Vitamin D and Nerve Conduction In Pediatric Type-1 Diabetes Mellitus.

INTRODUCTION: The aim of this study is to investigate a possible association between vitamin D deficiency and diabetic peripheral neuropathy in pediatric patients with type 1 diabetes mellitus. MATERIALS-METHODS: Twenty-nine patients with type 1 diabetes mellitus and 19 healthy controls were included to the study. All individuals were evaluated for diabetic peripheral neuropathy with nerve conduction studies. Complete blood cell count, biochemical investigations, serum vitamin D levels, hemoglobin A1c levels were recorded. RESULTS: No statistically significant differences between the diabetes and control groups in terms of gender, age, body weight, height, body mass index, systolic and diastolic blood pressures, laboratory investigations, serum vitamin D levels and nerve conduction studies was found. Patients with diabetes were grouped as patients with normal serum vitamin D levels and patients with vitamin D deficiency. Sensory nerve action potential of sural nerve and motor peroneal nerve velocity were statistically significantly lower in diabetic patients with vitamin D deficiency compared to diabetic patients with normal vitamin D levels (p 0.009 and 0.005 respectively). CONCLUSION: Our results suggested that hypovitaminosis D might lead to development of neuropathic changes particularly on the lower limb nerves even in the early stages of the disease. It should be kept in mind that patients with hypovitaminosis D should be elaborately examined and closely followed up for the development of diabetic neuropathic changes, even if glucose control is achieved.

Molecular Diagnosis of Monogenic Diabetes and Their Clinical/Laboratory Features in Turkish Children

Objective: Monogenic diabetes is a heterogeneous disease that causes functional problems in pancreatic beta cells and hyperglycemia. The aim of this study was to determine the clinical and laboratory features, the admission characteristics and distribution of monogenic form of diabetes in childhood in Turkey. Methods: Patients aged 0-18 years, who were molecularly diagnosed with monogenic diabetes, and consented to participate, were included in the study. Results: Seventy-seven (45.6%) female and 92 male cases with a mean age of 8.18±5.05 years at diagnosis were included. 52.7% of the cases were diagnosed with monogenic diabetes by random blood glucose measurement. The reason for genetic analysis in 95 (56.2%) of cases was having a family member diagnosed with diabetes under the age of 25. At the time of diagnosis, ketone was detected in urine in 16.6% of the cases. Mean hemoglobin A1c on admission, fasting blood glucose, fasting insulin, and c-peptide values were 7.3±2.1%, 184.9±128.9 mg/dL, 9.4±22.9 IU/L, 1.36±1.1 and ng/L respectively. GCK-MODY was found in 100 (59.2%), HNF1A-MODY in 31 (18.3%), and variants in ABCC8 in 6 (3.6%), KCNJ11 in 5 (3%), HNF4A in 2 (1.2%), and HNF1B in 2 (1.2%). Conclusion: Recent studies have indicated HNF1A-MODY is the most frequent of all the MODY-monogenic diabetes cases in the literature (50%), while GCK-MODY is the second most frequent (32%). In contrast to these reports, in our study, the most common form was GCK-MODY while less than 20% of cases were diagnosed with HNF1A-MODY.

Prevalence of Obesity and Metabolic Syndrome in Children with Type 1 Diabetes: A Comparative Assessment Based on Criteria Established by the International Diabetes Federation, World Health Organisation and National Cholesterol Education Program

Objective: To determine the prevalence of obesity and metabolic syndrome (MetS) in children and adolescents with type 1 diabetes (T1D) and to compare the widely accepted and used diagnostic criteria for MetS established by the International Diabetes Federation (IDF), World Health Organisation (WHO) and National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII). Methods: We conducted a descriptive, cross sectional study including T1D patients between 8-18 years of age. The three sets of criteria were used to determine the prevalence of MetS and findings compared. Risk factors related to MetS were extracted from hospital records. Results: The study included 200 patients with T1D (52% boys). Of these, 18% (n=36) were overweight/obese (body mass index percentile ≥85%). MetS prevalence was 10.5%, 8.5% and 13.5% according to IDF, WHO and NCEP criteria, respectively. There were no statistically significant differences in age, gender, family history of T1D and T2D, pubertal stage, duration of diabetes, hemoglobin A1c levels and daily insulin doses between patients with or without MetS. In the overweight or obese T1D patients, the prevalence of MetS was 44.4%, 38.8% and 44.4% according to IDF, WHO and NCEP-ATPIII criteria, respectively. Conclusion: Obesity prevalence in the T1D cohort was similar to that of the healthy population of the same age. Prevalence of MetS was higher in children and adolescents with T1D compared to the obese population in Turkey. The WHO criteria include microvascular complications which are rare in childhood and the NCEP criteria do not include a primary criterion while diagnosing non-obese patients according to waist circumference as MetS because the existence of diabetes is considered as a direct criterion. Our study suggests that IDF criteria which allows the diagnosis of MetS with obesity and have accepted criteria for the childhood are more suitable for the diagnosis of MetS in children and adolescents with T1D.

