Efficacy of Pulsatile Gonadotropin-Releasing Hormone Therapy in Male Patients: Comparison between Pituitary Stalk Interruption Syndrome and Congenital Hypogonadotropic Hypogonadism

ObjectivePulsatile gonadotropin-releasing hormone (GnRH), widely used to induce spermatogenesis in congenital hypogonadotropic hypogonadism (CHH) patients, can restore the pituitary-testis axis function in men with pituitary stalk interruption syndrome (PSIS). This retrospective study aimed to compare the differences in the long-term efficacy of pulsatile GnRH therapy on PSIS and CHH.MethodsPatients with PSIS (n = 25) or CHH (n = 64) who received pulsatile GnRH therapy for ≥3 months were included in this retrospective study. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, total testosterone, and testicular size were compared.ResultsBaseline characteristics were comparable except for the lower basal testosterone, triptorelin-stimulated peak luteinizing hormone (LH), and follicle-stimulating hormone in patients with PSIS. With similar duration of treatment and a significantly higher GnRH dose (P < .001), small increments in LH (2.82 [1.4, 4.55] vs 5.89 [3.88, 8.02] IU/L; P < .001), total testosterone (0.38 [0, 1.34] vs 2.34 [1.34, 3.66] ng/mL; P < .001), and testicular volume (5.3 ± 4.5 vs 8.8 ± 4.8 mL, P < .05) were observed. However, spermatogenesis rate (52.0% vs 70.3%, P > .05), median time of sperm appearance (14 vs 11 months, P > .05), sperm concentration, and progressive motility were comparable. Basal testicular volume (hazard ratio, 1.13; 95% CI, 1.01-1.27) and peak LH levels (hazard ratio, 1.11; 95% CI, 1.0-1.23) were predictors for early sperm appearance.ConclusionsPulsatile GnRH therapy can improve gonad function and induce spermatogenesis in men with PSIS. However, its efficacy may be inferior to that in CHH.     

Desmopressin Suppresses Gonadotropin-Induced Spermatogenesis in Patients With Pituitary Stalk Interruption Syndrome: A Retrospective,Single-Center Cohort Study

ObjectiveTo explore the influence of desmopressin on gonadotropin-induced spermatogenesis in patients with pituitary stalk interruption syndrome (PSIS).MethodsA single-center retrospective cohort study was conducted. All patients with PSIS had both gonadotropin and growth hormone (GH) deficiency. Patients were divided into desmopressin and nondesmopressin groups. The desmopressin and nondesmopressin groups were defined by the presence or absence of central diabetes insipidus, which determined whether the patient received desmopressin or not.ResultsThe average age of gonadotropin therapy was 24.3 and 26.1 in the desmopressin and nondesmopressin groups, respectively. The rate of successful spermatogenesis in the 2 groups was 31.58% and 77.27%, respectively. The period for first sperm appearance was 13.62 ± 5.95 and 13.48 ± 6.69 months, respectively. A multivariable Cox proportional hazards model found that the adjusted hazard ratio for desmopressin was 0.260, indicating a “possible” detrimental effect of desmopressin on spermatogenesis. Central diabetes insipidus would be expected to show a similar detrimental effect. The spermatogenesis rate decreased with increased dosage of desmopressin. In the nondesmopressin group, the rate of spermatogenesis was similar between the GH group and the non-GH subgroup. The GH group had higher sperm count and concentration than the non-GH group.ConclusionA minority of patients with PSIS had mild diabetes insipidus and received desmopressin therapy. The spermatogenesis rate decreased with increasing desmopressin dosage. In addition, GH supplementation did not affect the spermatogenesis rate.     

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.     

Increased Bone Mineral Density in Male Patients With Idiopathic Hypogonadotropic Hypogonadism Who Undergo Sex Hormone Therapy: Findings From Cross-Sectional and Longitudinal Studies

