Endocrine Practice最新文献

Objective: The management of refractory pituitary adenomas (RPAs) presents significant challenges. This study aimed to evaluate the long-term treatment outcomes of patients with RPA managed with temozolomide (TMZ) and to identify potential biomarkers for predicting TMZ treatment response.

Methods: This retrospective case series included patients with RPA who underwent trans-sphenoidal surgery (TSS) or craniotomy at a comprehensive medical center in China between January 2014 and December 2021.

Results: 39 patients with RPA (median age 42 years; 23 males [59%]) were treated with TMZ for a median of 9 cycles. The median follow-up was 34.4 months. Complete response (CR) was observed in 2 patients, partial response (PR) in 11 patients, stable disease (SD) in 9, progressive disease (PD) in 11, and death in 6 patients. O6-methylguanine DNA methyltransferase levels were significantly lower in patients with CR, PR, or SD compared to those with PD or mortality, with mean values of 24.2% and 58.1, respectively. MutS homologs 6 levels were significantly higher in patients with CR, PR, or SD compared to those with PD or mortality, with mean values of 64.2% and 36.9%, respectively. Patients who received concomitant TMZ and external beam radiotherapy showed a significant tumor size reduction of 178,837 mm³ (P < .001) compared to those treated with TMZ alone.

Conclusions: TMZ demonstrates promising efficacy in eliciting tumor responses in patients with PRA. O6-methylguanine DNA methyltransferase and MutS homologs 6 have emerged as potential biomarkers for predicting treatment response. Furthermore, radiation with concurrent TMZ may significantly improve outcomes in patients with RPA.

Objective: Primary hyperparathyroidism (PHPT) is accompanied by a decreased 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (DBP). High parathyroid hormone (PTH) is associated with elevated interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), yet the effect of parathyroidectomy (PTX) on DBP and cytokines is not clear. This study aims to prospectively evaluate the effect of PTX on inflammatory profiles, total and free 25OHD, and DBP in patients with PHPT.

Methods: Newly diagnosed patients with PHPT were recruited for the study (n = 70). Twenty-eight patients returned after PTX, 3 months later. Biochemical markers were measured before and after PTX. A group of age and body mass index-matched healthy subjects were included as controls (n = 70).

Results: Before PTX, patients had lower serum DBP (37.5 ± 6.0 vs 41.5 ± 6.1 mg/dL, P < .001) and total 25OHD (30.1 ± 9.5 vs 33.3 ± 7.9 ng/mL, P < .05) but similar free 25OHD when compared to controls. Serum IL-6, C-reactive protein, and MCP-1 were higher in patients with PHPT (P < .05), whereas interleukin-10 was similar to that in controls. PTX increased total and free 25OHD and DBP (P < .001) and decreased serum IL-6 and MCP-1 (P < .05), but not C-reactive protein and interleukin-10. Multiple regression analysis indicated that the preoperative PTH explained a significant portion of the variance of IL-6 and MCP-1 (P < .05).

Conclusion: These findings suggest that PTH may upregulate the production of MCP-1 and IL-6 and downregulate circulating DBP in patients with PHPT that are normalized by PTX. The exact mechanism of IL-6 and MCP-1 on DBP, vitamin D metabolites, and clinical outcomes in patients with PHPT is an area requiring further study.

Objective: No studies have investigated the predictors of an adequate cortisol response to the short synacthen test (SST) and the appropriateness of patient selection for SST in the Southeast Asian population. The aim of our study is to investigate the predictors and indications of SSTs and concondance of SSTs conducted with outcomes.

Methods: This is a retrospective study investigating all SSTs performed over a year in a tertiary center. Clinical data of patients with SSTs between February 2022 and February 2023 were extracted. We determined the appropriateness of SST testing. Binary logistic regression was used to assess the parameters that predict adequate cortisol response on SST. The proportion of individuals with biochemical "pass" or "fail" on SST was compared with the Χ² test. Baseline cortisol levels that predicted SST pass were determined using area under receiving operating characteristics curves.

Results: Of the 781 SSTs, 83.9% of SSTs showed an adequate cortisol response. Postural hypotension (26.9%) and exogenous glucocorticoid administration (14.2%) were common indications for SST. In our cohort, 50.2% of the SSTs were inappropriately indicated. Pretest serum cortisol and albumin predict biochemical pass on SST. A pretest cortisol level of 300 nmol/L predicted SST response with 93% sensitivity and a cortisol level of <100 nmol/L confirmed adrenal insufficiency (AI) with 97.3% specificity. Using these cortisol thresholds could avoid 302 (38.5%) of SSTs.

Conclusion: Our analysis showed that clinical features of AI do not reliably predict SST outcomes. We advocate careful assessment of the pretest probability of AI in patients referred for SST. A pretest cortisol level can reduce the number of SSTs, with cost savings implications.

Objective: To characterize the tolerability associated with incretin analog interchanges to equipotent or higher strengths based on an interchange process in an adult outpatient setting.

Methods: This was a retrospective chart review of adult patients receiving care through a participating family medicine or endocrinology clinic between January 1, 2022, and November 30, 2022 at a major academic medical center. An incretin analog equivalency table and protocol for interchange was created in response to ongoing shortages and need for therapy adjustments to different medications within the same class. Patients were included if a recommended incretin analog interchange was initiated and a tolerability assessment was conducted. Patients were excluded if they did not meet inclusion criteria or if they were unreachable for tolerability assessments for interchanged agents.

Results: There were 156 patients included for characterization and response to tolerability of interchange. It was determined that 96% of patients tolerated the incretin analog interchange. A dose escalation occurred in 58% of patients, 41% were transitioned to an equipotent dose, and a dose decrease was considered in 1 patient. Prior authorizations were required 74% of the time for the new therapy. The most common interchanges were dulaglutide 4.5 mg to tirzepatide 7.5 mg, dulaglutide 4.5 mg to tirzepatide 10 mg, and dulaglutide 3 mg to tirzepatide 7.5 mg. These interchanges made up 37.3% of the total population and were observed to have 93% tolerability. Seven patients did not tolerate incretin analog interchange. Five experienced gastrointestinal effects and 2 experienced injection site reactions. The interchange of incretin analog was estimated to reduce time to maximum dose by a median of 3 months. During this study, no patients experienced interruption of therapy defined as missing a dose of incretin analog.

Conclusion: This characterization report demonstrates an effective approach to addressing incretin analog interchanges. A high level of tolerability is evident with the defined interchange process. Future studies should continue to confirm effective and safe interchanges of incretin analogs from outcomes and tolerability reports.

Introduction: Individuals may seek gender-affirming hormone therapy (GAHT) to align their physical appearance with their gender identity. Feminizing GAHT typically involves the use of estrogen. This study investigates the effect of route of administration (ROA) and dose of estradiol on estradiol (E2) and testosterone (T) levels in transfeminine individuals.

Methods: We conducted a chart review of 573 patients with an active prescription for estradiol for feminizing GAHT and serum hormone levels available. Multiple linear regression and analysis of variance were used to analyze the effect of dose and ROA of estradiol on serum E2 and T.

Results: Oral estradiol was the only ROA demonstrating a linear dose-response, with each 1 mg/d increase associated with a reduction in T of 19.03 ng/dL (P = .005). Lower T levels were seen with higher doses of transdermal estradiol but a significant dose-response was not demonstrated. Intramuscular estradiol was associated with lower T and higher E2 compared to oral and transdermal ROAs (P < .001), with many achieving target hormone levels even at low doses. Higher doses of oral estradiol were associated with lower mean serum leutenizing hormone and follicle stimulating hormone levels (P < .05).

Conclusion: Oral estradiol can be titrated to achieve a stepwise decrease in serum T. The intramuscular ROA appears to be the most potent delivery of estradiol with impact on serum hormone levels with doses on the low end of guideline-suggested ranges. Serum leutenizing hormone and follicle stimulating hormone may also help with the management of feminizing GAHT.

Objective: Thyrotoxicosis can adversely affect pregnancy. The quality of care (QoC) for thyrotoxicosis in pregnancy at a tertiary care safety net hospital was evaluated based on current guidelines.

Methods: Pregnant patients with thyrotoxicosis or a history of Graves disease who delivered in 2015-2021 were divided into 3 groups: low thyroid stimulating hormone (TSH), active Graves disease, and past Graves disease. The QoC was assessed using thyroid hormone and thyroid stimulating immunoglobulin (TSI) levels, fetal ultrasound, and endocrine referrals. We assessed potential impacts of race/ethnicity and socioeconomic status (SES).

Results: We included 147 subjects (mean age 31.5 years, 76% Black, 86% non-Hispanic). Of patients with low TSH (n = 95), 75% had repeat TSH measurements and 33% had TSI measured. Hispanic patients were more likely to have TSI and repeat TSH measured than non-Hispanics (58% vs 29%; P = .04, and 100% vs 71%; P = .03, respectively). In patients with active Graves disease (n = 23, 70% treated with thionamides), 35% had free thyroxine levels at goal and 90% had endocrine care or referral. In patients with past Graves disease (n = 27), 56% had TSI measured, 78% had first-trimester TSH measurements, and 58% had TSH at goal. Black patients were less likely to have TSH checked in the first trimester than other races (85% vs 100%, P = .048).

Conclusion: The QoC of thyrotoxicosis in pregnancy at this tertiary care center can be improved. A larger study is needed to assess the potential impacts of race and SES on the care of pregnant patients with thyrotoxicosis.

Purpose: Determine the association between clinical and demographic factors and 30-day readmission risk after pituitary surgery.

Methods: Patients undergoing pituitary surgery between January 2018 and December 2022 were retrospectively reviewed. Cases were extracted from a converged electronic health record that included surgeries performed at the Midwest, Southeast, and Southwest campuses of the same healthcare Enterprise. Variables were compared between patients with 30-day readmission following discharge after pituitary surgery (N = 83) and a randomly sampled patient cohort with pituitary surgery but no readmission within 30 days (N = 174).

Results: In a multivariable regression model looking at the relationship between patient characteristics and readmission risk, every increase in the Medicare Severity Diagnosis Related Group score resulted in a nearly 2.3-fold increase in the risk of readmission (OR = 2.335, 95% CI 1.050, 5.562, P = .045). The presence of arginine vasopressin deficiency increased the odds of readmission by more than 2-fold (OR = 2.784, 95% CI 1.118, 7.124, P = .029). The Midwest site was observed to have a nearly 67% decrease in readmission risk compared to the Southwest site (OR = 0.334, 95% CI 0.134, 0.813, P = .016), with the Southeast site being comparable to the Southwest.

Conclusion: Our study identifies postoperative arginine vasopressin deficiency, greater co-morbidities, and geographic location as risk factors for 30-day readmission after pituitary surgery. Further investigation is required to determine how site-specific care processes can be adopted to lower readmission risk at other locations in the same healthcare enterprise.

Objective: Identification of prognostic biomarkers in pediatric diabetes is important for precision medicine. We assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes.

Methods: We prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the Aβ classification system ("A+": islet autoantibody positive, "β+": random serum C-peptide ≥1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2 hours postprandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6 to 12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score for each participant, and compared characteristics at baseline, and clinical outcomes at V2.

Results: The cohort was 50% male. Racial distribution was 76.4% White, 20.8% Black, and 2.8% Asian or other races. A total of 46.5% participants were Hispanic. Median age (Q1-Q3) was 12.4 (8.3-14.5) years. The Aβ subgroup frequencies were 46 A+β-(63.9%), 1 A-β-(1.4%), 4 A+β+(5.6%), and 21 A-β+(29.2%). Baseline serum C-peptide correlated with UCPCR at both V1 (r = 0.36, P = .002) and V2 (r = 0.47, P < .001). There were significant subgroup differences in age, race, frequency of diabetic ketoacidosis, and type 1 diabetes genetic risk score (P < .01). At V2, the 2 β-subgroups had lower UCPCR and higher hemoglobin A1c compared with the 2 β+ subgroups (P < .001 and P = .02, respectively). Thirty-eight percent of A-β+ but none of the other subgroups were insulin-independent at V2 (P < .001).

Conclusion: C-peptide and islet autoimmunity at diagnosis define distinct phenotypes and predict beta-cell function and insulin dependence 6 to 12 months later in racially/ethnically diverse children with new-onset diabetes.