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Background: The corona mortis is defined as the vascular connections between the obturator and external iliac systems. While detailed information on the arterial anastomoses in corona mortis is available, a complete description of the venous system is lacking. Although the tiny anastomoses behind the pubic symphysis between the obturator and external iliac arteries have been described in classical anatomy textbooks, these texts neglect to mention that these anastomoses can be life threatening. Attention needs to be paid to these anastomoses between the arterial and the venous system located over the superior pubic ramus during laparoscopic procedures.Methods: Fifty retroinguinal regions were dissected in seven cadavers and 28 patients.Results: During the dissections, a venous anastomosis on the superior pubic ramus was a consistent finding in 96% of cases. This vein coursed vertically to the inferior border of the superior pubic ramus and connected to the obturator vein. Accessory branches of the obturator artery were observed in only 8% of the dissections. The tiny connections between the obturator and external iliac arteries are less important, since their diameter is <1 mm.Conclusions: We have termed the venous connection between the external iliac and obturator veins over the superior pubic ramus "the communicating vein". This structure forms the corona mortis. Surgeons dealing with direct, indirect, femoral, or obturator hernias need to be aware of these anastomoses and their close proximity to the femoral ring. In classical anatomy textbooks, a description of the veins that form corona mortis is found less often than descriptions of the arteries. Since a venous connection is more probable than an arterial one, its importance must be appreciated by surgeons in order to avoid venous bleeding. [ABSTRACT FROM AUTHOR]

Noonan Syndrome (NS) diagnosis is challenging due to diverse clinical manifestations. Here, our case report highlights MAP3K7 's novel role in NS. A 10.4-year-old female patient presented with short stature and suggestive clinical findings of RASopathy. Despite atypical facial features, the patient met two major diagnostic criteria of Van der Burgt.Initial genetic testing for known NS-associated genes did not find any variants. Later, whole exome sequencing (WES) discovered a unique de novo heterozygous variant (c.65C>A, p.(P22H)) in the MAP3K7 . This variant, categorized as a variant of uncertain significance (VUS) by the American College of Medical Genetics and Genomics (ACMG) criteria, raised questions about its potential role in NS. The patient's clinical presentation deviated from classical manifestations of MAP3K7 -associated syndromes, underscoring the genetic and molecular mechanisms' complexity. Notably, this is the first case reported to associate MAP3K7 variants with NS, advancing knowledge of the condition's genetic causes. Despite challenges in NS diagnosis, proper management, including recombinant growth hormone therapy, is crucial for optimizing growth potential. The case underscores MAP3K7 as a potential candidate gene for NS, and more functional genetic investigations are required to clarify the delicate interaction between genetic abnormalities, the RAS/MAPK pathway, and clinical manifestations observed in NS cases.

Introduction: Proportional short stature is one of the most important features of Noonan Syndrome, and adult height often remains below the 3rd percentile. Although the pathophysiology of short stature in NS patients is not fully understood, it has been shown that GH treatment is beneficial in NS, and it significantly improves the height in respect to the results of short and long-term GH treatment., Methods: In this study, the efficacy of GH therapy was evaluated in children and adolescents with Noonan syndrome who attained final height. In this national cohort study, 67 cases with NS who reached final height from 14 centers were evaluated., Results: A total of 53 cases (mean follow-up time 5.6 years) received GH treatment. Height SDS of the subjects who were started on GH tended to be shorter than those who did not receive GH (-3.26± 1.07 vs. -2.53 ±1.23) at initial presentation. The mean final height and final height SDS in girls using GH vs those not using GH were 150.1 cm and -2.17 SD vs 47.4 cm and-2.8 SD, respectively. The mean final height and final height SDS in boys using GH vs. not using GH were 162.48 ± 6.19 cm and -1.81 SD vs 157.46 ± 10.16 cm and -2.68 ± 1.42 SD, respectively. The Δheight SDS value of the cases was significantly higher in the group receiving GH than in those not receiving GH (1.36 ± 1.12 SD vs. -0.2 ± 1.24, p<0.001). Cardiac findings remained stable in two patients with hypertrophic cardiomyopathy who received GH treatment. No significant side effects were observed in the cases during follow-up., Conclusion: In patients with Noonan syndrome who reach their final height, a significant increase in height is observed with GH treatment, and an increase of approximately +1.4 SDS can be achieved. It has been concluded that GH treatment is safe and effective.

