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Background Ellis-van Creveld syndrome (EvC) is a recessive disorder characterised by acromesomelic limb shortening, postaxial polydactyly, nail-teeth dysplasia and congenital cardiac defects, primarily caused by pathogenic variants in EVC or EVC2. Weyers acrofacial dysostosis (WAD) is an ultra-rare dominant condition allelic to EvC. The present work aimed to enhance current knowledge on the clinical manifestations of EvC and WAD and broaden their mutational spectrum. Methods We conducted molecular studies in 46 individuals from 43 unrelated families with a preliminary clinical diagnosis of EvC and 3 affected individuals from a family with WAD and retrospectively analysed clinical data. The deleterious effect of selected variants of uncertain significance was evaluated by cellular assays. Main results We identified pathogenic variants in EVC/ EVC2 in affected individuals from 41 of the 43 families with EvC. Patients from each of the two remaining families were found with a homozygous splicing variant in WDR35 and a de novo heterozygous frameshift variant in GLI3, respectively. The phenotype of these patients showed a remarkable overlap with EvC. A novel EVC2 C-terminal truncating variant was identified in the family with WAD. Deep phenotyping of the cohort recapitulated ’classical EvC findings’ in the literature and highlighted findings previously undescribed or rarely described as part of EvC. Conclusions This study presents the largest cohort of living patients with EvC to date, contributing to better understanding of the full clinical spectrum of EvC. We also provide comprehensive information on the EVC/EVC2 mutational landscape and add GLI3 to the list of genes associated with EvC-like phenotypes. [ABSTRACT FROM AUTHOR]

Objective: Abnormal uterine bleeding (AUB) is the most common gynecologic complaint in adolescent girls. The aim of this study was to identify the diagnostic and management differences between those with/without heavy menstrual bleeding. Methods: Retrospective data was collected from adolescents aged 10-19 years, diagnosed with AUB. Adolescents with known bleeding disorders at admission were excluded. All girls were classified according to the degree of anemia; group 1 had heavy bleeding [hemoglobin (Hb) <10 g/dL] and group 2 had moderate or mild bleeding (Hb >10 g/dL). Admission and follow-up characteristics were compared between the two groups. Results: The cohort consisted of 79 girls with a mean age of 14.3±1.8 years and mean age of menarche of 11.9±1.4 years, with 85% experiencing menstrual irregularity in the two years after menarche, rising to 95.3% in group 1 (p<0.01). Anovulation was evident in 80% of the cohort. Of these 79 girls, 13 (16.5%) had polycystic ovary syndrome and two (2.5%) had structural anomalies (uterus didelphys). Three girls (group 1, n=2) had previously undiagnosed clotting factor VII deficiency; no other clotting deficiencies were diagnosed. Nineteen of 34 (56%) with personal (n=2)/family history of thrombosis had MTHFR mutation. None had venous thromboembolism during follow-up of >6 months. Conclusion: The majority of AUB (85%) occurred in the first two years after menarche. A small proportion (3.8%) had undiagnosed clotting factor deficiency. The frequency of MTHFR mutation was 50% in girls with history of thrombosis; however this did not increase the risk of bleeding/thrombosis and so routine evaluation does not appear to be justified. [ABSTRACT FROM AUTHOR]

Context: Homozygous leptin (LEP) and leptin receptor (LEPR) variants lead to childhood-onset obesity. Objective: To present new cases with LEP and LEPR deficiency, report the long-term follow-up of previously described patients, and to define, based on all reported cases in literature, genotype-phenotype relationships. Methods: Our cohort included 18 patients (LEP = 11, LEPR = 7), 8 of whom had been previously reported. A systematic literature review was conducted in July 2022. Forty-two of 47 studies on LEP/LEPR were selected. Results: Of 10 new cases, 2 novel pathogenic variants were identified in LEP (c.16delC) and LEPR (c.40 + 5G > C). Eleven patients with LEP deficiency received metreleptin, 4 of whom had been treated for over 20 years. One patient developed loss of efficacy associated with neutralizing antibody development. Of 152 patients, including 134 cases from the literature review in addition to our cases, frameshift variants were the most common (48%) in LEP and missense variants (35%) in LEPR. Patients with LEP deficiency were diagnosed at a younger age [3 (9) vs 7 (13) years, P = .02] and had a higher median body mass index (BMI) SD score [3.1 (2) vs 2.8 (1) kg/m², P = 0.02], which was more closely associated with frameshift variants (P = .02). Patients with LEP deficiency were more likely to have hyperinsulinemia (P = .02). Conclusion: Frameshift variants were more common in patients with LEP deficiency whereas missense variants were more common in LEPR deficiency. Patients with LEP deficiency were identified at younger ages, had higher BMI SD scores, and had higher rates of hyperinsulinemia than patients with LEPR deficiency. Eleven patients benefitted from long-term metreleptin, with 1 losing efficacy due to neutralizing antibodies. [ABSTRACT FROM AUTHOR]

