Journal of Pediatric Endocrinology and Metabolism

Published by De Gruyter

Volume 28 Issue 7-8

Issue of Journal of Pediatric Endocrinology and Metabolism

Submit manuscript

Contents
Journal Overview

Publicly Available July 10, 2015

Highlight: Thyroid

Publicly Available July 10, 2015

Thyroid disorders revisited

Wieland Kiess, Melanie Penke, Julia Gesing, Julia Hoppmann, Eva Müller, Antje Körner, Jürgen Kratzsch, Roland Pfaeffle

Page range: 731-733

Download PDF

January 14, 2015

Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands

Malgorzata Kumorowicz-Czoch, Anna Madetko-Talowska, Adam Dudek, Dorota Tylek-Lemanska

Page range: 735-743

Abstract

Background: The morphological and biochemical phenotype of PAX8 mutation in patients with congenital hypothyroidism (CH) is variable. The contribution of mutations in PAX8 gene in children with CH and dysgenetic thyroid glands still remains a subject of interest for researchers. Patients and methods: Some 48 children (37 girls and 11 boys) with CH associated with thyroid ectopy (n=22), agenesis (n=10), hypoplasia (n=6), or thyroid dysgenesis of unknown cause (n=10) were enrolled. The study participants were born in south-eastern Poland in the years 1993–2012 and were selected for neonatal mass screening for CH. DNA was extracted from peripheral blood samples using Master Pure DNA Purification Kit (Epicentre Biotechnologies, Madison, WI, USA). The 12 exons of the PAX8 gene along with their exon-intron boundaries were amplified and sequenced by the Sanger method. Capillary electrophoresis was run on ABI 3500 (Applied Biosystems, Carlsbad, CA, USA). Results: Novel heterozygous transition in exon 3 (c.68G>A) was detected in a 3-year-old girl with a thyroid hypoplasia. This substitution was not identified in the patient’s parents (de novo event). Additionally, a novel genetic variant in 3′UTR region of exon 12 (c.*416C>T) occurred in a 3-year-old boy with ectopic thyroid tissue and concomitant congenital urogenital malformation. This heterozygous variant was also detected in other healthy family members. Thirteen well-described single nucleotide polymorphisms were revealed in the PAX8 gene. Conclusions: The study reports on the occurrence of two novel heterozygous substitutions in the PAX8 gene. Estimation of the contribution of the revealed c.68G>A variant to the etiology of CH in a girl with hypoplastic thyroid requires further functional analysis.

September 11, 2014

Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases

Chandra Sekhar Bal, Aayushi Garg, Saurav Chopra, Sanjana Ballal, Ramya Soundararajan

Page range: 745-751

Abstract

Aim: This study was aimed at identifying the prognostic factors predicting remission in pediatric differentiated thyroid cancer (DTC) patients presenting with pulmonary metastases. Little is known about the prognostic factors in reference to pediatric DTC patients presenting with pulmonary metastases. Methods: Fifty-three DTC patients aged ≤21 years were diagnosed with pulmonary metastases at initial presentation. The demographic and disease characteristics were compared between the patients who achieved remission and those who did not. Results: During the median follow-up of 72 months, 38 patients became disease free, 14 patients had biochemically and/or structurally persistent disease, and one patient died due to disease progression. Patient age >15 years, presence of macronodular pulmonary metastases, and surgical methods lesser than total/near-total thyroidectomy were identified as factors associated with reduced odds of remission. Conclusion: This study describes the disease course and depicts the disease related prognostic factors in pediatric DTC patients with pulmonary metastases.

April 16, 2015

Reclassification of cytologically atypical thyroid nodules based on radiologic features in pediatric patients

Nicoleta C. Arva, Sarah G. Deitch

Page range: 753-760

Abstract

Aim: In children the percentage of “Atypia of undetermined significance/follicular lesion of undetermined significance” (“AUS/FLUS”) cases is greater and the risk of malignancy is higher than expected. Our study aimed to determine if cytologically atypical nodules can be better characterized using imaging techniques for appropriate management of pediatric patients. Methods: Thyroid fine needle aspiration (FNA) specimens were reclassified using the Bethesda System for Reporting Thyroid Cytopathology (BSRTC). Cytologic-histologic correlation was performed to determine if the cytopathologic groups had different associations with the surgical outcome. The “AUS/FLUS” lesions were then subdivided based on radiologic features and the outcome was analyzed for each subgroup. Results: Histologically benign follicular nodules showed uniform distribution between the “benign” vs. “AUS/FLUS” (p=0.09) or between the “AUS/FLUS” vs. “follicular neoplasm” (“FN”) cytologic groups (p=0.27). The follicular neoplasms were also evenly distributed between the “FN” vs. “AUS/FLUS” categories (p=0.31). “Benign”, “AUS/FLUS”, and “FN” designations showed comparable associations with papillary thyroid carcinoma classical variant (PTC-cv). Reclassification of atypical lesions based on ultrasound findings yielded two subcategories with different risk of malignancy: one similar to the “benign” group (11% malignancy rate) and one comparable with the “FN” category (28% risk of malignant neoplasm). Conclusion: “AUS/FLUS” designation does not add significant value in categorization of pediatric thyroid nodules. These lesions can be reclassified based on radiologic features to provide accurate information for follow-up.

April 16, 2015

Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism

Ya-Li Qiu, Hong Zhu, Shao-Gang Ma, Hong Liu, Qing Li, Chun-Mei Ji

Page range: 761-765

Abstract

Objective: To investigate well-controlled congenital hypothyroidism on the markers associated with early kidney injury and oxidative DNA damage. Methods: Twenty-three children with euthyroid congenital hypothyroidism aged 3–6 years and 19 age- and gender-matched controls were enrolled. Serum levels of albumin, C-reactive protein, cysteine C, globulin, pre-albumin, and total protein were detected. Urine levels of albumin, fibrin degradation products, IgG, β 2 -microglobulin, and 8-hydroxydeoxyguanosine (8-OHdG) were also measured. Clinical and biochemical characteristics were evaluated between the two groups. Results: Serum levels of C-reactive protein were higher, but pre-albumin was lower in patients with congenital hyperthyroidism compared with the controls (all p<0.001). Urinary levels of IgG were higher in patients with congenital hyperthyroidism than in the controls (p=0.011). However, urinary levels of albumin excretion and 8-OHdG were similar to those in the controls. Serum pre-albumin levels were negatively correlated with urinary 8-OHdG levels (r=−0.479, p=0.016) in patients with congenital hypothyroidism. Conclusion: It is concluded that inflammatory and oxidative markers were slightly altered in well-controlled congenital hypothyroidism. The levels of urinary 8-OHdG and albumin excretion were not significantly different.

