A Case Report of Concurrent Graves' Disease and Subacute Thyroiditis Following SARS-CoV-2 Vaccination: An Autoimmune/Inflammatory Syndrome (ASIA).

BACKGROUND: The response against adjuvants in vaccines is presented as autoimmune/inflammatory syndrome (ASIA). In this case report, we presented both SAT and Graves' disease in a patient as ASIA following the BNT162b2 mRNA COVID-19 vaccination. CASE PRESENTATION: A 31-year-old woman was admitted to the endocrinology outpatient clinic with the complaint of neck pain following the second dose of the BNT162B2 SARS-CoV-2 (Pfizer/BioNTech) vaccine. On physical examination, her thyroid gland was tender on palpation. Her thyroid function tests were compatible with hyperthyroidism, and inflammatory markers were high. In the thyroid ultrasonography (US) examination, we observed bilateral diffuse hypoechoic areas in the thyroid gland and increased vascularity in some parts of the thyroid. Anti-thyroid stimulating hormone receptor antibodies (TRAB) were positive. Overall, we considered concurrent subacute thyroiditis (SAT) and Graves' disease. CONCLUSION: The present study may be the first report to evaluate SAT and Graves' disease as ASIA following mRNA COVID-19 vaccination. Clinicians should be aware of possible vaccine-related complications.

A Case Report of Conversion from Hashimoto's Thyroiditis to Graves' Disease in Type 1 Diabetic Patient Following the COVID-19 Vaccination.

BACKGROUND: A considerable number of COVID-19 vaccines became available following the outbreak. Yet, various inflammatory and autoimmune complications have been reported following vaccination. We aimed to report the case of a type 1 diabetic patient converting from Hashimoto's thyroiditis to Graves' disease after the fourth dose of COVID-19 vaccine, thought to trigger an autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). CASE PRESENTATION: A thirty-one-year-old female patient with type 1 diabetes and Hashimoto's thyroiditis applied to our clinic with complaints of palpitations, anxiety, and weight loss one month after the fourth dose of COVID-19 vaccine (2 doses of CoronaVac + 2 doses of Pfizer/BioNTech). She was receiving levothyroxine 50 mcg/day. When her thyroid function tests showed thyrotoxicosis, we initially considered thyroxine-related exogenous thyrotoxicosis. However, we considered Graves' disease upon persisting thyrotoxicosis despite thyroxine withdrawal, positive serum TSH receptor antibody titers, and other imaging findings. Therefore, various autoimmune and inflammatory events have been reported after the COVID-19 vaccination. Adjuvants in vaccines can trigger autoimmune events, which lead to ASIA syndrome. COVID-19 vaccines may cause increased TSH receptor antibody levels or change the balance in the activity of blocking and stimulating antibodies, which may cause a conversion from Hashimoto's to Graves' disease. CONCLUSION: This was the first case report where the patient experienced a conversion from Hashimoto's to Graves' disease after COVID-19 vaccination, which may ultimately be related to ASIA syndrome. Yet, more data is needed to elucidate such a relationship, and patients should closely be checked regularly after four doses of vaccination.

The Experience of our Center in Patients Undergoing Insulin Degludec/ Insulin Aspart Co-formulation Therapy.

AIM: A co-formulation containing insulin degludec and insulin aspart (IDegAsp) is available for the treatment of diabetes in Turkey. We aimed to evaluate the clinical results of switching to IDegAsp treatment for Type 2 diabetes. METHODS: A total of 217 patients with type 2 diabetes treated with IDegAsp and having follow-up data were included. The patients were divided into 3 groups. Group 1 switched from basal insulin to IDegAsp, group 2 switched from twice-daily premixed insulin regimen to IDegAsp, and group 3 switched from intensive and thrice-daily premixed insulin regimen to IDegAsp. Groups were evaluated in terms of changes in insulin dose, the number of injections, and changes in HbA1c. RESULTS: The mean follow-up period was 7.5 ± 4.4 months. The mean age was 62.8 ± 12.9 years. The mean duration of diabetes was 15.3 ± 8 years. There was a significant decrease in HbA1c and glucose (p < 0.0001 and p < 0.0001, respectively). HbA1c was significantly reduced in group 1 (p < 0.0001) while insulin dose and the number of injections increased (p < 0.0001 and p < 0.0001, respectively). HbA1c, insulin dose, and the number of injections in group 2 and group 3 (p = 0.001, p = 0.002, p < 0.0001, respectively, and p < 0.0001, p = 0.043, p < 0.0001, respectively) were significantly reduced. CONCLUSION: This study includes real-life experiences involving a remarkable number of patients in the literature. IDegAsp treatment provided effective blood glucose regulation and caused a significant decrease in the insulin dose and the number of injections, resulting in increased quality of life among those who had to receive twice or more insulin injections.

