CONTEXT:An increased risk of birth defects in children born to mothers with hyperthyroidism has been found, and uncertainties prevail on the role of maternal thyroid function and thyroid autoimmunity. OBJECTIVE:To evaluate the association between maternal thyroid function, thyroid autoantibodies, and birth defects. METHODS:Retrospective cohort study of 20 399 pregnant women with no known thyroid disease and their children from the Danish National Birth Cohort and the North Denmark Region Pregnancy Cohort. Blood samples from early pregnancy (median week 10) were assessed for maternal TSH and free T4 in both cohorts and for thyroid peroxidase antibodies and thyroglobulin antibodies as well as TSH receptor antibodies and thyroid stimulating immunoglobulin in the North Denmark Region Pregnancy Cohort. Information on birth defects was retrieved from hospital diagnoses. RESULTS:Altogether 702 children (3.4%) had birth defects, and maternal median TSH (no birth defects: 1.13 mIU/L; birth defects: 1.19 mIU/L; P = .1) and free T4 (no birth defects: 15.5 pmol/L; birth defects: 15.7 pmol/L; P = .3) did not differ by outcome of birth defect. The prevalence of birth defects was similar in children born to mothers who were thyroid peroxidase antibodies- or thyroglobulin antibodies-positive (4.3%) or negative (4.0%; P = .6) but higher (9.5%) when the mother was positive for TSH receptor antibodies or thyroid stimulating immunoglobulin (P = .003). CONCLUSION:In a large Danish pregnancy cohort, no evidence was found that maternal thyroid function in early pregnancy is associated with a risk of birth defects. A possible link with maternal thyroid stimulating antibodies warrants further investigation.

Thyroid hormones are involved in the regulation of haemostasis, and it has been hypothesised that abnormal levels of thyroid hormones are associated with an increased risk of excessive bleeding. However, this association is yet to be investigated in pregnant women. We performed a retrospective nationwide cohort study of Danish pregnant women from 1999 to 2015. Information on maternal hyperthyroidism and hypothyroidism diagnosed before/during or after the pregnancy, as well as outcomes of bleeding in early and late pregnancy, was collected via the Danish nationwide health registers on hospital diagnoses and drug prescriptions. Multivariate logistic regression was used to calculate adjusted odds ratio (aOR) with a 95

Background/Objectives: Patients with diabetes undergoing hemodialysis (HD) are at risk of asymptomatic hypo- and hyperglycemia within 24 hours of dialysis. Continuous glucose monitoring (CGM) can improve glycemic control, and machine learning offers a promising approach to detect and predict glycemic excursions based on CGM data. This study aimed to develop machine learning models to predict substantial hypo- and hyperglycemia on dialysis days using CGM data and baseline characteristics. Methods: Using data from 21 patients with diabetes receitarving HD, three classification models (Logistic Regression, XGBoost, and TabPFN) were trained and tested. Predictive features included CGM-derived metrics, HbA1c levels, and insulin use. A binary classification approach was used to predict level 2 hyperglycemia and level 1 hypoglycemia based on international consensus targets; CGM derived Time Above Range (TAR) ≥10% and Time Below Range (TBR) ≥1%. Results: A total of 555 dialysis days were included in the analysis. The Logistic Regression model achieved the best performance for predicting hyperglycemia (F1 score: 0.85 [CI95,0.75-0.91]; ROC-AUC: 0.87 [CI95,0.78-0.93]). For hypoglycemia, TabPFN performed best (F1 score: 0.48 [CI95,0.26-0.69]; ROC-AUC: 0.88 [CI95,0.77-0.94]). Conclusion: Prediction of substantial hypo- and hyperglycemia in patients with diabetes undergoing HD appears feasible using machine learning models. Additional studies are needed to confirm clinical utility and generalizability. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research received no external funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: In this study, prediction models were developed, trained, tested, and compared based on data collected as part of a 16-week crossover trial (ClinicalTrials.gov ID: [NCT05678712][1]) conducted in Denmark by Steno Diabetes Center North, Aalborg University Hospital, and the Department of Health Science and Technology, Aalborg University. The use of data for developing and testing prediction models was approved by The North Denmark Regional Committee on Health Research Ethics (journal number: N-20210070). The study complied with data responsibility requirements and the General Data Protection Regulation (GDPR). Informed consent was obtained from all participating patients, and the study was conducted in accordance with the ethical principles of the Declaration of Helsinki and adhered to relevant national and institutional guidelines for research ethics. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data cannot be published because it contains sensitive and identifying patient information. Access to the patient data through a remote desktop connection can be obtained after acceptance of a research/development/quality project application by the local approval body at Aalborg University. Contact information: Forskningsdata og Statistik, Forskningens Hus, Sdr. Skovvej 15 9000 Aalborg, Denmark, e-mail: forskningsanmeldelse{at}rn.dk. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05678712&atom=%2Fmedrxiv%2Fearly%2F2025%2F10%2F25%2F2025.10.24.25338707.atom