Comparison of Treatment Regimens in Management of Severe Hypercalcemia Due to Vitamin D Intoxication in Children

Objective: No large study has been conducted to date to compare the effectiveness of prednisolone, alendronate and pamidronate as first-line treatment in children with hypercalcemia due to vitamin D intoxication. The aim was to perform a multicenter, retrospective study assessing clinical characteristics and treatment results. Methods: A standard questionnaire was uploaded to an online national database system to collect data on children with hypercalcemia (serum calcium level >10.5 mg/dL) due to vitamin D intoxication [serum 25-hydroxyvitamin D (25(OH)D) level >150 ng/mL] who were treated in pediatric endocrinology clinics. Results: Seventy-four children [median (range) age 1.06 (0.65-1.60) years, 45 males (61%) from 11 centers] were included. High-dose vitamin D intake was evident in 77% of the cases. At diagnosis, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D and parathyroid hormone concentrations were 15±3.2 mg/dL, 5.2±1.2 mg/dL, 268±132 IU/L, 322 (236-454) ng/mL, and 5.5 (3-10.5) pg/mL, respectively. Calcium levels showed moderate correlation with 25(OH)D levels (rs=0.402, p<0.001). Patients were designated into five groups according to the initial specific treatment regimens (hydration-only, prednisolone, alendronate, pamidronate, and combination). Need for another type of specific drug treatment was higher in children who initially received prednisolone (p<0.001). Recurrence rate of hypercalcemia was significantly lower in children who were treated with pamidronate (p=0.02). Conclusion: Prednisolone is less effective in the treatment of children with severe hypercalcaemia secondary to vitamin D intoxication and timely implementation of other treatment regimens should be considered.

Acoustic Radiation Force Impulse Quantification in the Evaluation of Thyroid Elasticity in Pediatric Patients With Hashimoto Thyroiditis.

OBJECTIVES: To evaluate the parenchymal elasticity of the thyroid gland with acoustic radiation force impulse imaging in pediatric patients with Hashimoto thyroiditis and to compare it with healthy volunteers. METHODS: Twenty-six patients with Hashimoto thyroiditis and 26 healthy volunteers between 6 and 17 years were included. The shear wave velocity (SWV) values of both thyroid lobes in both groups were evaluated. RESULTS: The age and sex characteristics of the controls and patients with Hashimoto thyroiditis were similar. The SWV of the thyroid gland in patients with Hashimoto thyroiditis (mean ± SD, 1.67 ± 0.63 m/s) was significantly higher than that in the control group (1.30 ± 0.13 m/s; P < .001). There was no significant difference between the thyroid lobes in both groups. A receiver operating characteristic curve analyses showed an optimal cutoff value of 1.41 m/s, with 73.1% sensitivity, 80.8% specificity, a 79.2 % positive predictive value, and a 75.0% negative predictive value (area under the curve, 0.806; P < .001). In patients with Hashimoto thyroiditis, there was a positive correlation between the SWV values versus anti-thyroperoxidase (Pearson r = 0.46; P = .038). There were no correlations between age, body mass index, thyroid function test results, and anti-thyroglobulin values and versus SWV values. Also, no significant differences were seen between the groups for gland size, gland vascularity, and l-thyroxine treatment. CONCLUSIONS: Acoustic radiation force impulse elastography showed a significant difference in the stiffness of the thyroid gland between children with Hashimoto thyroiditis and the healthy group. Using acoustic radiation force impulse elastography immediately after a standard ultrasound evaluation may predict chronic autoimmune thyroiditis.

Does Type 1 Diabetes Mellitus Affect the Shear Wave Velocity of the Thyroid Gland of Children Without Autoimmune Thyroiditis?

OBJECTIVE: The aim of this study is to evaluate the shear wave velocity (SWV) of the thyroid gland with acoustic radiation force impulse elastography in children with type 1 diabetes mellitus (T1D). MATERIALS AND METHODS: Between November 2015 and April 2016, 35 T1D patients who were referred to our hospital's endocrinology outpatient clinic (mean age, 11.88 ± 4.1 years) and 30 children (mean age, 11.3 ± 3.08 years) in the control group were enrolled in the study. Five acoustic radiation force impulse elastography measurements from each lobe of the thyroid gland in m/s were recorded. Diabetes age, hemoglobin A1c, and C-peptide levels were recorded in T1D patients. Statistical analyses were performed using SPSS version 21 (IBM Corporation, Armonk, NY). RESULTS: The mean SWV of the thyroid gland in T1D patients and the control group was 1.11 ± 0.21 and 1.29 ± 0.23 m/s, respectively. The mean SWV of the thyroid gland in T1D patients was lower than that in the control group and this was significant (P = 0.002). The mean SWV of the thyroid gland was not correlated with hemoglobin A1c level, body mass index, or the insulin dose in T1D patients. CONCLUSIONS: The present study showed that T1D affects the thyroid gland stiffness even in patients without autoimmune thyroiditis. Acoustic radiation force impulse elastography may be a useful method in determining early changes in thyroid gland in T1D and may be used as a screening tool.

The Growth Characteristics of Patients with Noonan Syndrome: Results of Three Years of Growth Hormone Treatment: A Nationwide Multicenter Study.

OBJECTIVE: Noonan syndrome (NS) is a multisystem disorder, and short stature is its most striking manifestation. Optimal growth hormone (GH) treatment for NS is still controversial. In this study, using a nationwide registration system, we aimed to evaluate the growth characteristics and the clinical features of NS patients in Turkey and their growth response to GH treatment. METHODS: Children and adolescents with a diagnosis of NS were included inthe study. Laboratory assessment including standard GH stimulation test results were evaluated. Height increment of patients with or without GH treatment were analyzed after three years of therapy. RESULTS: A total of 124 NS patients from different centers were entered in the web-based system. Short stature and typical face appearance were the most frequently encountered diagnostic features of our patients. Of the 84 patients who were followed long-term, 47 hadreceived recombinant human GH (rhGH). In this group of 47 patients, height standard deviation score (HSDS) increased from -3.62±1.14 to -2.85±0.96 after three years of therapy, indicating significant differences from the patients who did not receive GH treatment. PTPN11 gene was analyzed in 61 patients, and 64% of these patients were found to have a mutation. HSDS at admission was similar in patients with or without PTPN11 gene mutation. CONCLUSION: A diagnosis of NS should be kept in mind in all patients with short stature showing systemic clinical findings. GH therapy is effective for improvement of short stature especially in the first two years of treatment. Further studies are needed for optimisation of GH therapy and evaluation of final height data in NS patients.

Transient Congenital Hypothyroidism in Turkey: An Analysis on Frequency and Natural Course.

OBJECTIVE: Prevalence of congenital hypothyroidism (CH) in Turkey at birth was reported to be as high as 1:650 in 2008-2010. Incidence rates of permanent and transient CH separately are unknown due to lack of follow-up data. We aimed to evaluate the impact of transient hypothyroidism on increasing incidence of CH and to determine the natural course and the clinical, biochemical, and imaging characteristics of transient CH. METHODS: Baseline and follow-up data of the infants with CH detected at screening in six provinces in the Black Sea Region were analyzed retrospectively during a time period covering the years 2008-2010. RESULTS: Among 138 cases (48% female), 16 (12%) showed transient hyperthyrotropinemia which resolved without intervention. Of the treated 122 cases, 63 (52%) had transient CH. While its frequency was 35% in 2008, it increased to 56% in 2009-2010, following a lowering of the thyroid stimulating hormone cutoff value. The frequency was higher in inland provinces than in coast (67% vs. 43%; p=0.01).Clinical characteristics of permanent and transient cases were similar except female-to-male sex ratios (1.5:1 vs. 0.6:1; p=0.02). L-thyroxine was discontinued in 70% of transient cases before 3 years of age at a median age of 19 (2-36) months. The only indication for early discontinuation of treatment was a low L-thyroxine dose, which was 1.25±0.27 µg/kg/day at withdrawal time. CONCLUSION: Our regional follow-up data showed that more than half of newborns with primary CH had transient thyroid dysfunction. In the majority of cases, discrimination between transient and permanent CH can be made before age 3 years, as indicated by cessation of L-thyroxine treatment.

Efficacy and safety of pamidronate in children with vitamin D intoxication.

BACKGROUND: Bisphosphonates are used in the treatment of vitamin D intoxication (VDI) after failure of conventional therapy including prednisolone. Safety concerns restrict the use of bisphosphonates from being used as first-line therapy for VDI in children. The aim of this study was to evaluate the efficacy and safety of pamidronate in comparison with prednisolone in children with VDI. METHODS: We reviewed the hospital records of children consecutively diagnosed with VDI at two medical centers in a 15 year period. RESULTS: The subjects consisted of 21 children (age, 0.3-4.2 years) who were treated with prednisolone and/or bisphosphonates. Pamidronate (n = 18) or alendronate (n = 3) was used in six patients after unsuccessful prednisolone treatment, and in 15 patients from baseline. Initial serum calcium and 25-hydroxyvitamin D were 16.1 ± 1.9 mg/dL and 493 ± 219 ng/mL, respectively. The median time to reach normocalcemia in the pamidronate, alendronate and prednisolone groups was 3 days (range, 2-12 days), 4 days (range, 3-6 days) and 17 days (range, 12-26 days), respectively (P = 0.013). The pamidronate group had a fivefold shorter hospital stay than the prednisolone group. Three patients initially treated with prednisolone developed nephrocalcinosis but this did not occur in any patient treated with bisphosphonates from baseline. Apart from transient fever and moderate hypophosphatemia, no side-effect of bisphosphonate treatment was observed. CONCLUSIONS: Pamidronate is efficient and safe for the treatment of VDI in children. Pamidronate use significantly shortens the duration of treatment, and thereby may prevent the development of nephrocalcinosis. Instead of prednisolone, pamidronate should be used together with hydration and furosemide as the first-line therapy for VDI.