Management of Mild-to-Moderate Hypertriglyceridemia

ObjectiveHypertriglyceridemia (HTG) is highly prevalent globally, and its prevalence is rising, with a worldwide increase in the incidence of obesity and diabetes. This review examines its current management and future therapies.MethodsFor this review, HTG is defined as mild-to-moderate elevation in the levels of triglyceride (TG): a fasting or nonfasting TG level of ≥150 mg/dL and <500 mg/dL. We reviewed scientific studies published over the last 30 years and current professional society recommendations regarding the evaluation and treatment of HTG.ResultsGenetics, lifestyle, and other environmental factors impact TG levels. In adults with mild-to-moderate HTG, clinicians should routinely assess and treat secondary treatable causes (diet, physical activity, obesity, metabolic syndrome, and reduction or cessation of medications that elevate TG levels). Because atherosclerotic cardiovascular disease risk is the primary clinical concern, statins are usually the first-line treatment. Patients with TG levels between ≥150 mg/dL and <500 mg/dL whose low-density lipoprotein cholesterol is treated adequately with statins (at “maximally tolerated“ doses, per some statements) and have either prior cardiovascular disease or diabetes mellitus along with at least 2 additional cardiovascular disease risk factors should be considered for added icosapent ethyl treatment to further reduce their cardiovascular disease risk. Fibrates, niacin, and other approved agents or agents under development are also reviewed in detail.ConclusionThe treatment paradigm for mild-to-moderate HTG is changing on the basis of data from recent clinical trials. Recent trials suggest that the addition of icosapent ethyl to background statin therapy may further reduce atherosclerotic cardiovascular disease risk in patients with moderate HTG, although a particular TG goal has not been identified.     

Comparison of Profile of Primary Hyperparathyroidism With and Without Type 2 Diabetes Mellitus: Retrospective Analysis From the Indian Primary Hyperparathyroidism Registry

ObjectiveTo describe the prevalence and compare the clinicobiochemical profile of patients with primary hyperparathyroidism (PHPT) with and without type 2 diabetes mellitus (T2DM).MethodsWe conducted a retrospective observational study wherein the details of patients with PHPT with T2DM (PHPT-T2DM) and without T2DM were retrieved from the Indian PHPT Registry (www.indianphptregistry.com) between 2005 and 2019. We compared the clinical, biochemical, and postoperative findings of patients with PHPT-T2DM with age-, sex-, and body mass index–matched patients with PHPT without T2DM (in 1:2 ratio).ResultsOf the 464 patients with PHPT, 54 (11.6%) had T2DM. We observed an increase in the prevalence of PHPT-T2DM cases over time; only 7 (7.1%) of the total patients with PHPT had T2DM between 2005 and 2009 that increased to 31 (12.8%) in the last half decade (2015-2019). Patients with PHPT-T2DM had a significantly lower prevalence of nephrolithiasis (18.5% vs 36.1%, respectively; P = .03) and a higher prevalence of pancreatitis (22.2% vs 5.6%, respectively; P = .007) than those without T2DM. Furthermore, intact parathyroid hormone (203 pg/mL [139.8-437.3 pg/mL] vs 285 pg/mL [166-692 pg/mL], respectively; P = .04) and serum creatinine (0.90 mg/dL [0.67-1.25 mg/dL] vs 1.10 mg/dL [0.73-1.68 mg/dL], respectively; P = .03) levels were significantly lower in patients with PHPT-T2DM than those without T2DM. Also, tumor weight tended to be lower in patients with PHPT-T2DM than in the non-T2DM counterparts (1.05 g [0.5-2.93 g] vs 2.16 g [0.81-7.0 g], respectively; P = .06).ConclusionThe prevalence of T2DM in Asian Indians with PHPT is 11.6%. Patients with PHPT-T2DM are characterized by a higher prevalence of pancreatitis, a lower prevalence of nephrolithiasis, and lower levels of intact parathyroid hormone/creatinine. Part of the clinical picture can possibly be explained by early detection of PHPT in patients with T2DM consequent to more frequent screening.     