Objective: In patients with classical congenital adrenal hyperplasia (CAH), virilization affects the brain and external genitalia due to antenatal androgen exposure. There are few studies on how the effects of androgens on brain virilization are reflected in behavior. However, there is no study focused on the adolescence period. The aim of this study was to evaluate the level of aggression in adolescent girls with classical CAH (due to 21 hydroxylase and 11β hydroxylase deficiency) and to investigate the disease‐related factors that may affect aggression. Design: Twenty female and 20 male patients aged 13–20 years, diagnosed with classical CAH, with 21 hydroxylase deficiency and 11β hydroxylase deficiency, and 20 healthy girls and 20 boys from the same age group were included. The Buss‐Perry Aggression Scale (BPAS), which consists of four subgroups measuring physical aggression, verbal aggression, hostility, and angry behaviors, was used. Results: The ages of the male and female patients with CAH were 16.30 ± 2.65 and 16.60 ± 2.41 years, respectively. Total aggression scale scores were 73.3 ± 14.6 in adolescent girls with CAH, 74.1 ± 11.2 in healthy girls, 71.5 ± 14.8 in boys with CAH, and 75.3 ± 14.5 in healthy boys (p >.05). There was no difference between the subscale scores of patients and healthy adolescents. Aggression scores in adolescents with CAH increased significantly with age. Conclusions: In this study, we found no difference between the aggression scores of adolescents with classical CAH compared to their healthy peers. The total aggression score and subscale were similar in unaffected female adolescents. [ABSTRACT FROM AUTHOR]

Objective: Primary osteoporosis is a rare and essential problem in childhood that can cause severe skeletal deformities. We aimed to reveal the spectrum of primary osteoporosis and assess the effectiveness and safety of bisphosphonates in increasing bone mineral density and reducing fractures. Materials and Methods: Patients with primary osteoporosis who received at least one course of pamidronate or zoledronic acid were included in the study. Patients were divided into 2 groups, osteogenesis imperfecta and non-osteogenesis imperfecta subjects. We evaluated bone densitometer parameters, activation scores, pain status, deformity status, and the number of fractures per year in all patients. Results: Of the 31 patients, 21 with osteogenesis imperfect, 3 patients with spondyloocular syndromes, 2 with Bruck Syndrome, and 5 with idiopathic juvenile osteoporosis were included. A total of 21 patients had received pamidronate treatment, while only 4 received zoledronic acid, and 6 of them switched from pamidronate to zoledronic acid. At the end of the treatment, the mean bone mineral density height-adjusted Z-score increased from −3.39 ± 1.30 to −0.95 ± 1.34. The number of fractures per year decreased from 2.28 ± 2.67 to 0.29 ± 0.69. The activation score increased from 2.81 ± 1.47 to 3.16 ± 1.48. The pain decreased significantly. There was no difference in bone mineral density increase in patients treated with pamidronate or zoledronic acid. Conclusion: Those with osteogenesis imperfecta were diagnosed at an earlier age with severe deformity and fractures. Pamidronate and zoledronic acid increased bone mineral density in all types of primary osteoporosis. [ABSTRACT FROM AUTHOR]

