Severe myxedema coma and pericardial effusion in a child with Down syndrome: the importance of adherence to levothyroxine therapy.

BACKGROUND: Myxedema coma is a rare, but life-threatening endocrinological emergency. Myxedema is characterized by altered mental status, and is accompanied by hypotension, bradycardia, hypothermia, bradypnea, hyporeflexia, hyponatremia, and hypoglycemia, all stemming from reduced metabolism due to severe hypothyroidism. Additionally, patients may exhibit signs of low cardiac output, edema in the extremities, peripheral circulatory disturbances, shock, and the development of pericardial and pleural effusions, ultimately leading to confusion and coma. We present a successfully treated case of severe myxedema coma with recurrent pericardial effusion and hypotensive shock. This case is characterized by an unusual clinical presentation and required a distinct treatment strategy highlighting its exceptional rarity. CASE: A 2-year-old boy with Down syndrome presented with recurrent pericardial effusion attributed to medication non-adherence. The critically-ill patient, experiencing a severe cardiogenic shock required mechanical ventilation and inotropic infusions in the pediatric intensive care unit. Elevated thyroid stimulating hormone (TSH), and low free T4 (fT4) and free T3 (fT3) levels prompted consideration of myxedema coma. Upon reviewing the patient's medical history, it was ascertained that he had an ongoing diagnosis of primary hypothyroidism, and exhibited non-adherence to the prescribed treatment regimen and failed to attend scheduled outpatient clinic appointments for follow-up assessments. The treatment plan, devised by the pediatric endocrinology team, included the peroral administration of L-thyroxine (L-T4) at a dose of 50 micrograms per day. After beginning regular oral L-T4 treatment, a gradual improvement in the patient's condition was observed. Notably, by the 15th day of oral therapy, the patient had made a full recovery. Contrary to the recommended intravenous treatment for myxedema coma, this patient was successfully treated with oral levothyroxine, due to the unavailability of the parenteral form in Türkiye. CONCLUSIONS: This case report presents an instance of non-adherence to L-T4 therapy, which subsequently progressed to severe myxedema coma. Changes in neurologic status and hemodynamic instability in a patient with a history of hypothyroidism should raise the concern of nonadherence and, though rare, myxedema coma should be in the differential diagnosis.

Genetic Findings in Short Turkish Children Born to Consanguineous Parents.

INTRODUCTION: The diagnostic yield of genetic analysis in the evaluation of children with short stature depends on associated clinical characteristics, but the additional effect of parental consanguinity has not been well documented. METHODS: This observational case series of 42 short children from 34 consanguineous families was collected by six referral centres of paediatric endocrinology (inclusion criteria: short stature and parental consanguinity). In 18 patients (12 families, group 1), the clinical features suggested a specific genetic defect in the growth hormone (GH) insulin-like growth factor I (IGF-I) axis, and a candidate gene approach was used. In others (group 2), a hypothesis-free approach was chosen (gene panels, microarray analysis, and whole exome sequencing) and further subdivided into 11 patients with severe short stature (height <-3.5 standard deviation score [SDS]) and microcephaly (head circumference <-3.0 SDS) (group 2a), 10 patients with syndromic short stature (group 2b), and 3 patients with nonspecific isolated GH deficiency (group 2c). RESULTS: In all 12 families from group 1, (likely) pathogenic variants were identified in GHR, IGFALS, GH1, and STAT5B. In 9/12 families from group 2a, variants were detected in PCNT, SMARCAL1, SRCAP, WDR4, and GHSR. In 5/9 families from group 2b, variants were found in TTC37, SCUBE3, NSD2, RABGAP1, and 17p13.3 microdeletions. In group 2c, no genetic cause was found. Homozygous, compound heterozygous, and heterozygous variants were found in 21, 1, and 4 patients, respectively. CONCLUSION: Genetic testing in short children from consanguineous parents has a high diagnostic yield, especially in cases of severe GH deficiency or insensitivity, microcephaly, and syndromic short stature.