Albumin-Corrected Calcium and the Prevalence and Categories of Hypercalcemia in Hospitalized Patients With 1-Year Follow-Up of Undiagnosed Cases

ObjectiveTo assess the impact of using corrected calcium versus total calcium on hypercalcemia case detection in hospitalized patients.MethodsPatients hospitalized from June 2012 to June 2017 with a corrected calcium level of ≥10.5 mg/dL were identified by medical record review. One-year follow-up data through June 2018 were acquired. Albumin-corrected calcium level was calculated: (4 − albumin concentration in g/dL) × 0.8 + total serum calcium in mg/dL.ResultsA group of 1067 patients had a corrected calcium level of ≥10.5 mg/dL. The prevalence of hypercalcemia was 0.73% with total calcium and 1.09% with corrected calcium, respectively, with a 49% relative increase. Most patients (62%) had mild hypercalcemia (10.5-11.9 mg/dL); 3.7% had severe hypercalcemia (>14 mg/dL). With corrected calcium, the most common categories of hypercalcemia were malignancy (35.4%), hypercalcemia that was not further evaluated (31.1%), and hyperparathyroidism (22.4%). All patients in the unidentified category had albumin levels <2.8 g/dL. At the 1-year follow–up, 63% of the unidentified cases had normal calcium levels, and 26.8% had mild persistent hypercalcemia. Of those with persisting hypercalcemia at 1 year, 16.8% were diagnosed with hyperparathyroidism.ConclusionUsing albumin-corrected calcium resulted in an ∼50% increase in the detection of hypercalcemia cases. Although hypercalcemia resolved in majority of the undiagnosed cases at 1 year, a number of these remained abnormal. Detecting hypercalcemic disorders by correcting for low albumin level can help identify conditions such as hyperparathyroidism. Adding auto-calculated albumin-corrected calcium to routine laboratory tests could be a cost-effective intervention to improve the detection of hypercalcemic disorders.     

Evaluating the Impact of Inadequate Meal Consumption on Insulin-Related Hypoglycemia in Hospitalized Patients

ObjectiveMeal intake is sometimes reduced in hospitalized patients. Meal-time insulin administration can cause hypoglycemia when a meal is not consumed. Inpatient providers may avoid ordering meal-time insulin due to hypoglycemia concerns, which can result in hyperglycemia. The frequency of reduced meal intake in hospitalized patients remains inadequately determined. This quality improvement project evaluates the percentage of meals consumed by hospitalized patients with insulin orders and the resulting risk of postmeal hypoglycemia (blood glucose [BG] <70 mg/dL, <3.9 mmol/L).MethodsThis was a retrospective quality improvement project evaluating patients with any subcutaneous insulin orders hospitalized at a regional academic medical center between 2015 and 2017. BG, laboratory values, point of care, insulin administration, diet orders, and percentage of meal consumed documented by registered nurses were abstracted from electronic health records.ResultsMeal consumption ≥50% was observed for 85% of meals with insulin orders, and bedside registered nurses were accurate at estimating this percentage. Age ≥65 years was a risk factor for reduced meal consumption (21% of meals 0%-49% consumed, P < .05 vs age < 65 years [12%]). Receiving meal-time insulin and then consuming only 0% to 49% of a meal (defined here as a mismatch) was not rare (6% of meals) and increased postmeal hypoglycemia risk. However, the attributable risk of postmeal hypoglycemia due to this mismatch was low (4 events per 1000) in patients with premeal BG between 70 and 180 mg/dL.ConclusionThis project demonstrates that hospitalized patients treated with subcutaneous insulin have a low attributable risk of postmeal hypoglycemia related to inadequate meal intake.     

Prevalence,Subtype Classification,and Outcomes of Treatment of Primary Aldosteronism: A Prospective Study in China

