Association of Daily Growth Hormone Injection Adherence and Height Among Children With Growth Hormone Deficiency

ObjectiveRecombinant human growth hormone (somatropin) is recommended for children with growth hormone deficiency (GHD) to normalize adult height. Prior research has indicated an association between adherence to somatropin and height velocity. Further research is needed using real-world data to quantify this relationship; hence the objective of this study was to investigate the association between adherence to somatropin and change in height among children with GHD.MethodsThis retrospective cohort study included patients in the IQVIA PharMetrics Plus and Ambulatory Electronic Medical Records databases aged 3 to 15 years, with ≥1 GHD diagnosis code claim and newly initiated on somatropin between January 1, 2007 and November 30, 2019. Adherence was measured over the follow-up using the medication possession ratio (MPR); patients were classified as adherent (MPR ≥ 0.8) or nonadherent (MPR < 0.8).ResultsAmong 201 patients initiated on somatropin, 74.6% were male, mean age was 11.4 years, and the mean follow-up was 343.3 days. Approximately 76.6% of patients were adherent to somatropin over the follow-up period. Adjusted growth trajectories were similar between adherent and nonadherent patients pre-treatment initiation (P = .15). Growth trajectories post-initiation were significantly different (P = .001). On average, adherent patients gained an additional 1.8 cm over 1 year compared with nonadherent patients, adjusted for covariates.ConclusionGreater adherence to somatropin therapy is associated with improved height velocity. As suboptimal adherence to daily somatropin therapy is an issue for children with GHD, novel strategies to improve adherence may improve growth outcomes.     

A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease

ObjectiveNonalcoholic fatty liver disease (NAFLD) affects much of the worldwide population and poses a significant burden to the global healthcare. The rising numbers of individuals with NAFLD and instances of mortality point toward the importance of understanding the association causes of mortality in NAFLD. This meta-analysis aimed to seek the associations of NAFLD with all-cause, cardiovascular disease (CVD)-related, liver-related, and cancer-related mortality.MethodsMEDLINE and Embase were searched for articles relating to causes of mortality between NAFLD and non-NAFLD. The DerSimonian and Laird random-effects model was used to analyze adjusted hazard ratios (HR), and a sensitivity analysis was conducted to reduce heterogeneity through a graphical display of study heterogeneity.ResultsFifteen studies involving 10 286 490 patients were included. Individuals with NAFLD exhibited an increased risk of all-cause mortality (HR, 1.32; 95% CI, 1.09-1.59; P < .01; I² = 96.00%), CVD-related mortality (HR, 1.22; 95% CI, 1.06-1.41; P < .01; I² = 81.00%), and cancer-related mortality (HR, 1.67; 95% CI, 1.15-2.41; P < .01; I² = 95.00%). However, no significant association was found between liver-related mortality and NAFLD (HR, 3.58; 95% CI, 0.69-18.46; P =.13; I² = 96.00%). The sensitivity analysis conducted with graphic display of heterogeneity and only population-based studies found similar results.ConclusionNAFLD was associated with an increased risk of all-cause, CVD-related, and cancer-related mortality but not liver-related mortality. The finding is likely because of low fibrosis prevalence in the community. However, the significant burden in other causes of mortality beyond the liver points to a need for multidisciplinary efforts to reduce the mortality risks.     

Fatty Liver Through the Ages: Nonalcoholic Steatohepatitis

ObjectiveThe global epidemic of obesity and type 2 diabetes mellitus is the main driver of the growing global prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to review the current literature on NAFLD and nonalcoholic steatohepatitis (NASH) as it impacts children and adults.MethodsWe performed a literature search on fatty liver specifically NAFLD and NASH among children and adults.ResultsThe prevalence of NAFLD in children ranges from 8% to 12%, while the prevalence in adults ranges 25% to 48%. The prevalence of NASH among children with NAFLD is 23%, while it ranges from 13% to 65% in adults. There are similar risk factors for NAFLD among children and adults. However, in children, the diagnostic tests in the studies of NAFLD are limited to the elevation of the alanine aminotransferase level or a liver biopsy. In adults, additional diagnostic modalities, including noninvasive tests, have been used. From the spectrum of NAFLD, patients with NASH are predominantly at risk of progressive liver disease to cirrhosis and liver-related mortality. NAFLD is associated with impairment of health-related quality of life and substantial economic burden.ConclusionThe comprehensive burden (clinical, health-related quality of life, and economic) of NAFLD is high and increasing.     

Antidiabetic Medications for Type 2 Diabetics with Nonalcoholic Fatty Liver Disease: Evidence From a Network Meta-Analysis of Randomized Controlled Trials

ObjectiveType 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD) are closely related, and antidiabetic medications have been shown to be potential therapeutics in NAFLD. Using a network meta-analysis, we sought to examine the effectiveness of antidiabetic agents for the treatment of NAFLD in patients with type 2 diabetes mellitus.MethodsMedline and Embase were searched for randomized controlled trials relating to the use of antidiabetic agents, including sodium-glucose transport protein 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor gamma (PPARγ) agonists, biguanides, sulfonylureas and insulin, on NAFLD in patients with diabetes. The p-score was used as a surrogate marker of effectiveness.ResultsA total of 14 articles were included in the analysis. PPARγ agonists were ranked as the best treatment in steatosis reduction, resulting in the greatest reduction of steatosis. There was statistical significance between PPARγ agonists [mean difference (MD): ?6.02%, confidence interval (CI): ?10.37% to ?1.67%] and SGLT2 inhibitors (MD: ?2.60%, CI: ?4.87% to ?0.33%) compared with standard of care for steatosis reduction. Compared with PPARγ agonists, SGLT2 inhibitors resulted in a statistical significant reduction in fibrosis (MD: ?0.06, CI: ?0.10 to ?0.02). Body mass index reduction was highest in SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists. Additionally, SGLT2 inhibitors were ranked as the best treatment for increasing high-density lipoprotein and reducing low-density lipoprotein.ConclusionGlucagon-like peptide-1 receptor agonists and SGLT2 inhibitors were suitable alternatives for the treatment of NAFLD in those with type 2 diabetes mellitus with a reduction in body mass index, fibrosis, and steatosis. SGLT2 inhibitors also have the added benefit of lipid modulation.     

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.     

What Potentially Modifiable Factors are Associated With Treatment Nonadherence in Pediatric Growth Hormone Deficiency? A Quantitative Study

ObjectiveA recent systematic review reported that up to 71% of patients with growth hormone deficiency and their families are nonadherent to treatment as prescribed. Nonadherence to growth hormone treatment presents a substantial and costly problem for the patient, health care provider, and health care system. The current study uniquely investigated the potentially modifiable factors associated with treatment nonadherence in this endocrine disorder.MethodsThe cross-sectional study was conducted among 82 parent/caregivers of children with growth hormone deficiency who were receiving growth hormone treatment. Self-report questionnaires investigated parent/caregiver perceptions and experiences of their child’s condition and prescribed treatment, in addition to their perceived relationship with their health care professional. The 8-item Morisky medication adherence scale was used for the assessment of treatment adherence.ResultsSixty-two percent of parents/caregivers were found to be nonadherent to growth hormone treatment as prescribed. Illness perceptions (consequences, identity, and coherence) and treatment concerns were found to be significantly associated with treatment adherence, as was the quality of the health care professional–parent/caregiver relationship.ConclusionThe study confirmed the extent of the adherence problem evident among the pediatric growth hormone deficiency population. In addition, it presented an insight into the explanatory factors that underpin nonadherence to growth hormone treatment. Our findings can be used to inform the development of adherence-focused interventions, with the purpose of supporting patients and their families and improving the use of prescribed growth hormone treatment within endocrine clinical practice.     