Objective: Parathyroid adenoma is less common than in adulthood, but its morbidity is higher in children. We aimed to evaluate the clinical characteristics of parathyroid adenoma and our clinical experience since the early disease is often asymptomatic and late diagnosed. Materials and Methods: From 2010 to 2020, all children diagnosed with parathyroid adenoma at our institution were reviewed. We evaluated clinical, biochemical, and radiological aspects and follow-up characteristics. Results: Eight subjects (F/M = 6/2) ranged in age from 10 to 17 years. Three were symptomatic. The symptoms and findings were stomachache (n = 3), myalgia (n = 2), weakness (n = 2), pancreatitis (n = 1), constipation (n = 1), nausea (n = 1), bone ache (n = 1), and anorexia (n = 1). Laboratory findings on admission were as follows: the mean calcium was 12.59 ± 1.28 (11.2-15.3) mg/dL and the mean parathyroid hormone was 244.81 ± 173.61 (74.9-645.4) pg/mL. The most common localization was the lower part of the left parathyroid gland. Parathyroid adenoma could not be demonstrated by ultrasonography in 2 patients. Tc-99m-Sestamibi scintigraphy revealed the presence of parathyroid adenoma in only 7 of 8 patients. All underwent parathyroidectomy. In our follow-up, 2 subjects needed reoperation. A molecular analysis of 6 cases could be done. One was MEN1 positive. RET sequence analysis of 2, and Casr, GNA11, and AP2S1 sequence analysis of 3 were normal. Conclusion: Parathyroid adenoma should be considered in children older than the first decade with hypercalcemia. Suspected cases should undergo both ultrasonography and scintigraphy. Early diagnosis prevents the patients from serious complications of hypercalcemia such as nephrocalcinosis, diabetes insipid, and arrhythmia. It is significant to perform surgery in centers experienced in parathyroidectomy to minimize postoperative complications. [ABSTRACT FROM AUTHOR]

Objective: Cardiac involvement is common in Noonan syndrome (NS). Concerns have been raised regarding the effect of recombinant growth hormone (rGH) use on ventricular wall thickness and a possible increased risk of cardiac side effects. This study aimed to investigate the effect of rGH on the development of hypertrophic cardiomyopathy and other cardiac findings in NS. Methods: Patients under the age of 18 years and diagnosed with NS according to the Van der Burgt criteria, were included. Patients were divided into two groups according to those receiving rGH or not at the time of obtaining cardiac measurements. Before and after the treatment, electrocardiographic and echocardiographic (ECHO) assessments were made, including interventricular septal thickness, left ventricular internal diameter, and left ventricular posterior thickness. Results were expressed as Z scores. Results: Twenty-four NS subjects (16 boys, eight girls) were included. At the beginning of the follow up, the overall height standard deviation score was -2.56±0.94. Sixteen were on rGH. The mean rGH treatment duration was 8.3±3.8 years, and the mean dose was 0.22±0.04 mg/kg/week. The final height was 169±8.2 cm, and 10 of 11 patients who reached the final height received rGH. There was no difference between the rGH and non-rGH groups in terms of ECHO parameters pre-and post-treatment. Conclusion: In this cohort, there was no change in ECHO parameters on rGH and during follow-up. These results suggest that rGH is safe in NS patients with cardiac pathology under close follow-up. [ABSTRACT FROM AUTHOR]

Background. Hyperprolactinaemia refers to increased circulating prolactin and is divided into functional and pathological hyperprolactinaemia. Prolactinoma is the most common cause of severe hyperprolactinaemia. Prolactinomas are rare in children. Treatment outcomes and long-term follow-up data in children are insufficient. Dopamine agonists are the first step in the treatment of prolactinomas. There are no recommendations supported by a high level of evidence regarding the dose and duration of cabergoline treatment. Methods. Patients with hyperprolactinaemia were evaluated for etiological, clinical, and follow-up characteristics. The case files of patients with high prolactin levels who were followed up in our clinic between 2001 and 2019 were reviewed retrospectively. Results. 27 cases (20 female, 7 male) with hyperprolactinemia were detected. The median age of the cases was 15 years (0.3-17.4). Prolactinoma was detected in 40.7% of the cases (n=11). Among these cases, six were macroadenomas. The median prolactin level was 118 ng/mL (34-4340) in those with prolactinoma and 60 ng/mL (22-200) in the hyperprolactinaemia group (p=0.007). In the prolactinoma group, the median age at presentation in macroadenoma cases (13.8 years) was lower than in microadenoma cases (17 years) (p=0.06). There was a negative correlation between prolactin level and height SDS (r=-0.770, p=0.06). In all cases, the median initial cabergoline dose was 0.5 mg/week, and prolactin levels returned to normal within an average of 2.6±2.4 months. Cabergoline treatment achieved a 50% reduction in adenoma size in the first year of treatment without high doses. Conclusions. Prolactinoma consists of an important group among hyperplolactinemia in children. In our study, prolactinoma was detected in 40.7% of children with hyperplolactinemia, and children with prolonged use (over 4 years) tolerated cabergoline well and prolactin levels normalized without high doses. Follow-up is required for relapse after discontinuing the treatment. [ABSTRACT FROM AUTHOR]