ObjectiveTo investigate the prevalence of primary aldosteronism (PA) among participants with hypertension, evaluate the concordance of PA classification between adrenal computed tomography and adrenal venous sampling, and compare the outcomes of surgery and medication for unilateral PA.MethodsA prospective study was conducted among all inpatients with hypertension (n = 7594) at the National Center for Cardiovascular Diseases, China, from May 2016 to April 2018.ResultsOf the 7594 participants, 8.12% (n = 617) with plasma aldosterone-renin ratio ≥3.7 were possible PA cases. Three hundred sixty-seven cases with plasma aldosterone-renin ratio ≥3.7 and plasma aldosterone concentration ≥10 ng/dL were confirmed using the recumbent saline infusion test (69.20%, 182 of 263) or the captopril challenge test (66.5%, 69 of 104, P > .05). The prevalence of PA was 3.31% (n = 251). Of the 251 patients with PA, all of them had multiple comorbidities, and 49.40% (n = 124) had spontaneous hypokalemia. The concordance of PA classification between adrenal computed tomography and adrenal venous sampling was only 47.11%. The patients’ blood pressure declined to normal ranges in the adrenalectomy (85.71%, 30 of 35) and spironolactone (63.04%; 29 of 46) groups (P < .05). Furthermore, hypokalemia was normalized in the adrenalectomy (100.00%; 26 of 26) and spironolactone (94.74%; 18 of 19) groups.ConclusionIt is necessary to incorporate PA screening into routine practice for those with hypertension in the Chinese population. This will assist in ensuring that the best therapeutic schedule based on PA subtypes is devised. Additionally, as a result, it may contribute to restoring the blood pressure levels and reducing the prevalence of comorbidities in these patients with PA.     

Life Expectancy and Treatment Patterns in Elderly Patients With Low-Risk Papillary Thyroid Cancer: A Population-Based Analysis

ObjectiveGuidelines endorse active surveillance for low-risk papillary thyroid carcinoma (PTC), but this is not commonly utilized. Those with limited life expectancy due to age and comorbidity may be best suited for active surveillance given their higher likelihood of other-cause mortality compared to disease-specific mortality.MethodsSurveillance, epidemiology, and end results-Medicare was queried for patients >65 years with T1, N0, M0 PTC who received surgery. We evaluated the overall survival, disease-specific survival (DSS), and survival based on tumor size and extent of surgery (hemi- vs total thyroidectomy). We created a competing risk model to identify the cumulative incidence of other-cause mortality to define patient groups with life expectancies of less than 10 and 15 years.ResultsA total of 3280 patients were included. The 20-year overall survival and DSS were 38.2% and 98.5%, respectively. DSS was comparable between patients based on tumor size and surgery. The cancer cohort had better survival compared to matched controls (P < .001). Life expectancy was less than 15 years for any patient aged >80 years regardless of Charlson comorbidity score (CCS ≥ 0) and any patient aged >70 years with CCS ≥ 1. Life expectancy was less than 10 years for any patient a >80 years with CCS ≥ 1 and aged >70 years with CCS ≥ 3.ConclusionOlder patients with comorbidities have limited life expectancies but excellent DSS from low-risk PTC. Incorporating life expectancy into management decisions and guidelines would likely promote selection of less aggressive management for populations that are most suited for this approach.     

Seated Saline Suppression Test Is Comparable With Captopril Challenge Test for the Diagnosis of Primary Aldosteronism: A Prospective Study

ObjectiveThe saline suppression test (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) has been reported to be superior to recumbent SST. Whether SSST is better than CCT remains unclear. We aimed to compare the diagnostic accuracy of SSST and CCT in a prospective study.MethodsHypertensive patients at a high risk of PA were consecutively included. Patients with an aldosterone-renin ratio of ≥1.0 ng/dL/μIU/mL were asked to complete SSST, CCT, and the fludrocortisone suppression test (FST). Using FST as a reference standard (plasma aldosterone concentration [PAC] post FST ≥ 6.0 ng/dL), area under the receiver-operating characteristic curve (AUC), sensitivity, and specificity of SSST and CCT were calculated, and multiple regression analyses were performed to identify potential factors leading to false diagnosis.ResultsA total of 196 patients diagnosed with PA and 73 with essential hypertension completed the study. Using PAC post SSST and PAC post CCT to confirm PA, SSST and CCT had comparable AUCs (AUC_SSST 0.87 [95% CI 0.82-0.91] vs AUC_CCT 0.88 [0.83-0.95], P = .646). When PAC post SSST and post CCT were set at 8.5 and 11 ng/dL, respectively, the sensitivity and specificity of SSST (0.72 [0.65, 0.78] and 0.86 [0.76, 0.93]) and CCT (0.73 [0.67, 0.80] and 0.85 [0.75, 0.92]) were not significantly different. In the multiple regression analyses, 1-SD increment of sodium intake resulted in a 40% lower risk of false diagnosis with SSST.ConclusionSSST and CCT have comparable diagnostic accuracy. Insufficient sodium intake decreases the diagnostic efficiency of SSST but not of CCT. Since CCT is simpler and cheaper, it is preferred over SSST.     

