Pediatric asthma comorbidities: Global impact and unmet needs.

Real-world data on the range and impact of comorbid health conditions that affect pediatric asthma are scant, especially from developing countries. Lack of data hinders effective diagnosis, treatment, and overall management of these complex cases. We, hereby, describe the common pediatric asthma comorbid conditions in terms of evidence for association, potential mechanisms of impact on asthma control, and treatment benefit. Obesity, upper airway allergies, dysfunctional breathing, multiple sensitizations, depressive disorders, food allergy, and gastro-esophageal reflux are common associations with difficult-to-treat asthma. On the other hand, asthma symptoms and/or management may negatively impact the well-being of children through drug adverse effects, worsening of anaphylaxis symptoms, and disturbing mental health. Awareness of these ailments may be crucial for designing the optimum care for each asthmatic child individually and may ultimately improve the quality of life of patients and their families. A multidisciplinary team of physicians is required to identify and manage such comorbidities aiming to mitigate the over-use of asthma pharmacotherapy. Asthma research should target relevant real-world difficulties encountered at clinical practice and focus on interventions that would mitigate the impact of such comorbidities. Finally, policymakers and global healthcare organizations are urged to recognize pediatric asthma control as a healthcare priority and allocate resources for research and clinical interventions. In other words, global asthma control needs support by compassionate scientific partnership.

Early age at menarche and the risk of gestational diabetes mellitus: a cohort study.

PURPOSE: To evaluate whether there is an association between age at menarche (AAM) and the risk of gestational diabetes mellitus (GDM). METHODS: A retrospective cohort study was conducted, including 5390 pregnant women who were screened for GDM at Alexandra Hospital in Athens, Greece over a 15-year period (2000-2014). Maternal age, pre-pregnancy body mass index (BMI), height, family history of type 2 diabetes mellitus, parity, educational and smoking status, and AAM were recorded. The results were expressed as odds ratios (OR) with a 95% confidence interval (95% CI). RESULTS: Pregnant women with GDM experienced earlier menarche compared to normoglycemic women (12.9 ± 1.5 vs 13.1 ± 1.6, p < 0.001, respectively). The OR for a woman with AAM <12 years to develop GDM was 1.08 (95% CI 1.03-1.14), while the OR to be obese was 1.70 (95% CI 1.50-1.90). The multivariate logistic regression analysis showed that AAM is a risk factor for GDM. However, that effect was lost after adjusting for BMI. CONCLUSION: Early AAM may be associated with an increased risk of GDM. Therefore, it can be used to identify high-risk women and implement preconception interventions for GDM prevention. Future studies should be conducted to confirm these findings.

Efficacy and safety of metformin during pregnancy: an update.

During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use during pregnancy is controversial. This review aimed to comprehensively assess the available data on the efficacy and safety of metformin during pregnancy, both for the mother and the offspring. Metformin has been validated for maternal efficacy and safety, achieving comparable glycemic control with insulin. Additionally, it reduces maternal weight gain and possibly the occurrence of hypertensive disorders. During the early neonatal period, metformin administration does not increase the risk of congenital anomalies or other major adverse effects, including lower APGAR score at 5 min, neonatal intensive care unit admissions, and respiratory distress syndrome. Several studies have demonstrated a reduction in neonatal hypoglycemia. Metformin has been associated with an increase in preterm births and lower birth weight, although this effect is controversial and depends on the indication for which it was administered. Evidence indicates possible altered fetal programming and predisposition to childhood obesity and metabolic syndrome during adulthood after use of metformin in pregnancy. With critical questions still requiring a final verdict, ongoing research on the field must be conducted.

Comparison of treatment with insulin detemir and NPH in women with gestational diabetes mellitus: glycemic control and pregnancy outcomes. A retrospective study.

