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.     

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.     

Revisiting Cushing Syndrome,Milder Forms Are Now a Common Occurrence: A Single-Center Cohort of 76 Subjects

ObjectiveGuidelines recommend initiating testing for Cushing syndrome (CS) based on strong clinical suspicion. Our recent experience suggests the absence of classical stigmata in the majority of patients with CS. We aimed to confirm this premise by revisiting the clinical features of this syndrome in a modern series of patients from a single center.MethodsComputerized records of subjects with CS diagnosed at Tel Aviv Sourasky Medical Center between 2000 and 2018 were reviewed. A Cushing inventory score, including all clinical components of the syndrome, was computed for each subject. Data were compared between the subtypes and evaluated in light of those in the literature.ResultsOf the 76 subjects with CS (60 women/16 men), 49 (64.5%) had Cushing disease; 16 (21.1%), adrenal adenoma; 7 (9.2%), adrenocortical carcinoma; and 4 (5.3%), ectopic adrenocorticotropic hormone secretion. In only 15 of 74 cases (20.3%), clinical suspicion of CS led to testing. Catabolic signs of CS were present in less than 30% of cases. The most common symptom was weight gain (52/67, 77.6%), and the most common comorbidity was hypertension (47/76, 61.8%). There were no differences in the Cushing inventory score between the subtypes. Signs, symptoms, and comorbidities were all significantly less common than in the classical syndrome.ConclusionsModern-day CS presents with subtler features than in the past. Initiating a testing cascade solely based on a strong clinical suspicion may lead to underdiagnosis of milder cases. A concerted effort to devise cost-efficient testing for CS in the current era is needed.     

Thionamide-induced Agranulocytosis: A Retrospective Analysis of 36 Patients With Hyperthyroidism

ObjectiveAgranulocytosis is a rare but serious adverse drug reaction (ADR) of thionamide antithyroid drugs (ATDs). We explored the characteristics of ADRs in patients with hyperthyroidism.MethodsThis retrospective study included 3558 inpatients with Graves disease treated in a Class A Grade 3 hospital between 2015 and 2019. The clinical presentation and laboratory workup of patients with antithyroid drug (ATD)-induced agranulocytosis was analyzed.ResultsAgranulocytosis was thought to be caused by ATDs in 36 patients. The hospital length of stay was 12 (10-16) days, and hospitalization costs were approximately $2810.89 ($2156.50-$4164.67). The median duration of ATD therapy prior to agranulocytosis development was 30 (20-40) days. Fever (83.33%) and sore throat (75%) were the most common symptoms as early signs of agranulocytosis. The lowest neutrophil counts were 0.01 (0.00-0.03) × 10⁹/L and 0.14 (0.02-0.29) × 10⁹/L in the methimazole and propylthiouracil groups, respectively (P = .037). The recovery times of agranulocytosis were 9.32 ± 2.89 days and 5.60 ± 4.10 days in the methimazole and propylthiouracil groups, respectively (P = .016). Patients with severe agranulocytosis required a longer time to recover (P < .001) and had closer to normal serum thyroxine and triiodothyronine levels. The interval between the first symptom of agranulocytosis and ATD withdrawal was 1 (0-3) day.ConclusionsPatients with agranulocytosis needed a long hospital length of stay and incurred high costs. Methimazole was prone to causing a more serious agranulocytosis than propylthiouracil. High thyroid hormone was unlikely to play a role in adverse drug reactions. Patient education is important.     

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.     

