Daily Endocrinology Research Analysis
Three studies stood out today in endocrinology and metabolic medicine: a multinational cohort introduced and externally validated a simple MASLD-HCC risk score; a JCEM study proposed a TSH-based time-in-range metric to quantify hypothyroidism control and uncover disparities; and a real-world analysis showed that adopting intermittently scanned CGM halved DKA hospitalizations in adults with type 1 diabetes while reducing costs.
Summary
Three studies stood out today in endocrinology and metabolic medicine: a multinational cohort introduced and externally validated a simple MASLD-HCC risk score; a JCEM study proposed a TSH-based time-in-range metric to quantify hypothyroidism control and uncover disparities; and a real-world analysis showed that adopting intermittently scanned CGM halved DKA hospitalizations in adults with type 1 diabetes while reducing costs.
Research Themes
- Risk stratification in metabolic liver disease
- Novel disease control metrics in endocrinology
- Digital health adoption and acute diabetes complications
Selected Articles
1. A Novel Risk Prediction Model for Hepatocellular Carcinoma in MASLD: A Multinational, Multicenter Cohort Study.
In 77,677 MASLD patients across 20 centers, a five-factor MASLD-HCC score (age, sex, platelets, overweight/central obesity, and prediabetes/diabetes) showed excellent discrimination (C-index 0.84 training; 0.83 internal; 0.93 external) and good calibration. High-risk groups had markedly higher HCC incidence by subdistribution hazard ratios across all cohorts.
Impact: Provides a simple, externally validated HCC risk tool for MASLD, enabling targeted surveillance and efficient allocation of hepatology resources globally.
Clinical Implications: Clinicians can stratify MASLD patients for HCC surveillance using age, sex, platelets, obesity, and dysglycemia without advanced imaging, prioritizing high-risk individuals and potentially improving early detection.
Key Findings
- Overweight/central obesity and prediabetes/diabetes were independently associated with incident HCC in MASLD.
- The MASLD-HCC score (5 variables) achieved C-index 0.84 (training), 0.83 (internal validation), and 0.93 (external validation).
- High- vs low-risk groups showed large risk separation (e.g., training cohort sHR 11.44; external validation sHR 56.84; all P < .001).
- The model demonstrated good calibration and positive net benefit on decision curve analysis.
Methodological Strengths
- Large, multinational, multicenter cohort with internal and external validation
- Time-varying Cox modeling, calibration, and decision curve analysis
Limitations
- Low event rate (0.2%) may affect precision and risk of overfitting despite validation
- Residual confounding and heterogeneity across regions and practice patterns
Future Directions: Prospective impact studies integrating fibrosis measures and imaging, evaluation of surveillance thresholds, and implementation studies across diverse healthcare systems.
BACKGROUND AND AIMS: It is unclear that which cardiometabolic risk factors (CMRFs) are significantly associated with hepatocellular carcinoma (HCC) development in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to develop and validate a novel CMRF-based HCC risk prediction model in MASLD. METHODS: This multicenter cohort study recruited 77,677 MASLD patients from 20 medical centers in Korea and other Asian and Western countries (2004-2023). A novel CMRF-based HCC risk prediction model (MASLD-HCC score) was developed based on time-varying Cox multivariable analysis in a training cohort (n = 36,800, Korea), which was validated internally (n = 36,799, Korea) and externally (n = 4078, 11 other Asia and Western countries). RESULTS: In the training cohort, 71 (0.2%) patients developed HCC (median follow-up 5.1 years). Overweight/obesity or central obesity and prediabetes/diabetes were independently associated with HCC development, along with age, sex, and platelets. The MASLD-HCC score with these 5 risk factors showed a Harrell's C-index of 0.84 for HCC development, which was maintained in the internal (C-index 0.83) and external validation cohorts (C-index 0.93), and the model was well calibrated.
2. Measuring hypothyroidism disease control using a TSH-based "time-in-range".
Using longitudinal data from 2,752 LT4-treated adults, the authors derived a TSH-based time-in-range metric (median 86%). Higher LT4 dose correlated with lower TIR, and male sex and Black race were associated with TIR <75%. Time-above-range showed a trend toward increased cardiovascular events.
Impact: Introduces a pragmatic, reproducible metric for chronic hypothyroidism control and reveals sociodemographic disparities in disease control.
Clinical Implications: TSH-TIR could inform quality metrics and personalized follow-up, flagging undertreated subgroups and potentially linking control to cardiovascular risk in future studies.
Key Findings
- Median TSH time-in-range was 86% over a median 3.8-year follow-up in 2,752 LT4-treated patients.
- Higher LT4 dose was negatively correlated with TIR (R = −0.23 to −0.30; both sexes p <0.001).
- Male sex and Black race were associated with TIR <75% (OR 1.30 and 1.37; both p <0.001).
- Time-above-range showed a trend toward increased cardiovascular events (OR 1.03 per +10% TAR; p = 0.078).