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McCune-Albright Syndrome is a rare syndrome characterized with excessive function of peripheral endocrine organs and activating mutations of the stimulatory G protein alpha subunit are involved in the pathogenesis. The three main findings of the disease include hyperpigmented café au lait spots, fibrous dysplasia and increased endocrine functions and excessive secretion of growth hormone is observed in 21% of the patients. Clinical signs may be missed in these patients because of precocious puberty and craniofacial fibrous dysplasia. Since radiotherapy causes to sarcomatous changes and transsphenoidal surgery may cause to severe thickening in the cranial bones, they are not appropriate treatment options and medical treatment is recommended. Bromocriptine, cabergoline and octreotide or different combinations of these drugs are used in treatment and pegvisomant has also been used in recent years. Here, we present a male patient aged 12 years and 7 months to show gigantism as a rare clinical reflection of McCune-Albright Syndrome with an excessive height (197 cm), café au lait spots, growht hormone levels which could not be supressed with oral glucose tolerance test and increased prolactin levels. (Turk Pediatri Ars 2015; 50: 114-7) [ABSTRACT FROM AUTHOR]

Uncontrolled eating behavior in obese subjects is very similar to behavior in food addiction, suggesting a relationship. This study was designed to evaluate the relationship between childhood obesity and food addiction and to determine the frequency of food addiction among obese children and adolescents. The study included 100 overweight and obese children. Food addiction was evaluated by the Yale Food Addiction Scale (YFAS). The cutoff value for food addiction was defined as the presence of 3 or more symptoms. Participants were between 10 and 18 years of age; 63% were girls. Of the participants, 71% had food addiction. The most addictive foods were chocolate, ice cream, carbonated beverages, French fries, white bread, rice, candy, chips and pasta, in decreasing order of frequency. Experiencing a frequent feeling of hunger was associated with a 2.2-fold increase in food addiction risk, while consumption of French fries =1-2 times per week was associated with a 2.3-fold increase in risk (p<0.05). The high YFAS scores in obese and overweight adolescents suggest that food addiction plays an important role in childhood obesity. Evaluation of food addiction in more detail may open a new perspective on the prevention and treatment of obesity. [ABSTRACT FROM AUTHOR]

Osteopenia of prematurity has become a common problem recently because of improved survival rates of infants with very low birth weight (VLBW). The incidence of neonatal osteopenia is inversely correlated with gestational age and birth weight. Herein, we present four cases of preterm osteopenia that were referred to the pediatric endocrinology outpatient clinic with diverse clinical and laboratory findings and we discuss the clinical course of these infants with regard to bone disease after discharge from the neonatal intensive care unit (NICU). This report highlights the importance of enteral calcium, phosphorus and vitamin D support at adequate doses following discharge from NICU for preterm infants with VLBW who are at risk of metabolic bone disease. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether glycosylated hemoglobin (HbA1c) and 1-hour glucose level in oral glucose tolerance test (OGTT) are useful parameters for evaluation of glucose homeostasis in childhood. Methods: The medical records of 106 obese/overweight children aged from 7 to 18 years who underwent OGTT were evaluated retrospectively. The subjects were divided into 2 groups according to their one-hour glucose concentration. Group 1 consisted of subjects whose one-hour glucose level was <155 mg/dL, and Group 2 consisted of subjects whose one-hour glucose level was ⩾155 mg/dL. The fasting and 2-hour glucose concentrations of the groups were compared. The sensitivity and specificity levels were determined using the ROC curve to assess the predictive value of HbA1c for impaired glucose tolerance (IGT). Results: The mean 2-hour glucose concentration of the subjects in Group 2 was significantly higher than that of the subjects in Group 1 (137.8±35.5 mg/dL versus 113.1±21.2 mg/dL, p<0.05). If a 5.5% cut-off value for HbA1c was accepted as predictor of IGT, the sensitivity was 63% and specificity was 70%. 31% of the subjects with HbA1c levels at or above 5.5% had IGT. This rate was significantly lower in subjects who had HbA1c levels below 5.5% (p<0.05). Conclusions: Obese/overweight children and adolescents whose 1-hour glucose level is ⩾155 mg/dL in the standard OGTT carry a high risk for IGT. Obese/overweight children and adolescents whose HbA1c level is at or above 5.5% may have IGT even though their fasting glucose level is normal, thus, OGTT is necessary to evaluate the glucose tolerance. [ABSTRACT FROM AUTHOR]