ObjectiveThis retrospective observational study assessed the long-term impact of pulsatile gonadotropin-releasing hormone, combined gonadotropin, or testosterone replacement therapy on total hip, femoral, and lumbar bone mineral density (BMD) and Z-scores in adult men with idiopathic hypogonadotropic hypogonadism (IHH).MethodsIn the cross-sectional study, 69 patients were allocated to untreated (n = 42) and treated (n = 27) groups. The untreated group included IHH patients without hormone therapy history, while the treated group included age- and body mass index-matched patients who had received hormone therapy for at least 5 years. The longitudinal study included 53 IHH patients, and their hip and lumbar BMDs were measured several times during hormone therapy. We then evaluated the changes in their BMD.ResultsOur cross-sectional study showed that the treated group had a significantly higher BMD and Z-score for total hip, femoral neck, and lumbar spine (P < 0.001 for all) than the untreated group, and the average bone mass even reached the age-matched normal range. The prevalence of low BMD was 80.95% and 11.11% in untreated and treated groups, respectively. In the longitudinal study (N = 53), the total hip, femoral neck, and lumbar spine BMD gradually increased during treatment. The lumbar spine showed a greater increment in BMD compared with the total hip and femoral neck (P < 0.05).ConclusionSex hormone therapy improved hip and lumbar spine BMD and Z-scores in patients with IHH. The lumbar spine showed a greater improvement in BMD compared with the total hip and femoral neck.     

Effect of Treatment of OSA With CPAP on Glycemic Control in Adults With Type 2 Diabetes: The Diabetes Sleep Treatment Trial (DSTT)

ObjectiveThe effect of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on glycemic measures in patients with type 2 diabetes (T2D) remains unclear. We aimed to determine whether CPAP treatment of OSA improves glycemic measures in patients with T2D.MethodsThis randomized controlled trial (N = 98) examined changes in glycemic measures following 12 weeks of active (n = 49) or sham (n = 49) CPAP and consideried participants’ adherence to CPAP therapy (percentage of days with ≥4 hours use and average hours/day of use).ResultsBaseline treatment groups were similar. Regarding the efficacy of active vs sham-CPAP over time, at 6 weeks, both groups had similar reductions in fructosamine (mean difference [MD], 95% confidence interval [CI]: CPAP ?13.10 [?25.49 to ?0.7] vs. sham ?7.26 [?20.2 to 5.69]; P = .519) but different in HbA1c (CPAP ?0.24 [?0.48 to ?0.003] vs sham 0.15 [?0.10 to 0.4]; P = .027). At 12 weeks, reductions in HbA1c values were similar by group (CPAP ?0.26 [?0.53 to 0.002] vs sham ?0.24 [?0.53 to 0.04]; P = .924). HbA1c reductions were associated with a greater percentage of cumulative days of CPAP usage ≥4 hours per day (b [SE] = 0.006 [0.002]; P = .013) and cumulative hours of CPAP use (b [SE] = 0.08 [0.08]; P = .012). CPAP use of ≥7 hours was associated with a significant reduction in HbA1c (b [SE] 0.54 [0.16]; P = .0012).ConclusionCPAP treatment of OSA did not result in sustained improved glycemic control compared to sham in the intent-to-treat analysis. CPAP adherence was associated with greater improvements in glycemic control.     

Bone Mineral Density in Pituitary Stalk Interruption Syndrome: The Role of Insulin-Like Growth Factor-1 and Testosterone at Different Skeletal Sites

ObjectiveThis study aimed to determine the clinical indicators influencing bone mineral density (BMD) of the lumbar spine and femoral neck in patients with pituitary stalk interruption syndrome (PSIS) who underwent multiple hormone replacement therapy (MHRT).MethodsMale patients with PSIS (n = 51) who underwent MHRT for at least 1 year were enrolled in this study. Their BMD parameters were recorded and compared with age-, weight-, and height-matched control adults. In addition, we performed multiple linear regression analysis to correlate clinical parameters with BMD parameters at 2 different sites.ResultsFifty-one patients with PSIS had a mean age of 30.39 ± 5.50 years. After 36 months of treatment, patients with PSIS who underwent MHRT had slightly lower BMD than those in the control group. Multiple linear regression models revealed a positive association between the Z-score values for the lumbar spine with treatment duration (r = 0.453, P < .001), insulin-like growth factor-1 (IGF-1) standard deviation score (SDS) values (r = 0.248, P = .038), and total testosterone level (r = 0.260, P = .036) and a positive association between the Z-score values for the femoral neck with treatment duration (r = 0.425, P < .001) and IGF-1 SDS values (r = 0.338, P = .009).ConclusionCollectively, long-term MHRT improves bone density in patients with PSIS to the normal range. A combination of recombinant human growth hormone replacement is more beneficial to the BMD than non–recombinant human growth hormone treatment. Moreover, serum IGF-1 contributes to femoral and lumbar mineralization, whereas serum testosterone plays a role in lumbar mineralization.     

