Screening and management of major endocrinopathies during pregnancy: an update.

Endocrinopathies during pregnancy constitute a challenging issue, being prevalent and requiring appropriate management to avoid maternal and fetal complications. This review aims to summarize and present major endocrine problems during pregnancy, the appropriate screening, maternal monitoring and management, fetal monitoring, and follow-up. Glucose metabolism, thyroid function, as well as calcium and vitamin D metabolism are the main endocrine domains that should be screened and monitored during pregnancy. Gestational diabetes mellitus (GDM) is the most prevalent endocrine disease during pregnancy, followed by thyroid disorders. Specific recommendations are provided for the optimal clinical care of pregnant women and their offspring for GDM, thyroid disorders, and calcium and vitamin D disorders.

Thyroid autoimmunity following alemtuzumab treatment in multiple sclerosis patients: a prospective study.

Autoimmune thyroid disease (AITD) is the most common adverse effect in alemtuzumab (ALZ) treated relapsing-remitting (RR) multiple sclerosis (MS) patients. The objective of this prospective study was to analyze the occurrence, timing of onset, clinical course, and laboratory characteristics of AITD post-ALZ. We evaluated 35 RRMS patients treated with ALZ at a single academic MS center; clinical and laboratory data were collected before ALZ initiation and thereafter quarterly on follow-up with a median of 43.5 months. Seventeen out of 31 patients (54.8%) with no prior history of thyroid dysfunction developed AITD with a mean onset of 19.4 months ± 10.2 (SD) after the first ALZ cycle; Graves' disease (GD) (n = 9); hypothyroidism with positive stimulating thyrotropin receptor antibodies (TRAb) (n = 1); Hashimoto thyroiditis (HT) (n = 6); HT with hypothyroidism (n = 1). Interestingly, seven of nine (77.7%) GD patients showed a fluctuating course. Three out of four patients with preexisting thyroid disease remained stable, whereas one with prior HT and hypothyroidism developed fluctuating GD. All patients with GD commenced antithyroid drugs (ATDs); five continued on "block and replace" treatment; one required radioactive iodine, and one total thyroidectomy. Our analysis showed earlier onset of ALZ-induced AITD in comparison to most other ALZ cohorts; overall, these patients required complex therapeutic approaches of the AITD. We observed a higher rate of fluctuating GD, with earlier onset and lower remission rate than previously reported, which in the majority of patients required prolonged "block and replace" therapy in the minimum dose of each therapeutic agent or more definitive interventions.

Patients with type 2 diabetes mellitus present similar immunological response to COVID-19 BNT162b2 mRNA vaccine to healthy subjects: a prospective cohort study.

AIM: To compare the kinetics of neutralizing antibodies (NΑbs) against SARS-CoV-2 after vaccination with the BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with T2DM and healthy controls. METHODS: NAb levels after the BNT162b2 mRNA vaccine were compared between 50 patients with non-insulin treated T2DM and 50 age-, gender-, and BMI-matched healthy controls up to 3 months after the second dose. The median age of both groups was 70 years. RESULTS: On day 1, mean NAbs of the control and T2DM groups were 14.64% (standard error, SE = 2.30) and 14.04% (SE = 2.14), respectively (p value = 0.926). Three weeks later, the mean NAb values were 39.98% (SE = 3.53) in the control group and 40.97% (SE = 3.99) in participants with T2DM (p value = 0.698). One month after the second vaccination, mean NAb values increased to 87.13% (SE = 2.94) in the control group and 89.00% (SE = 2.18) in the T2DM group. Three months after the second vaccine dose, the mean inhibitory titers decreased to 83.49% (SE = 3.82) (control group) and 76.36% (SE = 3.33) (T2DM group). On all occasions, no significant difference was found between the two groups (all p values > 0.05). CONCLUSIONS: Patients with T2DM present similar immunological response to COVID-19 BNT162b2 mRNA vaccine to that of healthy subjects.

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.

Benign and malignant thyroid nodules with autoimmune thyroiditis.