PURPOSE: The objective of this retrospective study was to compare glycemic control, pregnancy outcomes, and neonatal outcomes in women with gestational diabetes mellitus (GDM) treated with (a) insulin detemir and (b) insulin neutral protamine Hagedorn (NPH). METHODS: A total of 192 women with GDM were included in the analysis. Ninety-eight women received detemir, while 94 women received NPH. Data regarding medical history, glycemic control, and time and mode of delivery, as well as neonatal outcomes, were recorded. RESULTS: Baseline characteristics were comparable between the two groups. There were no differences with respect to the week of insulin initiation, total insulin dose, duration of insulin therapy, daily insulin dose/weight in early and late pregnancy, or the number of insulin injections per day. Maternal overall weight gain during pregnancy and weight gain per week did not differ either. The detemir group had slightly lower HbA1c levels at the end of gestation [median: det 5.2% (33 mmol/mol) vs NPH 5.4% (36 mmol/mol), p=0.035). There were no cases of hypoglycemia or allergic reactions in the two groups. There were also no differences regarding neonatal outcomes according to the available data, given that data in some cases were missing. CONCLUSION: The use of insulin detemir was found to be equally effective and safe compared to NPH in women with GDM.

Smoking during pregnancy and gestational diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: To investigate whether maternal cigarette smoking during pregnancy is a risk factor for developing GDM. METHODS: MEDLINE, Scopus, CENTRAL and Google Scholar databases were searched from inception to December 2022 to identify eligible original articles. A systematic review and meta-analysis (weighted data, random-effects model) were performed. The primary outcome was the development of GDM in pregnant women. The results were expressed as odds ratios (OR) with 95% confidence interval (CI) (inverse variance method). Subgroup analysis was planned according to the maternal smoking status and GDM diagnostic criteria. Statistical heterogeneity was checked with the Chi-squared (Chi2) test and the I2 index was used to quantify it. The studies were evaluated for publication bias. RESULTS: Thirty-five studies, including 23,849,696 pregnant women, met the inclusion criteria. The pooled OR of smoking during pregnancy compared with non-smoking (never smokers and former smokers) was 1.06 (95% CI 0.95-1.19), p = 0.30; I2 = 90%; Chi2 = 344; df=34; p < 0.001. Subgroup analysis was performed according to the two-step Carpenter-Coustan diagnostic criteria, due to the high heterogeneity among the other applied methods. The pooled OR for the Carpenter-Coustan subgroup was 1.19 (95% CI 0.95-1.49), p = 0.12; I2 = 63%; Chi2 = 27; df=10; p < 0.002. Further subgroup analysis according to maternal smoking status was not performed due to missing data. CONCLUSION: There is no evidence to support an association between maternal cigarette smoking during pregnancy and the risk for GDM. Universally accepted diagnostic criteria for GDM must be adopted to reduce heterogeneity and clarify the association between smoking and GDM.

A Study of the Metabolic Pathways Affected by Gestational Diabetes Mellitus: Comparison with Type 2 Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) remains incompletely understood and increases the risk of developing Diabetes mellitus type 2 (DM2). Metabolomics provides insights etiology and pathogenesis of disease and discovery biomarkers for accurate detection. Nuclear magnetic resonance (NMR) spectroscopy is a key platform defining metabolic signatures in intact serum/plasma. In the present study, we used NMR-based analysis of macromolecules free-serum to accurately characterize the altered metabolic pathways of GDM and assessing their similarities to DM2. Our findings could contribute to the understanding of the pathophysiology of GDM and help in the identification of metabolomic markers of the disease. METHODS: Sixty-two women with GDM matched with seventy-seven women without GDM (control group). 1H NMR serum spectra were acquired on an 11.7 T Bruker Avance DRX NMR spectrometer. RESULTS: We identified 55 metabolites in both groups, 25 of which were significantly altered in the GDM group. GDM group showed elevated levels of ketone bodies, 2-hydroxybutyrate and of some metabolic intermediates of branched-chain amino acids (BCAAs) and significantly lower levels of metabolites of one-carbon metabolism, energy production, purine metabolism, certain amino acids, 3-methyl-2-oxovalerate, ornithine, 2-aminobutyrate, taurine and trimethylamine N-oxide. CONCLUSION: Metabolic pathways affected in GDM were beta-oxidation, ketone bodies metabolism, one-carbon metabolism, arginine and ornithine metabolism likewise in DM2, whereas BCAAs catabolism and aromatic amino acids metabolism were affected, but otherwise than in DM2.

Effect of vaccination on SARS-CoV-2 reinfection risk: a case-control study in the Republic of Cyprus.