Serum Hormone Concentrations in Transgender Individuals Receiving Gender-Affirming Hormone Therapy: A Longitudinal Retrospective Cohort Study

ObjectiveTo examine the association of various gender-affirming hormone therapy regimens with blood sex hormone concentrations in transgender individuals.MethodsThis retrospective study included transgender people receiving gender-affirming hormone therapy between January 2000 and September 2018. Data on patient demographics, laboratory values, and hormone dose and frequency were collected. Nonparametric tests and linear regression analyses were used to identify factors associated with serum hormone concentrations.ResultsOverall, 196 subjects (134 transgender women and 62 transgender men), with a total of 941 clinical visits, were included in this study. Transgender men receiving transdermal testosterone had a significantly lower median concentration of serum total testosterone when compared with those receiving injectable preparations (326.0 ng/dL vs 524.5 ng/dL, respectively, P = .018). Serum total estradiol concentrations in the transgender women were higher in those receiving intramuscular estrogen compared with those receiving oral and transdermal estrogen (366.0 pg/mL vs 102.0 pg/mL vs 70.8 pg/mL, respectively, P < .001). A dose-dependent increase in the hormone levels was observed for oral estradiol (P < .001) and injectable testosterone (P = .018) but not for intramuscular and transdermal estradiol. Older age and a history of gonadectomy in both the transgender men and women were associated with significantly higher concentrations of serum gender-affirming sex hormones.ConclusionIn the transgender men, all routes and formulations of testosterone appeared to be equally effective in achieving concentrations in the male range. The intramuscular injections of estradiol resulted in the highest serum concentrations of estradiol, whereas transdermal estradiol resulted in the lowest concentration. There was positive relationship between both oral estradiol and injectable testosterone dose and serum sex hormone concentrations in transgender people receiving GAHT.     

Risk of Breast Cancer in Females With Hypothyroidism: A Nationwide,Population-Based,Cohort Study

ObjectivesThe results of studies investigating the relationship between breast cancer and hypothyroidism vary greatly from study to study. In this study, we analyzed a large and reliable, population-based database to gain a better understanding of the correlation.MethodsThis retrospective cohort study analyzed patients with hypothyroidism between January 1, 2000 and December 31, 2012 (hypothyroidism cohort) from the Longitudinal Health Insurance Database 2000 in Taiwan. For each woman with hypothyroidism, 1 woman without a history of breast cancer was randomly selected from the Longitudinal Health Insurance Database 2000 and frequency matched (1:4) with women without hypothyroidism by age and index year of hypothyroidism. The study outcome was the diagnosis of breast cancer during a 12-year follow-up period.ResultsIn this study, 6665 women with hypothyroidism and 26 660 women without hypothyroidism were identified. The hypothyroidism cohort had a significantly higher risk of breast cancer than the nonhypothyroidism cohort (adjusted hazard ratio [aHR] 1.69 [95% CI, 1.15-2.49]; P = .01), especially in the group aged 40 to 64 years (aHR 2.07 [95% CI, 1.32-3.23]; P = .01). Women in the hypothyroidism cohort taking levothyroxine for a duration ˃588 days showed a significantly decreased risk of breast cancer (aHR 0.37 [95% CI, 0.19-0.71]; P = .003).ConclusionWomen with hypothyroidism are at a higher risk of breast cancer than those without hypothyroidism. Levothyroxine may reduce the risk of breast cancer in a woman with hypothyroidism.     

COVID-19 Outcomes of Patients With Differentiated Thyroid Cancer: A Multicenter Los Angeles Cohort Study

ObjectiveCancer may be a risk factor for worse outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections. However, there is a significant variability across cancer types in the extent of disease burden and modalities of cancer treatment that may impact morbidity and mortality from coronavirus disease-19 (COVID-19). Therefore, we evaluated COVID-19 outcomes in patients with a differentiated thyroid cancer (DTC) history.MethodsThis is a retrospective cohort study of patients with a history of DTC and SARS-CoV2 infection from 2 academic Los Angeles healthcare systems. Demographic, thyroid cancer, and treatment data were analyzed for associations with COVID-19 outcomes.ResultsOf 21 patients with DTC and COVID-19, 8 (38.1%) were hospitalized and 2 (9.5%) died from COVID-19. Thyroid cancer initial disease burden and extent, treatment, or current response to therapy (eg, excellent vs incomplete) were not associated with COVID-19 severity in DTC patients. However, older age and the presence of a comorbidity other than DTC were significantly associated with COVID-19 hospitalization (P = .047 and P = .024, respectively). COVID-19–attributed hospitalization and mortality in DTC patients was lower than that previously reported in cancer patients, although similar to patients with nonthyroid malignancies in these centers.ConclusionThese data suggest that among patients with DTC, advanced age and comorbid conditions are significant contributors to the risk of hospitalization from SARS-CoV2 infection, rather than factors associated with thyroid cancer diagnosis, treatment, or disease burden. This multicenter report of clinical outcomes provides additional data to providers to inform DTC patients regarding their risk of COVID-19.     