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

BackgroundHypoparathyroidism following total thyroidectomy is globally the most common complication to thyroid surgery. The reported complication rates vary widely and might be highly dependent on the surgical experience. In this study we aimed to evaluate the rate of hypoparathyroidism following primary total thyroidectomy at a low-volume institution that only performs thyroid surgery and does not have any experience with parathyroid surgery.MethodsRetrospective cohort study. All patients undergoing primary total thyroidectomy at the ENT-Department, Goedstrup Hospital, Denmark, over a 5-year period (2016-2020) were identified through the procedure codes for total thyroidectomy. Medical records, pathology reports, biochemical and medical histories were fully assessed for each patient. The primary endpoint was the rate of hypoparathyroidism- both immediate and permanent. Secondary outcomes were parathyroid gland identification rates, rates of parathyroid gland autotransplantation, and rates of inadvertent parathyroid gland excision.ResultsA total of 89 patients were included in the final analysis. A total of 33 patients (37.1%) experienced immediate hypoparathyroidism following surgery, while 30 patients (33.7%) still were on active vitamin D two months postoperatively. One year following surgery, 28 patients (31.5%) were still on active vitamin D and were considered as having permanent hypoparathyroidism. Sixty-one percent of the parathyroid glands were identified intraoperatively, and 19% of the patients experienced parathyroid autotransplantation. Inadvertent parathyroid gland excision occurred for 21% of the patients and was associated with a significantly increased risk of permanent hypoparathyroidism (RR = 2.99; 95% CI: 1.36 – 6.62, p = 0.005).ConclusionBoth transient and permanent hypoparathyroidism following total thyroidectomy at a low-volume, non-parathyroid institution occurred with much higher frequencies than previously reported. The elevated rates were most likely due to the low-volume, non-parathyroid nature of the surgeons which in part was mirrored in low parathyroid gland identifications rates, and high rates of autotransplantation and inadvertent parathyroid gland excision.