The relationship between thyroid autoimmunity and poor response to ovarian stimulation in in vitro fertilization women with infertility.

INTRODUCTION: Thyroid autoimmunity (TAI) is the most common autoimmune disorder. Patients with TAI are usually euthyroid, and the presence of anti-thyroid peroxidase (anti-TPO) in patients with or without thyroid dysfunction is associated with infertility, recurrent embryo implantation failure, and early pregnancy loss. We aimed to investigate the relationship between low ovarian reserve, pregnancy outcomes, and TAI. MATERIAL AND METHODS: This retrospective cohort study was conducted in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients between 2010 and 2018. All patients (n = 1400) for whom thyroid autoantibody testing was requested were detected. A study group was formed from patients with anti-TPO positivity (n = 363). The control group (n = 555) comprised euthyroid anti-TPO negative patients matched to the study group regarding age and body mass index (BMI). RESULTS: Mean serum TSH value was 2.35 ± 1.70 mIU/mL in anti-TPO-positive patients and 1.81 ± 1.2 mIU/mL in controls, and the difference was significant (p < 0.05). Total dose of gonadotropins used in ovulation induction in anti-TPO-positive and control patients were 3000 IU and 2700 IU, respectively, and the difference was statistically significant (p < 0.05). The number of metaphase 2 oocytes was significantly lower in the anti-TPO-positive group (p < 0.05). Embryo transfer number and embryo grade were significantly lower in the anti-TPO-positive group (p < 0.01). Poor ovarian response was significantly higher in anti-TPO-positive patients (40%) as compared to anti-TPO-negative controls (30%) (p < 0.01). Clinical pregnancy rate was significantly lower in the anti-TPO-positive group (29.2%), as compared to the antibody-negative group (38.4%) (p < 0.01). CONCLUSIONS: There are controversial data regarding the impact of antithyroid antibodies on ovarian reserve and pregnancy outcome after IVF treatment. The results of this study indicate that there was a relationship between TAI and poor ovarian response, and that TAI adversely affects IVF outcomes. Further investigations are required to explore the mechanism behind these effects.

Acoustic Radiation Force Impulse Elastography and Ultrasonographic Findings of Achilles Tendon in Patients With and Without Diabetic Peripheral Neuropathy: A Cross-Sectional Study.

AIMS: We aimed to evaluate the elastographic features of Achilles tendon with Acoustic Radiation Force Impulse in patients with and without diabetic neuropathy. METHODS: According to the presence of peripheral neuropathy, 45 patients with type 2 diabetes were divided into 2 subgroups. Those with peripheral neuropathy were defined as group I (22 patients) and those without peripheral neuropathy were defined as group II (23 patients). A total of thirty age-, gender-, and body mass index-matched healthy individuals were selected as controls. All participants underwent both ultrasonographic and Acoustic Radiation Force Impulse elastographic examination in order to evaluate Achilles Tendon thickness and stiffness. RESULTS: Achilles tendon thicknesses were similar between groups (p=0.991). Achilles tendon thicknesses of both patient groups were significantly higher than the control group (group I vs control p=0.01; group II vs control p=0.006). Stiffness values of Achilles tendons were similar between the control group and group II (p=0.993). Shear Wave Velocity was significantly lower in group I than group IIand control group (p<0.001). CONCLUSION: Diabetic patients with neuropathy have thicker and softer Achilles tendon while the elasticity of Achilles tendon in diabetic patients without neuropathy is similar to the healthy controls. Softening of the Achilles tendon may be an early sign of diabetic foot and reveal the patients with a risk of diabetic foot.