Objective: The prevalence of autoimmune thyroiditis (AT) in papillary thyroid carcinoma (PTC) is still controversial. The aim of this study was to investigate the frequency of coexistence of PTC with AT versus that of the coexistence of benign nodules with AT. Materials and methods: This was a cross-sectional retrospective study including patients operated on for thyroid nodules from January 2011, to April 2021. The frequency of papillary carcinomas cooccurring with AT was compared to that of benign nodules cooccurring with AT, which was assessed based on cytopathological diagnosis after thyroidectomy. Results: The study included 668 cases of benign nodules and 420 cases with PTC. No statistically significant difference was observed between cases of benign and PTC nodules regarding the presence of AT (25% vs. 28%, respectively, p = 0.177). The size of the PTC compared to that of the benign predominant nodules was significantly smaller both in the absence (0.96 ± 1.09 cm vs. 2.19 ± 1.06 cm, p < 0.05) and in the presence (0.77 ± 0.76 cm vs. 1.67 ± 1.08 cm, p < 0.01) of AT. In the binary logistic regression analysis of the PTC, the only variable associated with AT was multifocality (odds ratio: 1.750, 95% confidence intervals: 1.131-2.706, p = 0.013). The incidences of lymph node involvement and advanced stage PTC were very low both in the presence and absence of AT. Conclusion: The nodules present with PTC were not more likely to coexist with AT than benign nodules were. The small incidence of advanced PTC indicates a significant improvement in early-stage diagnosis.

Recurring subacute thyroiditis after SARS-CoV-2 mRNA vaccine: A case report.

SARS-CoV-2 vaccination is the most powerful and promising tool against the COVID-19 pandemic. Millions of people have been vaccinated worldwide. Recently, few cases of subacute thyroiditis following SARS-CoV-2 vaccination with various types of vaccine have been reported. We describe here a 36-year-old woman who presented with subacute thyroiditis 10 days after she had received her first dose of the SARS-CoV-2 mRNA vaccine Comirnaty (Pfizer/BioNTech); the condition receded but then recurred 10 days after she received her second dose. As vaccination programmes proceed, clinicians' attention and vigilance for such cases will be increased. Physicians need to know that subacute thyroiditis is a mild and self-limiting condition in the majority of cases. Last but not least, the benefits of vaccination against COVID-19 outweigh the side-effects reported so far.

The effect of allopurinol on cardiovascular outcomes in patients with type 2 diabetes: a systematic review.

BACKGROUND: Cardiovascular disease (CVD) remains the main cause of death in patients with type 2 diabetes (T2D). Although hyperuricemia has been associated with multiple CV complications, it is not officially recognized as a target parameter for CVD risk reduction. AIM: To systematically review the literature in order to determine whether treating hyperuricemia with allopurinol in patients with T2D reduces CVD risk. METHODS: A thorough literature search in the PubMed, CENTRAL, and EMBASE databases from inception to August 2022 was performed. After application of selection criteria, 6 appropriate studies were identified. RESULTS: Detailed analysis of the data derived indicated that there is an association between allopurinol treatment and CV benefits, resulting in a reduced risk of CVD events and mortality rates. This association can be attributed mainly to the reduction of inflammation and oxidative burden, as well as to the improvement of glycemic and lipid profiles. CONCLUSIONS: This systematic review provides evidence that allopurinol may reduce CVD risk in patients with T2D. Randomized, placebo-controlled trials should be performed in order to confirm these findings and identify specific subgroups of patients who will benefit most.

Patients With Autoimmune Thyroiditis Present Similar Immunological Response to COVID-19 BNT162b2 mRNA Vaccine With Healthy Subjects, While Vaccination May Affect Thyroid Function: A Clinical Study.

Background: This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech). Methods: The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50). Results: Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG. Conclusions: This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function.

Early and late endocrine complications of COVID-19.

Endocrine system plays a vital role in controlling human homeostasis. Understanding the possible effects of COVID-19 on endocrine glands is crucial to prevent and manage endocrine disorders before and during hospitalization in COVID-19-infected patients as well as to follow them up properly upon recovery. Many endocrine glands such as pancreas, hypothalamus and pituitary, thyroid, adrenal glands, testes, and ovaries have been found to express angiotensin-converting enzyme 2 receptors, the main binding site of the virus. Since the pandemic outbreak, various publications focus on the aggravation of preexisting endocrine diseases by COVID-19 infection or the adverse prognosis of the disease in endocrine patients. However, data on endocrine disorders both during the phase of the infection (early complications) and upon recovery (late complications) are scarce. The aim of this review is to identify and discuss early and late endocrine complications of COVID-19. The majority of the available data refer to glucose dysregulation and its reciprocal effect on COVID-19 infection with the main interest focusing on the presentation of new onset of diabetes mellitus. Thyroid dysfunction with low triiodothyronine, low thyroid stimulating hormone, or subacute thyroiditis has been reported. Adrenal dysregulation and impaired spermatogenesis in affected men have been also reported. Complications of other endocrine glands are still not clear. Considering the recent onset of COVID-19 infection, the available follow-up data are limited, and therefore, long-term studies are required to evaluate certain effects of COVID-19 on the endocrine glands.

Taller-than-wide Thyroid Nodules With Microcalcifications Are at High Risk of Malignancy.

BACKGROUND/AIM: Previous studies have shown that there may be a diversity in the ultrasonographic (US) features discriminating a malignant from a benign thyroid nodule. We determined the reliability of the specific nodule shape in combination with other US features in predicting thyroid carcinomas. PATIENTS AND METHODS: This was a retrospective single-center study investigating the association of the morphological characteristics of nodular goiters from preoperative US and color Doppler images with malignancy based on pathology. RESULTS: We evaluated 254 thyroid nodules (malignant, n=131) from 205 patients. Multivariable logistic regression analysis showed that taller-than-wide shape [odds ratio (OR)=25.3, 95% confidence interval (CI)=5.4-118.9; p<0.001], microcalcifications (OR=4.9, 95% CI=2.5-9.5; p<0.001), hypoechogenicity (OR=4.5; 95% CI=2-10.3; p<0.001) and size (OR=0.93; 95% CI=0.89-0.98; p=0.002) were independently associated with thyroid nodule malignancy. Additionally, we found a strong negative correlation between size and taller-than-wide shape of a thyroid nodule (r=-0.41, p<0.001). CONCLUSION: Among the important indicators of thyroid malignancy, taller-than-wide nodules with microcalcifications are most likely to be malignant.

Benign and malignant thyroid nodules with autoimmune thyroiditis

ABSTRACT Objective: The prevalence of autoimmune thyroiditis (AT) in papillary thyroid carcinoma (PTC) is still controversial. The aim of this study was to investigate the frequency of coexistence of PTC with AT versus that of the coexistence of benign nodules with AT. Materials and methods: This was a cross-sectional retrospective study including patients operated on for thyroid nodules from January 2011, to April 2021. The frequency of papillary carcinomas cooccurring with AT was compared to that of benign nodules cooccurring with AT, which was assessed based on cytopathological diagnosis after thyroidectomy. Results: The study included 668 cases of benign nodules and 420 cases with PTC. No statistically significant difference was observed between cases of benign and PTC nodules regarding the presence of AT (25% vs. 28%, respectively, p = 0.177). The size of the PTC compared to that of the benign predominant nodules was significantly smaller both in the absence (0.96 ± 1.09 cm vs. 2.19 ± 1.06 cm, p < 0.05) and in the presence (0.77 ± 0.76 cm vs. 1.67 ± 1.08 cm, p < 0.01) of AT. In the binary logistic regression analysis of the PTC, the only variable associated with AT was multifocality (odds ratio: 1.750, 95% confidence intervals: 1.131-2.706, p = 0.013). The incidences of lymph node involvement and advanced stage PTC were very low both in the presence and absence of AT. Conclusion: The nodules present with PTC were not more likely to coexist with AT than benign nodules were. The small incidence of advanced PTC indicates a significant improvement in early-stage diagnosis.