Efficacy of Control-IQ Technology in a General Endocrine Clinic

ObjectiveRecent advances in technology have allowed for the expanded use of hybrid closed-loop insulin pump therapy and automated insulin delivery systems for the management of diabetes mellitus. We assessed the outcomes of introducing Tandem t:slim X2 with the Control-IQ technology in a general endocrine clinic.MethodsData from 66 adults with type 1 (n = 61) and type 2 (n = 5) diabetes mellitus were aggregated for analysis. Patients were either transitioned from traditional insulin pump therapy or multiple daily injection therapy to Tandem t:slim X2 with the Control-IQ technology from January 2020 to June 2021. The assessed clinical end points included changes in time below range, time above range, and time in target range. Changes in hemoglobin A1C before and after Control-IQ technology implementation were noted. The primary outcome was a change in time in target range with the Control-IQ technology.ResultsThere was a significant increase in time in target range when comparing pre- and post–Control-IQ technology (49.5% vs 63.3%, P < .0003) values. There was a reduction in time above range (46.8% vs 34.9%, P < .0013), a decrease in time below range (4.0% vs 1.7%, P = .017), and a decrease in hemoglobin A1C after transitioning to the Control-IQ technology (7.7% [61 mmol/mol] vs 7.1% [54 mmol/mol], P < .017). The patient dropout rate was low (7%).ConclusionThe Control-IQ technology system was effective in reducing hyperglycemia while increasing time in target range and decreasing hypoglycemia. This technology is a useful and effective addition to the growing number of automated insulin delivery systems. The clinical outcomes mirror the results found in the key adult pivotal trials.     

Comparison of the Subcutaneous and Intramuscular Estradiol Regimens as Part of Gender-Affirming Hormone Therapy

ObjectiveGender-affirming hormone therapy guidelines describe the estradiol (E2) doses for intramuscular (IM), but not subcutaneous (SC), routes. The objective was to compare the SC and IM E2 doses and hormone levels in transgender and gender diverse individuals.MethodsThis is a retrospective cohort study at a single-site tertiary care referral center. Patients were transgender and gender diverse individuals who received injectable E2 with at least 2 E2 measurements. The main outcomes were the dose and serum hormone levels between the SC and IM routes.ResultsThere were no statistically significant differences in age, body mass index, or antiandrogen use between patients on SC (n = 74) and those on IM (n = 56). The weekly doses of SC E2, 3.75 mg (IQR, 3-4 mg), were statistically significantly lower than those of IM E2, 4 mg (IQR, 3-5.15 mg) (P =.005); however, the E2 levels achieved were not significantly different (P =.69), and the testosterone levels were in the cisgender female range and not significantly different between routes (P =.92). Subgroup analysis demonstrated significantly higher doses in the IM group when the E2 and testosterone levels were >100 pg/mL and <50 ng/dL, respectively, with the presence of the gonads or use of antiandrogens. Multiple regression analysis demonstrated that the dose was significantly associated with the E2 levels after adjusting for injection route, body mass index, antiandrogen use, and gonadectomy status.ConclusionBoth the SC and IM E2 achieve therapeutic E2 levels without a significant difference in the dose (3.75 vs 4 mg). SC may achieve therapeutic levels at lower doses than IM .     

Type 1 Diabetes Mellitus and Lipohypertrophy - Impact of the Intervention on Glycemic Control via Patient’s Examination and Retraining on Change of Infusion Set

ObjectiveLipohypertrophy (LH) is a common complication of insulin therapy in type 1 diabetes mellitus (T1DM). We examined whether an intervention consisting of LH assessment and retraining on insulin infusion set use improves glycemic control on subcutaneous insulin infusion (CSII) in patients with T1DM.MethodsThe intervention was conducted in 79 consecutive patients with T1DM. Data on glucose levels, glycated hemoglobin (HbA1c), and insulin doses were collected at baseline and after a median of 22 weeks (20-31.75 weeks).ResultsA total of 46 patients with T1DM (23 [50%] women) participating in the follow-up were characterized by a median age of 29 years (25-33.8 years), body mass index of 24.6 ± 3.3 kg/m², T1DM duration of 16.5 years (8.3-20 years), and subcutaneous insulin infusion duration of 7 years (4-10.8 years). Patients’ median HbA1c fell from 7.4% (6.7%-8.2%) to 7.05% (6.4%-7.6%) (P < .001), daily insulin dose/kg decreased (0.7 ± 0.20 vs 0.68 ± 0.15 IU/kg; P = .017) together with the total daily insulin dose (50.3 [40.5-62.7] vs 47.6 [39.8-62.1] IU; P = .019]. Furthermore, the percentage of basal insulin dose increased (43.0% [36-50] vs 44.0% [39.0-50.0]; P = .010], whereas the percentage of bolus dose decreased (57% [50-64] vs 56% [50-61], P = .010).ConclusionsThe structured LH-related intervention in patients with T1DM on insulin pumps resulted in better glycemic control and a decrease in total daily insulin dose.     

