Growth Hormone Deficiency In The Transition Period

The importance of continuing growth hormone therapy in the transition and adulthood periods must be studied in adolescents with growth hormone deficiency with childhood onset. Continuation of growth hormone therapy during the transition period in patients with permanent growth hormone deficiency is recommended as the therapy has positive effects on adult body composition and regional body fat distribution as well as its promotion of an increase in bone mineral content. The chance of having permanent growth hormone deficiency is higher in patients with a mass lesion involving the pituitary area, multiple pituitary hormone deficiency, isolated growth hormone deficiency associated with an identified mutation (i.e., growth hormone 1 (GH1) gene, growth hormone releasing hormone receptor (GHRHR) gene, sex determining region Y(SRY)-box 3 (SOX3) gene), midline defects, and congenital structural hypothalamo-pituitary disorders, such as an ectopic posterior pituitary; thus, such patients do not require retesting. The patients with idiopathic isolated growth hormone deficiency are recommended to undergo retesting. The most appropriate time for a retest is the age when the child achieves 98-99% of the adult height. The insulin tolerance test is preferred during the transition period and a threshold level of <5 ng/mL is recommended as the diagnostic criterion for complete growth hormone deficiency. Growth hormone doses higher than those used in adults (e.g., 70 mcg/kg/day) should be used until linear growth has been achieved. Decreased quality of life is another criterion for the initiation of therapy. This review addresses the definition of growth hormone deficiency and indications and usage of growth hormone therapy during the transition period.WoSScopu

Clinical Approach to Hypocalcemia in Newborn Period and Infancy

Introduction Hypocalcemia is a common metabolic problem in newborn period and infancy. There is consensus on the treatment of the symptomatic cases while the calcium level at which the treatment will be initiated and the treatment options are still controversial in asymptomatic hypocalcemia. Methods This review article will cover hypocalcemia with specific reference to calcium homeostasis and definition, etiology, diagnosis, and treatment of hypocalcemia in newborn and infancy period. Results Hypocalcemia is defined as total serum calcium 1500 g at birth and total serum calcium <7 mg/dL (1.75 mmol/L) or ionized calcium <4 mg/dL (1 mmol/L) for very low birth weight infants weighing <1500 g. Early-onset hypocalcemia is generally asymptomatic; therefore, screening for hypocalcemia at the 24th and 48th hour after birth is warranted for infants with high risk of developing hypocalcemia. Late-onset hypocalcemia, which is generally symptomatic, develops after the first 72 h and toward the end of the first week of life. Excessive phosphate intake, hypomagnesemia, hypoparathyroidism, and vitamin D deficiency are commonest causes of late-onset hypocalcemia. Hypocalcemia should be treated according to etiology. Calcium replacement is the cornerstone of the treatment. Elementary calcium replacement of 40 to 80 mg/kg/d is recommended for asymptomatic newborns. Elementary calcium of 10 to 20 mg/kg (1–2 mL/kg/dose 10% calcium gluconate) is given as a slow intravenous infusion in the acute treatment of hypocalcemia in patients with symptoms of tetany or hypocalcemic convulsion. Conclusion Since most infants with hypocalcemia are usually asymptomatic, serum total or ionized calcium levels must be monitored in preterm infants with a gestational age <32 weeks, small for gestational age infants, infants of diabetic mothers, and infants with severe prenatal asphyxia with a 1 min Apgar score of <4. The treatment of hypocalcemia should be initiated immediately in infants with reduced calcium levels while investigating the etiology.PubMedWo

Changing Etiological Trends In Male Precocious Puberty: Evaluation Of 100 Cases With Central Precocious Puberty Over The Last Decade

Background/ Aims: There are few studies in the literature that have evaluated the etiological factors in boys with central precocious puberty (CPP), and these studies are limited in terms of the sample size. In the present study, we aimed to evaluate the etiological factors in male CPP cases. Methods: One hundred male CPP subjects, aged between 9 months and 10.5 years, were included. The medical records were screened, and age at diagnosis, bone age, body weight, height, pubertal stage, imaging findings of the pituitary gland, testosterone, and basal and stimulated gonadotropin levels were recorded. Results: There was no underlying cause in 74% of the cases, and an organic cause was determined in only 26%. Most of the organic cases had been diagnosed before the age of 7 years, whereas most of the idiopathic cases had been diagnosed after the age of 7 years. Conclusion: An organic cause was determined in 26% of the male patients with CPP. This rate is one of the lowest rates in the literature and indicates that the number of idiopathic male CPP cases is increasing over time. When a boy is diagnosed with CPP above the age of 7 years, the odds of detecting an underlying pathology are very low, and these cases are mostly idiopathic. (C) 2015 S. Karger AG, BaselWoSScopu