Transition Readiness in Adolescents and Young Adults Living With Congenital Adrenal Hyperplasia

ObjectiveCongenital adrenal hyperplasia (CAH) refers to a group of genetic disorders that affect cortisol biosynthesis and the need for glucocorticoid treatment is lifelong. The complexities of CAH can greatly affect teenage life and the transition from pediatric to adult care. The aim was to assess transition readiness and the impact on quality of life (QoL) as well as medication adherence rates in adolescents and young adults with CAH.MethodsProspective assessment of transition readiness was conducted through standardized questionnaires for adolescents and young adults (aged 16-35 years). Four open-ended questions on self-care were summarized in adolescents (aged 18-19 years) and their parents. Transition readiness was assessed using a modified CAH specific questionnaire: “Transition preparation and readiness to transfer from pediatric to adult care” with a cutoff level of >25 defined as good transition readiness. Measurement of QoL was performed using Rand 36. Medication adherence rate was measured using the self-reported questionnaire Adherence Starts with Knowledge.ResultsThirty-eight adolescents and young adults with CAH were included in the study. Transition readiness was classified as good in 26 (68%) of the participants. Good transition readiness was more frequent in participants with good medication adherence rates. A general linear model analysis showed a good transition readiness affected QoL by increasing QoL scores.ConclusionSelf-reported transition readiness was found in the majority of adolescents and young adults with CAH. A good medication adherence rate was associated with a better transition readiness and a good transition readiness was associated with increased QoL scores.     

Diagnosing Growth Hormone Deficiency: Can a Combined Arginine and Clonidine Stimulation Test Replace 2 Separate Tests?

ObjectiveGiven the large number of false-positive growth hormone deficiency (GHD) diagnoses from a single growth hormone (GH) stimulation test in children, 2 different pharmacologic tests, performed on separate days or sequentially, are required. This study aimed to assess the reliability and safety of a combined arginine-clonidine stimulation test (CACST).MethodsThis was a retrospective, single-center, observational study. During 2017-2019, 515 children aged >8 years underwent GH stimulation tests (CACST: n = 362 or clonidine stimulation test [CST]: n = 153). The main outcome measures used to compare the tests were GH response (sufficiency/deficiency) and amplitude and timing of peak GH and safety parameters.ResultsPopulation characteristics were as follows: median age of 12.2 years (interquartile range [IQR]: 10.7, 13.4), 331 boys (64%), and 282 prepubertal children (54.8%). The GHD rate was comparable with 12.7% for CACST and 14.4% for CST followed by a confirmatory test (glucagon or arginine) (P = .609). Peak GH was higher and occurred later in response to CACST compared with CST (14.6 ng/mL [IQR: 10.6, 19.4] vs 11.4 ng/mL [IQR: 7.0, 15.8], respectively, P < .001; 90 minutes [IQR: 60, 90] vs 60 minutes [IQR: 60, 90], respectively, P < .001). No serious adverse events occurred following CACST.ConclusionOur findings demonstrate the reliability and safety of CACST in detecting GHD in late childhood and adolescence, suggesting that it may replace separate or sequential GH stimulation tests. By diminishing the need for the second GH stimulation test, CACST saves time, is more cost-effective, and reduces discomfort for children, caregivers, and medical staff.     

Disparities in Utilization and Outcomes With Continuous Subcutaneous Insulin Infusion in Young Adults With Type 1 Diabetes

ObjectiveTo evaluate which factors determine utilization patterns and outcomes of continuous subcutaneous insulin infusion (CSII) in young adults with type 1 diabetes.MethodsUtilizing the Optum deidentified electronic health record data set between 2008 to 2018 to perform a retrospective cohort study, we identified 2104 subjects with type 1 diabetes aged 18 to 30 years. We evaluated the effect of race on determining CSII utilization, HbA1c (%), and hospital admission for diabetic ketoacidosis (DKA). Crude and adjusted estimates were computed using logistic regression and linear mixed models.ResultsThere was low CSII utilization among individuals who were Black, Hispanic, male, and those with governmental insurance. These groups also demonstrated higher HbA1c levels. Subjects who were Black, Hispanic, and those with governmental insurance had higher odds of DKA. Even when commercially insured, Black and Hispanic subjects demonstrated higher HbA1c levels, and Black individuals had higher odds of DKA.ConclusionIn a large electronic health record database in the U.S., there was low CSII utilization overall, particularly in Black and Hispanic minorities, despite CSII showing superior HbA1c control without an increase in DKA events.     