COVID-19 May Increase the Risk of Insulin Resistance in Adult Patients Without Diabetes: A 6-Month Prospective Study

ObjectiveDuring the coronavirus disease 2019 (COVID-19) pandemic, exploring insulin resistance and beta-cell activity is important for understanding COVID-19‒associated new-onset diabetes. We assessed insulin sensitivity and fasting insulin secretion in patients with COVID-19 without diabetes on admission and at 3 and 6 months after discharge.MethodsThis 6-month prospective study assessed data from the records of 64 patients without diabetes diagnosed with COVID-19 at Wenzhou Central Hospital, China. Each patient was followed up at 3 and 6 months after discharge. Repeated measures analysis of variance was used to investigate differences in multiple measurements of the same variable at different times. Linear regression analysis was performed to analyze the contributor for changes in the triglyceride-glucose (TyG) index.ResultsFasting C-peptide levels in patients at baseline were lower than the normal range. Compared with the baseline results, patients had significantly elevated fasting C-peptide levels (0.35 ± 0.24 vs 2.36 ± 0.98 vs 2.52 ± 1.11 μg/L; P < .001), homeostasis model assessment for beta-cell function (0.42, interquartile range [IQR] 0.36-0.62 vs 2.54, IQR 1.95-3.42 vs 2.90, IQR 2.02-4.23; P < .001), and TyG indices (8.57 ± 0.47 vs 8.73 ± 0.60 vs 8.82 ± 0.62; P = .006) and decreased fasting glucose levels (5.84 ± 1.21 vs 4.95 ± 0.76 vs 5.40 ± 0.68 mmol/L; P = .003) at the 3- and 6-month follow-up. Male gender, age, interferon-alfa treatment during hospitalization, and changes in total cholesterol and high-density lipoprotein levels were significantly associated with changes in the TyG index.ConclusionOur study provided the first evidence that COVID-19 may increase the risk of insulin resistance in patients without diabetes.     

Premature ventricular contractions in patients with an implantable cardioverter defibrillator cardiac resynchronization therapy device: Results from the UMBRELLA registry

BackgroundPremature ventricular contractions (PVC) are known to reduce the percentage of biventricular (BiV) pacing in patients with cardiac resynchronization (CRT), decreasing the clinical response. The aim of this study was to evaluate the prevalence of a high PVC burden, as well as therapeutic action (pharmacotherapy, catheter ablation or device programming), in a large CRT implantable-defibrillator (CRT-D) population.MethodsPatients with a CRT-D device from the UMBRELLA multicenter prospective remote monitoring registry were included. The PVC count was collected from each remote monitoring transmission. Patients were divided into two high (≥1 transmission ≥200/≥400 PVC/h, respectively) and one low (all transmissions <200 PVC/h) PVC count groups. The PVC burden following a high PVC count transmission was calculated.ResultsOf 1268 patients, 135 (11%) and 43 (3.4%) presented high PVC count (≥200/≥400 PVC/h, respectively). The majority of patients in the high PVC groups were not treated (61 [79%] and 32 [74%], respectively. Considering the untreated patients in the high PVC groups, median PVC/h was 199 (interquartile range [IQR]: 196) and 271 (IQR: 330), respectively. The PVC burden (proportion of time with PVC/h ≥ 200/≥400) was 40% (IQR 70) and 29% (IQR 59), respectively.ConclusionA significant proportion of CRT-D patients presented a high PVC count, however, few received treatment. In the untreated patients with a high PVC count, the PVC burden during follow-up varied substantially. Several consecutive recordings of a high PVC count should be warranted before considering therapeutic action such as catheter ablation.     