The Importance of Periodical Screening for Primary Hyperparathyroidism in a Pituitary Tumor Cohort in Searching Patients With MEN1 and Its Genetic Profile

ObjectiveMultiple endocrine neoplasia type 1 (MEN1) is a rare genetic syndrome characterized by parathyroid, anterior pituitary, and/or duodenopancreatic neuroendocrine tumors. Studies have indicated that investigating primary hyperparathyroidism (pHPT) with subsequent genetic screening may be an essential tool for the early diagnosis of MEN1 in patients with pituitary tumors (PTs). This study aimed to investigate the presence of pHPT in patients with PTs and, subsequently, to screen for genetic mutations and related tumors in patients with MEN1 syndrome.MethodsThis study included 255 patients with PTs who were assessed for the presence of MEN1 by serum calcium and parathyroid hormone measurements. Mutation screening of the MEN1, CDKN1B, and AIP genes was performed in the index cases showing the MEN1 phenotype.ResultsFive patients with PTs presented a clinical condition compatible with MEN1. These patients had a younger age of onset and a more severe clinical condition. Genetic analysis identified a frameshift mutation in the MEN1 gene in one of the cases with the MEN1 phenotype, but point mutations in CDKN1B and AIP were not detected in any of these patients.ConclusionOur results show that periodic screening for pHPT in patients with PTs may be useful to detect MEN1 syndrome; thus, it is recommended in those patients with both findings a genetic analysis of MEN1 gene and an additional search of related tumors. By contrast, our data suggest that CDKN1B and AIP mutations do not seem to play a relevant role in the pathogenesis of MEN1.     

Insulin Requirements in Patients With Type 2 Diabetes Undergoing Bariatric Surgery in the Inpatient Setting and Upon Discharge: A Single-Center Retrospective Analysis of Insulin Management Strategies

ObjectiveRapid improvement in blood glucose (BG) after weight-loss surgery (WLS) can make postoperative glucose management challenging in patients with type 2 diabetes mellitus (T2DM). Our study examined the safety and efficacy of insulin management strategies during hospitalization and after discharge following WLS.MethodsThis single-center retrospective cohort study included 160 adult patients with type 2 diabetes mellitus undergoing WLS. Patients with glycated hemoglobin A1C (HbA1C) level <7% (53 mmol/mol) and not on antihyperglycemic medications or metformin monotherapy were excluded. BG and insulin dosing during hospitalization and at 2-week follow-up, and impact of preoperative HbA1C level were analyzed.ResultsMean age was 46.3 years. Median preoperative HbA1C level was 8% (64 mmol/mol). Postoperatively, most patients received basal insulin plus sliding-scale insulin (SSI; 79/160, 49%) or SSI alone (77/160, 48%). The initial postoperative basal dose was 0.23 units/kg/day. The median basal insulin dose at discharge was 61% lower than preoperative dose. At 2-week follow-up, 34 of 44 patients (77%) had BG levels between 70-200 mg/dL and 1 of 44 (2.2%) had BG levels >200 mg/dL, with no hypoglycemia. Patients with HbA1C level >9% (75 mmol/mol) had higher BG on admission and during hospitalization, required higher insulin doses while hospitalized, and were more frequently discharged on insulin.ConclusionSSI is effective in managing BG in some patients immediately after WLS. However, about half of the patients may require basal insulin at doses similar to those required by other inpatients. Preoperative hyperglycemia may affect inpatient insulin needs and BG. Low-dose basal insulin appears safe and effective upon discharge for select patients.     