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., Competing Interests: Conflict of Interest: Three authors of this article, Damla Gökşen, Korcan Demir, Samim Özen, are member of the Editorial Board of the Journal of Clinical Research in Pediatric Endocrinology. However, they did not take part in any stage of the editorial decision of the manuscript. The editors who evaluated this manuscript are from different institutions. The other authors declared no conflict of interest., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Objective: Maturity onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY., Methods: MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated., Results: A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A ; 8 (3.6%) HNF4A , 8 (3.6%) KLF11 and 7 (3.1%) HNF1B . The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n= 3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral anti-diabetic treatment., Conclusion: This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Dyshormonogenesis (DG) is the failure of thyroid hormone production due to a defect in thyroid hormonogenesis. Loss-of-function mutations in the thyroglobulin ( TG ) gene are a cause of DG, leading to gland stimulation by thyroid-stimulating hormone (TSH), resulting in goiter. We report a mitotically active follicular nodule in an 11-year-old female with a novel mutation in the TG gene. The patient had been under follow-up for congenital hypothyroidism (CH) since the neonatal period, and she had normal TSH levels on replacement therapy. Genetic test revealed a novel compound heterogeneous mutation [c.2149C>T (p.R717*) (P.Arg717Ter) / c.5361&#95;5362delCCinsG (p.H1787Qfs*3) (p.His1787GlnfsTer3)] in the TG gene. She underwent total thyroidectomy for a thyroid nodule that was reported as Bethesda IV on fine needle aspiration biopsy (FNAB) and noted as suspicious for noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Pathological examination revealed a 16 mm, well-demarcated follicular nodule with a solid/insular pattern. Mitotic activity and Ki67 proliferation index were unusually high (10 mitoses/mm2 and 10%, respectively). Marked cellular pleomorphism and nuclear atypia are well-known diagnostic pitfalls in patients with dyshormonogenetic goiter. However, high mitotic activity is a feature that is less commonly reported in dyshormonogenetic goiter and may raise suspicion of poorly differentiated carcinoma when observed together with a solid pattern. The absence of signs of invasion, history of CH, and awareness of the presence of mutations compatible with dyshormonogenetic goiter can prevent the overinterpretation of such lesions. The risk of cancer development in the dyshormonogenetic thyroid gland is possible in childhood. The close follow-up is life-saving and prevents morbidities and possible mortality., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Objective: Secondary osteoporosis is a condition when the underlying disease or its treatment causes the bone mass to decrease and the bone structure to deteriorate, increasing the risk of fracture. The importance of diagnosis and treatment during childhood and adolescence is due to its long-term negative effects. In this study, our objectives were to determine the diagnostic findings, treatment efficacy, and follow-up characteristics of childhood with secondary osteoporosis., Methods: 61 patients diagnosed with secondary osteoporosis between January 2000 and January 2021 were included in the study. The research is a cross-sectional and descriptive study. Study participants had to be under 18 years of age when the primary underlying disease was diagnosed and received treatment for secondary osteoporosis. Patient data were collected from patient files. Patient data were obtained from patient files in hospitals and were interpreted through the IBM SPSS Statistics for Windows version 20.0 (IBM Corp, Armonk, NY, USA)., Results: 61 patients (28 women/33 men) were evaluated. The most common underlying primary diseases in patients with secondary osteoporosis were inflammatory diseases (57.7%), neuromuscular diseases (26.2%), immunodeficiency (13.1%), acute lymphoblastic leukemia (8.2%), metabolic diseases (8.2%), and solid organ transplantation. (8.2%), bone marrow transplantation (6.6%) and epilepsy (6.6%). The average chronological age when secondary osteoporosis was diagnosed was 11.89±4.88 years. They were evaluated for osteoporosis 6.39±5.13 years after the onset of the underlying primary chronic diseases. 78.7% of the patients had one or more chronic drug use. Systemic steroid use was 59%, chemotherapeutics 23%, immunomodulatory drugs 19.7%, antiepileptic drugs 8.2%, inhaled steroids 4.9%, IVIG 1.6%, and antituberculosis drugs 1.6%. Additionally, 1.6% of the patients were using testosterone as replacement, 3.3% L-Thyroxine, 1.6% estrogen, and 1.6% growth hormone. Bone pain was detected in 49.2% of the patients. All patients had vertebral fractures before treatment. Bisphosphonate treatment was given to 45 patients with secondary osteoporosis. There was a statistically significant increase in mean bone mineral density (BMD) and bone mineral content values six months after treatment, (p<0.001). There was a significant increase in BMD Z-score values for chronological and height age (p<0.001). The patients' BMD values increased on average by 31.15% with treatment. Following bisphosphonate treatment, there was a significant reduction in both fracture number and bone pain in patients (p<0.01). When patients who received and did not receive steroid treatment were compared, both groups received similar benefits from bisphosphonate treatment., Conclusion: Secondary osteoporosis is a condition that is influenced by many factors, such as the primary disease causing osteoporosis, chronic medication use, especially steroids. If left untreated, osteoporosis leads to important diseases such as bone pain, bone fractures, immobilization, and reduced linear growth of bone. When used to treat childhood secondary osteoporosis, Bisphosphonates significantly improve BMD and reduce fracture risk.