OBJECTIVES: We explored the effectiveness of COVID-19 vaccines in preventing reinfection in the Republic of Cyprus. STUDY DESIGN: This was a matched case-control study (1:2). METHODS: Cases were adults with a first episode of SARS-CoV-2 infection in 2020 and a second episode (i.e. reinfection) between June and August 2021. Controls were adults with only one infection episode in 2020 (i.e. not reinfected). Matching was performed by age, gender, and week of diagnosis for the first episode. The reinfection date of a case was applied to the matched controls for estimating full or partial vaccination status. Cases and controls were classified as unvaccinated, partially vaccinated (i.e. vaccination series not completed or final dose received ≤14 days before the reinfection date), or fully vaccinated (i.e. final dose received >14 days before the reinfection date). Conditional logistic regression was performed to calculate odds ratios and 95% confidence intervals for full or partial vaccination, against no vaccination, between controls and cases. RESULTS: This study showed that controls were more likely to be vaccinated (odds ratio for full vaccination: 5.51, 95% confidence interval: 2.43-12.49) than cases. CONCLUSIONS: This finding answers a pressing question of the public and supports the offer of vaccination to people with previous SARS-CoV-2 infection.

Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study.

AIMS: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

Societal Healing in Rwanda: Toward a Multisystemic Framework for Mental Health, Social Cohesion, and Sustainable Livelihoods among Survivors and Perpetrators of the Genocide against the Tutsi.

The genocide against the Tutsi in Rwanda left the country almost completely devastated, with tremendous consequences for mental health, social cohesion, and livelihoods. In the aftermath of such extreme circumstances and human rights violations, societal healing should be conceptualized and approached based on a multisystemic framework that considers these three sectors-mental health, social cohesion, and livelihoods-as well as their interactions. The aims of the present study are twofold: (1) to review evidence on multisystemic healing initiatives already applied in Rwanda using fieldwork notes from interviews and focus groups, alongside relevant scholarly and gray literature, and (2) to propose a scalable multisystemic framework for societal healing in Rwanda that builds on existing innovations. Within a participatory action research methodology, we used a grounded theory approach to synthesize fieldwork findings and compare them with literature to generate a set of principles for multisystemic recovery in Rwanda. Recognizing the strengths and limitations of the current mental health system and other initiatives, including sociotherapy and collaborative livelihood projects, we propose a scalable and rights-based multisystemic approach for recovery and resilience that would target mental health, social cohesion, and sustainable livelihoods within an integrative cross-sectoral framework, thus reducing the risk of post-genocide conflict.

Risk of Major Congenital Malformations or Perinatal or Neonatal Death With Insulin Detemir Versus Other Basal Insulins in Pregnant Women With Preexisting Diabetes: The Real-World EVOLVE Study.

OBJECTIVE: To compare the risk of severe adverse pregnancy complications in women with preexisting diabetes. RESEARCH DESIGN AND METHODS: Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations or perinatal or neonatal death (primary end point) following treatment with insulin detemir (detemir) versus other basal insulins. RESULTS: Of 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations or perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI -0.01, 0.04]; adjusted risk difference -0.003 [95% CI -0.03, 0.03]). The crude prevalence of one or more congenital malformations (major plus minor) was 9.4% vs. 12.6%, with a similar risk difference before (-0.032 [95% CI -0.064, 0.000]) and after (-0.036 [95% CI -0.081, 0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first trimester (6.5% vs. 6.7% [48 vs. 50 mmol/mol]; estimated mean difference -0.181 [95% CI -0.300, -0.062]) and the second trimester (6.1% vs. 6.3% [43 vs. 45 mmol/mol]; -0.139 [95% CI -0.232, -0.046]) and a lower prevalence of major hypoglycemia (6.0% vs. 9.0%; risk difference -0.030 [95% CI -0.058, -0.002]), preeclampsia (6.4% vs. 10.0%; -0.036 [95% CI -0.064, -0.007]), and stillbirth (0.4% vs. 1.8%; -0.013 [95% CI -0.024, -0.002]) with detemir compared with other basal insulins. However, differences were not significant postadjustment. CONCLUSIONS: Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth.

Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: study protocol for a randomized controlled trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance with onset or first recognition during pregnancy, which is characterized by an increased insulin resistance. Gestational diabetes mellitus is associated with pregnancy-related maternal and fetal morbidity (both antenatal and perinatal). Myo-inositol has been suggested to improve insulin resistance in women with polycystic ovary syndrome. The aim of this study is to examine the impact of myo-inositol supplementation during pregnancy on the incidence of gestational diabetes mellitus. METHODS: We will conduct a single-center, open-label, randomized controlled trial. A total of 160 healthy pregnant women with singleton pregnancy at 11-13+6 weeks of gestation will be randomly allocated in two groups: intervention group (N = 80) and control group (N = 80). The intervention group will receive myo-inositol and folic acid (4000 mg myo-inositol and 400 mcg folic acid daily) from 11 to 13+6 weeks of gestation until 26-28 weeks of gestation, while the control group will receive folic acid alone (400 mcg folic acid daily) for the same period of time as intervention group. The primary outcome will be gestational diabetes incidence rate at 26-28 weeks of gestation, according to the results of a 75 g oral glucose tolerance test held at 26-28 weeks of gestation. The secondary outcomes will include fasting blood glucose levels, glycated hemoglobin levels, insulin resistance level (evaluated by homeostasis model assessment of insulin resistance and Matsuda Index), and incidence rate of diet-treated gestational diabetes and diabetes requiring insulin therapy at 26-28 weeks of gestation. DISCUSSION: This trial will provide evidence for the effectiveness of myo-inositol supplementation during pregnancy in reducing the incidence of gestational diabetes mellitus. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16142533 . Registered on 9 March 2017.

Clinical practice guidelines on diabetes mellitus and pregnancy: Ι. Pre-existing type 1 and type 2 diabetes mellitus.

Women with type 1 (T1DM) or type 2 diabetes (T2DM) diagnosed prior to pregnancy are classified as having pre-existing diabetes mellitus (DM). The prevalence of hyperglycemia in pregnancy has been estimated at 17% globally and 5.4% in Europe, differences existing among racial and ethnic groups, following the prevalence of type 2 diabetes. Only a minority (approximately 15%) of the cases of diabetes during pregnancy represent women with pre-existing diabetes. Because of the rising prevalence of obesity and limited screening for diabetes in young women, there has been, globally, an increase in the diagnosis of previously unknown overt diabetes early in pregnancy; these women should be treated as women with pre-existing diabetes, as they may already have unrecognized complications (e.g., nephropathy and retinopathy). The Hellenic Endocrine Society and the Hellenic Society of Maternal-Fetal Medicine commissioned an expert group to construct national guidelines on "Diabetes mellitus and pregnancy: Pre-existing type 1 and 2 diabetes mellitus". Following a search for the best available evidence and critical appraisal of the search results, the writing group generated a series of consensus recommendations regarding preconception counseling and care, care during pregnancy, and care after the pregnancy in cases of pre-existing T1DM and T2DM.

Clinical practice guidelines on diabetes mellitus and pregnancy: ΙI. Gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disease of pregnancy and is associated with several perinatal complications. GDM is defined as diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation. In Europe, in 2016, the prevalence of GDM was estimated to be 5.4% (3.8-7.8). It varied depending on maternal age, year of data collection, country, area of Europe, week of gestation at testing, and diagnostic criteria. The Hellenic Endocrine Society and the Hellenic Society of Maternal-Fetal Medicine commissioned an expert group to construct national guidelines on "Diabetes mellitus and pregnancy: Gestational diabetes mellitus." Following a search for the best available evidence and critical appraisal of the results, the writing group generated a series of consensus recommendations regarding screening tests for the general population, monitoring and management, fetal monitoring, management of preterm labor, planning of labor and delivery, puerperium and breastfeeding, and long-term follow-up of GDM.

Improvement of metabolic control after 3-month use of real-time continuous glucose monitoring in patients with type 1 diabetes: a multicenter study in Greece.

