Higher Thyroid fT3-to-fT4 Ratio Is Associated with Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes.

Aim: To determine the association between thyroid function and the risk of developing gestational diabetes mellitus (GDM) and adverse pregnancy outcomes. Methods: This case−control study was a sub-analysis of the BEDIP-N study, in which 199 GDM women were matched for age and body mass index with 398 controls. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and thyroid peroxidase (TPO) antibodies were measured at 6−14 weeks and 26−28 weeks during pregnancy. TSH and fT4 were also measured in early postpartum in GDM women. Results: The fT3-to-fT4 ratio at 26−28 weeks was positively associated with GDM risk with an adjusted odds ratio (aOR for smoking, education, parity, ethnicity, gestational weight gain, and (family) history of diabetes or GDM) of 2.12 (95% CI 1.07; 4.23), comparing the highest with the lowest tertile. Higher fT3 levels and a higher fT3-to-fT4 ratio were associated with a less favorable metabolic profile with higher BMI and more insulin resistance during pregnancy and postpartum. Women in the upper fT3 tertile and the upper fT3-to-fT4 ratio had a higher rate of preeclampsia [4.6% (10) vs. 1.0% (2), p = 0.040, and 4.4% (9) vs. 0.5% (1), p = 0.020], gestational hypertension [8.3% (18) vs. 3.1% (6), p = 0.034 and 8.9% (18) vs. 2.0% (4), p = 0.003], and caesarean sections [29.4% (63) vs. 16.1% (31), p = 0.002 and 32.2% (65) vs. 12.7% (25), p < 0.001]. Conclusion: A higher fT3-to-fT4 ratio late into pregnancy was associated with GDM, adverse pregnancy outcomes, and an adverse metabolic profile in early postpartum.

Neoplasia in Turner syndrome: a retrospective cohort study in a tertiary referral centre in Belgium.

OBJECTIVES: Patients with Turner syndrome (TS), the most common sex chromosome abnormality in women, can suffer from a variety of well-researched reproductive, cardiovascular, metabolic, and autoimmune comorbidities. Few studies investigate the neoplasia risk. We assessed the general neoplasia risk in TS women, and more specifically, the gonadoblastoma/dysgerminoma risk in the subgroup with Y chromosome mosaicism, and evaluated potential risk factors for neoplasia development, such as karyotype, metabolic and autoimmune comorbidity, and treatment with growth hormone and/or estrogen replacement. DESIGN: 10-year retrospective cohort study in a tertiary referral centre in Belgium. RESULTS: 105 TS women were included (median age 29; range 2-69). Six malignant tumours were detected in 5 (4.8%) patients (SIR = 0.6, 95% CI 0.2-1.0). In addition, 2 benign meningiomas were observed, resulting in 3 (2.9%) tumours of the central nervous system (CNS; SIR = 19.9, 95% CI 4.0-35.8). No breast cancer was noted. Benign neoplasms occurred in 22 women (21.0%), with skin lesions being the most frequent. All patients with Y chromosome mosaicism (n = 9; 8.6%) underwent prophylactic gonadectomy, but gonadoblastoma/dysgerminoma was not detected. A weak association was found between any tumour type and autoimmune comorbidity (r = 0.24; p = 0.02). CONCLUSION: The overall malignancy risk was not increased, but a different pattern of occurrence is apparent, with an increased risk of CNS and skin tumours and a decreased breast cancer risk. Gonadoblastoma/dysgerminoma was not reported. There is a need for centralised multidisciplinary care and prospective research to unravel and predict the neoplasia risk.

Preference of Women for Gestational Diabetes Screening Method According to Tolerance of Tests and Population Characteristics.

Aims: To determine the preferred method of screening for gestational diabetes mellitus (GDM). Methods: 1804 women from a prospective study (NCT02036619) received a glucose challenge test (GCT) and 75g oral glucose tolerance test (OGTT) between 24-28 weeks. Tolerance of screening tests and preference for screening strategy (two-step screening strategy with GCT compared to one-step screening strategy with OGTT) were evaluated by a self-designed questionnaire at the time of the GCT and OGTT. Results: Compared to women who preferred one-step screening [26.2% (472)], women who preferred two-step screening [46.3% (834)] were less often from a minor ethnic background [6.0% (50) vs. 10.7% (50), p=0.003], had less often a previous history of GDM [7.3% (29) vs. 13.8% (32), p=0.008], were less often overweight or obese [respectively 23.1% (50) vs. 24.8% (116), p<0.001 and 7.9% (66) vs. 18.2% (85), p<0.001], were less insulin resistant in early pregnancy (HOMA-IR 8.9 (6.4-12.3) vs. 9.9 (7.2-14.2), p<0.001], and pregnancy outcomes were similar except for fewer labor inductions and emergency cesarean sections [respectively 26.6% (198) vs. 32.5% (137), p=0.031 and 8.2% (68) vs. 13.0% (61), p=0.005]. Women who preferred two-step screening had more often complaints of the OGTT compared to women who preferred one-step screening [50.4% (420) vs. 40.3% (190), p<0.001]. Conclusions: A two-step GDM screening involving a GCT and subsequent OGTT is the preferred GDM screening strategy. Women with a more adverse metabolic profile preferred one-step screening with OGTT while women preferring two-step screening had a better metabolic profile and more discomfort of the OGTT. The preference for the GDM screening method is in line with the recommended Flemish modified two-step screening method, in which women at higher risk for GDM are recommended a one-step screening strategy with an OGTT, while women without these risk factors, are offered a two-step screening strategy with GCT. Clinical Trial Registration: NCT02036619 https://clinicaltrials.gov/ct2/show/NCT02036619.