May 29, 2015

Investigation of autoimmune diseases accompanying Hashimoto’s thyroiditis in children and adolescents and evaluation of cardiac signs

Veysel Nijat Baş, Sebahat Yılmaz Agladioglu, Senem Özgür, Selmin Karademir, Zehra Aycan

Page range: 767-771

Abstract

Objective: In the present study, it was aimed to investigate the concomitance of additional cardiac problems, mainly mitral valve prolapse, in adolescents and pediatric patients with Hashimoto’s thyroiditis, by screening autoimmune markers. Materials and methods: Fifty-seven euthyroid patients, who applied to the Pediatric Endocrinology clinic at our institution with marked symptoms of hypothyroidism at the time of diagnosis, and were diagnosed and treated for Hashimoto’s thyroiditis, were included in the present study. All patients were evaluated by performing non-organ specific autoantibodies which could be tested at our institution, thyroid ultrasonography, two-dimensional echocardiography, and 24-h holter monitorization. Results: Of the 57 cases with Hashimoto’s thyroiditis, 48 (84.2%) were female, and nine (15.8%) were male. In the echocardiographic evaluation, mitral valve problems were detected in 10 (17.5%) of all cases; mitral valve prolapse was diagnosed in eight (seven females and one male) cases, and mitral insufficiency was diagnosed in two female cases. First-degree atrioventricular block was observed in only two patients during 24-h holter monitorization. Different non-organ specific autoantibody positivity was distributed as antinuclear antibody in 15 (26.3%) cases, anticardiolipin IgG in two cases, anticardiolipin IgM in three cases, tissue transglutaminase IgA in one, glutamic acid decarboxylase in one, anti-insulin antibody in four cases, antiphospholipid IgG in one, and antiphospholipid IgM in one case. Conclusion: It should be underlined that patients with Hashimoto’s thyroiditis should to be followed up closely for mitral valve prolapse and accompanying autoimmune diseases.

March 6, 2015

Neonatal thyroid storm accompanied with severe anaemia

Lu-Ying Cao, Hong Wei, Zheng-Li Wang

Page range: 773-776

Abstract

Neonatal thyroid storm is rare; the diagnostic criteria and management of neonatal thyroid storm have not been well established. In this paper, we report a preterm infant diagnosed with neonatal hyperthyroidism secondary to maternal Graves’ disease who was discharged after therapy. Unfortunately, he was rehospitalised for neonatal thyroid storm. We will discuss the diagnosis and general therapy of neonatal thyroid storm.

August 19, 2014

Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion

Taise Lima Oliveira Cerqueira, Aurore Carré, Lucie Chevrier, Gabor Szinnai, Elodie Tron, Juliane Léger, Sylvie Cabrol, Chrystelle Queinnec, Nicolas De Roux, Mireille Castanet, Michel Polak, Helton Estrela Ramos

Page range: 777-784

Abstract

Context: Thyroid dysgenesis may be associated with loss-of-function mutations in the thyrotropin receptor ( TSHR) gene. Objectives: The aim of this study was to characterize a novel TSHR gene variant found in one patient harboring congenital hypothyroidism (CH) from a cohort of patients with various types of thyroid defects. Materials and methods: This cross-sectional cohort study involved 118 patients with CH and their family members, including 45 with familial and 73 with sporadic diseases. The thyroid gland was normal in 23 patients, 25 patients had hypoplasia, 25 hemithyroid agenesis, 21 had athyreosis, and 21 had ectopy. Genomic DNA was extracted, and 10 exons of the TSHR gene were amplified and sequenced. Mutations in other candidate genes were investigated. Ortholog alignment was performed, and TSHR functional assays were evaluated. Results: We identified one previously unknown missense variation in the hinge region (HinR) of the TSHR gene (p.S304R) in one patient with thyroid hypoplasia. This variant is conserved in our ortholog alignment. However, the p.S304R TSHR variant presented a normal glycosylation pattern and signal transduction activity in functional analysis. Conclusion: We report the ocurrence of a novel nonsynonymous substitution in the HinR of the large N-terminal extracellular domain of the TSHR gene in a patient with thyroid hypoplasia. In contrast with four others in whom TSHR mutations of the hinge portion were previously identified, the p.S304R TSHR variation neither affected TSH binding nor cAMP pathway activation. This TSHR gene variant was documented in a CH patient, but the current data do not support its role in the clinical phenotype.

April 16, 2015

Subclinical hypothyroidism as a rare cofactor in chronic kidney disease (CKD) – related anemia

Agnieszka Bargenda, Kinga Musiał, Danuta Zwolińska

Page range: 785-788

Abstract

Background: Both chronic kidney disease (CKD) and hypothyroidism may cause anemia. However, the combination of the three above-mentioned phenomena in children has not been described yet. Methods: Our aim was to present a case of a 16-year-old girl hospitalized due to the renal impairment in the course of chemotherapy. Chronic kidney disease and severe anemia were diagnosed and erythropoiesis-stimulating agents (ESA) were administered. In view of unsatisfactory therapeutic effect, rare potential causes of hyporesponsiveness to ESA were analyzed. Laboratory tests revealed subclinical hypothyroidism. The thyroid hormone replacement therapy was applied and normalization of thyroid function was observed. Further increase of hemoglobin levels permitted discontinuation of ESA treatment. At the same time, partial amelioration of kidney function, as well as clinical improvement, were noticed. Conclusion: The thyroid gland function should be assessed both in differential diagnostics of anemia and in case of unsatisfactory treatment with ESA.

July 10, 2015

Cytometric analysis of perforin expression in NK cells, CD8+, and CD4+ lymphocytes in children with autoimmune Hashimoto’s thyroiditis – a preliminary study

Katarzyna Popko, Iwona Osińska, Anna Kucharska, Urszula Demkow

Page range: 789-792

Abstract

Perforin plays an essential role in cytotoxicity of natural killers (NK) and CD8+ lymphocytes. Cytotoxicity of T and NK cells is one of the mechanisms of destruction of cells in Hashimoto’s disease (HD). The aim of this study was analysis of the expression of perforin in CD8+, CD4+, and NK cells and cytotoxic abilities of these cells in children with HD compared to healthy controls. The expression of perforin and surface antigens, as well as cytotoxicity were analyzed with a flow cytometry. Lower expression of perforin in CD8+ and NK was found in HD compared to controls (p=0.01; p=0.004). A significant correlation between perforin expression in CD8+ lymphocytes and in NK was observed (p=0.05). The spontaneous cytotoxicity of NK was significantly higher in HD compared to controls (p=0.04). Our results suggest that perforin plays an important role in the pathogenesis of autoimmune Hashimoto’s thyroiditis.