Objective: This study aimed to investigate the quality of life of patients with central precocious puberty (CPP) who required treatment and premature thelarche (PT) followed up without treatment and to compare the groups with and without treatment among themselves and with healthy children., Design, Patients and Measurement: This study is designed as a case-control study. A total of 193 children including 59 children with CPP, 53 children with PT, 81 healthy children and their parents were included in the study. A questionnaire was applied to evaluate the sociodemographic characteristics that would affect the quality of life. The 'Pediatric Quality of Life Inventory (PedsQL)' was used to assess the quality of life., Results: The PedsQL total scale score was 78.10 ± 17.13, 79.35 ± 11.54 and 79.52 ± 14.65, the psychosocial health summary score was 78.86 ± 16.83, 79.40 ± 12.54 and 79.94 ± 14.94 and physical health summary score was 75.81 ± 20.69, 79.41 ± 15.04 and 78.25 ± 17.52 in CPP, PT and control groups, respectively; however, there was no statistical difference (p > .05). In the scale administered to the parents, scores were similar in the three groups. No difference was found between CPP, PT and control groups in terms of sociodemographic data in the study (p > .05)., Conclusion: Unlike previous studies, in this study the effects of sociodemographic characteristics and whether treatment was initiated or not on quality of life were investigated. Although the scale scores of the CPP group were lower than the PT and control group, there was no statistically significant difference, indicating that quality of life was not negatively affected in the CPP group receiving treatment., (© 2024 John Wiley & Sons Ltd.)

MIRAGE syndrome is a rare multisystemic disorder characterized by various manifestations, such as myelodysplasia, susceptibility to infections, growth retardation, adrenal hypoplasia, genital anomalies, and enteropathy. In the literature, there have been rare cases of dysautonomia. We present a 6.5-year-old girl, who was first admitted to our department with short stature. On follow up, she exhibited multiple endocrinological issues, including transient hypothyroidism, primary hypoparathyroidism and dysautonomia, along with multisystem involvement. Further investigations revealed recurrent moniliasis, low IgM levels, and transient monosomy 7 in the bone marrow. Whole exome sequencing revealed a heterozygous pathogenic variant of SAMD9 (c.2159del; p.Asn720ThrfsTer35). Additional complications observed during follow-up included medullary nephrocalcinosis, hypomagnesemia, hypermagnesiuria, hypophosphatemia, decreased glomerular filtration rate, and nephrotic proteinuria. The patient also developed hyperglycemia, which was managed with low-dose insulin. This case highlights the diagnostic challenges and the diverse phenotypic presentation observed in MIRAGE syndrome.

Here we report an adolescent boy diagnosed with ectopic ACTH (Adrenocorticotropin hormone) syndrome (EAS) caused by atypical bronchial carcinoid. The patient was evaluated multidisciplinaryly: he had surgery and took chemotherapy and radiotherapy treatments afterward. The patient is still under our follow-up. Until today eighteen pediatric and adolescent patients with EAS because of bronchial carcinoid tumors were reported in 13 case reports and literature reviews. Ectopic ACTH syndrome caused by bronchial carcinoids is very rare in children and adolescents. Careful diagnostic evaluation and rapid treatment should be started immediately. Although complete remission is possible in bronchial carcinoids, atypical carcinoids have a more aggressive nature. A multidisciplinary approach and follow-up will improve quality of life and survival.

Hereditary forms of Medullary thyroid carcinoma (MTC) are rare. Different phenotypes with the same mutation may be due to differences in the timing of RET activation steps, additional mutations in other regions of the gene, or the co-occurrence of germline and somatic mutations, which is an infrequent possibility. Here, we aim to present the different features and difficulties in the follow-up of three family members with the same germline mutation. A 4-year-old male patient with respiratory distress was diagnosed with MTC and found to have a heterozygous germline mutation C.2671T>G(S891A) in the RET gene (classified as intermediate risk according to ATA). As the tumor was inoperable, treatment with a tyrosine kinase inhibitor (sorafenib) was initiated. Sorafenib has prevented tumor progression for seven years. Whole exome sequencing (WES) did not identify additional mutations. Segregation analysis showed the same mutation in the asymptomatic mother and sister. In our case, thyroid tissues were examined for somatic mutations, and SDHA c.1223C>T (p.S408L) was found. The clinical presentation of rare mutations such as RET p.S891A differed among family members carrying the same germline mutation. Our index case's more severe clinical presentation may be due to an additional somatic mutation. Sorafenib treatment can be an option for advanced MTC and may prevent disease progression.