Impact of the Time-Weighted Average Glucose Concentration and Diabetes on In-Hospital Mortality in Critically Ill Patients Older Than 75 Years: A Retrospective Cohort Study

ObjectiveTo evaluate the effects of diabetes and hyperglycemia on in-hospital mortality in critically ill patients older than 75 years.MethodsThis was a single-center retrospective cohort study of patients older than 75 years in the first intensive care unit stay. The patients were divided into the following 4 groups: time-weighted average glucose (TWAG) <140 mg/dL without diabetes (group 1), TWAG ≥140 mg/dL without diabetes (group 2), TWAG <180 mg/dL with diabetes (group 3), and TWAG ≥180 mg/dL with diabetes (group 4). Clinical and laboratory data were analyzed.ResultsA total of 6760 patients over 75 years of age were included, including 2089 patients previously diagnosed with diabetes. The patients in group 2 had the highest in-hospital mortality (27.4%). In the fully adjusted regression model, the risk of in-hospital mortality increased by 76% (odds ratio = 1.76, 95% CI: 1.49-2.08) in group 2 as compared with group 1. Those from groups 3 and 4 exhibited risks equivalent to the risks of those in group 1; similar results were observed in the subgroup analysis. A J-shaped curve relationship and threshold effect were observed in patients without diabetes. For those with diabetes, a flatter curve pattern with a small slope was observed.ConclusionStress hyperglycemia was more detrimental to short-term prognosis than diabetes status in these patients. Looser glucose control may be suitable for patients older than 75 years with diabetes but unnecessary for those without diabetes. Patients with diabetes may be more resistant to the detrimental effects of glucose variations.     

Weight-Based Insulin During and After Intravenous Insulin Infusion Reduces Rates of Rebound Hyperglycemia When Transitioning to Subcutaneous Insulin in the Medical Intensive Care Unit

ObjectiveHyperglycemia often occurs after the transition from intravenous insulin infusion (IVII) to subcutaneous insulin. Weight-based basal insulin initiated earlier in the course of IVII in the medical intensive care unit (MICU), and a weight-based basal-bolus regimen after IVII, can potentially improve post-IVII glycemic control by 48 hours.MethodsThis prospective study included 69 patients in MICU who were on IVII for ≥24 hours. Exclusions were end-stage renal disease, type 1 diabetes mellitus, and the active use of vasopressors. The intervention group received weight-based basal insulin (0.2-0.25 units/kg) with IVII and weight-based bolus insulin after IVII. The control group received current care. The primary end points were glucose levels at specific time intervals up to 48 hours after IVII.ResultsThere were 25 patients in the intervention group and 44 in the control group. The mean age of the patients was 59 ± 15 years, 32 (47%) were men, and 52 (78%) had prior diabetes mellitus. The 2 groups were not different (acute kidney injury/chronic kidney disease, pre-existing diabetes mellitus, illness severity, or nothing by mouth status after IVII), except for the steroid use, which was higher in the control group than in the intervention group (34% vs 12%, respectively). Glucose levels were not lower until 36 to 48 hours after IVII (166.8 ± 39.1 mg/dL vs 220.0 ± 82.9 mg/dL, P < .001). When controlling for body mass index, nutritional status, hemoglobin A1C, and steroid use, glucose level was lower starting at 12 to 24 hours out (166.87 mg/dL vs 207.50 mg/dL, P = .015). The frequency of hypoglycemia was similar between the 2 groups (5.0% vs 7.1%). The study did not reach target enrollment.ConclusionThe addition of weight-based basal insulin during, and basal-bolus insulin immediately after, IVII in MICU results in better glycemic control at 24 hours after IVII with no increased hypoglycemia.     

Use of the Free Thyroxine Index to Refine the Lower Limit of a Free Thyroxine Immunoassay for Detection of Secondary Hypothyroidism

ObjectiveTo determine the utility of measuring free T₄ index (FT₄I) in patients with low free T₄ (FT₄) levels using immunoassay and normal thyroid-stimulating hormone for the evaluation of secondary hypothyroidism.MethodsWe performed a retrospective medical chart review of patients seen at a single institution as outpatients who had a simultaneously normal thyroid-stimulating hormone level, low FT₄ level, and any FT₄I measured between June 2014 and October 2016. Demographic, laboratory, and imaging data were collected. Using FT₄I as the reference for diagnosis of hypothyroidism, the sensitivity and specificity of the FT₄ immunoassay’s lower-limit thresholds were determined. Within each threshold group, available brain imaging and biochemical evaluation were categorized according to the presence or absence of pituitary disease.ResultsA total of 155 sets of result pairs (FT₄ and FT₄I) performed on 118 subjects were analyzed. The lower limit of a normal FT₄ level by immunoassay at this institution was 0.93 ng/dL, though all pairs with FT₄ ≥0.89 ng/dL had a normal FT₄I. All pairs with FT₄ ≤0.67 ng/dL had a low FT₄I. No pituitary macroadenomas were identified in any subject, though the rates of pituitary imaging in this patient sample were low.ConclusionPatients with a borderline low FT₄ level by immunoassay often have normal FT₄I. In such patients at our center, significant structural and biochemical pituitary pathology was uncommon.     

Guideline-Concordant Insulin Infusion Initiation Among Critically Ill Patients With Sepsis

ObjectiveOur objective was to benchmark rates of guideline-concordant insulin infusion initiation, identify factors associated with guideline-concordant insulin practices, and examine the association between hospital-level guideline concordance and mortality among critically ill patients with sepsis.MethodsWe performed a multicenter retrospective cohort study of intensive care patients with sepsis who were eligible for insulin infusion initiation according to American Diabetes Association and Surviving Sepsis guidelines (persistent blood sugar ≥180 mg/dL). We then identified patients who were initiated on insulin infusions within 24 hours of eligibility. We examined patient- and hospital-level factors associated with guideline-concordant insulin infusion initiation and explored the association between the hospital-level proportion of patients who received guideline-concordant insulin infusions and hospital mortality.ResultsAmong 5453 guideline-eligible patients with sepsis, 13.4% were initiated on insulin infusions. Factors most strongly associated with guideline-concordant insulin infusion initiation were mechanical ventilation and hospital of admission. The hospital-level proportion of patients who received guideline-concordant insulin infusions were not associated with mortality. Among 1501 intensive care unit patients with sepsis who were started on insulin infusions, 37.0% were initiated at a blood glucose level below 180 mg/dL, the guideline-recommended starting threshold.ConclusionGuideline-concordant insulin infusion initiation was uncommon among patients with sepsis admitted to U.S. intensive care units and was determined in large part by hospital of admission. The degree to which hospitals were guideline-concordant were not associated with mortality.     

Anemia in Patients With Diabetes and Prediabetes With Normal Kidney Function: Prevalence and Clinical Outcomes

ObjectiveAnemia is a known complication of diabetes mellitus (DM); however, its prevalence and prognostic relevance in patients with DM and pre-DM with normal kidney function have not been well defined. This study assessed the prevalence of anemia in patients with DM and pre-DM and evaluated its association with clinical outcomes during a 4-year follow-up period.MethodsThis retrospective analysis included patients with DM and pre-DM referred to the Meir Medical Center Endocrine Institute in 2015. Patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min or any other recognized cause of anemia were excluded. The risk of developing microvascular or macrovascular complications or of death during the 4-year follow-up period was determined.ResultsA total of 622 patients (408 with DM and 214 with pre-DM) were included. The mean age of the patients was 64 ± 10.6 years, and 70% were women. The baseline hemoglobin A1C level was 7.1% ± 1.7% (54 mmol/mol), and the eGFR was 86.1 ± 15.3 mL/min. At the time of inclusion, 77 patients (19%) with DM and 23 (11%) with pre-DM had anemia (hemoglobin level 11.9 ± 0.8 and 11.8 ± 0.8 g/dL, respectively), compared with normal hemoglobin levels of 13.8 ± 0.9 and 13.7± 0.9 g/dL, respectively, in the others. A multivariable analysis demonstrated an inverse correlation between baseline hemoglobin (as a continuous variable) and mortality (P = .035), microvascular complications (P = .003), and eGFR decline (P < .001) but not between baseline hemoglobin and macrovascular complications (P = .567).ConclusionThis study found a significant prevalence of anemia unrelated to renal failure, both in patients with DM and pre-DM. Anemia in these patients is associated with the development of microvascular complications, eGFR decline, and mortality. These results underscore the need for intensive lifestyle and pharmacologic interventions in these patients.     