It was aimed to evaluate the national congenital hypothyroidism program in terms of thyroid-stimulating hormone (TSH) cut-off level, frequency of cases that required treatment and the stages before treatment in the Kocaeli district area. This research was performed with the contribution of Kocaeli University Medical Faculty, Pediatric Endocrinology Department, and the Kocaeli Local Health District. 25,188 babies born in 2009 were evaluated. The previous laboratory data including heel prick samples and venous thyroid function tests (TSH, free/total T4 levels) of babies requiring investigation were evaluated retrospectively. 49,785 heel prick blood samples were collected from 25,188 babies born in our region. TSH levels of 3,355 babies in the first sampling were greater than the cut-off level (15 mIU/L) (recall rate was 13.3%). Venous sampling was required for 107 babies, and 39 of them needed to be treated (treatment rate was 1/645). Eleven of the babies who were treated were diagnosed with thyroid dysgenesis. Families of the babies who needed further venous sampling were given final results in an average of 28.5 days after the first heel sampling. We concluded that the recall rate is high, but raising the cut-off level for TSH may lead to overlooking the diagnosis of thyroid dysgenesis. The duration for providing final results to the families is quite long. It is necessary to take venous blood samples in the pediatric endocrinology units to reduce this duration. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency and rickets remain important for the evaluation of neonatal and infantile hypocalcemia; however, physicians sometimes experience difficulties in the differential diagnosis. Vitamin D deficiency can present with hypocalcemia and sometimes hyperphosphatemia due to the inadequate response of parathyroid hormone (PTH) to hypocalcemia during the neonatal period. Herein, a case who was admitted with seizure (hypocalcemic) at 8 days of age and diagnosed as congenital rickets is reported. Vitamin D deficiency should be considered primarily in the differential diagnosis of neonatal hypocalcemia, particularly in those areas where maternal vitamin D deficiency is common. Hypocalcemia due to congenital rickets can be prevented with adequate vitamin D supplementation during pregnancy. [ABSTRACT FROM AUTHOR]

Aim: To determine the effects of obesity on thyroid functions in children Material and Method: The records of 132 patients who were followed up in our Pediatric Endocrinology and Diabetes Division with the diagnosis of obesity from March 2006 to May 2009, were investigated retrospectively. Anthropometric measurements, serum lipid profiles, thyroid hormone levels, fasting blood glucose and insulin levels were evaluated. TSH levels of patients whose HOMA-IR <3.16 and HOMA-IR >3.16 were compared. Correlation between TSH levels and HOMA-IR, BMİ (body mass index) was investigated. Statistical evaluation was done using SPSS 13.0 statistical program. For comparasion of independent groups chi-square and for correlation analysis "Pearson method" were used. p<0.05 was accepted as significant. Results: Seventeen patients' (12.9%) TSH levels were above 97.5 persentile, fifty one patients' (38.7%) TSH levels were above 90 persentile. None of the patients whose TSH levels were above 97.5 persentile, has low free/ total T4 levels. There was no significant difference in the TSH levels, when the patients whose HOMA-IR <3.16 and HOMA-IR >3.16 were compared. There was an insignificant, positive, weak correlation between TSH levels and HOMA-IR, BMI. Conclusions: TSH levels of obese children may be elevated without any change in the peripheral thyroid hormone levels. This situation should not be evaluated as hypothyroidism and not be started L- throxine treatment in the first examination. [ABSTRACT FROM AUTHOR]

An abstract of the article "Genetic Analysis in Our Cases with Thyroid Dysgenesis," by Elif Özsu and colleagues is presented.

The article presents a case study of a patient diagnosed with hyperinsulinemia at the age of 40 days. The patient has abnormal glucose and insulin level and ammonia level which led to diagnosis of hyperinsulinaemic hypoglycaemia (HH). The article also recommends genetic analysis of HADH gene patients with diazoxide-responsive HH from consanguineous families.