The Prevalence of Cancer and Its Relation to Disease Activity in Patients With Acromegaly: Two Centers' Experience

ObjectiveAcromegaly is characterized by increased serum concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Although animal studies have demonstrated a relationship between these hormones and cancer risk, the results of human studies evaluating cancer prevalence in acromegaly are inconsistent. We aimed to investigate the prevalence of malignant neoplasms in patients with acromegaly.MethodsCancer risk was evaluated in a cohort of 280 patients (male/female: 120/160; mean age: 50.93 ± 12.07 years) with acromegaly. Patients were categorized into 2 groups according to the presence or absence of cancer. Standard incidence ratios were calculated as compared to the general population.ResultsFrom 280 patients, cancer was diagnosed in 19 (6.8%) patients; 9 (47%) of them had thyroid cancer, which was the most common cancer type. Standard incidence ratios of all cancers were 0.8 (95% CI, 0.5-1.1) and 1.0 (95% CI, 0.8-1.3) in men and women, respectively. Compared to patients without cancer, the current age was higher in patients with cancer (59 [49-65] to 51 [42-59], P = .027). In contrast, the age at diagnosis was similar in both groups. Not only was the time to diagnosis and disease duration similar in both groups but also the basal and current GH and IGF-1 levels. The prevalence of active disease was also similar between the groups (32% to 23%, P = .394).ConclusionOur findings were not consistent with the studies suggesting that patients with acromegaly encounter an increased cancer risk. Furthermore, there were similar basal and current GH and IGF-1 levels in patients with acromegaly, both with and without cancer.     

Association Between Non-Alcoholic Fatty Liver Disease and Diabetes-Related Microvascular Complications: A Retrospective Cross-Sectional Study of Hospitalized Patients

ObjectiveOwing to limited research, the effect of nonalcoholic fatty liver disease (NAFLD) on type 2 diabetes outcomes remains unclear. This study aimed to investigate the association between NAFLD and microvascular complications in hospitalized patients with type 2 diabetes.MethodsWe included 1982 patients with type 2 diabetes. NAFLD was defined as hepatic steatosis detected by ultrasound without secondary causes of fat accumulation. The diagnosis of diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy was based on clinical medical records. Risk for advanced liver fibrosis was categorized as “low risk,” “indeterminate risk,” and “high risk,” based on the NAFLD fibrosis score (NAFLD-FS). Logistic regression was used to test the association between NAFLD, risk for advanced fibrosis, and the presence of DR, DKD, and diabetic neuropathy.ResultsThe prevalence of NAFLD was 61.3%. The presence of DR and DKD was inversely associated with NAFLD, after adjusting for covariates. The presence of DR and DKD was higher in the “indeterminate risk” and “high risk” groups than in the “low risk” group, after adjusting for the same covariates. Only the presence of DKD significantly increased with high NAFLD-FS.ConclusionThe presence of DR and DKD was inversely associated with NAFLD among hospitalized patients with type 2 diabetes. DKD was closely associated with high NAFLD-FS among patients with NAFLD.     

Metabolic Associated Fatty Liver Disease Increases the Risk of Systemic Complications and Mortality. A Meta-Analysis and Systematic Review of 12 620 736 Individuals

ObjectiveThe recent introduction of the term metabolic associated fatty liver disease (MAFLD) sought to reclassify nonalcoholic fatty liver disease (NAFLD). MAFLD is thought to improve the encapsulation of metabolic dysregulation. However, recent evidence has found significant differences between MAFLD and NAFLD, and prevailing knowledge has largely arisen from studies on NAFLD. Hence, we conducted a meta-analysis and systematic review of the outcomes associated with MAFLD.MethodsMEDLINE and Embase databases were searched for articles relating to outcomes in MAFLD. Analysis was conducted in random effects with hazard ratios (HRs) to account for longitudinal risk assessment of mortality and systemic complications.ResultsA total of 554 articles were identified, of which 17 articles were included. MAFLD resulted in an increase in the overall mortality (HR, 1.24; confidence interval [CI], 1.13-1.34), cancer-related mortality (HR, 1.27; CI, 1.01-1.54), and cardiovascular disease mortality (HR, 1.28, 1.03-1.53; P = .04) compared with non-MAFLD. MAFLD also increases the risk of cardiovascular events (HR, 1.49; CI, 1.34-1.64; P < .01), stroke (HR, 1.55; CI, 1.37-1.73; P < .01), and chronic kidney disease (HR, 1.53; CI, 1.38-1.68). The presence of MAFLD was also associated with an increased risk of heart failure, obstructive sleep apnea, and malignancy.ConclusionMAFLD can significantly elevate the risk of systemic diseases and mortality. The care of MAFLD thus requires interdisciplinary collaboration, and future clinical trials conducted on MAFLD should aim to reduce the incidence of end-organ damage aside from improving liver histology.     

The Effect and Potential Mechanism Analysis of Growth Hormone–Secreting Pituitary Adenomas on Thyroid Function

ObjectiveCurrent studies on the effect of high growth hormone (GH)/insulin-like growth factor (IGF)-1 on thyroid function are inconsistent. The aim was to explore the effect and potential mechanism of high GH/IGF-1 on thyroid function by analyzing the changes of thyroid function in patients with growth hormone–secreting pituitary adenoma (GHPA).MethodsThis was a retrospective cross-sectional study. Demographic and clinical data of 351 patients with GHPA who were first admitted to Beijing Tiantan Hospital, Capital Medical University, from 2015 to 2022 were collected to analyze the relationship between high GH/IGF-1 levels and thyroid function.ResultsGH was negatively correlated with total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH). IGF-1 was positively correlated with total triiodothyronine (TT3), free triiodothyronine (FT3), and FT4 and negatively correlated with TSH. Insulin-like growth factor–binding protein (IGFBP)-3 was positively correlated with TT3, FT3, and FT3:FT4 ratio. The FT3, TT3, TSH, and FT3:FT4 ratio of patients with GHPA and diabetes mellitus (DM) were significantly lower than those with GHPA but without DM. With the increase of tumor volume, thyroid function gradually decreased. GH and IGF-1 were correlated negatively with age in patients with GHPA.ConclusionThe study emphasized the complex interaction between the GH and the thyroid axes in patients with GHPA and highlighted the potential effect of glycemic status and tumor volume on thyroid function.     

Effect of Bisphosphonates on Fracture Incidence in Young Adults With Low Bone Density

ObjectiveTo assess the effect of bisphosphonates on fracture incidence in young adults over a 5-year follow-up period.MethodsBased on the Kaiser Permanente electronic health record, this retrospective study investigated patients aged 19 to 40 years with abnormal bone density (either any Z-score of ≤−2 standard deviation [SD] or any T-score of ≤−2.5 SD). The incidence and time to fracture between the control (patients with <6 months of bisphosphonate exposure) and treatment (patients with ≥6 months of bisphosphonate use within 4 years of their first dual energy x-ray absorptiometry scan) groups were compared. Comparisons were analyzed with Χ² test for categorical variables and Wilcoxon rank sum test for continuous variables.ResultsA total of 422 patients met the inclusion and exclusion criteria. Fractures occurred in 18 patients (5.0%) of the control group (n = 358) and 5 patients (7.8%) of the treatment group (n = 64; P = .37). T-scores were significantly lower in the treatment group (−2.53 ± 0.58 SD) than those in the control group (−2.30 ± 0.80 SD; P = .002) but did not correlate with fracture risk. No significant differences were found in total fracture incidence (hazard ratio = 1.54; 95% confidence interval, 0.26-6.26). Similarly, no correlation was noted between the length of bisphosphonate therapy and fracture incidence (odds ratio = 0.99; 95% confidence interval, 0.966-1.026).ConclusionIn summary, we did not find a clear correlation of fracture incidence with the use of bisphosphonates in young adults. Further research into the pathophysiology, specific etiologies, and treatment options in this population is needed.     

Prevalence and Characteristics of Hyperthyroidism Among Patients With Sarcoidosis in the United States

ObjectiveWe aimed to determine the prevalence and clinical characteristics of self-reported hyperthyroidism in patients with sarcoidosis.MethodsA national registry-based study investigating 3836 respondents to the Sarcoidosis Advanced Registry for Cures questionnaire in the period between June 2014 and August 2019 was conducted. This registry is generated from a web-based questionnaire that is self-reported by patients with sarcoidosis. We compared patients with sarcoidosis who had hyperthyroidism with those who did not. We used multivariate logistic regression analysis to study the association between hyperthyroidism and different cardiac manifestations in patients with sarcoidosis.ResultsThree percent of the study respondents self-reported having hyperthyroidism and were generally middle-aged Caucasian women. Compared with patients without hyperthyroidism, patients with hyperthyroidism had more sarcoidosis-related comorbidities (59% vs 43%, P = .001) and more steroid-related comorbidities (56% vs 44%, P = .01), but there was no difference in the sarcoidosis-specific treatments they received, which included corticosteroids. Patients with hyperthyroidism reported sarcoidosis involvement of the heart (26.6% vs 14.9%, P = .005), kidneys (14.9% vs 8%, P = .033) and sinuses (17.7% vs 10.2%, P = .030) more frequently. Cardiac manifestations that were more frequently reported in patients with hyperthyroidism included atrial arrhythmias (11.3% vs 6.3%, P = .046), ventricular arrhythmias (17.2% vs 7.5%, P < .001), congestive heart failure (10.4% vs 5%, P = .017), and heart block (9.4% vs 4.7%, P = .036).ConclusionHyperthyroidism is infrequent in patients with sarcoidosis but is potentially associated with different cardiac manifestations. We suggest considering routine screening for hyperthyroidism in patients with sarcoidosis, especially in those with cardiac involvement. Further studies are needed to investigate the impact of identifying and treating hyperthyroidism in patients with sarcoidosis.     

Health Benefit Costs and Absenteeism Among Employed Patients With Acromegaly

ObjectiveAcromegaly is associated with increased morbidity and mortality. Limited data are available on these patients’ utilization and costs of health care. This study assessed the impact of acromegaly on employees’ health benefit (direct and indirect) costs and absenteeism.MethodsA retrospective analysis was conducted of drug and medical claims and employer data (from January 2010 to April 2019) of patients with an acromegaly diagnosis and matched controls from a U.S. employee database. Patient claims were tracked for 12 months postdiagnosis (or matched) date. Outcomes were analyzed using separate 2-part regression models, controlling for clinical, demographic, and job-related variables.ResultsForty-seven patients with acromegaly and 940 controls were identified. Cohorts were similar in most demographic and job-related variables. Patients with acromegaly had a significantly higher Charlson comorbidity index score and higher incidence of claims for several comorbidities. Acromegaly drugs represented 16.3% of the acromegaly cohort’s total costs. Total health benefit costs were $54 821 higher (P < .05) for patients compared with controls, with direct costs representing 79.8% of the difference. Total indirect costs were higher for patients with acromegaly, with short-term and long-term disability comprising most of the difference between the acromegaly and control groups. Patients with acromegaly had significantly more short-term disability days than controls, but total sick days were similar for the 2 groups.ConclusionThe presence of acromegaly was associated with increased direct and indirect employee health benefit costs and increased work absenteeism.     

Prevalence and Clinical Determinants of Obesity in Adults With Type 1 Diabetes Mellitus: A Single-Center Retrospective Observational Study

ObjectiveTo determine the prevalence of obesity and assess the cardiometabolic risk profile and treatments associated with obesity management in the type 1 diabetes mellitus adult population.MethodsWe reviewed the records of all patients with type 1 diabetes mellitus seen in our institution’s outpatient endocrinology clinic between 2015 and 2018. We stratified the patients into 4 weight categories on the basis of body mass index (BMI) (normal, overweight, obesity class I, and combined obesity class II and III) and evaluated their associated clinical characteristics and relevant medications.ResultsOf 451 patients, 64% had a BMI of >25 kg/m², and 25% had a BMI of ≥30 kg/m². Over 40% of patients with a BMI of >30 kg/m² had a history of cardiovascular disease. The off-label use of the glucagon-like peptide 1 receptor agonist was 12% and the sodium glucose cotransporter 2 inhibitor use was 5% in those with obesity. Only 2 patients were prescribed phentermine and 3 had undergone bariatric surgery. Hemoglobin A1C and low-density lipoprotein did not significantly differ between the normal weight and obesity groups. The obesity groups had significantly higher levels of median triglycerides and lower high-density lipoprotein than the normal weight group.ConclusionObesity was prevalent in a population of patients with type 1 diabetes mellitus seen in a specialty clinic. Those with obesity had a higher prevalence of cardiovascular disease than their normal weight counterparts. The use of weight loss medications was scarce. Studies exploring the safety and efficacy of obesity-targeted therapy in the type 1 diabetes mellitus population are needed.     