Comprehensive Insights Into Pediatric Craniopharyngioma: Endocrine and Metabolic Profiles, Treatment Challenges, and Long-term Outcomes from a Multicenter Study

Objective: Craniopharyngiomas (CPG) have complex treatment challenges due to their proximity to vital structures, surgical and radiotherapeutic complexities, and the tendency for recurrence. The aim of this study was to identify the prevalence of endocrine and metabolic comorbidities observed during initial diagnosis and long-term follow-up in a nationwide cohort of pediatric CPG patients. A further aim was to highlight the difficulties associated with CPG management. Methods: Sixteen centers entered CPG patients into the ÇEDD NET data system. The clinical and laboratory characteristics at presentation, administered treatments, accompanying endocrine, metabolic, and other system involvements, and the patient's follow-up features were evaluated. Results: Of the 152 evaluated patients, 64 (42.1%) were female. At presentation, the mean age was 9.1±3.67, ranging from 1.46 to 16.92, years. The most common complaints at presentation were headache (68.4%), vision problems (42%), short stature (15%), and nausea and vomiting (7%). The surgical procedures were gross total resection (GTR) in 97 (63.8%) and subtotal resection in 55 (36.2%). Radiotherapy (RT) was initiated in 11.8% of the patients. Histopathological examination reported 92% were adamantinamatous type and 8% were papillary type. Postoperatively, hormone abnormalities consisted of thyroid-stimulating hormone (92.1%), adrenocorticotropic hormone (81%), antidiuretic hormone (79%), growth hormone (65.1%), and gonadotropin (43.4%) deficiencies. Recombinant growth hormone treatment (rhGH) was initiated in 27 (17.8%). The study showed hesitancy among physicians regarding rhGH. The median survival without relapse was 2.2 years. Median (range) time of relapse was 1.82 (0.13-10.35) years. Relapse was related to longer followups and reduced GTR rates. The median follow-up time was 3.13 years. Among the last follow-up visits, the prevalence of obesity was 38%, but of these, 46.5% were already obese at diagnosis. However, 20% who were not obese at baseline became obese on follow-up. Permanent visual impairment was observed in 26 (17.1%), neurological deficits in 13 (8.5%) and diabetes mellitus in 5 (3.3%) patients. Conclusion: Recurrence was predominantly due to incomplete resection and the low rate of postoperative RT. Challenges emerged for multidisciplinary regular follow ups. It is suggested that early interventions, such as dietary restrictions and increased exercise to prevent obesity, be implemented.

Assessment of Thyroid Gland in Children with Point-of-Care Ultrasound (POCUS): Radiological Performance and Feasibility of Handheld Ultrasound in Clinical Practice

