Pteridine and tryptophan pathways in children with type 1 diabetes: Isoxanthopterin as an indicator of endothelial dysfunction.

AIM: Type 1 diabetes (T1D) and its complications are known to be associated with oxidative stress. Pteridine derivatives and indoleamine 2,3-dioxygenase (IDO) activity can be used as biomarkers in the evaluation of oxidative stress. In this study, our aim is to compare the concentrations of serum and urinary pteridine derivatives, as well as serum IDO activity, in children and adolescents diagnosed with T1D and those in a healthy control group. METHOD: A cross-sectional study was performed and included 93 patients with T1D and 71 healthy children. Serum and urine biopterin, neopterin, monapterin, pterin, isoxanthopterin, and pterin-6-carboxylic acid (6PTC) and serum tryptophan and kynurenine levels were analyzed and compared with healthy controls. High-performance liquid chromatography was used for the analysis of pteridine derivatives, tryptophan, and kynurenine. Xanthine oxidase (XO) activity, a marker of oxidative stress, was defined by measurement of serum and urine isoxanthopterin. As an indicator of indolamine 2,3-dioxygenase (IDO) activity, the ratio of serum kynurenine/tryptophan was used. RESULTS: Serum isoxanthopterin and tryptophan concentrations were increased, and serum 6PTC concentration was decreased in children with T1D (p=0.01, p=0.021, p<0.001, respectively). In children with T1D, IDO activity was not different from healthy controls (p>0.05). Serum neopterin level and duration of diabetes were weakly correlated (p=0.045, r=0.209); urine neopterin/creatinine and isoxanthopterin/creatinine levels were weakly correlated with HbA1c levels (p=0.005, r=0.305; p=0.021, r=0.249, respectively). Urine pterin/creatinine level negatively correlated with body mass index-SDS. (p=0.015, r=-0.208). CONCLUSION: We found for the first time that isoxanthopterin levels increased and 6PTC levels decreased in children and adolescents with T1D. Elevated isoxanthopterin levels suggest that the XO activity is increased in TID. Increased XO activity may be an indicator of vascular complications reflecting T1D-related endothelial dysfunction.

Acute Kidney Injury After Thyroid Hormone Withdrawal in an Adolescent with Papillary Thyroid Carcinoma.

Objectives: We report a patient with papillary thyroid carcinoma (PTC) who developed acute kidney injury (AKI) and elevated creatine kinase (CK) after thyroid hormone withdrawal (THW) prior to radioiodine therapy. Case presentation: A 12-year-old female patient who had undergone total thyroidectomy for PTC one year ago presented with leg pain for the past 2 days. Following THW 3 weeks ago, the case had received 70 mCI radioiodine treatment 6 days ago. Serum creatinine (1.53 mg/dL, normal range [NR]: 0.3-1.1), aspartate aminotransferase (102 IU/L, NR: 0-40) and CK (3451 IU/L, NR: 26-174) levels were elevated. Thyrotropin level was elevated (>100 µIU/ml, NR: 0.51-4.3), and free T4 level was decreased (0.05 ng/dL, NR: 0.98-1.63). Serum creatinine and CK levels decreased after intravenous hydration and levothyroxine treatment. Conclusion: In PTC cases with thyroidectomy, kidney function and CK elevation should be assessed after THW and dehydration should be prevented.

Ovarian reserve in children with juvenile idiopathic arthritis using biologic disease-modifying anti-rheumatic drugs.

BACKGROUND/OBJECTIVES: The aim of the study is to assess the effect of juvenile idiopathic arthritis (JIA) and biologic disease-modifying anti-rheumatic drugs (bDMARDs) on ovarian reserve in children. MATERIALS AND METHODS: A cross-sectional study was performed from March 2021 to March 2022 and included 81 patients with JIA and 49 healthy children. Serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels were analyzed using electrochemiluminescence methods. RESULTS: The mean of current age (13.5 ± 3.2 vs. 14.4 ± 2.4 years), height standard deviation score (SDS) (- 0.35 ± 1.18 vs. - 0.44 ± 0.94), body mass index SDS (0.12 ± 1.33 vs. 0.25 ± 1.28), and the median weight SDS (- 0.13 (- 2.27-3.23) vs. - 0.52 (- 3.4-3.3)) were similar in JIA patients and controls (p > 0.05). Patients with JIA were divided into two groups according to their treatment regimens: treated with methotrexate (MTX) (biologic naive) (n = 32) and treated with MTX plus bDMARDs (n = 49). No significant differences were detected between the 3 groups regarding menarche age, menstrual cycle length, and flow duration (for all p > 0.05). The median serum concentration of AMH was 2.94 (1.12-7.88) ng/ml in the control group, 3.02 (0.36-8.54) ng/ml in the biologic naïve group, and 3.01 (0.99-8.26) ng/ml in the MTX plus bDMARD group. There were no significant differences between 3 groups according to serum AMH, FSH, LH, and estradiol levels (p > 0.05). CONCLUSION: Biologic DMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. Prospective studies with larger sample sizes are needed to confirm our findings and to evaluate the impact on the future fertility of patients. Key Points • Although biologic disease-modifying anti-rheumatic drugs (bDMARDs) are being game-changing treatment options in juvenile idiopathic arthritis, their effect on fertility and ovarian reserve is one of the most discussed issues. • In addition to treatment used, autoimmune diseases might also have a negative effect on fertility. • In this cross-sectional study, we found that anti-Mullerian hormone level of patients who were on bDMARDs, patients who were on methotrexate, and healthy controls were similar. • Our results suggest that bDMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment.

Psychopathological Analysis of Adolescent Girls With Autoimmune Thyroiditis.

AIM: Clinical studies indicate that there is an association between high levels of thyroid autoantibodies and psychiatric disorders, independent of impairment of thyroid function. Therefore, we aimed to investigate the association between thyroid autoimmunity and mood disorders in euthyroid girls with Hashimoto's thyroiditis (HT) in a case-control study. MATERIAL AND METHODS: We recruited 82 participants: 41 pubertal female patients with thyroiditis from endocrine outpatient clinics and a control group of 41 healthy pubertal girls from the University Hospital. Age ranged from 12 to 18 years; the diagnosis of HT was based on high levels of anti-TPO and/or anti-Tg antibodies associated with a hypoechogenic or normal thyroid ultrasound pattern. Other comorbidities known to affect mental and physical health were exclusion factors. All participants underwent a complete thyroid evaluation, assays of serum-free T4, TSH, anti-TPO antibodies, anti-Tg antibodies, and thyroid ultrasonography. They were then referred to a child psychiatrist. A psychiatric diagnosis was made in two steps. First, the Children's Depression Inventory (CDI) and Screen for Child Anxiety-Related Emotional Disorders (SCARED) tests were implemented according to the DSM-IV diagnostic criteria to be calculated. Second, the same psychiatrist conducted a K-SADS-PL semi-structured interview while unaware of the children's data. RESULTS: There was no significant difference in CDI score between patients with and without HT (p = 0.47). Patients with HT had significantly higher SCARED scores than patients without HT (p < 0.05). In the SCARED test, the subcategories of separation anxiety and social anxiety were significantly higher in the HT group (p = 0.04 and p = 0.01, respectively). During the K-SADS interview by the attending child psychiatrist, psychopathology diagnoses were detected in 27 of 41 patients (66%) with HT and in 8 of 41 individuals (19.5%) in the control group. Psychopathology was significantly higher in the HT group (p < 0.01). The incidences of depressive disorder, generalized anxiety disorder, and social phobia were significantly higher in the HT group than in the control group (p < 0.05). Multivariate logistic regression analysis revealed that the anti-TPO value was the most significant independent risk factor for the presence of depressive disorder (p < 0.01). CONCLUSION: This study described severe psychometric impairment in patients with euthyroid HT. We have demonstrated that autoimmune thyroid diseases, even in a euthyroid state, are associated with psychiatric disorders.

Temporary Thyroid Dysfunction and Catecholamine Excess Due to Mercury Poisoning in 6 Cases.

OBJECTIVE: Mercury poisoning is a condition with multiple-organ dysfunction that has effects on the central nervous system, gastrointestinal system, cardiovascular system, skin, lungs, and kidneys. It can be fatal or may result in sequelae such as neurological disturbances, if treated late or left untreated. The endocrinological effects of mercury exposure are not well-known. We aimed to evaluate patients with mercury poisoning. MATERIALS AND METHODS: A total of 6 cases of mercury poisoning from 3 families were included in the study. Clinical, laboratory, and follow-up data were recorded. RESULTS: Thyroid dysfunction was presented as high thyroid hormones and normal thyrotropin level (unsuppressed) in 5 cases (83.3%). On the other hand, pheochromocytoma-like syndrome was detected in 5 cases (83.3%) with hypertension. The 4 cases were the first to use methimazole for mercury poisoning due to tachycardia and hypertension despite antihypertensive treatment due to catecholamine excess and thyroid dysfunction. Hyponatremia was detected in 3 cases (50%). CONCLUSION: Mercury poisoning is difficult to diagnose because it is rare and presents with nonspecific physical and laboratory findings. Early diagnosis and providing appropriate treatment are essential in order to prevent sequelae. Mercury poisoning should be considered in patients with unexplained hypertension and tachycardia suggesting the involvement of thyroid hormones and catecholamines.

Insulin resistance in children with juvenile systemic lupus erythematosus and investigation of the possibly responsible factors.

OBJECTIVE: Insulin resistance (IR) has been described in adults with systemic lupus erythematosus (SLE), though its mechanism has not been fully clarified. In this study, it was aimed to investigate insulin sensitivity for the first time in children with juvenile SLE (jSLE) by considering the effect of the already known contributing factors of IR. METHOD: This is a cross-sectional study including 43 patients with jSLE and the same number of healthy controls matched for age, gender, pubertal stage, body mass index, and physical activity level. IR, as calculated by both homeostatic model assessment for insulin resistance (HOMA-IR) and a relatively new method, triglyceride glucose (TyG) index, was compared between the patients and their matched controls, also among the patients stratified by disease duration, corticosteroid use, and disease activity. RESULTS: Insulin resistance in the patient group was higher than the controls according to both HOMA-IR and TyG index (p < 0.001 for both). In the patient group, no significant effect of disease duration, corticosteroid use, disease activity, and levels of anti-dsDNA, anti-cardiolipin IgM, anti-cardiolipin IgG, C3, and C4 on IR was demonstrated. CONCLUSION: Children with jSLE were found to have higher IR even after neutralizing the effects of the contributing factors which are expected to aggravate IR. This elevation in IR in jSLE seems not to be associated with corticosteroid use, disease duration, disease activity, or autoantibody levels. Thus, the presence of IR in jSLE cannot be explained solely with neither the already known contributing factors nor the increased inflammation of the disease. Key Points • In this study, insulin sensitivity was investigated for the first time in children with jSLE. • Children with jSLE have higher insulin resistance than healthy ones. • Insulin resistance in children with jSLE is independent of corticosteroid use, disease duration, disease activity or autoantibody, and complement levels.