Efficacy and Safety of Analog Insulin in Comparison With Human Insulin for Hyperglycemia in Hospitalized Patients With Acute Stroke: A Randomized,Open-Label,Single-Center Trial

ObjectiveTo assess the efficacy and safety of analog insulins in comparison with human insulins for hyperglycemia in hospitalized patients with acute stroke.MethodsIn this single-center, open-label, randomized trial, 102 patients (age 59.4 ± 11.7 years, 54 women) admitted with acute stroke (52 ischemic, 50 hemorrhagic) and hyperglycemia were assigned to analog insulin (n = 52) or human insulin (n = 50) group during February to June 2021. Insulin was initiated and titrated according to the predefined standard protocol. The capillary blood glucose (BG) level was monitored by standardized glucometers. The primary outcomes were mean daily BG and the number of hypoglycemic events.ResultsBetween the 2 treatment groups, there was no significant difference in the mean daily BG (P >.05 for all days) or in the frequency of hypoglycemic episodes (P =.727). Four participants experienced severe hypoglycemia; all were receiving human insulin (P =.054). In the analog insulin group, there was a tendency toward lower daily total requirement for insulin (P =.053). The difference in bolus insulin dose was significantly lower in the analog insulin group (P =.029), but the difference in basal insulin dose was similar (P =.167). Between the 2 groups, there were no significant differences in the hospital mortality rate, modified Rankin Scale score on outcome, or length of hospital stay (P =.729,.658, and.918, respectively).ConclusionHospitalized patients acute stroke and hyperglycemia exhibited similar mean BG but a trend of lower incidence of severe hypoglycemia when treated with analog insulins in comparison with human insulin.     

The Risk Factors for Developing Clustered Vertebral Compression Fractures: A Single-Center Study

ObjectiveVertebral compression fractures (VCFs) are common among elderly individuals, but clustered VCFs (C-VCFs) are rare and more severe. The risk factors for C-VCFs remain unclear. Thus, we investigated the clinical characteristics of C-VCFs to identify the imminent fracture risk and improve the treatment for such patients.MethodsWe reviewed the records of patients with VCF at a single medical center between January 2011 and September 2020. Patients who had 4 or more VCFs within 1 year were categorized into the C-VCF group, and the remaining patients were paired into the control group at a ratio of 2:1. We collected demographic, clinical, laboratory, and radiologic information regarding these patients. Univariate analyses, stratified analyses, and multivariate logistic regression were performed to identify the risk factors for C-VCFs.ResultsA total of 156 patients were enrolled, of whom 52 were patients with C-VCF. Patients with C-VCF had more severe fractures and pain, with fractures occurring at uncommon sites of the spine. The independent risk factors for C-VCFs included glucocorticoid (GC) treatment (P < .001; hazard ratio [HR], 12.7), recent fracture history (P = .021; HR, 5.5), and lower trabecular bone score (TBS) (P = .044; HR, 1.6). TBS and bone mineral density had greater predictive values in patients without GC treatment (P < .001). Sex, age, and bone turnover biomarkers were not independent risk factors for C-VCFs.ConclusionC-VCFs are rare adverse consequences of severe osteoporosis, for which GC treatment, recent fracture history, and lower TBS are unique risk factors that are valuable for the early identification and prevention of C-VCFs.     