August 12, 2014

Papillary thyroid cancer and autoimmune polyglandular syndrome

Alessandro Mussa, Patrizia Matarazzo, Andrea Corrias

Page range: 793-795

Review article

Publicly Available February 18, 2015

Should radioiodine be the first-line treatment for paediatric Graves’ disease?

James D. West, Timothy D. Cheetham, Carole Dane, Anuja Natarajan

Page range: 797-804

More Download PDF

Abstract

Background: Debate exists regarding the optimal treatment strategy for paediatric Graves’ disease with radioiodine (RAI), and surgery, usually reserved for failure of medical therapy. We present our own experience to introduce a review of the published literature focussing on the predictors of remission after antithyroid drug (ATD) therapy from diagnosis, and discuss whether RAI should be considered as a first-line therapy. Method: A retrospective analysis of all diagnosed cases of paediatric Graves’ disease presenting to a large District General Hospital. Results: Thirteen patients were diagnosed with Graves’ disease between February 2004 and May 2013. The median age at diagnosis was 13.7 years (range 7.2–17.1 years) with a female:male ratio of 11:2. Some nine patients completed a 2-year course of carbimazole out of which 8 relapsed after a mean duration of 0.82 years (range 0.08–1.42 years); the ninth currently remains in remission. Of the eight patients who relapsed, three have undergone RAI treatment. Two patients failed to tolerate carbimazole treatment, one of whom received RAI treatment because surgery was contraindicated and one patient with severe autism proceeded to RAI treatment due to poor compliance and persistent hyperthyroidism. Literature Review: Prognostic factors at presentation predicting a low likelihood of remission following ATD treatment include younger age, non-Caucasian ethnicity, and severe clinical and/or biochemical markers of hyperthyroidism. Psycho-social factors including compliance also influence management decisions. Conclusion: In specifically selected patients presenting with paediatric Graves’ disease, the benefits and risks of radioactive iodine as a potential first-line therapy should be communicated allowing families to make informed decisions.

Image in pediatric endrocrinology

April 16, 2015

Diffusion-weighted magnetic resonance imaging in a case of severe classic maple syrup urine disease

Wei Xia, Wenzhong Yang

Page range: 805-808

Original articles

May 13, 2015

Novel mutations of DAX1 (NR0B1) in two Chinese families with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism

Guijun Qin, Hongfei Ji, Xialian Li, Xiaokun Ma, Danping Wang

Page range: 809-814

Abstract

Objective: To analyze the DAX1 (NR0B1) (dosage-sensitive sex reversal-adrenal hypoplasia congenita (AHC) critical region on the X chromosome gene 1) gene in two Chinese families with AHC and hypogonadotrophic hypogonadism (HHG). Patients and methods: Two families with 4 affected males, 5 carrier females, and 4 unaffected males were investigated. Sequencing of the entire 1413-bp coding region of DAX1 (NR0B1) gene was performed in both patients and their family members. Results: Two different novel DAX1 (NR0B1) mutations located within exon 1, an insertional mutation at codon 35 leading to a frameshift and a premature stop at codon 46, and a deletion mutation at codon 331 leading to a frameshift and a premature stop at codon 371 were detected. The mothers and sisters of the patients were heterozygotes for the mutations, while their fathers did not carry the mutations. Conclusions: Two novel DAX1 (NR0B1) mutations were detected in two Chinese families. These data indicate that molecular analysis of the DAX1 (NR0B1) gene is important for the diagnosis and genetic counseling of children with primary adrenal insufficiency.

March 4, 2015

Rickets and vitamin D deficiency in Alaska native children

Rosalyn Singleton, Rachel Lescher, Bradford D. Gessner, Matthew Benson, Lisa Bulkow, John Rosenfeld, Timothy Thomas, Robert C. Holman, Dana Haberling, Michael Bruce, Michael Bartholomew, James Tiesinga

Page range: 815-823

Abstract

Background: Rickets and vitamin D deficiency appeared to increase in Alaskan children starting in the 1990s. We evaluated the epidemiology of rickets and vitamin D deficiency in Alaska native (AN) children in 2001–2010. Methods: We analyzed 2001–2010 visits with rickets or vitamin D deficiency diagnosis for AN and American Indian children and the general US population aged <10 years. We conducted a case-control study of AN rickets/vitamin D deficient cases and age- and region-matched controls. Results: In AN children, annual rickets-associated hospitalization rate (2.23/100,000 children/year) was higher than the general US rate (1.23; 95% CI 1.08–1.39). Rickets incidence increased with latitude. Rickets/vitamin D deficiency cases were more likely to have malnutrition (OR 38.1; 95% CI 4.9–294), had similar breast-feeding prevalence, and were less likely to have received vitamin D supplementation (OR 0.23; 95% CI 0.1–0.87) than controls. Conclusions: Our findings highlight the importance of latitude, malnutrition, and lack of vitamin D supplementation as risk factors for rickets.

May 13, 2015

Persistent elevation of fibroblast growth factor 23 concentrations in healthy appropriate-for-gestational-age preterm infants

Tarah Fatani, Asma Binjab, Hope Weiler, Atul Sharma, Celia Rodd

Page range: 825-832

Abstract

Objective: To explore the temporal evolution of 25-hydroxyvitamin D [25(OH)D], its epimer, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and minerals in healthy appropriate-for-gestational-age preterms. Patients: A prospective study was undertaken in infants born at 28–32 weeks with monitoring at 1, 3, 5 weeks and term. Methods: Morning plasma and urine calcium; phosphorus; creatinine; PTH, C-terminal and intact FGF23 (iFGF23) and liquid chromatography-tandem mass spectrometry measurements of 25(OH)D were undertaken. Analyses included regression models. Results: Some 11 infants (5 males) were recruited at a median gestational age of 31.2 weeks (interquartile range: 28.1–31.8). Standard chemistries were normal. No infant was vitamin D deficient; 58% achieved 50 nmol/L with a median intake of 540 IU/day. High concentrations of C-3 epimer were detected. iFGF23 and C-terminal concentrations were persistently elevated (double and ten times adult norms, respectively). Tubular resorption of phosphorus was normal (88%±8%). Conclusions: Most infants achieved acceptable 25(OH)D 3 concentrations. The biologic significance of the elevated FGF23 is unclear.

June 12, 2015

Parents’ experiences of having a baby with ambiguous genitalia

Mailme de Souza Oliveira, Roberto Benedito de Paiva-e-Silva, Gil Guerra-Junior, Andréa Trevas Maciel-Guerra

Page range: 833-838

Abstract

Health professionals must be aware of the impact on parents of the birth of children with ambiguous genitalia. This study aimed to analyze the experiences and perceptions of such parents. Parents of 30 children who were evaluated in a reference center for disorders of sex development (DSD) were interviewed. The questionnaire covered the prenatal period, the moment they were told about the disorder, initial management by health professionals, and problems they experienced. Only two cases were detected during pregnancy. The news was usually given to the mother alone by pediatricians. Most parents kept it secret and avoided exposing the baby to the prejudice of others. Parents of children who were referred without sex assignment usually held a personal belief of their child’s sex. Previous assignment was based on clinical examination and/or karyotype. Spreading knowledge about DSD could increase awareness of this issue, thus reducing parents’ shock and societal stigma. Training of neonatal care teams is required to avoid assignment before evaluation.

February 21, 2015

Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty

Yan Liang, Hong Wei, Jie Li, Ling Hou, Jianling Zhang, Wei Wu, Yanqin Ying, Xiaoping Luo

Page range: 839-846

Abstract

Objective: To evaluate the long-term efficacy of triptorelin 3.75 mg subcutaneously every 6 weeks on the final height in girls with idiopathic central precocious puberty (ICPP). Methods: Forty females with ICPP received triptorelin 3.75 mg every 6 weeks subcutaneously in our hospital from 2002 to December 2010 and reached their final heights were enrolled. These patients were treated with triptorelin alone (group A, n=17) or triptorelin+recombinant human growth hormone (rhGH) (group B, n=23). Height, weight, annual growth velocity (GV), sexual development, predicted adult height (PAH), and adverse effects were observed. Bone age (BA) and height standard deviation score (SDS) were monitored yearly. Results: Final adult heights (FAHs) were 159.81±1.20 cm and 161.01±1.02 cm in group A vs. group B, which exceeded target height (THt) by 1.51±1.04 cm, 4.86±0.94 cm, respectively. The values of (FAH-THt), (FAH-PAH posttreatment) showed significant difference between the two groups (p<0.05). FAH was positively correlated with Ht SDS-BA at the end of treatment, THt, course of rhGH treatment, and age of menarche (r2=0.66). Body mass index (BMI) increased after treatment in group B. However, there was no significant tendency of increase compared with healthy children at the same age. Ages of menarche and time to menarche from discontinuation were 11.74±0.16 vs. 12.18±0.15 years and 17.41±1.69 vs. 14.71±1.04 months in two groups. Conclusion: The FAH was improved effectively by triptorelin 3.75 mg subcutaneously every 6 weeks, and more height gain could be achieved when rhGH was used concomitantly. BMI maintained steadily and ovarian function restored quickly after treatment discontinuation with the age of menarche similar to that of normal children. Neither significant side effect nor polycystic ovary syndrome was observed.

March 7, 2015

Congenital adrenal hyperplasia in children – a survey on the current practice in the UK

Usha Niranjan, Anuja Natarajan

Page range: 847-851

Abstract

Background: Congenital adrenal hyperplasia (CAH) in children varies in presentation and progression with several challenges in optimal management. Effective treatment is to achieve normal growth and development while avoiding adrenal crisis and hyperandrogenisation. Aim: Our aim was to ascertain the current practice in the UK on CAH management in children in comparison with the recommendations made by the Endocrine Society. Methods: An online survey was emailed to the British Society of Paediatric Endocrinology (BSPED) members requesting a response from each centre regarding CAH management. Results: The survey was completed by 35 out of 92 centres (38% response rate). Tertiary centres constituted 22/35, while 8/35 were district general hospitals providing tertiary services. Treatment varied among centres with 25/35 using 10–15 mg/m 2 /day of hydrocortisone and 21/35 of centres using 50–150 μg/day of fludrocortisone. The frequency of clinical reviews was contentious and varied depending on the child’s age and clinical status. Reviews were done 3–4 monthly in 68% and 6 monthly in 31% of centres. The frequency of investigations including 17-hydroxyprogesterone (66% 3–6 monthly; 34% yearly), testosterone/dehydroepiandrosterone sulphate (37% 6 monthly; 51% yearly), renin/aldosterone (31% 6 monthly; 69% yearly) and bone age (83% yearly, 6% 2 yearly) varied significantly among centres. Genetic counselling was provided at diagnosis in 69% of the centres while surgical (66%) and psychology (80%) input were provided on an as required basis. Conclusion: Our survey highlights the diversity in managing children with CAH in the UK as compared with the recommendations of the Endocrine Society. It also demonstrates inconsistent involvement of essential specialist services, which are essential for optimal management of this condition.

March 7, 2015

Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome

Hiba Al-Zubeidi, Karen O. Klein

Page range: 853-858

Abstract

Background: Polycystic ovarian syndrome (PCOS) is characterized by irregular menses, elevated androgens, and insulin resistance. Little information is published about the treatment of adolescent PCOS. Objectives: The aim of this study was to evaluate metformin versus oral contraceptive pills (OCP) in treating adolescent PCOS. Twenty-two girls were randomized to either treatment for 6 months. The outcomes variables included body mass index (BMI) and free testosterone (FT). Results: BMI decreased in all patients (metformin p=0.004, OCP p=0.045). FT decreased significantly only with OCP. Insulin resistance measures decreased in all patients but did not reach significance. The only significant difference in any of the variables between the two groups was number of menses. BMI and FT remained less than baseline for 3 months off treatment. Conclusions: Metformin and OCP have a positive effect on BMI, which persists after treatment is discontinued. FT decreased with both treatments, but only reached significance with OCP.

March 7, 2015

Influence of the body weight on the onset and progression of puberty in boys

Analia Tomova, Ralitsa Robeva, Philip Kumanov

Page range: 859-865

Abstract

Background: Unlike in girls, the data on the relationship between pubertal development and body weight in boys are controversial. Methods: We measured the height, body weight, body mass index (BMI), pubic hair stages, testicular volume, penis length and circumference of 4030 boys, aged between 7 and 19 years. According to their body weight, the investigated children and adolescents were divided in four groups at each age: underweight boys (BMI <12th percentile), boys with normal weight (12th–84.99th percentile), overweight boys (85th–94.99th percentile) and boys with obesity (BMI ≥95th percentile), and their data were compared. Results: The onset of puberty occurred when the boys’ weight gained 40.33±9.03 kg (median 39.00) and BMI was 18.62±3.12 kg/m 2 (median 17.80), whereas the late stage was reached at weight of 62.44±10.39 kg (median 61.00) and BMI 21.47±2.84 kg/m 2 (median 21.20). Earlier maturing boys were heavier than their coevals, whereas underweight boys developed puberty later. Conclusions: The onset and progression of puberty in boys are in a significant positive relationship with weight and BMI. Moreover, in the overweight boys pubertal development begins and comes to the late stage earlier in comparison with normal weight children, whereas in those who are underweight a delay at every stage of the development is observed.

March 7, 2015

Therapy monitoring in congenital adrenal hyperplasia by dried blood samples

Isabelle Wieacker, Michael Peter, Katrin Borucki, Susann Empting, Friedrich-Wilhelm Roehl, Klaus Mohnike

Page range: 867-871

Abstract

Careful monitoring of the therapy is crucial for patients with congenital adrenal hyperplasia (CAH) in order to prevent the effects of increased androgen production as well as life-threatening salt-wasting crisis. The key metabolite, 17α-hydroxyprogesterone (17-OHP) can be detected in serum, saliva or dried blood. In clinical practice there are challenges due to discomfort of venous blood sampling and complicated retrieval of saliva during infancy. Furthermore, the immunoassay method is limited in its specificity due to cross-reactions. In this observational study we prospectively examined over a period of 5 years, 20 patients with CAH due to 21-hydroxylase deficiency using standard immunoassays for serum samples (radioimmunoassay and enzyme immunoassay) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in dried blood spots. Bland-Altman plots show goodness of agreement between both the methods for the desirable therapeutic concentration range of 17-OHP. LC-MS/MS is characterized by a high accuracy in the therapeutic concentration range of 17-OHP <100 nmol/L ( r =0.91). Dried blood samples are convenient and reliable specimen for 17-OHP measured by LC-MS/MS. This method could be used for home monitoring of hydrocortisone replacement therapy both in salt-waster and simple virilizer CAH.

March 7, 2015

Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene

Christel Tran, Vassiliky Konstantopoulou, Michelle Mecjia, Kusiel Perlman, Saadet Mercimek-Mahmutoglu, Jonathan B. Kronick

Page range: 873-876

Abstract

Background: Hyperinsulinism-hyperammonemia syndrome (HI/HA) is a rare autosomal dominant disorder presenting with hypoglycemia and hyperammonemia. It is caused by activating mutations in the GLUD1 gene. Case reports: Three patients from two different centers, a 14-month-old female, a 28-year-old female (mother of the first patient) from Toronto and an unrelated 2.5-year-old male from Vienna, presented with multiple episodes of seizures associated with hypoglycemia. Results: All patients had mild to moderate hypoglycemia, inappropriate insulin levels and mild hyperammonemia, thus suggesting a disorder of glutamate dehydrogenase (GDH). Molecular genetic testing of the GLUD1 gene identified heterozygous mutations in all patients (patient 1 and her mother a novel c.1526G>C mutation; patient 3 a known c.809C>G mutation). Conclusion: We present three new patients with GDH caused by heterozygous mutation in the GLUD1 gene. Mild hyperammonemia and inappropriately elevated insulin levels should suggest a GLUD1 mutation. Early onset hypoglycemia associated with seizures, and especially a good response to diazoxide treatment, should include this disorder in the differential diagnosis of hyperinsulinemic hypoglycemia.

March 14, 2015

Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds

Miaoying Zhang, Xiuli Chen, Shuixian Shen, Tang Li, Linqi Chen, Min Hu, Lingfeng Cao, Ruoqian Cheng, Zhuhui Zhao, Feihong Luo

Page range: 877-884

Abstract

Objective: The pathogenic base of neonatal diabetes mellitus (NDM) is highly heterogeneous. Sulfonylurea (SU) has been successfully applied in majority of NDM patients with K ATP channel mutations; however, its rationality and effectiveness among patients with NDM stemmed from other genetic mutations have not been established. The objective of the present study was to investigate the effectiveness of SU therapy in NDM patients with heterogeneous genetic backgrounds. Methods: We identified 16 patients with NDM. These patients underwent SU titration and were followed after successful SU monotherapy. All patients were sequenced for all exons and adjacent intron-exon junctions of ABCC8 , KCNJ11 , and INS , and analyzed for 6q24 methylation defects. SU regimens were applied and glycemic status was evaluated in each patient. Results: Of the 16 patients, 15 (94%) reached glycemic goal (7–10 mmol/L) after SU monotherapy except one patient with the INS mutation. No significant side effects or organ damage were found in any of the 16 patients. Among these patients, five were found to harbor ABCC8 mutations, another five had mutations in KCNJ11 , two had INS gene mutations, one with 6q24 hypomethylation, and three were absent for defects in genes tested. Conclusion: Our study showed that SU monotherapy resulted in satisfactory glycemic control in most of the patients with NDM whose genetic defects are heterogeneous. The usage of SU may be considered as first-line therapy for patients with NDM in developing countries where effective genetic screening is not established.

March 7, 2015

Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods

Amnon Zung, Ella Burundukov, Mira Ulman, Tamar Glaser, Zvi Zadik

Page range: 885-893

Abstract

Aim: The objective of this study was to validate basal, post-gonadotropin-releasing hormone analogue (post-GnRHa) and first-voided urinary LH (ULH) as alternatives to an LHRH stimulation test in monitoring treatment efficacy in central precocious puberty (CPP). Methods: Seventeen girls with CPP were followed over 22.5±9.1 months during GnRHa (triptorelin) treatment. ULH and post-GnRHa LH levels were obtained every 4 months before and 24 h after GnRHa administration, respectively, along with clinical and bone age (BA) evaluation. LHRH stimulation tests were performed annually. Results: A total of 36 LHRH stimulation tests demonstrated adequate suppression with a peak LH of 0.57±0.33 IU/L. The corresponding basal LH was 0.27±0.16 IU/L. Ninety post-GnRHa LH measurements were similar to LHRH-stimulated LH levels (0.56±0.31 IU/L), whereas 8% of ULH levels were above prepubertal threshold. Fourteen episodes of growth acceleration and ten episodes of BA advancement resolved without treatment modification. Conclusion: Suppressed basal and post-GnRHa LH levels indicate adequate suppression of puberty. Clinical breakthroughs during treatment are transient and resolved spontaneously.

March 7, 2015

Dietary intake, body composition, and physical activity among young patients with type 1 diabetes mellitus

Constanza Mosso, Victoria Halabi, Tamara Ortiz, Maria Isabel Hodgson

Page range: 895-902

Abstract

Objective: The aim of this study was to assess dietary intake, nutritional status, body composition, and physical activity level in a group of Chilean children and adolescents with Type 1 diabetes mellitus (T1DM), compare these parameters with the recommendations of the International Society for Pediatric and Adolescent Diabetes (ISPAD), and determine the relationships between dietary intake, body composition, and diabetes control. Methods: A total of 30 patients with T1DM (aged 15.2±4.0 years) were included. Dietary intake was assessed using a 92-item quantitative food frequency questionnaire. Body composition was determined using dual-energy X-ray densitometry. Physical activity was assessed by means of a survey. Results: The energy intake of these patients was derived from 21.4% protein, 48% carbohydrates, and 31.2% fat. The glycosylated hemoglobin (HbA1c) was significantly correlated with fat as grams per day (r: 0.363, p<0.05) and calories per day (r: 0.364, p<0.05). The mean body fat percentage in females was 31.2% and 20.2% in males (p < 0.01) and the mean amount of physical activity was 4.5±2.7 h per week. Conclusions: The study patients had a higher protein intake than recommended by ISPAD. Dietary carbohydrate intake was rather low, and dietary fat intake was the same as the limits recommended by ISPAD. Diabetic control was significantly correlated with protein, carbohydrates, fat, and sodium intake. The girls in the study had a higher percentage of body fat than the standard recommendations for their age. The level of physical activity was adequate.

March 4, 2015

Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors

Rade Vukovic, Dragan Zdravkovic, Katarina Mitrovic, Tatjana Milenkovic, Sladjana Todorovic, Ana Vukovic, Ivan Soldatovic

Page range: 903-909

Abstract

Objective: To assess the prevalence of metabolic syndrome (MS) in obese children and adolescents in Serbia. Subjects and methods: The study group consisted of 254 subjects (148 female and 106 male), aged 4.6–18.9 years with diet-induced obesity (body mass index ≥95th percentile). Presence of MS using the International Diabetes Federation definition was assessed in all subjects, as well as oral glucose tolerance test and insulin resistance indices. Results: Overall prevalence of MS in all subjects aged ≥10 years was 31.2%, namely, 28.7% in children aged 10 to <16 years and 40.5% in adolescents ≥16 years. When adjusted for age, gender and pubertal development, higher degree of obesity was a strong predictor of MS. Multivariate analysis showed that taller subjects and those with higher degree of insulin resistance were at significantly higher risk of MS, independent of the degree of obesity. Conclusions: High prevalence of MS emphasizes the need for prevention and treatment of childhood obesity.

April 18, 2015

Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy

Maria H. Lin, Nawaporn Numbenjapon, Emily L. Germain-Lee, Pisit Pitukcheewanont

Page range: 911-918

Abstract

Introduction: Progressive osseous heteroplasia (POH) is a condition of invasive heterotopic ossification. Reports of patients with mild POH with Albright hereditary osteodystrophy (AHO), specifically pseudohypoparathyroidism type Ia (PHP Ia) with hormonal resistance, suggest the possibility of a common molecular basis. GNAS has been implicated to account for overlapping features of POH and PHP Ia. Case 1: A 4-year-old boy with obesity, speech delay, and expanding subcutaneous masses on buttock/forearm. Physical exam revealed round facies and brachydactyly. Blood tests showed normal Ca, P, Mg, 25-OH vitamin D levels but elevated parathyroid hormone (PTH) and thyroid-stimulating hormone (TSH). Abdominal computed tomography (CT) showed areas with calcifications in the subcutaneous tissue, fat, and muscle. Pathology of excised tissue revealed ossifications. Genomic study revealed no GNAS mutation. He had POH and PHP Ia. Case 2: A 3-year-old boy with painful ossifications in the left lower extremity. Lab tests were notable for elevated PTH and high-normal TSH. The CT-scan showed subcutaneous/intramuscular calcifications. Genetic testing showed GNAS mutation in exon 12 [c.1024C>T (R342X)]. Patient had POH and PHP Ia. Case 3: A 9-year-old boy with knee pain and subcutaneous ossifications in back and upper/lower extremity, causing significantly limited joint mobility. Lab tests were normal. The CT-scan showed areas corresponding to subcutaneous/intramuscular ossifications throughout torso and extremities, consistent with POH. There was no GNAS mutation. Conclusions: Patients with heterotopic ossifications present with a wide spectrum of disease. Although GNAS -based mutations have been postulated to account for overlapping features of AHO and POH, normal DNA studies in certain patients with POH/AHO suggest that there may exist other molecular/epigenetic mechanisms explaining their overlapping features.

Patient reports

February 23, 2015

17α-Hydroylase/17,20-lyase deficiency related to P.Y27(c.81C>A) mutation in CYP17A1* gene

Melikşah Keskin, Aylin Kılınç Uğurlu, Şenay Savaş-Erdeve, Elif Sağsak, Sare Gülfem Akyüz, Semra Çetinkaya, Zehra Aycan

Page range: 919-921

Abstract

17α-Hydroxylase/17-20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia. Genetic defects causing combined 17OHD lead to the impaired production of cortisol and sex steroids, accumulation of mineralocorticoids, and compensatory overproduction of pituitary adrenocorticotropic hormone. Consequently, individuals with this enzymatic defect present with both adrenal cortical hyperplasia and variable degrees of hypertension, hypokalemia, and sexual immaturity. The patient was aged 15 years and 3 months and she was diagnosed with 17OHD while she was being evaluated for complaints of delayed puberty. In the present case, p.Y27*(c.81C>A) mutation was revealed in the sequence analysis of the CYP17A1 gene. The same mutation was reported in a 20-year-old Turkish girl in Germany, who was investigated for delayed puberty in 2005. The previous case was reported to be normotensive and normokalemic. The presence and differences in the severity of hypertension in cases with the same mutation and total enzymatic deficiency may indicate that genes predisposed to hypertension, obesity due to genetic and environmental factors, and some other factors may play a role in the clinical presentation of hypertension.

February 23, 2015

A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature

Deniz Ökdemir, Nihal Hatipoğlu, Himmet Haluk Akar, Ülkü Gül, Leyla Akın, Fulya Tahan, Selim Kurtoğlu

Page range: 923-925

Abstract

Gonadotropin-releasing hormone analogues are used in the treatment of prostate cancer, breast cancer, endometriosis, and uterine leiomyomas in adults and often in the treatment of precocious puberty in children. Many adverse effects have been reported for gonadotropin-releasing hormone analogues, but anaphylaxis is rarely reported as an adverse effect. Frequent cross-reactions, particularly during childhood, and diversity of the time of onset of anaphylactic manifestations complicate the diagnosis. A patient who exhibited anaphylactic allergic reactions to two different agents used in the treatment of central precocious puberty presented here because the case has an atypical course and is the first in the literature.