Objective: Point-of-Care Ultrasound (POCUS) refers to the use of portable ultrasound machines to perform quick and focused ultrasound examinations at a patient's bedside or point-of-care. POCUS can be performed by all health workers with specific training to use POCUS. The aim of this study was to investigate the radiological performance and feasibility of POCUS using a handheld ultrasound device (HHUSD) in children for examining the thyroid gland. Methods: A pediatric endocrinologist performed thyroid imaging in children referred to our hospital with suspected thyroid disease using an HHUSD. The same children underwent ultrasonography (US) imaging using the same device by the first radiologist, and a second radiologist performed thyroid US using an advanced high-range ultrasound device (AHUSD) (defined as the gold-standard method) within two hours. The data obtained by the three researchers were compared with each other. Results: This study included 105 patients [68.6% girls (n=72)] with a mean age 12.8±3.6 years. When the thyroid volume was evaluated, a strong correlation was found between the measurements of the three researchers (AA vs. MG: r=0.963, AA vs. GT: r=0.969, MG vs. GT: r=0.963, p<0.001). According to the Bland-Altman analysis for total thyroid volume, AA measured 0.43 cc [95% confidence interval (CI): -0.89-0.03] smaller than MG, and 0.11 cc (95% CI: -0.30-0.52) larger than GT, whereas MG measured 0.52 cc (95% CI: 0.09-0.94) larger than GT. When evaluated for the presence of goiter and nodules, a near-perfect agreement was found between the results of the three researchers (AA vs. GT; κ=0.863, MG vs. GT; κ=0.887, p<0.001, and AA vs. GT; κ=1.000, MG vs. GT; κ=0.972, p<0.001, respectively). When evaluated in terms of the longest axis of nodules, a high correlation was found between the measurements of the three researchers (AA vs. MG; r=0.993, AA vs. GT; r=0.996, MG vs. GT; r=0.996, p<0.001). When evaluated in terms of the final diagnosis, the evaluations of the three researchers showed excellent agreement with each other (AA vs. GT; κ=0.893, MG vs. GT; κ=0.863, p<0.001, accuracy rate AA vs. GT: 93.3%; MG vs. GT: 91.4%). Conclusion: A pediatric endocrinologist, equipped with sufficient training in thyroid US evaluation, incorporated HHUSD examination as a routine clinical tool in an outpatient setting. It was shown that, they could effectively assess normal thyroid tissue in pediatric patients. Moreover, the HHUSD proved to be useful in detecting thyroid pathologies. However, it is important to note that for a more comprehensive evaluation of thyroid nodules, including detailed assessment and Thyroid Imaging Reporting and Data System (TIRADS) classification, patients should be referred to radiology departments equipped with AHUSD systems. These specialized devices, along with the expertise of radiologists, are essential for in-depth evaluations and accurate classification of thyroid nodules.

The Effect of Childhood Obesity on Intraocular Pressure, Corneal Biomechanics, Retinal Nerve Fiber Layer, and Central Macular Thickness.

PRCIS: Elevated corneal hysteresis (CH) and resistance factor (CRF) in obese and overweight children imply weight's effect on corneal biomechanics. Increased Goldmann-correlated intraocular pressure (IOPg) in obese children indicates glaucoma risk, emphasizing screening for IOP and retinal changes. PURPOSE: To evaluate the effect of obesity on corneal biomechanics, retinal nerve fiber layer (RNFL), and central macular thickness (CMT) in children. PATIENTS AND METHODS: In this prospective, cross-sectional, comparative study, 146 eyes of normal-weight, over-weight, and obese children aged between 6 to 17 years were evaluated. The IOPg, corneal compensated IOP (IOPcc), CH, CRF, and the average retinal nerve fiber layer (RNFL), average cup-to-disk ratio (c/d), and central macular thickness (CMT) were measured by Ocular Response Analyser and Spectral-Domain Optical Coherence Tomography (SD-OCT), respectively. RESULTS: There was no statistically significant difference regarding age, gender, IOPcc, average RNFL thickness, c/d ratio, and CMT among the groups ( P ≥0.05). The IOPg was significantly higher in obese children compared with normal-weight children, while CH and CRF values were significantly higher in both obese and over-weight children compared with healthy ones ( P <0.05). There was a positive correlation between BMI percentile and IOPg, CH, and CRF values. CONCLUSION: In our study, higher IOPg, corneal hysteresis, and corneal resistance factor values suggest that obese children could be potential candidates for glaucoma. Therefore, it would be appropriate to screen them for IOP and retinal alterations. Further investigations with larger sample size and longer follow-up are needed to understand the risk of glaucoma in obese children.

Thyroid volume in Turkish school-age children living in an iodine-sufficient region.

OBJECTIVES: We aimed to obtain local normative data on thyroid volume evaluated by ultrasonography and iodine status by measuring urine iodine levels in school-age children living in Aydin province. METHODS: In this cross-sectional study, a sample comprising 1,553 cases was meticulously selected from a total cohort of 170,461 children aged 6-17, drawn from 21 distinct educational institutions located within the Aydin region, as participants in the investigation. Those with a known chronic disease or thyroid disease were excluded from the study. The children underwent physical examinations and ultrasonography imaging of the thyroid gland, and urine samples were collected to measure urinary iodine concentration (UIC). RESULTS: The median UIC was 189.5 (IQR=134.4) µg/L, which was optimal according to WHO criteria. Thyroid volume was found to be 4.6 (IQR=3.5) mL in girls and 4.2 (IQR=4.0) mL in boys (p=0.883). The thyroid volumes in our study were found to be smaller when compared to the WHO. According to WHO age and body surface area criteria, thyroid volume was over 97 % in 0.9 % (n=15) of cases. Thyroid volume was found to have a positive correlation with age, height, weight, body mass index (BMI), and body surface area (BSA) in both genders (p<0.001). However, there was no significant correlation between thyroid volume and UIC. CONCLUSIONS: This cross-sectional study provides normative data on thyroid volume and iodine status in school-age children in iodine-sufficient population, revealing a low prevalence of goiter and correlations between thyroid volume and anthropometric measures.

Associations of Adipocyte-derived Versican and Macrophage-derived Biglycan with Body Adipose Tissue and Hepatosteatosis in Obese Children

Objective: In animal models of obesity, adipocyte-derived versican, and macrophage-derived biglycan play a crucial role in mediating adipose tissue inflammation. The aim was to investigate levels of versican and biglycan in obese children and any potential association with body adipose tissue and hepatosteatosis. Methods: Serum levels of versican, biglycan, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were measured by ELISA. Fat deposition in the liver, spleen, and subcutaneous adipose tissue was calculated using the IDEAL-IQ sequences in magnetic resonance images. Bioimpedance analysis was performed using the Tanita BC 418 MA device. Results: The study included 36 obese and 30 healthy children. The age of obese children was 13.6 (7.5-17.9) years, while the age of normal weight children was 13.0 (7.2-17.9) years (p=0.693). Serum levels of versican, hsCRP, and IL-6 were higher in the obese group (p=0.044, p=0.039, p=0.024, respectively), while no significant difference was found in biglycan levels between the groups. There was a positive correlation between versican, biglycan, hsCRP, and IL-6 (r=0.381 p=0.002, r=0.281 p=0.036, rho=0.426 p=0.001, r=0.424 p=0.001, rho=0.305 p=0.017, rho=0.748 p<0.001, respectively). Magnetic resonance imaging revealed higher segmental and global hepatic steatosis in obese children. There was no relationship between hepatic fat content and versican, biglycan, IL-6, and hsCRP. Versican, biglycan, hsCRP, and IL-6 were not predictive of hepatosteatosis. Body fat percentage >32% provided a predictive sensitivity of 81.8% and a specificity of 70.5% for hepatosteatosis [area under the curve (AUC): 0.819, p<0.001]. Similarly, a body mass index standard deviation score >1.75 yielded a predictive sensitivity of 81.8% and a specificity of 69.8% for predicting hepatosteatosis (AUC: 0.789, p<0.001). Conclusion: Obese children have higher levels of versican, hsCRP, and IL-6, and more fatty liver than their healthy peers.

Clinical Characteristics of Children with Combined Pituitary Hormone Deficiency and the Effects of Growth Hormone Treatment.

AIM: We aimed to describe the clinical characteristics of patients with congenital combined pituitary hormone deficiency (CPHD) and evaluate the first-year growth responses of individuals with CPHD and isolated growth hormone deficiency (IGHD) in order to establish the influence of other hormone deficiencies on growth response. PATIENTS AND METHODS: This retrospective study was conducted in four tertiary care centers in Turkey. The records of patients diagnosed with CPHD (n=39) and severe IGHD (n=50) were collected. Cases with acquired lesions or chronic diseases were not included in the study. Data are presented as median (interquartile range). RESULTS: Among 39 patients (13 females; 33%) with a diagnosis of CPHD, the majority of patients (64%) presented initially with combined deficits at baseline examination, whereas isolated deficiencies (36%) were less prevalent. Among all patients with GH deficiency, TSH, ACTH, FSH/LH, and ADH deficiencies were present in 94%, 74%, 44%, and 9% of patients, respectively. Patients with CPHD were diagnosed at a younger age (4.9 (8.4) vs. 11.6 (4.1), p<0.001, respectively) and had lower peak GH concentrations (0.4 (1.8) vs. 3.7 (2.9), p<0.001, respectively) than patients with IGHD. Patients with IGHD and CPHD had similar first-year growth responses (Δheight SD score of 0.55 (0.63) vs. 0.76 (0.71), respectively, p=0.45). CONCLUSIONS: We established the nature and timing of numerous hormonal deficits emerging over time. We also identified that the existence of CPHD did not hinder growth response.

Which method is more effective in predicting adult height in pubertal girls treated with gonadotropin-releasing hormone agonist?

PURPOSE: The aim of the present study was to determine the efficiency of three different predictive models [Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner-Whitehouse 2 (TW2)] by comparing their predictions with near-adult height data of girls receiving gonadotropin-releasing hormone agonist (GnRHa) therapy. METHODS: Clinical findings were retrospectively analyzed. Bone ages obtained before treatment were evaluated from left hand and wrist radiographs by three researchers. Predicted adult height (PAH) was calculated using the BP, RWT, and TW2 methods for each patient at the beginning of therapy. RESULTS: The median age at diagnosis of the 48 patients included in the study was 8.8 (8.9-9.3) years. There was no significant difference between the mean bone ages evaluated separately with the Greulich-Pyle atlas and the TW3-RUS method (p=0.34). Among the PAH methods, only PAH measured by the BP method was very close to and no different from near adult height (NAH) [159.8±6.3 vs. 158.8±9.3 cm. p=0.3; (-0.5±1.1) vs. (-0.7±1.6) standard deviation score, p=0.1]. Accordingly, the BP method was found to be the most accurate prediction tool in girls with puberty treated with GnRHa. CONCLUSION: The BP method is more effective at predicting adult height than the RWT and TW2 methods in female patients who will receive GnRHa treatment.

Growth Hormone Dosing Estimations Based on Body Weight Versus Body Surface Area

Objective: Both body weight (BW)- and body surface area (BSA)-based dosing regimens have been recommended for growth hormone (rhGH) replacement. The aim was to compare the two regimens to determine if either resulted in inadequate treatment depending on anthropometric factors. Methods: The retrospective study included children diagnosed with idiopathic isolated growth hormone deficiency. BW-based dosing in mcg/kg/day was converted to BSA in mg/m2/day to determine the equivalent amounts of the given rhGH. Those with a BW-to-BSA ratio of more than 1 were allocated to the "relatively over-dosed group", while the remaining patients with a ratio of less than 1 were assigned to the "relatively under-dosed" group. Patients with a height gain greater than 0.5 standard deviation score (SDS) at the end of one year were classified as the height gain at goal (HAG), whereas those with a height gain of less than 0.5 SDS were assigned as the height gain not at goal (NHAG). Results: The study included 60 patients (18 girls, 30%). Thirty-six (60%) patients were classified as HAG. The ratio of dosing based on BW-to-BSA was positively correlated both with the ages and body mass index (BMI) levels of the patients, leveling off at the age of 11 at a BMI of 18 kg/m2. The relative dose estimations (over- and under-dosed groups) differed significantly between the patients classified as HAG or NHAG. Fifty-six percent of NHAG compared to 44% of HAG patients received relatively higher doses, while 79% of HAG compared to 21% of NHAG received relatively lower doses (p=0.006). When the patients were subdivided according to their pubertal status, higher doses were administrated mostly to the pubertal patients in both the NHAG and HAG groups. In the pre-pubertal age group, 73% of NHAG compared to 27% of HAG received relatively higher doses, while 25% of NHAG compared to 75% of HAG received relatively lower doses (p=0.01). Conclusion: Dosing based on BW may be preferable in both prepubertal and pubertal children who do not show adequate growth responses. In prepubertal children, relatively lower doses calculated based on BW rather than BSA provide similar efficacy at lower costs.