A Pheochromocytoma Case Diagnosed As Adrenal Incidentaloma

There are two problems that needs to be addressed in cases of an adrenal incidentaloma. The first is to decide whether the adrenal mass is benign or malignant, and the second is to determine whether the mass is hormonally active or not. A 17-year-old male was admitted with the complaint of progressive weight gain. Abdominal ultrasonography was performed for elevation in transaminases which revealed a hypoechoic mass located in the left adrenal gland. Hormonal investigations revealed an increase in fractionated catecholamine and metanephrine levels in 24-hour urine. Surgery was performed and pathological examination was in accordance with pheochromocytoma. Mutation analysis was carried out. This is a rare case of pheochromocytoma presenting as adrenal incidentaloma during adolescence. In view of this case, we review the approach to incidentally discovered adrenal masses and the approach to pheochromocytoma. A mutation analysis should be performed on all cases with pheochromocytoma that are diagnosed below age 20.WoSScopu

Surgical and Clinical Strategies in the Management of Thyroid Medullary Carcinoma in Children with and without Ret Protooncogene Mutations

Boybeyi-Turer O, Vuralli D, Karnak I, Gonc N, Yalcin ES, Orhan D, Kandemir N, Tanyel FC. Surgical and clinical strategies in the management of thyroid medullary carcinoma in children with and without ret proto-oncogene mutations. Turk J Pediatr 2016; 58: 436-441. Medullary thyroid carcinoma (MTC) may arise sporadically or in familial manner. We presented sporadic and familial cases with MTC in order to raise awareness on management of such patients. Three medullary thyroid carcinoma (MTC) cases were presented. Case 1 had RET634 mutation; managed with total thyroidectomy (TT) and cervical lymph node dissection (CLND). Case 2 had RET804 mutation; managed with prophylactic TT. Case 3 had thyroid nodule; managed with TT and CLND. Case 1 had micro-carcinomatosis foci, Case 2 had normal thyroid tissue in histopathological examination and Case 3 had medullary thyroid carcinoma with tumor negative surgical borders. Case 1 was re-operated for persisting focus of disease. Follow-up of cases were uneventful. Clinicians and surgeons should be aware of critical timing for surgery and various surgical and clinical strategies in the management of MTC in children.WoSScopu

儿童新发1型糖尿病诊断后早期体重增加可能对缓解状态产生影响

Abstract Background Residual beta‐cell function and improvement in insulin sensitivity by reversal of glucose toxicity are two phenomena thought to be related to partial remission (PR). Body fat mass is the major determinant of insulin sensitivity. The aim of this study is to investigate the relationship between the rate of body weight gain after diagnosis of type 1 diabetes mellitus (T1DM) and other clinical factors for the development and duration of PR. Methods Children (2–16 years) with new‐onset T1DM (n = 99) were grouped into remitters and non‐remitters by using insulin dose‐adjusted glycosylated hemoglobin (HbA1c) values. Laboratory and clinical data as well as daily insulin requirement per kilogram of body weight at diagnosis and each visit were recorded, and the duration of PR was determined. Changes in body mass index standard deviation score (BMI‐SDS) were calculated by the auxological data collected every 6 months. Results There were 47 remitters (47.5%) and 52 (52.5%) non‐remitters. The mean increase in BMI‐SDS at the first 6 months of diagnosis was higher in the non‐remitters than in the remitters (p = 0.04). Duration of PR was negatively correlated with the change in BMI‐SDS between 6 and 12 months after diagnosis. Male sex, younger age, prepubertal status, and lower HbA1c were predictors of remission, among which male sex had the highest chance by multivariate regression. Conclusions Early rapid weight gain after diagnosis of T1DM may play a role in the lack of remission and shorter duration of PR. Interventions to prevent early rapid weight gain can maintain the development and prolongation of remission