PURPOSE: To assess the efficacy of a real-time continuous glucose monitoring (RT-CGM) system added to insulin pump therapy for 3 months, in sub-optimally controlled adults with type 1 diabetes mellitus (T1D). METHODS: This was a prospective, multicenter, non-randomized, post-market release study. A total of 43 adult patients with T1D on insulin pump therapy and inadequate glycemic control (HbA1c > 7.0%) participated in the study. The primary endpoint was the change from baseline HbA1c levels. Secondary objectives were to evaluate the impact of the RT-CGM system on glucose variability, daily insulin requirements, and the frequency of hypoglycemic and ketoacidosis events. RESULTS: At 3 months, the baseline HbA1c values decreased from 8.0 (7.6, 8.7) to 7.1 (6.7, 8.0) % (p < 0.001). Nineteen participants (44.2%) had a posttreatment HbA1c level ≤ 7%. Average total daily insulin requirements, as well as the average number of insulin boluses per day, increased significantly after the use of the RT-CGM system. The number of hypoglycemic events recorded did not differ between the first week and last week of RT-CGM usage, while no severe hypoglycemic episodes, ketoacidosis events, or hospitalizations related to diabetes occurred during the 3-month follow-up period. CONCLUSION: Addition of a RT-CGM system to insulin pump therapy for 3 months in inadequately controlled patients with T1D resulted in improved HbA1c levels, without increasing the risk of hypoglycemic events.

The effect of smoking on the risk of gestational diabetes mellitus and the OGTT profile during pregnancy.

OBJECTIVE: To analyze the relationship between smoking and the risk of GDM, as well as with the OGTT profile during pregnancy. PATIENTS AND METHODS: A total of 7437 pregnant women were studied. OGTT was performed at the 3rd trimester. Women were categorized as non-smokers (A), as those who ceased smoking at pregnancy (B), and as smokers (C). RESULTS: 5434 (73.1%) women were group A, 1191 (16%) group B and 812 (10.9%) group C. The rates of GDM among the groups were: A 33.7%, B 34.2%, C 34.2% (ns). However, the number of individuals requiring insulin treatment was significantly different: A 39.2%, B 47.5%, C 50.6% (p < 0.001). Regarding OGTT, fasting glucose levels were significantly higher in group C (89 ±â€¯13 vs 86 ±â€¯12 mg/dl) compared to A, whereas 3-h glucose values were significantly lower (104 ±â€¯33 vs 112 ±â€¯32 mg/dl) (p < 0.001). Group B demonstrated intermediate glucose concentrations. Similar findings were observed in women without GDM. In women with GDM, higher 1-h glucose levels were measured in group C (210 ±â€¯31 vs 205 ±â€¯28 mg/dl) compared with A (p = 0.024). Further, group C sub-analysis found that those who smoked more than 10 cigarettes showed significantly lower 3-h glucose levels (111 ±â€¯31 vs 128 ±â€¯40 mg/dl) compared to those who smoked less than 10 (p = 0.006). HbA1c in women with GDM was higher in group C (4.6 ±â€¯0.6 vs 4.5 ±â€¯0.6%) compared with A (p = 0.027). CONCLUSIONS: The present study did not show any correlation between smoking and GDM risk. However, OGTT profile and HbA1c differed according to smoking status in women with and without GDM.

Follow-up at 1 year and beyond of women with gestational diabetes treated with insulin and/or oral glucose-lowering agents: a core outcome set using a Delphi survey.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is linked with a higher lifetime risk for the development of impaired fasting glucose, impaired glucose tolerance, type 2 diabetes, the metabolic syndrome, cardiovascular disease, postpartum depression and tumours. Despite this, there is no consistency in the long-term follow-up of women with a previous diagnosis of GDM. Further, the outcomes selected and reported in the research involving this population are heterogeneous and lack standardisation. This amplifies the risk of reporting bias and diminishes the likelihood of significant comparisons between studies. The aim of this study is to develop a core outcome set (COS) for RCTs and other studies evaluating the long-term follow-up at 1 year and beyond of women with previous GDM treated with insulin and/oral glucose-lowering agents. METHODS: The study consisted of three work packages: (1) a systematic review of the outcomes reported in previous RCTs of the follow-up at 1 year and beyond of women with GDM treated with insulin and/or oral glucose-lowering agents; (2) a three-round online Delphi survey with key stakeholders to prioritise these outcomes; and (3) a consensus meeting where the final COS was decided. RESULTS: Of 3344 abstracts identified and evaluated, 62 papers were retrieved and 25/62 papers were included in this review. A total of 121 outcomes were identified and included in the Delphi survey. Delphi round 1 was emailed to 835 participants and 288 (34.5%) responded. In round 2, 190 of 288 (65.9%) participants responded and in round 3, 165 of 190 (86.8%) participants responded. In total, nine outcomes were selected and agreed for inclusion in the final COS: assessment of glycaemic status; diagnosis of type 2 diabetes since the index pregnancy; number of pregnancies since the index pregnancy; number of pregnancies with a diagnosis of GDM since the index pregnancy; diagnosis of prediabetes since the index pregnancy; BMI; post-pregnancy weight retention; resting blood pressure; and breastfeeding. CONCLUSIONS/INTERPRETATION: This study identified a COS that will help bring consistency and uniformity to outcome selection and reporting in clinical trials and other studies involving the follow-up at 1 year and beyond of women diagnosed with GDM treated with insulin and/or oral glucose-lowering agents during pregnancy.

