Does Subclinical Hypothyroidism Affect Dynamic Thiol / Disulfide Homeostasis and Ischemia-modified Albumin Levels in Children?

OBJECTIVE: To determine the effects of subclinical hypothyroidism on oxidative stress in children. STUDY DESIGN: A cross-sectional study. PLACE AND DURATION OF STUDY: Department of Paediatrics, Paediatric Endocrinology, and General Outpatient Clinics, Kirikkale University, School of Medicine, from May 2017 to October 2018. METHODOLOGY: This study included 92 subjects aged between 2 and 18 years. The subjects were divided into two groups. Forty-seven children with subclinical hypothyroidism and 45 healthy controls were evaluated. In order to evaluate oxidative damage, native thiol, total thiol, disulfides, their ratios, and ischemia-modified albumin (IMA) levels were compared between the two groups. The relationship between TSH and IMA levels was assessed. RESULTS: Age and gender were not significantly different in the two groups. Native thiol, total thiol, disulfides and their ratios were similar in the two groups. Ischemia-modified albumin levels were significantly higher in the patient group than the controls (p<0.001). There was no correlation between TSH and IMA levels in the patient group (r=0.069 p=0.645). CONCLUSION: Subclinical hypothyroidism may be related to the impairment of IMA, and have a neutral effect on thiol/disulfide balance. Further research is needed to explain the effects of oxidative stress in subclinical hypothyroidism. Key Words: Subclinical hypothyroidism, Childhood, Oxidative stress.

Methylphenidate and Central Precocious Puberty: A Probable Side Effect among Seven Children with the Attention Deficit Hyperactivity Disorder.

Methylphenidate (MPH) is the most preferred drug for treatment of the attention deficit hyperactivity disorder (ADHD). Here, we aimed to discuss the possible effects and mechanisms of MPH on precocious puberty (PP) via a case series with seven children who had normal body mass index. In this case series we evaluated seven children with ADHD, who had received MPH for at least 6 months (0.5 mg/kg/dose three times a day, maximum 60 mg) and admitted to Department of Pediatric Endocrinology with PP symptoms. The mean age was 8.16 years. Basal hormonal levels (luteinizing hormone [LH], follicle stimulating hormone, and estrogen/testosterone) were within normal range. Results of LH-releasing hormone stimulation tests demonstrated central pubertal responses. Glutamine, dopamine and noradrenaline are most important excitatory neurotransmitters that have a role at the beginning of puberty. The effect of MPH, cumulating dopamine and noradrenaline in the synaptic gap could be associated with the acceleration of puberty with the excitatory effect of dopamine’s gonadotropin-releasing hormone (GnRH) release, excitatory effect of noradrenaline’s GnRH release and the disappearance of GnRH receptor expression suppressor effect on prolactin disinhibitory effect.

Amylase/creatinine clearance ratio in diabetic ketoacidosis: a case report.

Diabetic ketoacidosis (DKA) accompanies any other intra-abdominal pathology. Serum amylase/lipase levels are commonly used in order to rule out acute pancreatitis in patients having abdominal pain in DKA. A more specific and noninvasive diagnostic tool - amylase/creatinine clearance ratio (ACCR) - can be used to rule out pancreatitis in patients with DKA. A 14-year-old girl was admitted with abdominal pain and nausea. She had been followed up for type 1 diabetes mellitus for the last 5 years. The serum amylase levels were increased up to 687 U/L (normal: 28-120 U/L) on the third day of hospitalization. Simultaneous serum and urinary amylase concentrations were measured, and ACCR was calculated (1.2%). The diagnosis of pancreatitis was ruled out. The serum amylase levels decreased in the following days, and she was discharged. ACCR determination is a simple and specific test to diagnose pancreatitis, especially in patients with DKA.

Neurocognitive functions in children and adolescents with subclinical hypothyroidism.

OBJECTIVE: Hypothyroidism is a metabolic condition that can lead to cognitive and behavioral deficits in children and adolescents. However, there is less evidence about subclinical hypothyroidism (SH) as a risk factor for neuropsychological disorders in childhood. The aim of this study was to evaluate cognitive functions like active/passive attention, maintaining attention, and response inhibition in pediatric patients with SH. METHODS: Seventeen patients (between 7-17 years old) with SH were tested with the Stroop test, Verbal Fluency test and the sub-tests of the Wechsler intelligence scale for children-Revised (WISC-R). SH diagnosis was based on the mild increase of serum thyrotropin (TSH) level together with a normal serum free thyroxine level and an exaggerated TSH response to thyrotropin-releasing hormone. RESULTS: Out of seventeen cases, 10 (59%) were girls and 7 (41%) were boys. Six cases were obese and 5 were overweight. The children in the SH group, as compared to the control group, obtained significantly lower scores on both the Digit Span subtest of the WISC-R and the Stroop subtests, which are sensitive to attention. No significant differences were found between the SH group and the healthy controls in verbal fluency and encoding tests. CONCLUSION: In this study, pediatric patients with SH showed poor performance in tests measuring attention. Therefore, we want to stress the importance of close collaboration between pediatric endocrinology and child and adolescent psychiatry departments.

Bloody nipple discharge in 2 infants with interesting cytologic findings of extramedullary hematopoiesis and hemophagocytosis.

Bloody nipple discharge in the infantile period is an uncommon finding. Despite its stressful course to the parents, it is generally a benign condition with a spontaneous resolution. The approach to bloody nipple discharge in the infantile period is well documented in the literature even though the number of these cases is limited. We report 2 infants with unilateral bloody nipple discharge. Their physical examination, laboratory, and ultrasound findings were normal but the cytologic examinations of the discharge revealed signs of extramedullary hematopoiesis and hemophagocytosis. These extraordinary findings made us brainstorm on the probable ongoing processes in the infantile breast tissue.

Evaluation of thyroid functions with respect to iodine status and TRH test in chronic autoimmune thyroiditis.

OBJECTIVE: Chronic autoimmune thyroiditis (CAT) is the most common form of thyroiditis in childhood and a frequent cause of acquired hypothyroidism. The objective of this study was to evaluate the thyroid status of children and adolescents with CAT with respect to iodine status and diagnostic values of thyrotropin-releasing hormone (TRH) test. METHODS: Seventy-one children (mean age: 11.6 years) were studied in a retrospective analysis. Free thyroxine (T4), thyrotropin (TSH), TSH response to TRH test, thyroid autoantibodies, thyroid sonography, and urinary iodine excretion (UIE) were evaluated. RESULTS: At diagnosis, 8.5% of patients had overt hypothyroidisim and 36.6% subclinical hypothyroidism; 5.6% had overt hyperthyroidisim and 8.5% had subclinical hyperthyroidism. Of them, 40.8% were euthyroid. Median UIE was 51 mg/L in overt hypothyroidism and 84 mg/L in subclinical hypothyroidism. The values were 316 mg/L and 221 mg/L in overt and subclinical hyperthyroidism, respectively. Basal TSH showed a strong correlation with peak TSH level on TRH test. Thirty-four percent of patients with normal basal TSH level showed an exaggerated TSH response. CONCLUSION: Iodine deficiency was seen more in cases with hypothyroidism, while excess of iodine was observed to be more frequent in hyperthyroid patients. Iodine status was a strong predictorof the thyroid status in CAT. TRH test may be helpful in further delineating patients with subclinical hypothyroidism.

Celiac disease and autoimmune thyroid disease in children with type 1 diabetes mellitus: clinical and HLA-genotyping results.

OBJECTIVE: Increased prevalence of celiac disease (CD) and autoimmune thyroid disorders (ATD) in patients with Type 1 diabetes mellitus (T1D) has been widely reported. Such an association may lead to adverse effects on the growth, bone metabolism and fertility, and response to therapy may become difficult. The aim of this study was to evaluate the clinical findings and HLA typing results in patients with T1D associated with CD or ATD. METHODS: The association of CD and ATD was evaluated in 38 children with T1D aged 1.5-16.8 years who had been followed for 48.3±28 months. Diagnosis of CD was based on positivity for serum endomysial IgA antibody and histopathological findings of intestinal biopsy specimens. Thyroid autoimmunity was assessed by antithyroglobulin and antithyroid peroxidase antibodies and with diagnostic ultrasonographic findings. RESULTS: ATD was detected in 31.5%, and CD-in 7.8% of T1D patients. Subjects with CD showed either no symptoms or suggestive problems such as short stature, hepatosteatosis, pubertal delay and difficulties in the control of diabetes. Patients with ATD had no clinical symptoms. DQ8 was the most prominent finding in CD. CONCLUSIONS: It is essential that patients with T1D, regardless of presence or absence of symptoms, should be investigated for CD and ATD.

Vitamin D deficiency in Turkish mothers and their neonates and in women of reproductive age.