Diagnostic Values of Intraoperative (1-84) Parathyroid Hormone Levels are Superior to Intact Parathyroid Hormone for Successful Parathyroidectomy in Patients With Chronic Kidney Disease

ObjectivePersistent secondary hyperparathyroidism (SHPT) may occur because of residual cervicothoracic parathyroids in parathyroidectomy (PTX) patients with chronic kidney disease. We prospectively compared the predictive values of intraoperative plasma (1-84) parathyroid hormone (PTH) and intact PTH (iPTH) levels to improve the safety and efficacy of PTX.MethodsWe included 100 healthy controls, 162 stage 5 chronic kidney disease patients without SHPT, and 214 patients who underwent PTX because of SHPT. Plasma iPTH and (1-84) PTH levels were measured before incision (io-iPTH0 and io-[1-84]PTH0, respectively) and 10 minutes (io-iPTH10 and io-[1-84]PTH10, respectively) and 20 minutes (io-iPTH20 and io-[1-84]PTH20, respectively) after removing all parathyroids. The percentage reduction of iPTH and (1-84) PTH at 10 minutes (io-iPTH10% and io-[1-84]PTH10%, respectively) and 20 minutes (io-iPTH20%, and io-[1-84]PTH20%, respectively) was calculated. iPTH and (1-84) PTH were measured using second- and third-generation PTH assays, respectively.ResultsCompared with the controls and non-PTX patients, the PTX group had more obvious mineral metabolism disorders. There were 187 successful PTXs, 19 patients with persistent SHPT, and 8 patients lost to follow-up. The receiver operating characteristic curves revealed that io-(1-84)PTH10% >86.6% and io-(1-84)PTH20% >87.5% suggested successful PTX. The sensitivity of io-iPTH20% and io-(1-84)PTH20% were higher than those at the timepoint of 10 minutes. Moreover, the specificity and sensitivity of the (1-84) PTH reduction percentage were superior to that of iPTH.ConclusionIntraoperative reduction percentages of plasma (1-84) PTH levels are superior to iPTH for accurately predicting successful PTX, especially at 20 minutes after all cervicothoracic parathyroids had been resected.     

Are We Restoring Thyroid Hormone Signaling in Levothyroxine-Treated Patients With Residual Symptoms of Hypothyroidism?

IntroductionLevothyroxine (LT4) at doses that maintain the serum thyroid-stimulating hormone levels within the normal range constitutes the standard of care for the treatment of hypothyroidism. After a few months, this eliminates the signs and symptoms of overt hypothyroidism in the majority of patients, owing to the endogenous activation of thyroxine to triiodothyronine, the biologically active thyroid hormone. Still, a small percentage of the patients (10%-20%) exhibit residual symptoms, despite having normal serum thyroid-stimulating hormone levels. These symptoms include cognitive, mood, and metabolic deficits, with a significant impairment in psychological well-being and quality of life.ObjectiveTo provide a summary of progress in the approach of patients with hypothyroidism that exhibit residual symptoms despite treatment.MethodsWe reviewed the current literature and here we focused on the mechanisms leading to a deficiency of T3 in some LT4-treated patients, the role of residual thyroid tissue and the rationale for combination therapy with LT4 + liothyronine (LT3).ResultsA score of clinical trials comparing therapy with LT4 versus LT4 + LT3 concluded that both are safe and equally effective (neither is superior); however, these trials failed to recruit a sufficiently large number of patients with residual symptoms. New clinical trials that considered LT4-treated symptomatic patients revealed that such patients benefit from and prefer therapy containing LT4 + LT3; desiccated thyroid extract has also been used with similar results. A practical approach to patients with residual symptoms and on initiation of combination therapy with LT4 + LT3 is provided.ConclusionA recent joint statement of the American, British, and European Thyroid Associations recommends that a trial with combination therapy be offered to patients with hypothyroidism that do not fully benefit from therapy with LT4.