Mild Aromatic L-Amino Acid Decarboxylase Deficiency: As A Reason For Hypoketotic Hypoglycemia In A 4-Year-Old Girl.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a disease in which neurological findings are dominant due to deficiencies in neurotransmitter synthesis; hypoglycemia caused by autonomic dysfunction is one of the symptoms that may be encountered. Here we report a mild AADC deficiency presenting with hypoglycemia without a neurological sign. A 4-year-old girl presented with recurrent hypoglycemia. Her growth and development were normal. Plasma insulin and cortisol values were normal in the sample at the time of hypoglycemia. The C8:1-Carnitine elevation was detected in the acylcarnitine profile. The clinic exome panel was performed with the suggestion of a fatty acid oxidation defect. However, a homozygous variant in the DDC gene was detected. On top of that, CSF neurotransmitter analysis revealed low 5-hydroxy indol acetic ( 5 HIAA ) and homovanillic acid ( HVA ) and high 3-O-methyl-dopa and methyltetrahydrofolate ( 5 MTHF ) consistent with AADC deficiency. Plasma AADC enzyme activity was low. The episodes of hypoglycemia were treated with uncooked cornstarch. Our case emphasizes that AADC deficiency should be considered in patients with hypoglycemia.

Cooccurring Type 1 Diabetes Mellitus and Autoimmune Thyroiditis in a Girl with Craniofrontonasal Syndrome: Are EFNB1 Variants Associated with Autoimmunity?

Craniofrontonasal syndrome (CFNS), also known as craniofrontonasal dysplasia, is an X-linked inherited developmental malformation caused by mutations in the ephrin B1 (EFNB1) gene. The main phenotypic features of the syndrome are coronal synostosis, hypertelorism, bifid nasal tip, dry and curly hair, and longitudinal splitting of nails. A 9-year-and-11-month-old girl with CFNS was admitted due to polyuria, polydipsia, fatigue, and abdominal pain. On physical examination, she had the classical phenotypical features of CFNS. Genetic tests revealed a c.429_430insT (p.Gly144TrpfsTer31) heterozygote variant in the EFNB1 coding region. The patient was diagnosed with type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis based on laboratory findings and symptoms. The mother of the patient, who had the same CFNS phenotype and EFNB1 variant, was screened for autoimmune diseases and was also with autoimmune thyroiditis. This is the first report describing the association of CFNS with T1DM and autoimmune thyroiditis in patients with EFNB1 mutation.

Frequency and Characteristics of Metacarpal Pseudoepiphyses in Healthy Children Aged 5-15 Years.

OBJECTIVE: Pseudoepiphyses are notches and clefts located at the non-epiphyseal ends of the metacarpal bones. There are very few studies regarding the frequency of pseudoepiphysis. MATERIAL AND METHODS: Subjects between the ages of 5 and 15, whose hand radiographs were obtained between 2015 and 2021 in our Radiology Department, were included in this study. A total of 1071 patients were included in the study. A single radiologist evaluated these radiographs in 3 different time periods. Pseudoepiphyses that involve one cortex of the metacarpal bone are considered as partial pseudoepiphyses, whereas those that involve both cortices are considered as complete pseudoepiphyses. RESULTS: Of the 1071 patients included in the study, 65.9% (n = 706) were girls. The mean age was 9.5 ± 2.6 years. Pseudoepiphysis was detected in 222 (20.7%) cases. Pseudoepiphysis was more common in boys (27.4%) than girls (17.3%) (P < .001). The frequency of partial pseudoepiphysis was found to be significantly higher than that of complete pseudoepiphysis [n = 212 (19.8%) and n = 20 (1.9%), respectively, P < .001]. Partial pseudoepiphysis was most frequently detected in the second metacarpal bone, and complete pseudoepiphysis was most frequently detected in the first metacarpal bone. Of 222 cases with pseudoepiphysis, 76.6% (n = 170) had in 1 location, while 21.2% (n = 47) had in 2 locations, 1.8% (n = 4) in 3 locations, and 0.5% (n = 1) in 4 locations. CONCLUSION: Pseudoepiphysis is a normal variant of metacarpal ossification; it does not adversely affect the development of the bone and is frequently seen in healthy children.