Sick Euthyroid Syndrome on Presentation of Patients With COVID-19: A Potential Marker for Disease Severity

ObjectivePrecise risk stratification and triage of coronavirus disease 2019 (COVID-19) patients are essential in the setting of an overwhelming pandemic burden. Clinical observation has shown a somewhat high prevalence of sick euthyroid syndrome among patients with COVID-19. This study aimed to evaluate the predictive value of free triiodothyronine (FT3) at the clinical presentation of COVID-19 for disease severity and death.MethodsThis retrospective cohort study was based on electronic medical records. The study was conducted at Sheba Medical Centre, a tertiary hospital where several acute and chronic wards have been dedicated to the treatment of patients with COVID-19. The primary outcome measure was death during hospitalization; secondary outcomes included hospitalization in intensive care, mechanical ventilation, and length of hospitalization.ResultsOf a total of 577 polymerase chain reaction-positive patients with COVID-19 hospitalized between February 27 and July 30, 2020, 90 had at least 1 measurement of thyroid-stimulating hormone, free thyroxine, and FT3 within 3 days of presentation. After applying strict exclusion criteria, 54 patients were included in the study. Patients in the lowest tertile of FT3 had significantly higher rates of mortality (40%, 5.9%, and 5.9%, P = .008), mechanical ventilation (45%, 29.4%, and 0.0%; P = .007) and intensive care unit admission (55%, 29.4%, and 5.9%, P = .006). In multivariate analyses adjusted for age, Charlson comorbidity index, creatinine, albumin, and white blood cell count. FT3 remained a significant independent predictor of death.ConclusionFT3 levels can serve as a prognostic tool for disease severity in the early presentation of COVID-19.     

Personalized Medical Treatment of Patients With Acromegaly: A Review

Acromegaly is associated with significant morbidity and mortality if it is not appropriately treated. In addition to insulin-like growth factor 1 and growth hormone normalization as well as tumor shrinkage, the treatment goals include relieving symptoms, managing complications, and improving patients’ quality of life. Surgical resection is a first-line treatment option for most patients, with few being pretreated preoperatively with medications. Somatostatin receptor ligands (SRLs), injectable and, more recently, oral capsules, have been the cornerstone of first-line medical therapy for persistent disease. However, several factors, including sparsely granulated adenomas, absent or low somatostatin receptor status, T2-hyperintensity imaging, young age, and aryl hydrocarbon receptor-interacting protein mutations, can predict first-generation SRL resistance. Patients with these characteristics may be better candidates for the growth hormone receptor antagonist pegvisomant, or in cases of large tumors, the second-generation SRL pasireotide. Combination therapy should be further pursued in patients who remain biochemically uncontrolled or have a high remnant tumor after monotherapy. An efficacious and cost-effective pegvisomant dose-sparing effect of SRLs when used in combination has been demonstrated. With such a wide array of medical treatment options, it is becoming increasingly important to tailor treatment to patients’ unique characteristics and preferences, with a goal of personalizing management to achieve high-quality outcomes.     

Withdrawal of Denosumab in Patients With Primary Hyperparathyroidism: A Follow-up Report of the DENOCINA Study

ObjectivesWe investigated the development in the primary outcomes: changes in bone mineral density (BMD) measured by dual x-ray absorptiometry at the lumbar spine, total hip, and femoral neck after 2 years.MethodsIn patients with primary hyperparathyroidism, we investigated the effects of 30-mg cinacalcet per day plus 60 denosumab every 6 months for 1 year (Deno group), versus denosumab plus placebo for 1 year (DenoPlacebo-group), versus placebo plus placebo injection for 1 year (Placebo group). After the study’s termination, most patients receiving denosumab were switched to bisphosphonate treatment.ResultsForty-three out of 45 participants were subject to follow-up. A total of 35 patients completed a 2-year follow-up dual x-ray absorptiometry-scan (Deno: n = 13; DenoPlacebo: n = 12; and Placebo: n = 10). None of the groups showed statistically significant changes in BMD or experienced decreases in mean BMD below the study’s baseline level. Overall, the changes in T-scores from the final study measurement to follow-up were similar among the groups (P = .38 for lumbar spine T-score, .63 for total hip, and .97 for femoral neck by 1-way ANOVA). P-calcium was not different over time (P = .20 for change over time and P = .08 for the difference between the groups by repeated measures ANOVA). A total of 5 participants suffered a fracture during the study or follow-up periods, all but one was in the placebo group.ConclusionEvidence suggests that it is possible to at least maintain BMD, and thus potentially lower the fracture risk by a short course of denosumab followed by antiresorptive therapy, where applicable in patients with primary hyperparathyroidism.     