Correlation Between Hemoglobin Glycation Index Measured by Continuous Glucose Monitoring With Complications in Type 1 Diabetes

ObjectiveHbA1C is the “gold standard” parameter to evaluate glycemic control in diabetes; however, its correlation with mean glucose is not always perfect. The objective of this study was to correlate continuous glucose monitoring (CGM)-derived hemoglobin glycation index (HGI) with microvascular complications.MethodsWe conducted a cross-sectional study including permanent users of CGM with type 1 diabetes mellitus or latent autoimmune diabetes of the adult. HGI was estimated, and presence of microvascular complications was compared in subgroups with high or low HGI. A logistic regression analysis to assess the contribution of high HGI to chronic kidney disease (CKD) was performed.ResultsIn total, 52 participants who were aged 39.7 ± 14.7 years, with 73.1% women and 15.5 years (IQR, 7.5-29 years) since diagnosis, were included; 32.7% recorded diabetic retinopathy, 25% CKD, and 19.2% neuropathy. The median HbA1C was 7.6% (60 mmol/mol) and glucose management indicator (GMI) 7.0% (53 mmol/mol). The average HGI was 0.55% ± 0.66%. The measured HbA1C was higher in the group with high HGI (8.1% [65 mmol/mol] vs 6.9% [52 mmol/mol]; P < .001), whereas GMI (7.0% [53 mmol/mol] vs 7.0% [53 mmol/mol]; P = .495) and mean glucose were similar in both groups (153 mg/dL vs 153 mg/dL; P = .564). In the high HGI group, higher occurrence of CKD (P = .016) and neuropathy were observed (P = .025). High HGI was associated with increased risk of CKD (odds ratio [OR]: 5.05; 95% CI: 1.02-24.8; P = .04) after adjusting for time since diagnosis (OR: 1.09; 95% CI: 1.02-1.16; P = .008).ConclusionHigh HGI measured by CGM may be a useful marker for increased risk of microvascular diabetic complications.     

Parathyroidectomy Is Associated With Reversed Nondipping Heart Rate That Impacts Mortality in Chronic Kidney Disease Patients

ObjectiveNondipping heart rate (HR), defined as a night/day HR ratio >0.90, has been associated with increased mortality in epidemiologic studies. However, its prognostic value in stage 5 chronic kidney disease (CKD5) patients and the effects of parathyroidectomy (PTX) on nondipping HR remain unknown.MethodsThis case-control study of 162 healthy controls and 502 CKD5 patients was performed between 2011 and 2018, in which CKD5 patients were further divided into non-PTX (n = 186) and severe secondary hyperparathyroidism (SHPT) with PTX (n = 316) subgroups. Each participant underwent 24-hour Holter monitoring for HR ratio. Mortality was followed up in CKD5 patients (median time: 46.0 months).ResultsThe HR ratio in CKD5 patients was higher than in controls (0.92 ± 0.08 vs 0.81 ± 0.08, P <.001), associated with a 44% increase in mortality risk per 0.1 increment (hazard ratio, 1.44; 95% CI: 1.02-2.03; P =.04), and was positively related to serum intact parathyroid hormone levels (P <.001). PTX reversed nondipping HR in SHPT patients (n = 50, median time: 6.3 months, P <.001). Survival probabilities for PTX (n = 294) were better than non-PTX (n = 47) (hazard ratio, 0.31; 95% CI: 0.14-0.67; P <.01) in SHPT patients (serum intact parathyroid hormone >500.0 pg/mL).ConclusionCKD5 patients displayed a nondipping HR pattern, which is a prognostic marker of all-cause mortality. PTX for SHPT patients was associated with a reversal in nondipping HR ratio, which may mediate a better outcome.     

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.     