Estimating the risk of gestational diabetes mellitus based on the 2013 WHO criteria: a prediction model based on clinical and biochemical variables in early pregnancy.

AIMS: We aimed to develop a prediction model based on clinical and biochemical variables for gestational diabetes mellitus (GDM) based on the 2013 World Health Organization (WHO) criteria. METHODS: A total of 1843 women from a Belgian multi-centric prospective cohort study underwent universal screening for GDM. Using multivariable logistic regression analysis, a model to predict GDM was developed based on variables from early pregnancy. The performance of the model was assessed by receiver-operating characteristic (AUC) analysis. To account for over-optimism, an eightfold cross-validation was performed. The accuracy was compared with two validated models (van Leeuwen and Teede). RESULTS: A history with a first degree relative with diabetes, a history of smoking before pregnancy, a history of GDM, Asian origin, age, height and BMI were independent predictors for GDM with an AUC of 0.72 [95% confidence interval (CI) 0.69-0.76)]; after cross-validation, the AUC was 0.68 (95% CI 0.64-0.72). Adding biochemical variables, a history of a first degree relative with diabetes, a history of GDM, non-Caucasian origin, age, height, weight, fasting plasma glucose, triglycerides and HbA1c were independent predictors for GDM, with an AUC of the model of 0.76 (95% CI 0.72-0.79); after cross-validation, the AUC was 0.72 (95% CI 0.66-0.78), compared to an AUC of 0.67 (95% CI 0.63-0.71) using the van Leeuwen model and an AUC of 0.66 (95% CI 0.62-0.70) using the Teede model. CONCLUSIONS: A model based on easy to use variables in early pregnancy has a moderate accuracy to predict GDM based on the 2013 WHO criteria.

Evolution in the management of thyroid cancer: an observational study in two referral centres in Belgium.

Objective Thyroid cancer incidence is increasing. The rise is most pronounced for microcancers (≤10 mm, T1a). In 2006, landmark European and American guidelines for the management of thyroid cancer were published. We studied thyroid cancer characteristics and initial management before and after 2006. Methods We conducted a retrospective observational study of non-medullary thyroid cancer patients that underwent thyroidectomy in two Belgian referral centres comparing pre-, per- and post-operative management in a cohort before and after 2006. Results Cancer subtypes and dimensions in cohort 1 (C1, n = 69) and cohort 2 (C2, n = 60) were comparable, with papillary thyroid cancer (PTC) as main subtype (86 and 82%, respectively), and T1a as main dimension (30 and 38%). In C2, a comparable proportion presented as incidentaloma (20 vs. 14% in C1). Pre-surgical fine needle aspiration (FNA) was performed in 75% in C1 and 83% in C2. The indications for thyroidectomy were comparable, with Bethesda 5-6 as main indication (43% in C1, 52% in C2). No differences were observed for execution of lymph node dissection in the PTC subgroup, hypoparathyroidism and recurrent nerve paresis after 1 year. Less radioiodine was administered in C2 (57 vs 74% in C1, p = 0.04). More neck ultrasonography at 1 year was performed in >T1aN0/x patients (73 vs 49% in C1, p = 0.02). Conclusion The use of FNA is high and established. The proportion of T1a cancers is stable. A shift in the post-operative management is observed towards more restrictive use of radioiodine and increased use of ultrasonography, in accordance with the international guidelines.

MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset.

Macrophages contribute in the initiation and progression of insulitis during type 1 diabetes (T1D). However, the mechanisms governing their recruitment into the islets as well as the manner of retention and activation are incompletely understood. Here, we investigated a role for macrophage migration inhibitory factor (MIF) and its transmembrane receptor, CD74, in the progression of T1D. Our data indicated elevated MIF concentrations especially in long-standing T1D patients and mice. Additionally, NOD mice featured increased MIF gene expression and CD74+ leukocyte frequencies in the pancreas. We identified F4/80+ macrophages as the main immune cells in the pancreas expressing CD74 and showed that MIF antagonism of NOD macrophages prevented their activation-induced cytokine production. The physiological importance was highlighted by the fact that inhibition of MIF delayed the onset of autoimmune diabetes in two different diabetogenic T cell transfer models. Mechanistically, macrophages pre-conditioned with the MIF inhibitor featured a refractory capacity to trigger T cell activation by keeping them in a naïve state. This study underlines a possible role for MIF/CD74 signaling pathways in promoting macrophage-mediated inflammation in T1D. As therapies directed at the MIF/CD74 pathway are in clinical development, new opportunities may be proposed for arresting T1D progression.