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.     

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.     

The Evaluation of Low- and High-Dose Steroid Treatments in Subacute Thyroiditis: A Retrospective Observational Study

ObjectiveThe optimal steroid regimen in the treatment of subacute thyroiditis (SAT) is controversial. This study aims to compare low- and high-dose steroid regimens in the treatment of SAT.MethodsA single-center, retrospective observational cohort study with up to 1 year of follow-up was conducted. A total of 44 patients in the 16-mg methylprednisolone (MPS) group and 47 patients in the 48-mg MPS group were enrolled. Clinical and laboratory findings from the time of diagnosis to 1-year of the follow-up were assessed. Treatment response, recurrence, and hypothyroidism (HPT) rates were evaluated.ResultsClinical symptoms, sedimentation rates, C-reactive protein, and thyroid hormone levels of the patients were similar in the 2 groups. Recovery was achieved in all patients at the end of the treatments; however, treatment duration needed to be extended for 6 (13.6%) and 1 (2.1%) of the patients in the 16-mg and 48-mg MPS groups, respectively. The 48-mg MPS group had a higher SAT recurrence rate than the 16-mg MPS group (P = .04). Logistic regression analysis suggested that a lower thyroid-stimulating hormone level at the end of the treatment was a predictor of recurrence (β = –0.544, P = .014, 95% CI: 0.376-0.895). While the transient HPT rate was 10 (21.3%) and 10 (22.7%) in the 48-mg and 16-mg MPS groups, respectively, a permanent HPT developed in 5 (10.6%) of patients in the 48-mg MPS and 3 (6.8%) in the 16-mg MPS group. The permanent and transient HPT rates were determined to be similar in the low- and high-dose groups (P > .05).ConclusionLow-dose steroid therapy may be sufficient to achieve a complete recovery and better outcomes in SAT.     

Association of Body Mass Index With Clinicopathological Features of Papillary Thyroid Carcinoma: A Retrospective Study

ObjectiveWe examined the effect of body mass index (BMI) on clinicopathological features of papillary thyroid carcinoma (PTC).MethodsThe clinical data of 4476 patients with PTC who underwent surgical treatment were retrospectively analyzed. According to the different BMI of patients, it can be divided into underweight (BMI < 18.5 kg/m²), normal weight (18.5 ≤ BMI < 24.0 kg/m²), overweight (24 ≤ BMI < 28 kg/m²), and obese (BMI ≥ 28 kg/m²). Spearman correlation analysis was performed to assess the relationship between the BMI and the size of PTC tumor. Multivariate binary logistic regression analysis was performed to estimate the association of overweight and obesity with clinicopathological features of PTC.ResultsThere was a positive correlation between the BMI and PTC tumor size (r = 0.087, P < .001). As compared with normal weight patients with PTC, overweight and obese patients with PTC had a greater risk of bilaterality (odds ratio [OR] = 1.295, OR = 1.669), multifocality (OR = 1.273, OR = 1.617), extrathyroidal extension (OR = 1.560, OR = 2.477), T (3 + 4) stage (OR = 1.482, OR = 2.392), and recurrence risk (intermediate-high risk) (OR = 1.215, OR = 1.718) (P < .05 for all). As compared with normal weight patients with papillary thyroid microcarcinoma (PTMC), overweight and obese patients with PTMC had a greater risk of bilaterality (OR = 1.341, OR = 1.737), multifocality (OR = 1.244, OR = 1.640), extrathyroidal extension (OR = 1.992, OR = 2.080), T (3 + 4) stage (OR = 1898, OR = 2.039), and recurrence risk (intermediate-high risk) (OR = 1.458, OR = 1.536) (P < .05 for all).ConclusionOverweight and obesity were significantly associated with aggressive clinicopathological features of PTC and PTMC. The impact of overweight and obesity should be considered when choosing treatment decisions for PTC and PTMC.