Early Predictors of Gestational Diabetes Mellitus in IVF-Conceived Pregnancies

ObjectiveGestational diabetes mellitus (GDM) is associated with adverse maternal and fetal outcomes. This study aimed to identify early and reliable GDM predictors that would enable implementation of preventive and management measures.MethodsThe participants were a 28-week prospective cohort of in vitro fertilization (IVF)-conceived pregnant women (≤39 years, body mass index [BMI] 18.5-38 kg/m²) without a known history of diabetes mellitus. Fasting blood samples were analyzed at baseline (pre-IVF) and 12 weeks’ gestation for reproductive hormones, glucose, serum insulin, lipids, thyroid function, adiponectin, and lipopolysaccharide-binding protein. At 28 weeks, a 75-g oral glucose tolerance test was used to screen for GDM.ResultsFor the overall group at baseline, 22% had BMI ≥30 kg/m², 45% had polycystic ovary syndrome, 16% had hemoglobin A1C of 5.7% to 6.1%, and 14% had a past history of GDM. At 28 weeks of gestation (n = 158), 34 women had developed GDM and 124 had not. Significant baseline predictors of GDM onset included greater BMI (29.0 vs 25.8 kg/m²), older age (34 vs 32 years), higher levels of follicle-stimulating hormone/luteinizing hormone ratio (1.2 vs 1.0), hemoglobin A1C (5.5 vs 5.2%), insulin (10.6 vs 7.1 μIU/mL), homeostatic model assessment of insulin resistance (2.2 vs 1.7), total cholesterol (199 vs 171 mg/dL), and low-density lipoprotein cholesterol (123 vs 105 mg/dL), and lower triglyceride levels (74 vs 76 mg/dL). Significant 12-week GDM predictors included greater maternal weight gain (delta: 3.4 vs 1.5 kg) and higher levels of insulin (11.3 vs 7.6 μIU/mL), triglycerides (178 vs 120 mg/dL), and homeostatic model assessment of insulin resistance (2.3 vs 1.5). Twelve-week BMI is a predictor of GDM following adjustment for polycystic ovary syndrome status and maternal age.ConclusionWhile preconception maternal BMI, age, and follicle-stimulating hormone/luteinizing hormone ratio are predictors of subsequent development of GDM, early IVF-conceived gestational weight gain is the best predictor of GDM onset.     

Using a Diabetes Risk Score to Identify Patients Without Diabetes at Risk for New Hyperglycemia in the Hospital

ObjectiveTo assess the value of a validated diabetes risk test, the Cambridge Risk Score (CRS), to identify patients admitted to hospital without diabetes at risk for new hyperglycemia (NH).MethodsThis retrospective cross-sectional study included adults admitted to a hospital over a 4-year period. Patients with no diabetes diagnosis and not on antidiabetics were included. The CRS was calculated for each patient, and those with available glycated hemoglobin (HbA1C) results were investigated in a second analysis. Multivariate regression analyses were performed to assess the association among CRS, HbA1C, and the risk for NH.ResultsA total of 19,830 subjects comprised the sample, of which 38% were found to have developed NH, defined as a blood glucose level ≥140 mg/dL. After accounting for covariates, the CRS was significantly associated with NH (odds ratio [OR], 1.19 [1.16, 1.22]; P < .001). Only 17% of patients had their HbA1C values checked within 6 months of admission. Compared with patients without diabetes, patients with prediabetes based on their HbA1C level (OR, 1.59 [1.37, 1.86]; P < .001) and patients with undiagnosed diabetes (OR, 5.95 [3.50, 10.65]; P < .001) were also significantly more likely to have NH.ConclusionResults of this study show that the CRS and HbA1C levels were significantly associated with the risk of developing NH in inpatient adults without diabetes. Given that an HbA1C level was missing in most medical records of hospitalized patients without diabetes, the CRS could be a useful tool for early identification and management of NH, possibly leading to better outcomes.     