Cutaneous manifestations of obesity in Turkish children: A comparative study.

BACKGROUND: Cutaneous changes in obese adults have been investigated in numerous studies, but this issue has not been adequately investigated in children. OBJECTIVES: We aimed to determine the prevalence of skin manifestations in children with obesity by comparing them to normal-weight children. METHODS: A cross-sectional study was conducted between June 2017 and January 2019 in which 82 children with obesity and 86 normal-weight healthy control children were enrolled. Study participants had detailed full-body skin examinations performed by the same dermatologist; mycological and Wood's lamp examinations were performed when necessary. Sociodemographic and anthropometric measurements of the participants were recorded. RESULTS: Striae distensae were the most common skin manifestation in children with obesity; striae were significantly higher in the obese than in the control group (72% vs. 26.7%, p < .001). The anatomical distribution of the striae distensae in the groups differed significantly. Striae distensae were most commonly observed on the buttocks in the control group, while the thighs were the most common site in the obese group. Acanthosis nigricans (63.4% vs. 3.5%, p < .001), acrochordons (17.1% vs. 1.2%, p < .001), keratosis pilaris (32.9% vs. 17.4%, p = .021), intertrigo (11% vs. 0%, p = .001), folliculitis (31.7% vs. 5.8%, p < .001), seborrheic dermatitis (12.2% vs. 3.5%, p = .035) and facial erythema (7.3% vs. 0%, p = .012) were found to be statistically significantly more common in the obese group compared to the control group. CONCLUSIONS: Obesity in children is associated with numerous cutaneous manifestations. Further study is needed to identify whether weight loss can reduce skin manifestations in obese children.

Association Between Umbilical Cord Levels of Glypican-1, Glypican-3, Syndecan-1, WISP1, Leptin and Birth Weight of Small, Appropriate, and Large for Gestational Age Infants.

BACKGROUND: Many factors are affecting intrauterine growth. The role of Wingless-type (Wnt) inducible signaling pathway protein-1 (WISP1), a novel adipokine and placental proteoglycans in intrauterine growth, is not known. We aimed to measure umbilical cord blood levels of glucose, insulin, leptin, WISP1, and placental proteoglycans [glypican-1 (GPC1), glypican-3 (GPC3), and syndecan-1 (SDC1)] which are thought to have an important role in fetal growth and investigate their relation with birth weight. METHODS: Full-term neonates were included in this prospective, cross-sectional study and classified as appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA) according to their birth weight. Umbilical cord blood levels of glucose, insulin, leptin, WISP1, GPC1, GPC3, and SDC1 were measured. RESULTS: Leptin levels were higher in LGA newborns compared to AGA and SGA newborns, while WISP1, GPC1, GPC3, and SDC1 levels were not different between the three groups. Leptin and GPC1 levels were higher in infants of mothers with gestational diabetes mellitus compared to infants of non-diabetic mothers, while WISP1, GPC3, and SDC1 were not different between the groups. Leptin was positively correlated with insulin, birth weight, and maternal weight. While there was a strong correlation between the WISP1, GPC1, GPC3, and SDC1 levels; there was no correlation between the birth weight, maternal weight, glucose, insulin, and WISP1, GPC1, GPC3, and SDC1 levels. CONCLUSION: Umbilical cord blood levels of GPC1, GPC3, SDC1, and WISP1 were not different between SGA, AGA, and LGA infants. The significance of serum levels of these adipokines and proteoglycans remains to be elucidated.

Steroid Hormone Profiles and Molecular Diagnostic Tools in Pediatric Patients With non-CAH Primary Adrenal Insufficiency.

CONTEXT: There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology. OBJECTIVE: This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin. METHODS: Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology. RESULTS: A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology. CONCLUSION: Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES.