUIL RAMPAKAKIS†, CARLE RYCKMAN† Thronhill, ON
Background: The effects of body mass index (BMI) on the diagnostic accuracy for primary aldosteronism (PA) are inconsistent and yet important considering the high prevalence and frequent co-occurrence of obesity and hypertension. Methods: The current study included 59 patients, with a mean age of 49.3±16.0 years and mean BMI of 32.6±6.8 kg/m2 (66.1% were women) who underwent a stepwise evaluation for PA, using aldosterone to renin ratio (ARR) for case detection and plasma aldosterone concentration (PAC) after saline suppression test (SST) and/or 24-hour urinary aldosterone after oral sodium loading for case confirmation. Results: BMI showed a significant quadratic (U-shaped) correlation with PAC (r=.5, P=.03; P for r change .04), plasma renin activity (PRA), ARR, and PAC after SST. The receiver operating characteristic curve for the full study population (n=46, AUC=0.798) and for patients with BMI <30 kg/m2 (n=18) and ≥30 kg/m2 (n=27) revealed excellent accuracy of ARR for case detection of PA among patients with BMI <30 kg/m2 (AUC=0.970), compared with a lower accuracy among patients with obesity (AUC=0.621). The positive predictive value for ARR ≥20 and ARR ≥30 among patients with BMI <30 kg/m2 was 100%, whereas the parallel values among patients with obesity were 76.5% and 63.6%, respectively.
Objective: To explore regional variability in patients enrolled thus far in the CV-CARE registry. Design: CV-CARE is a National, multicenter, community-based, registry conducted in patients initiating treatment with MetforminER, Azilsartan, Azilsartan/Chlorthalidone, and/or Colesevelam. Results: A total of 2,427 patients were included (Metformin-ER [n=648]; Azilsartan [n=691]; Azilsartan/Chlorthalidone [n=167]; Colesevelam [n=921]). Most patients initiating Metformin-ER switched from Metformin-IR (65.8%). First-line use (21.6%) was more common in BC compared to QC and ON. Metformin-ER patients in QC were significantly older, more likely to smoke, and had longer T2D duration compared to ON and BC patients. For patients treated with Azilsartan and Azilsartan/Chlorthalidone: approximately half switched from prior treatments, essentially from ACEIs and ARBs, due to lack of efficacy (49%). First-line use was more common with Azilsartan (37% vs. 13%). Smoking and patient BMI were significantly lower in BC compared to QC and ON. Colesevelam was used as monotherapy in 45% of patients, most commonly due to statin intolerance (57%). Colesevelam as add-on therapy (20% on Ezetimibe) was usually due to intolerance to highdose statin (48.1%). Patients in BC were younger, had shorter
77 Cardiovascular Outcomes in Subclinical Cushing’s Syndrome versus Non-functioning Adrenal Adenoma: A Systematic Review JANE PARK, ALYSSA DE LUCA, HEIDI DUTTON, JANINE MALCOLM, MARY-ANNE DOYLE Ottawa, ON
S29
Conclusion: Obesity results in a nonlinear correlation with PAC, PRA, and ARR, which affects the accuracy of case detection for PA. Patients with a BMI ≥30 kg/m2 are less accurately identified as having PA if SST and/or 24-hour urinary aldosterone after oral sodium loading are used. 79 Weight Loss as an Initial Manifestation of Cushing’s Syndrome PARUL KHANNA*, TISHA JOY London, ON
Background: There is growing evidence that subclinical Cushing’s syndrome (SCS) is associated with increase prevalence of cardiovascular (CV) risk factors. It is, however, unclear if SCS is associated with increased CV outcomes compared with non-functioning adrenal adenomas (NFAA). The objectives of this study were to evaluate 1) CV outcomes and 2) CV risk factors in patients with SCS versus NFAA. Methods: A literature review was performed using EMBASE, Medline, Cochrane Library and reference lists within selected articles. The study protocol was registered with PROSPERO. Results: A literature search yielded 4 studies that met inclusion criteria. Studies varied on their definitions of SCS and CV outcomes. The prevalence of CV outcomes in SCS was>3 times greater than in patients with NFAA. Two longitudinal studies further demonstrated increased incidence of new CV events (SCS 20.5% vs NFAA 8.4%, p=0.04), CAD (SCS 18% vs NFAA 9%, p=0.03), stroke (13% vs 7%, p=0.03) and increased CV mortality in patients with SCS (SCS 22.6% vs 2.5%, p=0.02). Only 2/4 studies found that SCS was associated with higher prevalence of DM. There was no difference in HTN or dyslipidemia demonstrated in any study. Conclusion: There is significant heterogeneity among the few studies evaluating the association between SCS and CV outcomes. While these studies suggest an increased risk of CV outcomes in patients with SCS, many did not adjust for known confounders. Larger, high quality, prospective studies are needed to evaluate this association and to identify modifiable risk factors.