Parathyroid hormone (PTH) is a routine biochemical analysis, and it varies whether a second- or third-generation assay is used. Information on the levels obtained with different assays and evidence to substantiate local assay-specific reference ranges are important to inform clinical practice. Prior to a shift from the second- to the third-generation PTH assay (Cobas 8000, Roche Diagnostics) in the Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark, a total of 59 EDTA-plasma samples were collected for method comparison (Passing-Bablok). Furthermore, 120 EDTA-plasma samples were randomly obtained from adult blood donors and used for the establishment of reference intervals using the third-generation PTH assay (Cobas 8000, Roche Diagnostics) and two second-generation assays (Atellica, Siemens Healthineers; Alinity, Abbott Laboratories). Method comparison (Cobas 8000, Roche Diagnostics) showed lower levels with the third-generation (y) as compared to the second-generation assay (x) depending on the measurement range (PTH < 10 pmol/L: y = 0.8 (95% CI: 0.7; 0.9) x + 0.3 (95% CI: 0.2; 0.5), PTH >= 10 pmol/L: y = 0.6 (95% CI: 0.5; 0.6) x + 3.2 (95% CI: 1.1; 5.2)). Method-specific reference intervals (2.5 and 97.5 percentiles) after the exclusion of samples (n = 31) with 25-hydroxy-vitamin D below 50 nmol/L were: 1.8-8.5 pmol/L (second-generation, Atellica, Siemens Healthineers); 2.4-10.9 pmol/L (second-generation, Alinity, Abbott Laboratories), and 1.8-7.0 pmol/L (third-generation, Cobas 8000, Roche Diagnostics). PTH levels with second- and third-generation assays are not interchangeable. Clinicians should be informed when a laboratory assay is changed, and method-specific reference ranges are needed.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Objective Thyroid disease in women of reproductive age is mainly of autoimmune origin, and thyroid peroxidase antibodies (TPO-Ab) as well as thyroglobulin antibodies (Tg-Ab) are key markers. Adding to this, much focus in pregnancy is on euthyroid women who are thyroid antibody positive. Evidence to substantiate the cut-offs for the definition of thyroid autoantibody positivity in early pregnant women is warranted. Methods Stored serum samples from 14,030 Danish pregnant women were used for the measurement of TPO-Ab, Tg-Ab, TSH, and free thyroxine (ADVIA Centaur XPT, Siemens Healthineers). Among all women, a reference cohort of 10,905 individuals was identified for the establishment of antibody cut-offs. Percentile cut-offs for TPO-Ab and Tg-Ab were determined using regression on order statistics (the reference cohort). The established cut-offs were then applied (the full cohort), and frequencies of early pregnancy as well as later diagnosis of hypothyroidism were evaluated. Results The highest established cut-offs (95th, 97.5th, and 99th percentiles) were 59, 68, and 81 U/mL for TPO-Ab and 33, 41, and 52 U/mL for Tg-Ab. When the cut-offs were applied in the full cohort, 11.0, 10.2, and 9.7% were TPO-Ab positive, whereas 13.3, 12.3, and 11.2% were Tg-Ab positive. Antibody-positive women (TPO-Ab and/or Tg-Ab) had higher median TSH and were more likely to have hypothyroidism in early pregnancy and to be diagnosed with hypothyroidism during follow-up. Conclusions This large study established and evaluated pregnancy-specific cut-offs for TPO-Ab and Tg-Ab. The findings are important regarding the classification of exposure in pregnancy and assessment of thyroid autoimmunity per se.

OBJECTIVE:Hypothyroidism has been associated with pregnancy complications, but uncertainty prevail regarding the severity and the role of thyroid autoimmunity. This study aimed to evaluate adverse pregnancy outcomes by exposure to maternal hypothyroidism and thyroid autoimmunity.DESIGN:Retrospective cohort study.PATIENTS:14,744 singleton pregnancies from the North Denmark Region Pregnancy Cohort (2011-2015).MEASUREMENTS:Maternal thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) were retrospectively measured in early pregnancy blood samples (ADVIA Centaur XPT, Siemens Healthineers). Adjusted odds ratio (aOR) with 95% confidence interval (CI) was used to estimate associations between maternal hypothyroidism (TSH cut-offs: 6.0 and 10 mIU/L), thyroid autoimmunity (TPO-Ab cut-off: 60 U/ml, Tg-Ab cut-off: 33 U/ml), and adverse pregnancy outcomes.RESULTS:Pregnancy outcomes were 93.2% live births, 6.5% spontaneous abortions, and 0.3% stillbirths. The frequency of spontaneous abortion was 6.5% when TSH was below 6.0 mIU/L, 6.5% when above 6.0 mIU/L (aOR 1.0 [95% CI: 0.5-2.0]), and 12.5% when above 10 mIU/L (aOR: 2.0 [95% CI: 0.8-5.2]). For outcome of preterm birth, the frequency was 5.4% when TSH was below 6.0 mIU/L, 7.8% when above 6.0 mIU/L (aOR 1.5 [95% CI: 0.7-2.9]), and 11.4% when above 10 mIU/L (aOR: 2.6 [95% CI: 0.9-7.3]). No association was found between thyroid autoantibodies and spontaneous abortion (TPO-Ab: aOR: 1.0 [0.8-1.3], Tg-Ab: 1.0 [0.8-1.2]) or preterm birth (TPO-Ab: aOR: 1.0 [0.8-1.2], Tg-Ab: 0.9 [0.7-1.2]).CONCLUSION:A high frequency of adverse pregnancy outcomes was seen among pregnancies exposed to maternal TSH above 10 mIU/L, whereas no association with thyroid autoantibodies was seen.

Objective A high activity of the deiodinase type 2 has been proposed in overweight, obese, and smoking pregnant women as reflected by a high triiodothyronine (T3)/thyroxine (T4) ratio. We speculated how maternal adiposity and smoking would associate with different thyroid function tests in the early pregnancy. Design Cross-sectional study within the North Denmark Region Pregnancy Cohort. Methods Maternal thyroid-stimulating hormone (TSH), total T4 (TT4), total T3 (TT3), free T4 (fT4), and free T3 (fT3) were measured in stored blood samples (median gestational week 10) by an automatic immunoassay. Results were linked to nationwide registers, and live-birth pregnancies were included. The associations between maternal adiposity (overweight or obese), smoking, and log-transformed TSH, fT3/fT4 ratio, and TT3/TT4 ratio were assessed using multivariate linear regression and reported as adjusted exponentiated β coefficient (aβ) with 95% CI. The adjusted model included maternal age, parity, origin, week of blood sampling, and diabetes. Results Altogether 5529 pregnant women were included, and 40% were classified with adiposity, whereas 10% were smoking. Maternal adiposity was associated with higher TSH (aβ 1.13 (95% CI 1.08–1.20)), whereas maternal smoking was associated with lower TSH in the early pregnancy (0.875 (0.806–0.950)). Considering the T3/T4 ratio, both maternal adiposity (fT3/fT4 ratio: 1.06 (1.05–1.07); TT3/TT4 ratio: 1.07 (1.06–1.08)) and smoking (fT3/fT4 ratio: 1.07 (1.06–1.09); TT3/TT4 ratio: 1.10 (1.09–1.12)) were associated with a higher ratio. Conclusions In a large cohort of Danish pregnant women, adiposity and smoking showed opposite associations with maternal TSH. On the other hand, both conditions were associated with a higher T3/T4 ratio in early pregnancy, which may reflect altered deiodinase activity.

OBJECTIVE:Abnormal thyroid function in pregnant women is a matter of concern. Knowledge on the occurrence of known and unidentified thyroid function abnormalities in a large unselected cohort of pregnant women is warranted as part of the debate on benefits and risks of routine testing.DESIGN:Cohort study.PARTICIPANTS:A total of 14 323 pregnant women in the North Denmark Region, who had a blood sample drawn as part of the prenatal screening program in early pregnancy (2011-2015).MEASUREMENTS:TSH, free thyroxine, thyroid peroxidase and thyroglobulin antibodies were measured in the stored blood samples using an automatic immunoassay (ADVIA Centaur XPT, Siemens Healthineers). Cohort-, method- and week-specific reference ranges were used for classification of maternal thyroid function, and a cut-off of 60 U/mL was used for thyroid autoantibodies. Information in Danish nationwide registers was used to identify diagnosed and treated maternal thyroid disease.RESULTS:Overall, 15.2% had thyroid function abnormalities in the early pregnancy and 14.9% were thyroid peroxidase and/or thyroglobulin antibody positive. Among women with known thyroid disease (n = 365), the frequency of abnormal thyroid function was 45.7%, and 62.8% in women (n = 172) who received current treatment in the pregnancy. When maternal thyroid disease was diagnosed in the years following pregnancy (n = 313), 46.7% had abnormal thyroid function and 54.3% were thyroid peroxidase and/or thyroglobulin antibody positive in the early pregnancy.CONCLUSION:Thyroid function abnormalities and thyroid autoantibodies were common in Danish pregnant women, particularly in women with known or later diagnosed thyroid disease, which raises concern about inadequately treated and unidentified abnormal thyroid function.

CONTEXT:Physiological alterations challenge the assessment of maternal thyroid function in pregnancy. It remains uncertain how the reference ranges vary by week of pregnancy, and how the classification of disease varies by analytical method and type of thyroid function test.DESIGN:Serum samples from Danish pregnant women (n = 6282) were used for the measurement of thyrotropin (TSH), total and free thyroxine (T4), total and free 3,5,3'-triiodothyronine (T3), and T-uptake using "Method A" (Cobas 8000, Roche Diagnostics). TSH and free T4 were also measured using "Method B" (ADVIA Centaur XP, Siemens Healthineers).MAIN OUTCOME MEASURES:Pregnancy week- and method-specific reference ranges were established among thyroid antibody-negative women (n = 4612). The reference ranges were used to classify maternal thyroid function, and results were compared by analytical method and type of thyroid function test.RESULTS:The reference ranges for TSH showed a gradual decrease during pregnancy weeks 4 to 14, a gradual increase was observed for total T4, total T3, and T-uptake, whereas free T4 and free T3 showed less variation. When TSH and free T4 were used, Method A classified 935 (14.9%) with abnormal thyroid function, Method B a total of 903 (14.4%), and the methods agreed on 554 individuals. When TSH and total T4 were used, 947 (15.1%) were classified with abnormal thyroid function, and classifications by either total T4 or free T4 agreed on 584 individuals.CONCLUSIONS:Even when pregnancy week- and method-specific reference ranges were established, the classification of maternal thyroid dysfunction varied considerably by analytical method and type of thyroid function test.

CONTEXT:Antithyroid drug (ATD) therapy in early pregnancy is associated with birth defects, but more data are needed to substantiate the risk associated with different types of ATD. Furthermore, the role of abnormal maternal thyroid function per se remains unclarified.OBJECTIVE:To evaluate the risk of birth defects associated with the use of ATD in an extended nationwide cohort and the role of abnormal maternal thyroid function in birth cohorts including stored maternal blood samples from early pregnancy.PARTICIPANTS:Danish pregnant women and their live-born children, including 1,243,353 children from a Nationwide Register-Based Cohort (NRBC), 1997 to 2016; 8830 children from the Danish National Birth Cohort (DNBC), 1997 to 2003; and 14,483 children from the North Denmark Region Pregnancy Cohort (NDRPC), 2011 to 2015.MAIN OUTCOME MEASURES:Birth defects diagnosed before 2 years of age.RESULTS:In the NRBC, altogether 2718 (0.2%) children had been exposed to ATD in early pregnancy. The overall frequency of birth defects was 6.7% (95% CI, 6.7% to 6.8%) in nonexposed children and higher after exposure to methimazole/carbimazole (9.6%; 95% CI, 8.2% to 11.2%) and propylthiouracil (8.3%; 95% CI, 6.7% to 10.3%). On the other hand, the frequency of maternal thyroid dysfunction in early pregnancy was similar in the random cohort and in cases of birth defect in the DNBC (12.4 vs 12.6%, P = 0.8) and the NDRPC (15.1 vs 15.4%, P = 0.8).CONCLUSIONS:Results corroborate an increased risk of birth defects associated with the use of ATD in early pregnancy and suggest that abnormal maternal thyroid function is not a major risk factor for birth defects.