Ion Transporters, Channelopathies, And Glucose Disorders

Ion channels and transporters play essential roles in excitable cells including cardiac, skeletal and smooth muscle cells, neurons, and endocrine cells. In pancreatic beta-cells, for example, potassium KATP channels link the metabolic signals generated inside the cell to changes in the beta-cell membrane potential, and ultimately regulate insulin secretion. Mutations in the genes encoding some ion transporter and channel proteins lead to disorders of glucose homeostasis (hyperinsulinaemic hypoglycaemia and different forms of diabetes mellitus). Pancreatic KATP, Non-KATP, and some calcium channelopathies and MCT1 transporter defects can lead to various forms of hyperinsulinaemic hypoglycaemia (HH). Mutations in the genes encoding the pancreatic KATP channels can also lead to different types of diabetes (including neonatal diabetes mellitus (NDM) and Maturity Onset Diabetes of the Young, MODY), and defects in the solute carrier family 2 member 2 (SLC2A2) leads to diabetes mellitus as part of the Fanconi–Bickel syndrome. Variants or polymorphisms in some ion channel genes and transporters have been reported in association with type 2 diabetes mellitus.PubMedWoSScopu

Hdac4 Mutations Cause Diabetes And Induce Β‐Cell Foxo1 Nuclear Exclusion

Background Studying patients with rare Mendelian diabetes has uncovered molecular mechanisms regulating β‐cell pathophysiology. Previous studies have shown that Class IIa histone deacetylases (HDAC4, 5, 7, and 9) modulate mammalian pancreatic endocrine cell function and glucose homeostasis. Methods We performed exome sequencing in one adolescent nonautoimmune diabetic patient and detected one de novo predicted disease‐causing HDAC4 variant (p.His227Arg). We screened our pediatric diabetes cohort with unknown etiology using Sanger sequencing. In mouse pancreatic β‐cell lines (Min6 and SJ cells), we performed insulin secretion assay and quantitative RT‐PCR to measure the β‐cell function transfected with the detected HDAC4 variants and wild type. We carried out immunostaining and Western blot to investigate if the detected HDAC4 variants affect the cellular translocation and acetylation status of Forkhead box protein O1 (FoxO1) in the pancreatic β‐cells. Results We discovered three HDAC4 mutations (p.His227Arg, p.Asp234Asn, and p.Glu374Lys) in unrelated individuals who had nonautoimmune diabetes with various degrees of β‐cell loss. In mouse pancreatic β‐cell lines, we found that these three HDAC4 mutations decrease insulin secretion, down‐regulate β‐cell‐specific transcriptional factors, and cause nuclear exclusion of acetylated FoxO1. Conclusion Mutations in HDAC4 disrupt the deacetylation of FoxO1, subsequently decrease the β‐cell function including insulin secretion, resulting in diabetes.PubMedWoSScopu

Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross-sectional study

Aims To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. Methods A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. Results After exclusion of the children with a BMI Z-score 50% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists

Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross-sectional study

Aims To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. Methods A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. Results After exclusion of the children with a BMI Z-score < 1 SD, those with genetic syndromes associated with Type 2 diabetes, and those whose C-peptide and/or insulin levels were not available, 227 cases were included in the study. Mean age was 13.8 +/- 2.2 (range 6.5-17.8) years, with female preponderance (68\%). Family history of Type 2 diabetes was positive in 86\% of the children. The mean BMI was 31.3 +/- 6.5 kg/m(2) (range 18.7-61) and BMI Z-score was 2.4 +/- 0.8 (range 1-5). More than half (57\%) of the children were identified by an opportunistic diabetes screening due to existing risk markers without typical symptoms of diabetes. Only 13\% (n = 29) were treated solely by lifestyle modification, while 40.5\% (n = 92) were treated with metformin, 13\% (n = 30) were treated with insulin, and 33.5\% (n = 76) were treated with a combination of insulin and metformin initially. Mean HbA(1C) levels of the insulin and combination of insulin and metformin groups were 98 (11.1\%) and 102 mmol/mol (11.5\%), respectively, and also were significantly higher than the lifestyle modification only and metformin groups mean HbA(1C) levels (70(8.6\%) and 67 mmol/mol (8.3\%), respectively). Conclusions An opportunistic screening of children who are at high risk of Type 2 diabetes is essential, as our data showed that > 50\% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38\%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists