Endocrine Practice最新文献

Objectives: For indeterminate thyroid nodules, molecular tests offer high negative predictive value (NPV), reducing missed malignancies, but have limited positive predictive value (PPV), potentially leading to unnecessary surgeries. We evaluated how integrating artificial intelligence-based imaging (AIBx V2) with ThyroSeq v3 could enhance diagnostic accuracy.

Methods: We retrospectively analyzed 108 indeterminate thyroid nodules. Surgical pathology was available for 42 nodules for primary analysis; the remaining 66, without surgical pathology, were deemed benign for analytic purposes and included in the total cohort for secondary analysis reflecting real-world practice. We calculated test performance for AIBx V2 alone, ThyroSeq v3 alone, and a combined approach (AIBx V2+Mol). In the combined approach, when ThyroSeq v3 reported "Malignant", but the estimated malignancy probability was intermediate or lower, the final classification deferred to AIBx V2.

Results: In the surgical pathology subset (n=42), ThyroSeq v3 demonstrated high sensitivity (0.95) but moderate specificity (0.45), leading to a PPV of 0.65. AIBx V2 improved specificity (0.60) but had lower sensitivity (0.77). The AIBx V2+Mol approach retained high sensitivity (0.95) while raising specificity to 0.60, improving PPV to 0.72 and AUC from 0.70 to 0.77. In the entire cohort (n=108), AIBx V2+Mol maintained excellent sensitivity (0.95) and further enhanced specificity, 0.90 vs 0.87, PPV 0.72 vs 0.65, and AUC 0.93 vs 0.91.

Conclusions: Integrating AIBx V2 imaging model with ThyroSeq v3 preserved the high sensitivity of molecular testing while improving specificity and PPV. These exploratory results need validation in larger studies before the combined model is incorporated into clinical practice.

Objective: We described treatment approaches after 20 doses of denosumab, including continuation or transition to zoledronic acid or romosozumab, and examined subsequent BMD trajectories.

Methods: This retrospective single-centre cohort included patients who received ≥20 consecutive doses of denosumab at the Osteoporosis Centre between June 2012 and December 2024. Characteristics of patients who continued denosumab were compared with those who transitioned to zoledronic acid or romosozumab. BMD was obtained from DXA, and trajectory analyses were restricted to patients without delayed dosing and with BMD reassessment after the 20^th dose.

Results: Fifty-four patients received ≥20 doses (mean age 72.9 years, 98.1% female). The 20th-dose BMD T-score was the major determinant of subsequent treatment: two patients with the lowest T-scores transitioned to romosozumab, four with the highest transitioned to zoledronic acid, and 48 continued denosumab. Continuing denosumab led to further BMD gains at the lumbar spine and femoral neck but not the total hip. Transition to zoledronic acid led to partial loss of the year-10 BMD gains. Transition to romosozumab led to further BMD gain at the lumbar spine only. No cases of atypical femoral fracture or osteonecrosis of the jaw were reported.

Conclusion: After ≥20 doses of denosumab, most patients continued treatment, guided largely by the 20th-dose BMD T-score. Continuing denosumab beyond 10 years resulted in further increases in BMD at the lumbar spine and maintenance of BMD at the femoral neck, whereas transition to zoledronic acid led to partial loss of previous gains and transition to romosozumab increased lumbar spine BMD only.

Objective: Lower extremity complications significantly impact morbidity and healthcare costs among people with type 2 diabetes (T2D). Evidence regarding the impact of different glucose-lowering medications on these outcomes remains inconclusive.

Methods: We emulated a target trial using two linked national claims databases (OptumLabs Data Warehouse, Medicare fee-for-service). We included adults with T2D at moderate cardiovascular risk who initiated GLP-1RA, SGLT2i, DPP-4i, or sulfonylurea between 2014-2021, and used propensity score inverse probability of treatment weighted Cox proportional hazards models to compare the incidence rates of the primary composite outcome of incident foot ulcer/abscess, osteomyelitis, Charcot arthropathy, or amputation across the four medication classes under the intention-to-treat framework.

Results: The weighted study cohort included 81,998 DPP4i-initiators, 43,734 GLP-1RA-initiators, 57,399 SGLT2i-initiators, and 206,374 sulfonylurea-initiators; they were well balanced on all examined baseline characteristics. Sulfonylurea use was associated with a higher risk of the composite lower extremity complications outcome compared to DPP-4i (HR 1.15; 95%CI 1.11-1.19), GLP-1RA (HR 1.20; 95%CI 1.13-1.28), and SGLT2i (HR 1.08; 95%CI 1.02-1.14). SGLT2i use was also associated with a higher risk compared to GLP-1RA (HR 1.11; 95%CI 1.03-1.21). Amputation events were rare in all treatment groups.

Conclusion: We observed greater relative risk of lower extremity complications with sulfonylurea use compared to DPP4i, GLP-1RA, and SGLT2i use, and with SGLT2i use compared to GLP-1RA use. Reassuringly, the absolute differences between the medication classes were <1%. Diabetes management teams may consider these medication-associated risks when selecting glucose-lowering therapies for individuals without high cardiovascular risk, especially those predisposed to lower extremity morbidity.

Objective: To review the pathophysiology, risk factors, clinical implications, monitoring strategies, and therapeutic approaches for glucocorticoid-induced hyperglycemia (GCIH), with a focus on patients with cancer.

Methods: This narrative review integrates findings from clinical studies, expert guidelines, and recent advances in glucose monitoring and pharmacologic therapy, particularly in oncologic settings where glucocorticoid use is common.

Results: GCIH is a frequent and often underrecognized complication, even in individuals without preexisting diabetes. In patients with cancer, GCIH is associated with increased risk of infections, chemotherapy delays, longer hospital stays, and higher mortality. Key mechanisms include enhanced insulin resistance, increased hepatic gluconeogenesis, and β-cell dysfunction. Afternoon and postprandial hyperglycemia are typical due to the pharmacodynamics of once-daily morning glucocorticoids. Self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) are essential tools. HbA1c may assist in baseline assessment, but fructosamine better reflects short-term glycemic changes. Insulin is the treatment of choice for moderate to severe GCIH, with basal-bolus regimens, especially using NPH insulin aligned with glucocorticoid timing, providing effective control. Selected non-insulin agents may be considered in stable outpatients with mild hyperglycemia. However, standardized definitions, evidence-based algorithms, and randomized trials remain limited.

Conclusion: Optimal GCIH management requires proactive monitoring and individualized treatment strategies tailored to glucocorticoid type, dose, and clinical setting. Further research should aim to refine diagnostic criteria, validate therapeutic protocols, and assess emerging technologies such as automated insulin delivery systems and selective glucocorticoid receptor modulators.

Objectives: The optimal blood pressure (BP) target for stroke prevention in patients with primary aldosteronism (PA) remains to be determined. This cohort study examined the association between mean BP levels during follow-up and stroke incidence in this population.

Methods: The study retrospectively enrolled patients with PA aged ≥30 years who were hospitalized at our hypertension center between January 2008 and December 2019. The exposure variable was the mean BP from ≥3 follow-up visits per patient. The primary outcome was incident stroke during follow-up. The association of mean follow-up BP with risk of stroke was assessed using Cox proportional hazard models and restricted cubic splines.

Results: The cohort comprised 3138 patients with PA (median age 49 years, 55% male). During a median follow-up of 6 years, 101 patients experienced incident stroke (ischemic, n=79; hemorrhagic, n=22). After adjusting for age, sex,pretreatment BP, and other relevant confounders, the mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) during follow-up showed significant positive associations with the risk of incident stroke (HR 1.04, 95% CI 1.02-1.06, P<0.001 and HR 1.05, 95% CI 1.01-1.08, P=0.005, respectively). In multivariable survival analysis, compared with the SBP ≥140 mmHg group, the risk of stroke was decreased by 54% in the SBP <130 mmHg group (HR 0.46, 95% CI 0.26-0.80, P=0.006) and by 47% in the SBP 130-139 mmHg group (HR 0.53, 95% CI 0.33-0.84, P=0.007). No association was observed when DBP was analyzed categorically. When variables were modeled using restricted cubic splines, the risk of stroke increased linearly with SBP and DBP. The risk of stroke began to increase rapidly at a BP of around 133/83 mmHg. In subgroup and sensitivity analyses, the association between mean follow-up SBP and stroke incidence remained consistent.

Conclusions: A target BP of <130/80 mmHg might be associated with a reduced risk of stroke in patients with primary aldosteronism. Nevertheless, additional validation remains necessary through prospective, randomized controlled trials.

Objectives: Testosterone replacement therapy (TRT) in prostate cancer survivors with hypogonadism remains controversial due to concerns that restoring testosterone may increase the risk of disease recurrence. We performed a cohort study of men with localized prostate cancer treated with radiotherapy with or without androgen deprivation therapy (ADT), who received TRT, and a narrative review of published studies evaluating TRT after radiotherapy.

Methods: Biochemical and clinical recurrence, patient-reported symptoms, PSA, testosterone, and hemoglobin were analyzed in this cohort and published studies.

Results: Among 33 men with pathology-confirmed prostate cancer treated with radiation without or with ADT, who received TRT (median age at TRT initiation, 75 [IQR 69.0-77.0] years), median testosterone increased from 66.0 (IQR 16.0-140.0) to 299.3 (IQR 152.5-569.0, p<0.001) ng/dL. PSA rose from 0.04 (IQR 0.02-0.17) to 0.17 ng/mL (IQR 0.04-0.44) (p=0.018). TRT was associated with improvements in fatigue, mood, and sexual symptoms; anemia was corrected in 9 of 21 (42.9%) patients with anemia. One patient (3%) developed metastatic disease 3 years after starting TRT. In narrative review of published case-reports, weighted mean biochemical recurrence rate was 3.3% during mean 42.6 months of follow-up.

Conclusions: Our cohort study and narrative review found a low incidence of biochemical recurrence in prostate cancer survivors treated with radiation therapy with or without ADT. TRT was associated with correction of anemia and improvements in fatigue, energy, and sexual symptoms. These findings provide the ethical and scientific rationale for a randomized controlled trial to evaluate the safety and efficacy of TRT in this population.

Objectives: To compare two levothyroxine (LT4) dosing regimens during Ramadan; pre-Iftar and pre-Dawn, with respect to thyroid biochemical control and patient satisfaction.

Methods: This multicenter, open-label randomized controlled trial recruited adults with primary hypothyroidism from three Saudi cities (Jeddah, Riyadh, Al-Ahsa). Patients with thyroid cancer were excluded. Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured 2 weeks before and 4-6 weeks after Ramadan. Participants were randomized to take LT4 either before breaking the fast (pre-Iftar) or just before fasting began (pre-Dawn).

Results: A total of 303 participants completed the study (156 pre-Iftar, 147 pre-Dawn). Groups were comparable in demographics and comorbidities. Mean age was 49 ± 12 years; 87% were female; mean disease duration was 9.7 ± 8.3 years. Weekly LT4 dose was 753 ± 349 μg (pre-Iftar) vs. 733 ± 266 μg (pre-Dawn; p=0.001). Pre-Ramadan TSH was 2.56 ± 2.16 mIU/L vs. 2.46 ± 1.72 mIU/L (p=0.3), and FT4 was 13.45 ± 2.1 vs. 13.08 ± 2.4 pmol/L (p=0.16). Post-Ramadan TSH was 3.64 ± 4.1 vs. 4.07 ± 4.2 mIU/L (p=0.78), and FT4 was 12.96 ± 0.1 vs. 12.64 ± 0.2 pmol/L (p=0.003). Within-group post-Ramadan changes were non-significant. Repeated-measures ANOVA showed no significant differences in TSH or FT4 over time or between groups (p=0.47 and p=0.81). Compliance and satisfaction were comparable.

Conclusion: Both pre-Iftar and pre-Dawn LT4 regimens maintained thyroid stability during Ramadan. Either can be safely adopted according to patient preference.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver condition worldwide, closely linked to obesity, type 2 diabetes, and cardiometabolic risk factors. Despite lifestyle interventions and pharmacological advances, therapeutic options remain limited. Bariatric surgery, particularly sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), has demonstrated sustained weight loss and durable improvements in metabolic health. Beyond weight reduction, these procedures induce profound physiological, hormonal, and molecular changes that improve hepatic steatosis, reduce inflammation, and may partially reverse fibrosis. Evidence indicates that bariatric surgery decreases the risk of cirrhosis, hepatocellular carcinoma, and cardiovascular events, while enhancing overall survival and quality of life. This review summarizes the mechanisms by which SG and RYGB influence liver metabolism and highlights their role as disease-modifying interventions for MASLD. Bariatric surgery should thus be considered an integral component in the multidisciplinary management of MASLD, especially in patients with obesity and advanced metabolic risk profiles.