Background: Cushing’s syndrome is a disorder of hypercortisolism that is typically characterized by truncal weight gain, easy bruising, purple striae, glucose intolerance/diabetes, and hypertension. Ectopic secretion of adrenocorticotropin hormone (ACTH) from tumours is rare, accounting for 10% of cases of Cushing’s syndrome. Case: A 51 year-old man (BMI 18.3 kg/m2), non-smoker, presented with a history of weight loss in the setting of new-onset diabetes. Although his blood sugars improved with the use of insulin, he had ongoing weight loss. History of proximal muscle weakness and erectile dysfunction prompted further biochemical testing. In addition to secondary hypogonadism and hypothyroidism, he had an elevated ACTH level of 22.95 pmol/L with a 24 hour urine cortisol of 13184 (normal <346) nmol/d. Imaging documented a right upper lobe lung mass measuring 3.5cm×3.6cm and multiple metastatic lesions to the brain, pituitary and liver as well as bilateral adrenal enlargement. Histology confirmed the diagnosis of large cell neuroendocrine tumor with primary lung origin. Discussion: Although diabetes and Cushing’s syndrome are often associated with weight gain, weight loss rather than weight gain may occur in the setting of ectopic Cushing’s syndrome. This case therefore demonstrates the importance of keeping a broad differential for patients with ongoing weight loss.
78
80
Obesity and the Diagnostic Accuracy for Primary Aldosteronism FADY HANNAH-SHMOUNI, AMIT TIROSH, CHARALAMPOS LYSSIKATOS, ELENA BELYAVSKAYA, MIHAIL ZILBERMINT, SMITA B. ABRAHAMMAYA, B. LODISH, CONSTANTINE A. STRATAKIS Bethesda, MD
Regional Variability in the Baseline Profile and Treatments of Patients with Type 2 Diabetes, Hypertension and Hypercholesterolemia in Canadian Routine Care: First Results from the CV-CARE Registry RONALD GOLDENBERG*,†, ALAN BELL†, WILL CHENG, MONIQUE GIGUERE†, JOHN S. SAMPALIS†, EMMANOUIL RAMPAKAKIS†, CARLE RYCKMAN† Thronhill, ON
Background: The effects of body mass index (BMI) on the diagnostic accuracy for primary aldosteronism (PA) are inconsistent and yet important considering the high prevalence and frequent co-occurrence of obesity and hypertension. Methods: The current study included 59 patients, with a mean age of 49.3±16.0 years and mean BMI of 32.6±6.8 kg/m2 (66.1% were women) who underwent a stepwise evaluation for PA, using aldosterone to renin ratio (ARR) for case detection and plasma aldosterone concentration (PAC) after saline suppression test (SST) and/or 24-hour urinary aldosterone after oral sodium loading for case confirmation. Results: BMI showed a significant quadratic (U-shaped) correlation with PAC (r=.5, P=.03; P for r change .04), plasma renin activity (PRA), ARR, and PAC after SST. The receiver operating characteristic curve for the full study population (n=46, AUC=0.798) and for patients with BMI <30 kg/m2 (n=18) and ≥30 kg/m2 (n=27) revealed excellent accuracy of ARR for case detection of PA among patients with BMI <30 kg/m2 (AUC=0.970), compared with a lower accuracy among patients with obesity (AUC=0.621). The positive predictive value for ARR ≥20 and ARR ≥30 among patients with BMI <30 kg/m2 was 100%, whereas the parallel values among patients with obesity were 76.5% and 63.6%, respectively.
Objective: To explore regional variability in patients enrolled thus far in the CV-CARE registry. Design: CV-CARE is a National, multicenter, community-based, registry conducted in patients initiating treatment with MetforminER, Azilsartan, Azilsartan/Chlorthalidone, and/or Colesevelam. Results: A total of 2,427 patients were included (Metformin-ER [n=648]; Azilsartan [n=691]; Azilsartan/Chlorthalidone [n=167]; Colesevelam [n=921]). Most patients initiating Metformin-ER switched from Metformin-IR (65.8%). First-line use (21.6%) was more common in BC compared to QC and ON. Metformin-ER patients in QC were significantly older, more likely to smoke, and had longer T2D duration compared to ON and BC patients. For patients treated with Azilsartan and Azilsartan/Chlorthalidone: approximately half switched from prior treatments, essentially from ACEIs and ARBs, due to lack of efficacy (49%). First-line use was more common with Azilsartan (37% vs. 13%). Smoking and patient BMI were significantly lower in BC compared to QC and ON. Colesevelam was used as monotherapy in 45% of patients, most commonly due to statin intolerance (57%). Colesevelam as add-on therapy (20% on Ezetimibe) was usually due to intolerance to highdose statin (48.1%). Patients in BC were younger, had shorter