Effect of Steroid Replacement on Long-Term Kidney Function in Patients With Adrenal Insufficiency

ObjectiveThe prevalence of adrenal insufficiency (AI) is increasing with an increase in the elderly population. Steroid replacement therapy (SRT) is often required in patients with AI because of acute symptoms and complications. The long-term effects of SRT on kidney function have not been well elucidated.MethodsOverall, 788 patients diagnosed with AI between 2010 and 2015 at Yonsei University Health System were retrospectively evaluated. SRT was defined when an equivalent dose of ≥5 mg/d of hydrocortisone was initiated within 30 days of AI diagnosis and maintained for >30 days. Those not included in the SRT group were identified as the no-SRT group. The primary outcome was 40% reduction in the estimated glomerular filtration rate compared with baseline sustained for ≥30 days or end-stage kidney disease development.ResultsThe mean age of was 63.1 ± 15.4 years, and 43.0% were men. The SRT group comprised 387 patients. During a median follow-up duration of 4.1 years, the primary outcome occurred in 118 (15.0%) patients. The outcome incidence rate was higher in the SRT group (4.61/100 patient-years) than in the no-SRT group (2.76/100 patient-years). When the subdistribution hazard ratio for kidney outcome was assessed with death as a competing risk, the risk was 67% higher in the SRT group than in the no-SRT group (subdistribution hazard ratio, 1.67; 95% confidence interval, 1.16-2.45; P = .006). This association was maintained with inverse probability of treatment weighting and adjustment for confounding variables.ConclusionKidney function decline was more prominent in patients with AI who received SRT. Further prospective evaluations are needed to confirm these findings.     

Association of Parathyroidectomy With 5-Year Clinically Significant Kidney Stone Events in Patients With Primary Hyperparathyroidism

ObjectivePatients with primary hyperparathyroidism (PHPT) are at increased risk of kidney stones. Guidelines recommend parathyroidectomy in patients with PHPT with a history of stone disease. This study aimed to compare the 5-year incidence of clinically significant kidney stone events in patients with PHPT treated with parathyroidectomy versus nonoperative management.MethodsWe performed a longitudinal cohort study of patients with PHPT in a national commercial insurance claims database (2006-2019). Propensity score inverse probability weighting-adjusted multivariable regression models were calculated.ResultsWe identified 7623 patients aged ≥35 years old with continuous enrollment >1 year before and >5 years after PHPT diagnosis. A total of 2933 patients (38.5%) were treated with parathyroidectomy. The cohort had a mean age of 66.5 years, 5953 (78.1%) were female, and 5520 (72.4%) were White. Over 5 years, the unadjusted incidence of ≥1 kidney stone event was higher in patients who were managed with parathyroidectomy compared with those who were managed nonoperatively overall (5.4% vs 4.1%, respectively) and among those with a history of kidney stones at PHPT diagnosis (17.9% vs 16.4%, respectively). On multivariable analysis, parathyroidectomy was associated with no statistically significant difference in the odds of a 5-year kidney stone event among patients with a history of kidney stones (odds ratio, 1.03; 95% CI, 0.71-1.50) or those without a history of kidney stones (odds ratio, 1.16; 95% CI, 0.84-1.60).ConclusionBased on this claim analysis, there was no difference in the odds of 5-year kidney stone events in patients with PHPT who were treated with parathyroidectomy versus nonoperative management. Time horizon for benefit should be considered when making treatment decisions for PHPT based on the risk of kidney stone events.     

Glucocorticoid-Induced Hyperglycemia Including Dexamethasone-Associated Hyperglycemia in COVID-19 Infection: A Systematic Review