Assessment of Parotid and Submandibular Glands With Shear Wave Elastography Following Radioactive Iodine Therapy for Papillary Thyroid Carcinoma.

OBJECTIVES: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Radioactive iodine (RAI) therapy is used for remnant ablation following thyroidectomy. Side effects such as dysphagia, xerostomia, and sialoadenitis may occur. We aimed to determine the differences in the parotid and submandibulary glands between healthy patients and patients with PTC who had undergone RAI therapy and have dry mouth symptoms using both shear wave elastography and ultrasonography. METHODS: We enrolled 30 patients with PTC who had undergone RAI therapy following surgery and 30 healthy controls. Ultrasonography and shear wave elastography of submandibular and parotid glands were performed. The volume of the submandibular glands and the thickness of parotid glands were determined. Ten independent measurements were obtained from each gland, with the region of interest placed at different points on the glands. The mean shear wave velocities (SWVs) were calculated and compared between the patients and controls. RESULTS: In the PTC group, there was a significant reduction in the volume of the submandibular glands (P < .05) and in the thickness of the parotid glands (P < .05) compared with the control group. The mean SWVs of the parotid glands and submandibular glands were significantly higher in the PTC group compared with the control group (P < .0001). The SWVs of the parotid glands were higher than the SWVs of the submandibular glands (P < .0001). CONCLUSIONS: Shear wave elastography could be a noninvasive and easy assessment method of parotid and submandibular glands in patients who had undergone RAI therapy and experience dry mouth.

Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures.

OBJECTIVE: Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood. DESIGN: We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders. METHODS: Exome sequencing data were used to identify rare variants in known genes in CHH (n = 116), CDGP (n = 72) and control cohorts (n = 36 874 ExAC and n = 405 CoLaus). RESULTS: Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, P = 7.6 × 10-11) or controls (18%, P = 5.5 × 10-12). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, P = 0.002) and controls (2%, P = 6.4 × 10-7). CONCLUSIONS: Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty.

Lymph node fine-needle aspiration washout thyroglobulin in papillary thyroid cancer: Diagnostic value and the effect of thyroglobulin antibodies.

PURPOSE: Thyroglobulin (Tg) assessment in the needle washout after fine-needle aspiration biopsy (FNAB) of a suspicious neck lymph node (LN) is known to improve the diagnostic accuracy in patients with papillary thyroid cancer (PTC). However, there is still controversy on the best diagnostic cut-off levels for FNAB-Tg and whether thyroglobulin antibody (TgAb) positivity affects FNAB-Tg. The objectives of this study were to determine (i) the diagnostic power of different cut-offs for FNAB-Tg and (ii) if serum TgAb(+) negatively affects the FNAB-Tg evaluation. METHODS: This was a retrospective cohort study analyzing PTC patients with suspicious neck LNs, in a university hospital setting, from October 2009 to October 2013. In total, 103 patients with PTC (226 LNs) undergoing ultrasound-guided FNAB for LNs were included. Cytology and FNAB-Tg levels were compared in reference to LN histopathology and the effect of TgAb(+) on FNAB-Tg levels was evaluated. RESULTS: The diagnostic accuracies of FNAB-Tg cut-off of 1 and 10 ng/mL were 94.1% and 88.2%, respectively. Raising the cut-off from 1 to 10 ng/mL led to decreased sensitivity rates (91.9% vs. 83.9%). The receiver operating characteristic curve analysis demonstrated that the best FNAB-Tg cut-off was 1.2 ng/mL. There were no LNs with an FNAB-Tg ≥ 10 ng/mL that turned out to be cytologically or histopathologically benign. FNAB-Tg levels of the histopathologically malignant LNs were similar between TgAb (+) and TgAb (-) patients (p = 0.546). Serum Tg predicted FNAB-Tg levels above 1 ng/mL (p = 0.002) and FNAB-Tg predicted malignant histopathology (p = 0.004), both independently of the TgAb status of the patient. CONCLUSIONS: FNAB-Tg ≥ 1 ng/mL has a superior diagnostic power, irrespective of TgAb (+), in PTC patients with suspected LN involvement.

Serum levels of fetuin A are increased in women with gestational diabetes mellitus.