Methodological Strengths
- Innovative interpolation-based TIR metric using serial TSH values
- Robust longitudinal analyses (GEE, survival models) with sociodemographic covariates
Limitations
- Single-center observational design; causality cannot be inferred
- TSH-only control metric without integrating FT4/FT3 or patient-reported outcomes
Future Directions: Multi-center validation of TSH-TIR, linkage to hard outcomes, and integration with biochemical (FT4/FT3) and patient-reported measures.
CONTEXT: Time-in-range (TIR) using sequential thyroid stimulating hormone (TSH) levels during levothyroxine (LT4) treatment could serve as a measure of chronic disease control in hypothyroidism. OBJECTIVES: Primary objectives: 1) develop a method of estimating TIR, and 2) determine the impact of patient sociodemographic characteristics on TIR. Secondary objective: investigate the relationship between TIR and time to cardiovascular event. METHODS: The study was conducted using longitudinal clinical data (2016-2022) from a single academic institution. Study participants were ≥18 years old, LT4-treated, and had ≥3 unique TSH levels collected over a minimum of 2 years. For each patient, TIR, time-above-range (TAR), and time-below-range (TBR) were estimated using linear interpolation of log-transformed TSH levels. Fitted linear regression was used to evaluate the relationship between TIR/TAR/TBR and LT4 dose over the study period. Generalized estimating equations (GEE) were used to model annualized TIR/TAR/TBR with sociodemographic and clinical covariates. Survival analysis was used to characterize the relationship between TIR and occurrence of cardiovascular events. RESULTS: A total of 2752 LT4-treated patients had a median TIR of 86% over the study enrollment period (median 3.8 years). For both males and females, LT4 dose was negatively correlated with TIR (R = -0.23 and -0.30, respectively; p <0.001 for both). Male sex and Black race were associated with TIR <75% (OR 1.30, p <0.001; OR 1.37, p <0.001). The association between TAR and cardiovascular events approached significance (OR 1.03 per +10% TAR, p = 0.078).
3. Intermittently scanned continuous glucose monitoring adoption decreases diabetic ketoacidosis hospitalizations and healthcare costs in adults with type 1 diabetes.
In a regional real-world cohort of 13,616 adults with type 1 diabetes, DKA hospitalization incidence halved after isCGM adoption (79.26 to 40.28 per 10,000 person-years; RR 0.5). The largest benefit was observed in those with HbA1c ≥10%, and overall cost savings were approximately €783,000.
Impact: Demonstrates population-level clinical and economic benefits of isCGM, supporting policy and reimbursement decisions to broaden access in high-risk adults with type 1 diabetes.
Clinical Implications: Health systems should prioritize isCGM access for adults with poorly controlled T1D (e.g., HbA1c ≥10%) to reduce DKA admissions and associated costs; evaluation of complementary education and support may further enhance benefits.
Key Findings
- DKA hospitalization incidence decreased from 79.26 to 40.28 per 10,000 person-years after isCGM adoption (RR 0.5, 95% CI 0.40–0.63).
- Greatest reduction in DKA observed among patients with HbA1c ≥10% (136 fewer events per 10,000 person-years).
- Estimated direct cost savings totaled €782,836.81 over the evaluation period.
Methodological Strengths
- Large regional population with pre–post evaluation of a system-wide technology adoption
- Objective outcome (DKA hospitalization) and cost estimation at population level
Limitations
- Before–after observational design without a concurrent control group; potential secular trends and confounding
- Limited granularity on adherence, education, and concurrent technologies
Future Directions: Quasi-experimental or randomized rollout studies to confirm causality, assessment of long-term outcomes (mortality, severe hypoglycemia), and cost-effectiveness across diverse health systems.
AIMS: This study analyzed the impact of implementing intermittently scanned continuous glucose monitoring (isCGM) on hospitalization rates for diabetic ketoacidosis (DKA) among adults with type 1 diabetes mellitus (T1DM). Additionally, it assessed the direct costs and savings associated with these hospital admissions. METHODS: A comprehensive regional dataset from Andalusia, Spain, was used to extract emergency care codes for DKA in individuals with T1DM who started using isCGM between January 1, 2020, and December 31, 2021. Hospitalization rates for DKA were compared during the 12 months before and after isCGM implementation to determine population-level incidence rates. RESULTS: The study included 13,616 individuals with T1DM (mean age: 43.7 ± 13.5 years, 46.9 % women). The incidence rate of DKA hospitalizations decreased from 79.26 to 40.28 admissions per 10,000 person-years (rate ratio [RR]: 0.5 [0.40-0.63]). The most significant reduction was observed in patients with HbA1c ≥ 10 %, with 136 fewer events per 10,000 person-years. This reduction resulted in an estimated cost saving of €782,836.81. CONCLUSION: The implementation of isCGM significantly reduced DKA hospital admissions in adults with T1DM, leading to substantial cost savings. These findings highlight the clinical and economic benefits of isCGM in improving patient outcomes and optimizing healthcare resources.