ObjectiveOptimal glucocorticoid-induced hyperglycemia (GCIH) management is unclear. The COVID-19 pandemic has made this issue more prominent because dexamethasone became the standard of care in patients needing respiratory support. This systematic review aimed to describe the management of GCIH and summarize available management strategies for dexamethasone-associated hyperglycemia in patients with COVID-19.MethodsA systematic review was conducted using the PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases with results from 2011 through January 2022. Keywords included synonyms for “steroid-induced diabetes” or “steroid-induced hyperglycemia.” Randomized controlled trials (RCTs) were included for review of GCIH management. All studies focusing on dexamethasone-associated hyperglycemia in COVID-19 were included regardless of study quality.ResultsInitial search for non-COVID GCIH identified 1230 references. After screening and review, 33 articles were included in the non-COVID section of this systematic review. Initial search for COVID-19–related management of dexamethasone-associated hyperglycemia in COVID-19 identified 63 references, whereas 7 of these were included in the COVID-19 section. RCTs of management strategies were scarce, did not use standard definitions for hyperglycemia, evaluated a variety of treatment strategies with varying primary end points, and were generally not found to be effective except for Neutral Protamine Hagedorn insulin added to basal-bolus regimens.ConclusionFew RCTs are available evaluating GCIH management. Further studies are needed to support the formulation of clinical guidelines for GCIH especially given the widespread use of dexamethasone during the COVID-19 pandemic.     

Association of Serum Parathyroid Hormone Levels With All-Cause and Cause-Specific Mortality Among U.S. Adults

ObjectiveTo examine whether parathyroid hormone (PTH) is associated with mortality among U.S. adults.MethodsThis study included 8286 U.S. adults aged ≥20 years with a measurement of serum intact PTH from the National Health and Nutrition Examination Survey 2003-2006 linked to national mortality data through 2015. Multivariable Cox proportional hazard regression models were employed to estimate the adjusted hazard ratio (aHR) of all-cause and cause-specific (cardiovascular and cancer) mortality according to intact PTH levels (low or low-normal, <38; middle-normal, 38-56; high-normal, 57-74; high, >74 pg/mL). We also stratified the analyses by serum albumin-adjusted calcium and 25-hydroxy vitamin D (25OHD) levels.ResultsDuring a median follow-up of 10.1 years, the mean age was 49 years, and 48% were men. After adjusting for potential confounders, both the high-normal and high PTH groups showed higher risks of all-cause mortality than the low or low-normal PTH group (high-normal PTH, aHR, 1.28; 95% confidence interval [CI], 1.10-1.48; high PTH, aHR, 1.42; 95% CI, 1.19-1.69]. When stratified by calcium and 25OHD levels, the association between high PTH and mortality was also found among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL (aHR, 1.53; 95% CI, 1.17-2.01) and those with 25OHD levels of ≥20 ng/mL (aHR, 1.46, 95% CI, 1.17-1.82). We found no evidence of the increased cause-specific mortality risks in the high PTH group.ConclusionHigher PTH levels were associated with an increased risk of all-cause mortality, particularly among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL or 25OHD levels of ≥20 ng/mL.     

Preoperative Calcium and Parathyroid Hormone Values Are Poor Predictors of Gland Volume and Multigland Disease in Primary Hyperparathyroidism: A Review of 2000 Consecutive Patients

ObjectiveCalcium and parathyroid hormone (PTH) values are believed to have a linear relationship in patients with primary hyperparathyroidism and correlate with parathyroid gland size, with higher values predicting single-gland disease. In this modern series, these preoperative values were correlated with operative findings to determine their utility in predicting the gland involvement at parathyroid exploration.MethodsTwo thousand consecutive patients who underwent initial surgery for sporadic primary hyperparathyroidism from 2000 to 2014 were reviewed. All patients underwent a 4-gland exploration. Relationships between preoperative calcium and PTH values with the total gland volume of each patient were examined and stratified using the number of involved glands: single adenoma (SA), double adenoma (DA), and hyperplasia (H).ResultsThere were 1274 (64%) SA, 359 (18%) DA, and 367 (18%) H cases. There was a poor correlation between preoperative calcium and PTH values (R = 0.37) and both poorly correlated with the total gland volume (R < 0.40). Similarly, subgroup analysis using the number of involved glands showed poor correlation. The mean total gland volume was similar among all subgroups (SA = 1.28 cm³, DA = 1.43 cm³, and H = 1.27 cm³; P = .52), implying that individual glands were smaller in multigland disease. SA was found in 271 (53%) of patients with calcium levels of ≤10.5 mg/dL and 122 (78%) with levels of ≥12 mg/dL (P < .001).ConclusionThis is the largest series correlating preoperative calcium and PTH values with operative findings of gland size and number of diseased glands. Although a lower calcium value predicts somewhat more multigland disease, the overall poor correlation should make the parathyroid surgeon aware that gland size and multigland disease cannot be predicted by preoperative laboratory testing.