PURPOSE: Fetuin A is associated with insulin resistance and type 2 diabetes mellitus (DM). We aimed to investigate circulating fetuin A concentrations in gestational diabetes mellitus (GDM). METHODS: Serum fetuin A levels were studied in 26 pregnant women with GDM and 24 healthy pregnant women between 24th and 28th gestational weeks. Fetuin A levels were also evaluated in 18 of women with GDM at postpartum. RESULTS: Fetuin A concentrations were significantly increased in women with GDM compared to healthy pregnant women (35.0 ± 3.2 vs. 32.0 ± 4.4 ng/ml; p = 0.01). Also, fetuin A levels in women with GDM significantly decreased at postpartum period (35.0 ± 3.2 vs. 31.7 ± 3.9 ng/ml; p = 0.001). In whole pregnant women, there were positive correlations between fetuin A and HbA1c (r = 0.418, p = 0.002), total cholesterol (r = 0.332, p = 0.018) and triglycerides (r = 0.306, p = 0.031). Multivariate regression analysis demonstrated that HbA1c was the important predictor of circulating fetuin A level (beta = 0.375, p = 0.01). CONCLUSION: In conclusion, our results indicate that serum fetuin A concentrations are increased in women with GDM and decreased after delivery. Therefore, fetuin A might have a role in the development of insulin resistance and the metabolic changes in GDM.

Hyperparathyroid crisis presenting with hyperemesis gravidarum.

PURPOSE: Primary hyperparathyroidism during pregnancy is a rare condition, and the diagnosis may be confounded by pregnancy related conditions. Since the appropriate management reduces the maternal and fetal complications; differential diagnosis becomes quite crucial. METHOD: Clinical course of a patient with hyperparathyroid crisis will be discussed with the review of the literature. A 22-year- old, (gravida 2, para 1) woman was presented with hyperparathyroid crisis at the 11th weeks' gestation. She was hospitalized twice due to hyperemesis gravidarum. When she was admitted to the hospital for the third time due to increased vomiting and weight-loss, serum biochemistry panel was performed and it revealed severe hypercalcemia that serum Ca was 17.59 mg/dl, and she was referred to our hospital as parathyroid crisis. Maternal hypercalcemia was resolved after urgent parathyroidectomy. She was diagnosed as preeclampsia at the 30 weeks' gestation and delivered a male infant weighing 1,090 g at 33 weeks' gestation with APGAR scores 6 at 1 min, and 7 at min 5, without evidence of neonatal hypocalcemia or tetany. RESULTS: Urgent parathyroidectomy is the definite treatment in symptomatic patients with hyperparathyroidism during pregnancy. Resolving maternal hypercalcemia prevents neonatal tetany and hypocalcemia. CONCLUSION: Hyperemesis may lead to hypercalcemic crisis in patients with hyperparathyroidism, so serum Ca level should be checked in patients with hyperemesis gravidarum especially who detoriate rapidly. Although they share some common pathogenetic mechanisms, there is not enough evidence for attributing preeclampsia to primary hyperparathyroidism.

Elevated mean platelet volume is associated with gestational diabetes mellitus.

The mean platelet volume (MPV) is an indicator of the average size and activity of platelets. Elevated MPV values are associated with larger and more active platelets and perceived as a new independent cardiovascular risk factor. The aim of this study was to determine the MPV in women with gestational diabetes mellitus (GDM) and to determine the correlation of MPV with metabolic parameters in GDM. We retrospectively analyzed 30 women with GDM and 38 body mass index-matched women with healthy pregnancies as controls. MPV and platelet counts were recorded in the third trimester and at postpartum 6-12 months for GDM group and in the third trimester for control group. Third-trimester MPV was significantly higher in GDM group compared to control group (8.8 ± 1.0 versus 8.1 ± 0.7 fl, p = 0.002). In women with GDM, there was a significant decrease in MPV in the postpartum period (8.8 ± 1.0 versus 8.1 ± 0.8 fl, p < 0.001). Fasting plasma glucose levels and glucose area under the curve were positively correlated with third trimester MPV (r = 0.346, p = 0.007 and r = 0.346, p = 0.02, respectively). Our results indicate that MPV is increased in GDM. Monitoring MPV, which is widely available in clinical practice, may potentially identify women who will develop gestational diabetes during pregnancy.