Decreased Mortality After Long-Term Treatment With Dipeptidyl Peptidase-4 Inhibitors: A Retrospective Study of U.S. Veterans With Type 2 Diabetes

ObjectiveThe prevalence of chronic kidney disease (CKD) in the United States is 13% of the general population. Among those with CKD, diabetic nephropathy is the leading cause of end-stage renal disease. This is a retrospective study examining the effect of long-term use of dipeptidyl peptidase-4 (DPP-4) inhibitors on all-cause mortality and progression of renal disease in the veteran population.MethodsData was extracted using the Veterans Administration Informatics and Computing Infrastructure. A large cohort of veterans diagnosed with type 2 diabetes mellitus were used to identify patients on DPP-4 inhibitors and without DPP-4 inhibitors. Groups were compared to determine the effect of DPP-4 inhibitors on the progression of CKD and all-cause mortality. Data were analyzed using SAS.ResultsSubjects in the treatment group (n = 40 558) had baseline variables (age, body mass index, race) similar to the control group (n = 40 558). Diabetes control improved in the treatment group (HgbA1c, 8.3% [67 mmol/mol] to 7.8% [62 mmol/mol]; P < .001) but not in the control group (HgbA1c, 7.4% [57 mmol/mol] to 7.3% [56 mmol/mol]). New diagnoses of heart failure and coronary artery bypass grafts were clinically significant (odds ratios = 0.66 and 0.52). No change in progression of CKD was seen in either group. All-cause mortality was reduced by 59%.ConclusionWe conclude that DPP-4 inhibitors are associated with a significant reduction in all-cause mortality independent of glucose control, albeit with no clear cause, including obtainable cardiovascular outcomes. Our data is consistent with prior trials in that DPP-4 inhibitors did not show a significant change in serum creatinine or microalbuminuria.     

Low Diagnostic Utility of Overnight High-Dose Dexamethasone Suppression Test in ACTH-Dependent Cushing’s Syndrome

ObjectiveOvernight high-dose dexamethasone suppression test (ON-HDDST) is a simple test to localize the source of ACTH in patients with ACTH-dependent Cushing’s syndrome (CS). However, previous studies have reported its varying accuracy. We studied the utility of ON-HDDST in diagnosing Cushing’s disease (CD) in a series of patients with CD and ectopic ACTH syndrome (EAS).MethodsWe conducted a retrospective study of 88 patients with ACTH-dependent CS (plasma ACTH > 20.0 pg/mL), who underwent an ON-HDDST. CD and EAS were diagnosed in 68 and 20 patients, respectively. Patients were investigated using MRI of the sellar region, CT of the thorax/abdomen, Gallium-68-DOTANOC PET scan, and bilateral inferior petrosal sinus sampling as required.ResultsPatients with EAS had a significantly higher serum cortisol after ON-HDDST than patients with CD (median [IQR], 19.9 [12.4-31.1] μg/dL vs 9.9 [5.1-25.0] μg/dL, P <.01). A suppressed ON-HDDST (≥50% fall from baseline) was noted in 44 (65%) patients with CD and 3 (15%) patients with EAS (P <.0001). Among patients with CD, cortisol suppression >50% was noted in 35 (76%) of patients with microadenoma and 7 (44%) with macroadenoma. Among patients with EAS, ON-HDDST was suppressed in 1 of 6 patients (17%) with an occult tumor and 2 of 14 patients (14%) with a localized tumor. The ROC curve plotted for the percentage suppression of cortisol had an area under the curve (AUC) of 0.72 (P =.01). The best test parameters, with 65% sensitivity, 85% specificity, 94% positive predictive value, 42% negative predictive value, and 69% accuracy, were at 50% cutoff level.ConclusionThe ON-HDDST had a poor diagnostic value in differentiating CD and EAS.     

Preconception Vitamin D Level and In Vitro Fertilization: Pregnancy Outcome

ObjectiveVitamin D deficiency impairs female fertility and the success of in vitro fertilization (IVF). The recommended serum 25-hydroxyvitamin D (25(OH)D) level in IVF-conceived pregnancies is still debated. We aimed to explore the relationship of the preconception serum 25(OH)D level with pregnancy outcome following IVF treatment. We also explored the utility of the currently recommended serum 25(OH)D cutoff of ≥50 nmol/L for women undergoing IVF therapy.MethodsRetrospective cohort of women who had undergone IVF therapy. Of the women who started IVF therapy (n = 354), 218 completed the study. They were divided into 2 groups: (1) women who achieved a successful pregnancy (pregnant group, n = 160) and (2) those who did not achieve a successful pregnancy (nonpregnant group, n = 58). Preconception serum samples were analyzed for reproductive hormones, fasting glucose, insulin, and 25(OH)D levels.ResultsOverall, the median (interquartile range) age, body mass index, and hemoglobin A1c level were 32 (6) years, 25.7 (7.4) kg/m², and 5.2% (0.6%), respectively. The 25(OH)D level was significantly higher at preconception in the pregnant group (56.4 [21.4] vs 47.9 [29.16] for nonpregnant, P = .001). The preconception 25(OH)D level was a significant predictor of IVF outcome (B = 0.04; 95% CI, 1.01-1.06; P = .001), with greater IVF success associated with a serum 25(OH)D level of ≥50 nmol/L (odds ratio, 0.46; P = .01).ConclusionPreconception 25(OH)D sufficiency (≥50 nmol/L) is associated with successful pregnancy outcome following IVF therapy.     