Different outcomes in sporadic versus familial medullary thyroid cancer.

BACKGROUND: Medullary thyroid carcinoma (MTC) has varying clinical course with familial cases (fMTC) diagnosed earlier than sporadic MTC (spMTC). METHODS: A total of 273 MTCs (familial: n = 110 [40.3%], males: 38.5%) were followed for 1-35 years (median 5.0 years). Fifty one of the familial cases were operated because of positive findings at genetic screening. Disease extent at diagnosis and follow-up was recorded. RESULTS: Mean age at diagnosis was: fMTC = 33.85 ± 16.5 years (range 4-74) and spMTC = 52.6 ± 14.0 years (range 16-81, P < .001). This difference remained when genetic screening cases were excluded. fMTCs had more frequently multifocality, smaller size, and more favorable stage at diagnosis (stages I and II: 60.9% vs 47.9%, stage III: 30.0% vs 23.9%, stage IV: 9.1% vs 28.9%, P = .01). fMTC had lower preoperative and postoperative calcitonin, more frequently remission (59.1% vs 47.2%) and less frequently progressive disease (8.2% vs 35.0%, P < .001). After excluding genetic screening cases, no difference in stage at diagnosis was observed. Outcome was more favorable in fMTC compared to sporadic (P = .002); the 10-year probability of lack of progression of disease differed significantly between fMTCs and spMTCs (86.4% vs 65.0%, P < .001). CONCLUSION: After excluding genetic screening cases, although stage at diagnosis is similar, disease outcome remains worse in sporadic compared to fMTCs.

Fetal hyperthyroidism associated with maternal thyroid autoantibodies: A case report.

A 33-year-old Caucasian woman was referred at 24 + 3 weeks of gestation due to fetal tachycardia and hydrops. She had an uncomplicated pregnancy 16 years previously and was on levothyroxine after total thyroidectomy for Graves' disease 6 years previously, when she developed moderate exophthalmos. Laboratory evaluation revealed appropriate thyroid function for this time of gestation: thyroid stimulating hormone (TSH) 1.7 µU/ml (1-3), fT4 18.53 pmol/l (12-22), with positive antibodies: anti-TPO 157 U/ml (<35), TSH receptor antibodies (TRAb) 171.95 U/l (<1.75). The diagnosis was fetal hyperthyroidism due to transplacental passage of stimulating maternal TRAb. Methimazole and digoxin were initiated. The patient remained euthyroid, with fT4 levels in the upper normal range. The fetus showed intrauterine growth retardation, oligohydramnios, aggravating hydrops, goiter with increased central vascularization and improved heart rate without signs of cardiac failure. At 30 + 3 weeks a hydropic hyperthyroid male newborn (birthweight 1560 g) was delivered by cesarean section and admitted to the neonatal intensive care unit. Cord serum showed neonatal hyperthyroidism. Methimazole and propranolol were administered to the newborn. On the 5th postnatal day the infant died because of severe infection inducing respiratory dysfunction, hemodynamic deterioration and cardiac asystole. Graves' disease occurs in about 0.2% of pregnancies. Hyperthyroidism occurs in 1-5% of neonates born to mothers with Graves' disease and the risk correlates with the maternal TRAb titer. Early diagnosis and treatment are crucial not only in pregnant women with active disease, but also in mothers with a history of Graves' disease, even after definitive treatment such as thyroidectomy or ablative therapy.