March 4, 2015

Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene

Jose Bernardo Quintos, Michael H. Guo, Andrew Dauber

Page range: 927-932

Abstract

Background: Recently, whole exome sequencing identified heterozygous defects in the aggrecan ( ACAN ) gene in three families with short stature and advanced bone age. Objective: We report a novel frameshift mutation in ACAN in a family with dominantly inherited short stature, advanced bone age, and premature growth cessation. This is the first case of targeted sequencing of ACAN in this phenotype and confirms that ACAN sequencing is warranted in patients with this rare constellation of findings. Results: We present a 5 1/2-year-old male with a family history of short stature in three generations. The maternal grandfather stands 144.5 cm (Ht SDS –4.7), mother 147.7 cm (Ht SDS –2.6), and index case 99.2 cm (Ht SDS –2.7). Our prepubertal patient has significant bone age advancement (bone age 8 years at chronologic age 5 1/2 years) resulting in a poor predicted adult height of 142 cm (Ht SDS –5.1). DNA sequencing identified a novel heterozygous variant in ACAN , which encodes aggrecan, a proteoglycan in the extracellular matrix of growth plate and other cartilaginous tissues. The mutation (p.Gly1797Glyfs*52) results in premature truncation and presumed loss of protein function. Conclusion: Mutations in the ACAN gene should be included in the differential diagnosis of the child with idiopathic short stature or familial short stature and bone age advancement.

March 7, 2015

Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty

Haidar Bustanji, Bashar Sahar, Angela Huebner, Kamel Ajlouni, Dana Landgraf, Hanan Hamamy, Katrin Koehler

Page range: 933-936

Abstract

Triple A syndrome, formerly known as Allgrove syndrome, is an autosomal recessive disorder characterized clinically by adrenal insufficiency, alacrima, achalasia, and neurological abnormalities. We report a 17-year-old boy presented to the endocrine clinic with delayed puberty and a 4-year’s history of fatigue and muscle weakness. He had achalasia, alacrima, and skin and mucosal hyperpigmentation. Hormonal assessment revealed isolated glucocorticoid deficiency. Clinical diagnosis of triple A syndrome was confirmed by sequencing the entire coding region including exon-intron boundaries of the AAAS gene. Analysis revealed a homozygous novel indel mutation encompassing intron 7 to intron 10 of the gene (g.16166_17813delinsTGAGGCCTGCTG; NG_016775) . This is the first report of triple A syndrome in Jordan with a novel indel mutation and presenting with delayed puberty.

March 7, 2015

Case report: long-term follow-up of a 45,X male with SHOX haploinsufficiency

Monica Grover, Shannon French, Parvin Yazdani

Page range: 937-941

Abstract

The 45,X disorder of sexual differentiation (DSD) is a rare disorder. We report long-term follow-up of a 5-year-old African-American male whose evaluation for short stature revealed a karyotype of 45,X der(X)t(X;Y)(p22.3;p11.2)(SRY+). Presence of the SRY (sex-determining region Y) gene resulted in his male development. His chromosome abnormality also resulted in a deletion of the SHOX (short stature homeobox-containing) gene, which partly contributed to his short stature and skeletal features. He underwent normal spontaneous pubertal development, but his final height remained compromised due to advanced bone age, non-optimal response to recombinant human growth hormone (rhGH) treatment during the period of compliance and ultimately non-compliance with rhGH therapy. To our knowledge, this is the first case report describing long-term follow-up of a 45,X male DSD which highlights the similarities and differences from Turner syndrome females.

March 5, 2015

Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review

Itai Gross, Yael Siedner-Weintraub, Ari Simckes, David Gillis

Page range: 943-946

Abstract

Antenatal type I Bartter syndrome (ABS) is usually identified by the presence of polyhydramnios, premature delivery, hypokalemia, metabolic alkalosis, hypercalciuria, and nephrocalcinosis caused by mutations in the Na-K-2Cl cotransporter (NKCC2)-encoding SLC12A1 gene. In this report, we describe a novel presentation of this syndrome with hypercalcemic hypercalciuric hyperparathyroidism, and review the literature of the variable atypical presentations of ABS.

March 7, 2015

Successful use of continuous subcutaneous hydrocortisone infusion after bilateral adrenalectomy secondary to bilateral pheochromocytoma

Julia R. Broussard, Naim Mitre

Page range: 947-949

Abstract

We report the use of continuous subcutaneous hydrocortisone infusion in an adolescent patient with primary adrenal insufficiency. This novel hydrocortisone delivery method proved to be a feasible, well-tolerated and safe option for selected patients with poor response to conventional therapy.

March 4, 2015

Donohue syndrome: a new case with a new complication

Rasha Odeh, Abeer Alassaf, Abdelkarim A. Al-Qudah

Page range: 951-954

Abstract

Donohue syndrome (DS) is a very rare autosomal recessive disease affecting less than one in a million live births. It represents the most severe form of insulin resistance due to mutations involving the insulin receptor gene. DS is characterized by pre- and postnatal growth retardation with failure to thrive, lipoatrophy, muscle wasting, acanthosis nigricans, hypertrichosis, and dysmorphic features. Glucose homeostasis is affected with hyperinsulinemia, fasting hypoglycemia, and postprandial hyperglycemia. We report a Jordanian patient with genetically proven DS who had the classical physical features, progressive hypertrophic cardiomyopathy, cholestasis, and hyperglycemia, followed by hypoglycemia. In addition, the patient developed polyuria and uremia despite normal creatinine levels, hypernatremia, and hypertension. To our knowledge, these metabolic derangements were not previously reported in patients with DS.

March 7, 2015

Euprolactinemic galactorrhea secondary to domperidone treatment

Arzu Meltem Demir, Zarife Kuloglu, Merih Berberoglu, Aydan Kansu

Page range: 955-956

Abstract

Milk leakage from the breast, which is known as galactorrhea, can be caused by a number of pharmacological, physical, and tumoral factors. Galactorrhea is a well-known side effect of domperidone, and is usually associated with hyperprolactinemia. However, euprolactinemic galactorrhea secondary to domperidone is very rarely seen and has yet to be reported in children before. Here, we report an adolescent with euprolactinemic galactorrhea caused by domperidone.

April 18, 2015

17βHSD-3 enzyme deficiency due to novel mutations in the HSD17B3 gene diagnosed in a neonate

Elif Sagsak, Zehra Aycan, Senay Savas-Erdeve, Meliksah Keskin, Semra Cetinkaya, Kadri Karaer

Page range: 957-959

Abstract

17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) is present almost exclusively in the testes, and converts androstenedione (A) to testosterone (T). 17βHSD-3 deficiency is rare. The diagnosis can be missed in early childhood as the clinical presentation may be subtle. The most frequent presentation of 17 HSD-3 deficiency is a 46,XY individual with female external genitalia, labial fusion and a blind ending vagina, with or without clitoromegaly. A low testosterone/androstenedion (T/A) ratio is suggestive of 17βHSD-3 deficiency, and such diagnosis can be confirmed with molecular genetic studies. A 12-day newborn was referred to our hospital because of palpable gonads in the labia majora. On physical examination, the baby had female external genitalia and palpable gonads in the labia majora. T/A ratio was 0.26 and the diagnosis was 17βHSD-3 deficiency, which was confirmed by the evidence of compound heterozygousity novel frameshift mutations in exon 9 and 10 of HSD17B3 gene.