Influence of Levothyroxine With Recombinant Human Thyroid-Stimulating Hormone on Urinary Iodine Excretion Before Radioactive Iodine Administration

ObjectiveStimulation with recombinant human thyroid-stimulating hormone (rhTSH) before radioactive iodine administration for patients with thyroid cancer may increase the body iodine pool in the presence of continued levothyroxine; however, the precise significance of its influence remains unclear.MethodsThis was a prospective observational study conducted between March 2017 and August 2020. We measured the 24-hour urinary iodine excretion and urinary iodine-to-creatinine ratio in patients with thyroid cancer stimulated by rhTSH or thyroid hormone withdrawal (THW) before radioactive iodine administration. Oral iodine intake was controlled by a 7-day self-managed low iodine diet, followed by a strict 3-day low iodine diet while in the hospital.ResultsOverall, 343 subjects were included (rhTSH: n = 181; THW: n = 162). The mean levothyroxine dose in the rhTSH group was 115.2 μg daily. The median 24-hour urinary iodine and urinary iodine-to-creatinine ratio in the rhTSH group (71.0 [interquartile range, 57.5-88.0] μg/day and 80.0 [59.0-97.5] μg/gCr, respectively) were significantly higher than those in the THW group (42.0 [30.0-59.0] μg/day and 39.0 [28.0-61.3] μg/gCr, respectively; both P < .001). After propensity score matching by age, sex, body weight, and renal function (rhTSH: n = 106; THW: n = 106), consistent results for both values were observed for both methods. The increase in urinary iodine with the rhTSH method was smaller than the expected value calculated from the amount of levothyroxine.ConclusionUrinary iodine excretion was significantly higher among patients with rhTSH stimulation than those with THW, indicating that the rhTSH method slightly increases the body iodine pool.     

Nordic Walking Improves Cardiometabolic Parameters,Fitness Performance,and Quality of Life in Older Adults With Type 2 Diabetes

ObjectiveTo assess the effect of Nordic walking (NW) on cardiometabolic health, physical performance, and well-being in sedentary older adults with type 2 diabetes (T2D).MethodsFifteen subjects with T2D (female, 5; male, 10; age, 65 ± 6.2 years [mean ± standard deviation]; body mass index, 27.3 ± 4.9 kg/m² [mean ± standard deviation]) were enrolled in a 6-month NW training program. The fasting glucose and glycosylated hemoglobin levels, lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), systolic blood pressure (SBP), and diastolic blood pressures were measured before and after the intervention. Participants’ quality of life (Short-Form Health Survey) and physical fitness (6-minute walking test) were also evaluated.ResultsCompared with baseline, NW significantly improved the fasting glucose level (103.5 ± 18.5 vs 168.7 ± 37.7 mg/dL, P = .01), SBP (121.8 ± 12.2 vs 133 ± 14.4 mm Hg, P = .02), physical fitness (759.88 ± 69 vs 615.5 ± 62.6 m, P < .001), and both mental health (54.5 ± 4.4 vs 45.7 ± 5.6, P < .01) and physical health (49.8 ± 4.7 vs 40.3 ± 5.9, P < .01). The levels of glycosylated hemoglobin (6.15% ± 0.8% vs 6.4% ± 1%, P = .46), total cholesterol (162.2 ± 31.2 vs 175.5 ± 28.8 mg/dL, P = .13), low-density lipoprotein cholesterol (95.2 ± 24.2 vs 106.3 ± 32.3 mg/dL, P = .43), and triglycerides (135.5 ± 60.8 vs 127.6 ± 57.4 mg/dL, P = 0.26) improved without reaching significance.ConclusionNW training improved the glycemic levels, SBP, physical fitness, and perception of quality of life in older adults with T2D. NW represents a suitable complementary strategy to improve the global health status in this population.