Thyroid-stimulating hormone is not the primary regulator of thyroid development in euthyroid children and adolescents living in an iodine-replete area.

OBJECTIVES: It is known that there are multiple factors which can affect thyroid gland development during childhood and adolescence. Our aim was to investigate this issue by examining the relationships between age, sex, several anthropometric parameters, pubertal status, thyroid function tests, and iodine intake status with thyroid volume (TV) in children and adolescents. STUDY DESIGN: This was a cross-sectional field study conducted in 11 representative cities and villages of Uzbekistan. Six hundred and ten children and adolescents participated. Anthropometric indices and TV were estimated. In addition, thyroid function tests (TFTs) and urinary iodine excretion (UIE) measures were obtained. RESULTS: Median UIE was 151 µg/L, thus the studied areas were iodine-sufficient. TFTs fluctuated in both genders during childhood and adolescence and the thyroid growth spurt was observed, in both sexes, at the ages of 12 and 13 years, which coincided with the age of menarche in girls. Thyroid volume was positively correlated with body surface area (BSA) (r = 0.800, p < 0.001), age (r = 0.780, p < 0.001), fat-free mass (FFM) (r = 0.797, p < 0.001) and negatively correlated with serum TSH (r = -0.154, p = 0.05). No association between thyroid volume and UIE was observed. CONCLUSIONS: In euthyroid children and adolescents living in iodine-replete areas, thyroid gland development appears to follow the pattern of linear growth and displays a growth spurt at the onset of puberty, probably due to the abrupt increase of circulating sex steroids. At this age, TSH does not appear to be the main regulator of thyroid gland development.

HbA1c presents low sensitivity as a post-pregnancy screening test for both diabetes and prediabetes in Greek women with history of gestational diabetes mellitus.

BACKGROUND AND AIM: Women with a history of gestational diabetes mellitus (GDM) are at increased risk for type 2 diabetes (T2D). It is thus recommended that an oral glucose tolerance test (OGTT) be performed after delivery. Recently, the use of glycated haemoglobin A1c (HbA1c) has been proposed as a simpler and faster method to diagnose glucose disorders. The aim of this study was to investigate whether HbA1c measurement can replace OGTT in the detection of prediabetes and T2D in women with a history of GDM. PATIENTS AND METHODS: We studied 1336 women (35.3 ± 5.8 years old) with a history of GDM 16.6 ± 28.2 months after delivery. All women were evaluated through an OGTT and a simultaneous HbA1c measurement. American Diabetes Association (ADA) criteria were used for the assessment of glucose disorders. Sensitivity and specificity of HbA1c were measured for the prediction of T2D and prediabetes, while Cohen's coefficient of agreement (k) was calculated. ROC analysis was performed to evaluate the sensitivity and specificity of HbA1c. RESULTS: Based on OGTT, 725 women (54.3%) were normal, 406 (30.4%) presented impaired fasting glucose (IFG), 48 (3.6%) impaired glucose tolerance (IGT), 74 (5.5%) combined IFG+IGT, and 83 presented with T2D (6.2%). By contrast, using HbA1c as a screening test, 1150 women (94.1%) were normal, while 49 (4.0%) had prediabetes and 23 (1.9%) T2D. Sensitivity of HbA1c for the diagnosis of prediabetes was 5.3% in comparison to OGTT, specificity was 99.2%, while for the diagnosis of T2D, the percentages were 29.6 and 100%, respectively. The consistency in classifying impaired glucose tolerance between HbA1c and OGTT was 59.7%. Cohen's coefficient of agreement was k = 0.116, indicating slight agreement. Performing a ROC curve, the optimal value of distinctive ability of HbA1c was 4.6% in the case of prediabetes, while for diabetes, it was 5.5%. CONCLUSION: This study provided evidence that HbA1c can identify fewer women with prediabetes and T2D than OGTT, indicating that HbA1c cannot be recommended as an alternative post-pregnancy screening method.