OBJECTIVE: Materno-fetal vitamin D deficiency (VDD) may occur in the early neonatal period. We aimed to evaluate the vitamin D (vitD) status and risk factors for VDD in healthy newborns and their mothers, and also in fertile women. METHODS: Serum 25 hydroxyvitamin D3 (25(OH)D), calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) levels were measured in 70 mothers (study group) and their newborns, and in umbilical cord samples. 104 nonpregnant fertile women comprised the control group. Demographic factors such as education and clothing habits of the mother, number of pregnancies and month of delivery were recorded. A serum 25(OH)D level below 11 ng/ml was accepted as severe, 11-25 ng/ml as moderate VDD, and a value over 25 ng/ml as normal. RESULTS: Severe VDD was found in 27% of the mothers, and moderate deficiency in 54.3%. Severe VDD was detected in 64.3% of the neonates, and moderate deficiency in 32.9%. Only 18.6% of the mothers and 2.9% of the neonates had normal vitD levels. In the control group, severe VDD was observed in 26.9%, and moderate deficiency in 45.2%. Only 27.8% of the controls had normal vitD levels. In the control group, the 25(OH)D levels of the women dressed in modern clothes were significantly higher than those of the women wearing traditional clothes. This difference was not observed in the study group because 75% of these 70 mothers wore modern clothes. Mothers giving birth during the summer months and their neonates had significantly higher serum 25(OH)D levels than those of the mothers giving birth during the winter months and their neonates. CONCLUSION: The study has shown that in Turkey VDD is an important problem in women of reproductive age, in mothers and their neonates. The 25(OH)D levels obtained from the cord may serve as a guide in the determination of the high risk groups.

Latent autoimmune diabetes mellitus in children (LADC) with autoimmune thyroiditis and Celiac disease.

Latent autoimmune diabetes mellitus in adults (LADA) is characterized by clinical presentation as type 2 diabetes mellitus after 25 years of age, initial control achieved with oral hypoglycemic agents for at least 6 months, presence of autoantibodies and some immunogenetic features of type 1 diabetes mellitus. An 8.3 year-old girl was referred to our pediatric endocrinology department because of incidental glucosuria. She did not complain of polyuria, polydipsia, or weight loss. Her body mass index (BMI) was at the 80th percentile. Fasting glucose was 126 mg/dl, and OGTT glucose level at 120 min was 307 mg/dl. Although C-peptide levels were normal, her first phase insulin response (FIR) was lower than the 1st percentile. Anti-insulin antibody (AIA), islet cell antibody (ICA), and anti-glutamic acid decarboxylase (antiGAD) were negative. According to the clinical and laboratory findings, she was diagnosed as having type 2 diabetes mellitus. She was started with oral anti-diabetic treatment for a period of 1 year. Insulin had to be initiated for worsening of HbA1c levels. In the fourth year of follow-up, she was admitted to our hospital with diabetic ketoacidosis although she was on an intensive insulin regimen. At this time, C-peptide levels were low, antiGAD and AIA were positive with HLA DR3/DQ2 haplotype. In addition, her thyroid peroxidase antibody and endomysium antibody were found to be high at follow-up. Small intestinal biopsy revealed celiac disease. This patient may represent the first case of latent autoimmune diabetes mellitus in children (LADC) with autoimmune thyroiditis and celiac disease.

Meckel-gruber syndrome associated with gastrointestinal tractus anomaly.

Meckel-Gruber syndrome (MGS) is rare autosomal recessive disorder characterized by occipital encephalocele, postaxial polydactyly and polycystic kidneys. A one-day-old girl was admitted to our clinic with occipital encephalocele, polydactyly, ulnar deviation of left hand and failure to thrive. Patient's parents were first-degree relatives. It was learned that the patient's two sisters had died from similar anomalies. In our case, prenatal sonographic examination revealed oligohydramnios and hydrocephaly in the 33rd week of gestation. At birth her weight was 2200 g. Both physical and radiological examinations diagnosed MGS. Cranial computed tomography (CT) showed agenesis of cerebellar vermis and corpus callosum, and cystic dilatation of the 4th ventricle and lateral ventricles. The case died due to severe respiratory distress in the Intensive Care Unit on day 38. In the postmortem examination, longitudinally located intestine-like stomach was determined without a fundus. In conclusion, intestinal malrotation and hepatic portal fibrosis have been reported in MGS in the literature. In this case, a longitudinally located intestine-like stomach in MGS is reported for the first time. No such association to our knowledge has been previously reported.

Normal thyroid volume by ultrasonography in healthy children.

With the objective of creating standards for the volume of the thyroid gland by ultrasonography in the 0-16-year age group, thyroid volumes of 302 healthy children (150 boys, 152 girls) were measured by ultrasonography. The transverse (x), sagittal (y) and anteroposterior (z) lengths of the right and left lobes and isthmus were measured. Volumes of these were calculated by the ellipsoid volume formula [V = (pi/6) x x x y x z]. Statistical analysis was done using the Kruskal-Wallis and Student t tests. The cases were divided into six and eight groups by age and height, respectively. There was a significant positive correlation between thyroid volume, age, height and weight. Thyroid volumes in children of 12 years and over were significantly different from those in the younger age groups.