Daily Endocrinology Research Analysis
Across endocrinology, three clinically impactful studies stand out: a large multi-database cohort found no increased thyroid tumor risk with GLP-1 receptor agonists; a province-wide interrupted time series showed that changing gestational diabetes screening policies increased lifestyle-treated diagnoses without affecting infant birth weight; and a prospective diagnostic study demonstrated that adding procalcitonin to calcitonin improves medullary thyroid cancer identification in the gray-zone ra
Summary
Across endocrinology, three clinically impactful studies stand out: a large multi-database cohort found no increased thyroid tumor risk with GLP-1 receptor agonists; a province-wide interrupted time series showed that changing gestational diabetes screening policies increased lifestyle-treated diagnoses without affecting infant birth weight; and a prospective diagnostic study demonstrated that adding procalcitonin to calcitonin improves medullary thyroid cancer identification in the gray-zone range.
Research Themes
- Cardio-metabolic drug safety and endocrine neoplasia
- Policy shifts in gestational diabetes screening and perinatal outcomes
- Biomarker-driven precision diagnostics in thyroid oncology
Selected Articles
1. Effects of a Province-Wide Change in Gestational Diabetes Mellitus Screening Policy on Treatment and Newborn Birth Weight.
In a population-wide interrupted time series including 463,881 singleton pregnancies, shifting from a two-step to mixed one-step/two-step GDM screening immediately increased lifestyle-treated GDM by 1.85% but did not change large or small for gestational age rates or endocrinology visits. Medication-treated GDM rose gradually over time, but short-term analyses showed no immediate change.
Impact: This quasi-experimental evaluation at population scale directly informs the trade-offs of adopting one-step GDM screening by separating diagnostic inflation from meaningful perinatal outcomes.
Clinical Implications: Health systems considering one-step GDM screening should anticipate more lifestyle-treated diagnoses without clear neonatal weight benefits; implementation should balance resource use and potential overtreatment against targeted support for high-risk pregnancies.
Key Findings
- Immediate level increase of lifestyle-treated GDM by 1.85 percentage points (95% CI 1.19–2.51) after policy change.
- Gradual increase in medication-treated GDM over time (trend +0.23 per year; 95% CI 0.09–0.37), but no immediate change in a 3-year postpolicy window.
- No detectable change in infant birth weight outcomes (LGA/SGA) or endocrinology visits.
Methodological Strengths
- Population-wide interrupted time series with 16 years of data and clear policy inflection point.
- Large sample (N=463,881) with objective outcomes and segmented regression estimating level and trend changes.
Limitations
- Observational ITS design susceptible to concurrent secular trends and unmeasured confounders.
- Generalizability limited to one province and specific implementation mix of one-step and two-step screening.
Future Directions: Assess maternal glycemia trajectories, cesarean rates, hypertensive disorders, and long-term offspring metabolic outcomes under different screening strategies; evaluate cost-effectiveness and equity impacts.
OBJECTIVE: To evaluate changes in gestational diabetes mellitus (GDM) treatment and newborn birth weight after a 2010 change in GDM screening recommendations from a two-step (50-g glucose challenge test + 3-h, 100-g oral glucose tolerance test [OGTT] with Carpenter-Coustan criteria) to a mix of one-step and two-step (2-h, 75-g OGTT with International Association for Diabetes in Pregnancy Study Group criteria). RESEARCH DESIGN AND METHODS: We estimated effects of the screening change on the incidence of lifestyle or medication treatment, infant birth weight >90th percentile or <10th percentile for gestational age (large and small for gestational age), and endocrinologist visits using interrupted time series analysis in all 463,881 individuals with singleton pregnancies (>28 gestational weeks) from British Columbia, Canada, between 2004 and 2019. RESULTS: After the screening change, lifestyle-treated GDM increased immediately (level change 1.85 [95% CI 1.19-2.51]), corresponding to a 1.85% increase in incidence. Medication-treated GDM increased gradually (trend change 0.23 [95% CI 0.09-0.37] per year), but there was no change in medication-treated GDM using a shorter (3-year) postpolicy period (level change -0.31 [95% CI -0.9 to 0.29]; trend change 0.03 [95% CI -0.36 to 0.43]). We detected no change in infant birth weight outcomes and endocrinology visits. CONCLUSIONS: Changing the screening approach substantially increased diagnoses of lifestyle-treated GDM but did not impact medication-treated GDM or infant birth weight.
2. Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study.
Across U.S. datasets that met diagnostics, incident thyroid tumor rates among 460,032 GLP-1RA users were comparable to users of SGLT2 inhibitors, DPP-4 inhibitors, or sulfonylureas. Meta-analytic hazard ratios ranged from 0.78 to 1.03 versus comparators, with similar findings for thyroid malignancy and after applying a 1-year exposure lag.
Impact: This large, rigorously controlled active-comparator study addresses a high-profile safety concern around GLP-1RAs and provides reassurance for clinicians and patients.
Clinical Implications: For patients with T2DM initiating second-line therapy, GLP-1RAs do not appear to increase thyroid tumor risk compared with other common agents, supporting their continued use where indicated.
Key Findings
- Thyroid tumor incidence among GLP-1RA users was 0.88–1.03 per 1,000 person-years.