April 16, 2015

Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency

Korcan Demir, Melek Yıldız, Özlem Nalbantoğlu Elmas, Hüseyin Anıl Korkmaz, Selma Tunç, Özgür Olukman, Filiz Hazan, Keramettin Uğur Özkan, Behzat Özkan

Page range: 961-965

Abstract

We report two newborns with female external genitalia and bilateral inguinal swelling who were diagnosed with 17β-hydroxysteroid dehydrogenase type 3 deficiency, a rare cause of 46,XY disorder of sexual development. The first case had normal clitoral size and vaginal and urethral openings, palpable gonads in the inguinal region, low testosterone, and low levels of basal and GNRH-stimulated gonadotropin. The second case had similar external genitalia, low testosterone but borderline basal and normal stimulated gonadotropin levels. Low testosterone/androstenedione ratios (0.22 and 0.24, respectively; normal, >0.8) after human chorionic gonadotropin stimulation indicated 17β-hydroxysteroid dehydrogenase type 3 deficiency. HSD17B3 sequencing revealed a homozygous novel mutation (c.464A>C, p.H155P) in exon 6 in the first case and homozygous c.239G>A (p.R80Q) in exon 3 in the second.

Short communication

March 4, 2015

Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1

Elisabeth Steichen-Gersdorf, Bettina Lorenz-Depiereux, Tim Matthias Strom, Nicholas J. Shaw

Page range: 967-970

Abstract

Autosomal recessive hypophosphatemic rickets 2 (ARHR2) is a rare form of renal tubular phosphate wasting disorder. Loss of function mutations of the ecto-nucleotide pyrophosphatase/pyrophosphodiesterase 1 gene ( ENPP1 ) causes a wide spectrum of phenotypes, ranging from lethal generalized arterial calcification of infancy to hypophosphatemic rickets with hypertension. Hearing loss was not previously thought to be one of the features of the disease entities and was merely regarded as a complication rather than a part of the disease. We report two children who presented in mid to late childhood with progressive varus deformity of their legs due to hypophosphatemic rickets caused by mutations in the ENPP1 gene. Both children had evidence of progressive hearing loss requiring the use of hearing aids. This report of two unrelated infants with compound heterozygous mutations in ENPP1 and previously published cases confirms that mild to moderate hearing loss is frequently associated with ARHR2. Early onset conductive hearing loss may further distinguish the autosomal recessive ENPP1 related type from other types of hypophosphatemia.

About this journal

Objective
The aim of the Journal of Pediatric Endocrinology and Metabolism (JPEM) is to diffuse speedily new medical information by publishing clinical investigations in pediatric endocrinology and basic research from all over the world. JPEM is the only international journal dedicated exclusively to endocrinology in the neonatal, pediatric and adolescent age groups. JPEM is a high-quality journal dedicated to pediatric endocrinology in its broadest sense, which is needed at this time of rapid expansion of the field of endocrinology. JPEM publishes Reviews, Original Research, Case Reports, Short Communications and Letters to the Editor (including comments on published papers). JPEM publishes supplements of proceedings and abstracts of pediatric endocrinology and diabetes society meetings.

Topics

Pediatric endocrinology
Pediatric diabetes
Inherited metabolic diseases

Article formats

Original Research, Reviews, Mini Reviews, Opinion Papers, Case Report, Short Communications, Letters to the Editor (including comments on published papers)

Volume 28 Issue 7-8

Issue of Journal of Pediatric Endocrinology and Metabolism

Frontmatter

Thyroid disorders revisited

Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands

Abstract

Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases

Abstract

Reclassification of cytologically atypical thyroid nodules based on radiologic features in pediatric patients

Abstract

Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism

Abstract

Investigation of autoimmune diseases accompanying Hashimoto’s thyroiditis in children and adolescents and evaluation of cardiac signs

Abstract

Neonatal thyroid storm accompanied with severe anaemia

Abstract

Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion

Abstract

Subclinical hypothyroidism as a rare cofactor in chronic kidney disease (CKD) – related anemia

Abstract

Cytometric analysis of perforin expression in NK cells, CD8+, and CD4+ lymphocytes in children with autoimmune Hashimoto’s thyroiditis – a preliminary study

Abstract

Papillary thyroid cancer and autoimmune polyglandular syndrome

Should radioiodine be the first-line treatment for paediatric Graves’ disease?

Abstract

Diffusion-weighted magnetic resonance imaging in a case of severe classic maple syrup urine disease

Novel mutations of DAX1 (NR0B1) in two Chinese families with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism

Abstract

Rickets and vitamin D deficiency in Alaska native children

Abstract

Persistent elevation of fibroblast growth factor 23 concentrations in healthy appropriate-for-gestational-age preterm infants

Abstract

Parents’ experiences of having a baby with ambiguous genitalia

Abstract

Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty

Abstract

Congenital adrenal hyperplasia in children – a survey on the current practice in the UK

Abstract

Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome

Abstract

Influence of the body weight on the onset and progression of puberty in boys

Abstract

Therapy monitoring in congenital adrenal hyperplasia by dried blood samples

Abstract

Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene

Abstract

Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds

Abstract

Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods

Abstract

Dietary intake, body composition, and physical activity among young patients with type 1 diabetes mellitus

Abstract

Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors

Abstract

Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy

Abstract

17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A) mutation in CYP17A1 gene

Abstract

A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature

Abstract

Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene

Abstract

Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty

Abstract

Case report: long-term follow-up of a 45,X male with SHOX haploinsufficiency

Abstract

Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review

Abstract

Successful use of continuous subcutaneous hydrocortisone infusion after bilateral adrenalectomy secondary to bilateral pheochromocytoma

Abstract

Donohue syndrome: a new case with a new complication

Abstract

Euprolactinemic galactorrhea secondary to domperidone treatment

Abstract

17βHSD-3 enzyme deficiency due to novel mutations in the HSD17B3 gene diagnosed in a neonate

Abstract

Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency

Abstract

Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1

Abstract

17α-Hydroylase/17,20-lyase deficiency related to P.Y27(c.81C>A) mutation in CYP17A1* gene