- Pooled HRs showed no increased risk versus SGLT2is (0.83–0.95), SUs (0.95–1.03), or DPP-4is (0.78–0.93).
- Analyses focused on thyroid malignancy and those with a 1-year lag period yielded similar null associations.
Methodological Strengths
- Active-comparator new-user design with propensity score matching/stratification and intention-to-treat and on-treatment analyses.
- Large multi-database cohort with negative control outcomes and calibrated HRs to probe unmeasured confounding.
Limitations
- Only U.S. cohorts met diagnostics; results may not generalize to other healthcare systems.
- Residual confounding and outcome misclassification remain possible in claims/EHR research.
Future Directions: Longer-term surveillance in broader populations, evaluation by thyroid tumor subtype (e.g., medullary), dose-response with higher obesity doses, and inclusion of non-diabetic obesity cohorts.
OBJECTIVE: To assess the association between glucagon-like peptide 1 receptor agonist (GLP-1RA) use and risk of incident thyroid tumors. RESEARCH DESIGN AND METHODS: The retrospective, active-comparator new-user cohort study used international administrative claims and electronic health record databases. Participants included patients with type 2 diabetes mellitus (T2DM) with prior metformin therapy initiating a GLP-1RA versus new users of sodium-glucose cotransporter 2 inhibitors (SGLT2is), dipeptidyl peptidase 4 inhibitors (DPP-4is), and sulfonylureas (SUs). The outcome was incident thyroid tumor and thyroid malignancy. Propensity score matching and stratification were used to adjust for confounders with an intention-to-treat and on-treatment strategy. Cox regression was used to estimate hazard ratios (HRs) pooled using a random-effects meta-analysis. Unmeasured confounding was evaluated using negative outcomes, with calibration of the HR.
3. Combining Procalcitonin and Calcitonin for the Diagnosis of Medullary Thyroid Cancer: A Two-Step Approach.
In a prospective thyroidectomy cohort (n=478), calcitonin >10 pg/mL showed high sensitivity (0.91) and specificity (0.98) for MTC. When calcitonin was 10–100 pg/mL, adding procalcitonin at a 0.04 ng/mL cut-off correctly classified 80.9% of cases, supporting a two-step diagnostic strategy to avoid overtreatment.
Impact: Provides pragmatic, prospectively collected diagnostic thresholds and a stepwise algorithm to refine MTC detection in the clinically challenging calcitonin gray zone.
Clinical Implications: Use calcitonin >10 pg/mL as the primary rule-in threshold; in cases with calcitonin 10–100 pg/mL, add procalcitonin (cut-off 0.04 ng/mL) to distinguish MTC from non-MTC and potentially reduce unnecessary extensive surgery.
Key Findings
- Calcitonin >10 pg/mL: sensitivity 0.91, specificity 0.98, PPV 0.70, NPV 0.99 for MTC.
- Procalcitonin alone was less sensitive than calcitonin, but added value in the 10–100 pg/mL calcitonin gray zone.
- In the calcitonin 10–100 pg/mL subgroup, procalcitonin 0.04 ng/mL correctly identified 80.9% as MTC vs non-MTC.
Methodological Strengths
- Prospective enrollment with histology-confirmed outcomes.
- Head-to-head preoperative measurement of calcitonin and procalcitonin with prespecified cut-offs.
Limitations
- Single-center study with a relatively small number of MTC cases (n=23).
- Assay-dependent thresholds may limit external generalizability; stimulation tests were not addressed.
Future Directions: Multi-center validation of the two-step algorithm, evaluation across assays and stimulated testing, and assessment of surgical decision impacts and cost-effectiveness.
OBJECTIVE: Calcitonin (CT) represents the most important biochemical marker of medullary thyroid cancer (MTC), but has certain limits. Procalcitonin (ProCT) has been recognized as an alternative or additional marker for MTC. The aim of the study is to evaluate prospectively the role of ProCT combined with CT in the identification of MTC. DESIGN: Patients and measurements: 478 patients undergoing thyroidectomy in Padua between January 2023 and June 2024 were enrolled to investigate ProCT levels in comparison with CT for MTC diagnosis. Serum levels of ProCT and CT were dosed preoperatively. RESULTS: At histological diagnosis, 23/478 (4.8%) patients tested positive for MTC. CT with a cut-off > 10 pg/mL performed as follows: sensitivity 0.91, specificity 0.98, positive predictive value (PPV) 0.7, negative predictive value (NPV) 0.99. CT with a cut-off > 10 pg/mL performed better than ProCT both using the cut-off of 0.04 ng/mL (sensitivity 0.87; specificity 0.96; PPV 0.56; NPV 0.99) and the cut-off of 0.07 ng/mL (sensitivity 0.78; specificity 0.98; PPV 0.72; NPV 0.99). Within the sample of patients with a CT value between 10 and 100 pg/mL, 17/21 (80.9%) patients would have been correctly identified as MTC or non-MTC based on a positive or negative ProCT using the 0.04 ng/mL cut-off. CONCLUSIONS: CT is more sensitive than ProCT as a diagnostic marker for MTC. However, a two-step approach using ProCT as a supplementary marker can help to refine the diagnosis avoiding overtreatment, particularly when CT serum levels lie between 10 and 100 pg/mL.