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.

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Diabetic ketoacidosis (DKA) is a common endocrine emergency in pediatric patients. Early presentation to health facilities, diagnosis, and good management in the pediatric intensive care unit (PICU) are crucial for better outcomes in children with DKA., Methods: This was a single-center, retrospective cohort study conducted between February 2015 and January 2022. Patients with DKA were divided into two groups according to pandemic status and diabetes diagnosis., Results: The study enrolled 59 patients, and their mean age was 11±5 years. Forty (68%) had newly diagnosed type 1 diabetes mellitus (T1DM), and 61% received follow-up in the pre-pandemic period. Blood glucose, blood ketone, potassium, phosphorus, and creatinine levels were significantly higher in the new-onset T1DM group compared with the previously diagnosed group (P=0.01, P=0.02, P<0.001, P=0.01, and P=0.08, respectively). In patients with newly diagnosed T1DM, length of PICU stays were longer than in those with previously diagnosed T1DM (28.5±8.9 vs. 17.3±6.7 hours, P<0.001). The pandemic group was compared with pre-pandemic group, there was a statistically significant difference in laboratory parameters of pH, HCO3, and lactate and also Pediatric Risk of Mortality (PRISM) III score. All patients survived, and there were no neurologic sequelae., Conclusions: Patients admitted during the pandemic period were admitted with more severe DKA and had higher PRISM III scores. During the pandemic period, there was an increase in the incidence of DKA in the participating center compared to that before the pandemic.

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.

The tRNA methyltransferase 10 homologue A ( TRMT10A ) gene encodes tRNA methyl transferase, and biallelic loss of function mutations cause a recessive syndrome of intellectual disability, microcephaly, short stature and diabetes. A case with intellectual disability and distinctive features including microcephaly was admitted. She was diagnosed with epilepsy at 2.5 years old. At 3.6 years of age, severe short stature related to growth hormone (GH) deficiency was detected. She had an incidental diagnosis of diabetes at age 11.4 years which was negative for diabetes antibodies with persistent C-peptide level and she was treated with metformin. Spontaneous puberty did not begin until 15.7 years of age and she was found to have primary ovarian failure. A homozygous p.Arg127* mutation in TRMT10A was detected. In addition to the typical clinical features which characterize TRMT10A syndrome, we observed an unusual form of impaired glucose metabolism which presented in early childhood with hypoglycemia followed by diabetes in late childhood. GH deficiency and primary ovarian failure may also be additional findings of this syndrome. Patients with slow onset diabetes who are negative for auto-antibodies and have extra-pancreatic features should be tested for all known subtypes of monogenic diabetes., (©Copyright 2023 by Turkish Society for Pediatric Endocrinology and Diabetes | The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

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.

Objective: The harmful or beneficial effect of obesity on bone mineral density (BMD) remains controversial in children and adolescents. Fibroblast growth factor 21 (FGF21) is a metabolic factor that plays a specific role in the regulation of carbohydrate and lipid metabolism. However, the role of FGF21 in bone metabolism appears paradoxical and is complex. To determine whether serum FGF21 level was associated with BMD in obese children and adolescents., Methods: The study was conducted with the participation of children and adolescents aged 8-18 years. Ninety-eight obese children were included in the study group and 44 children were included in the control group. BMD, in addition to the routine obesity workup, which includes fasting blood glucose, fasting insulin levels, lipid profile, and liver enzymes; serum FGF21 levels have been analyzed., Results: The mean age of the obese group (n=98) was 13.34±2.24 years and the mean age of controls (n=44) was 13.48±2.87 years. Based on International Diabetes Federation criteria, 15 of 98 (15.3%) patients were metabolically unhealthy. FGF21 levels were 193.54±139.62 mg/dL in the obese group and 158.69±151.81 mg/dL in the control group (p=0.06). There was no difference between the FGF21 and BMD z-score values of girls and boys in the obese and control groups (p>0.05)., Conclusion: BMD-z-score was increased in obese children compared to healthy control. Moreover, BMD-z-score tended to be higher when more metabolic risk factors were present. However, there was no significant relationship between FGF21 levels and BMD z-score values in obese children.

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.

Sotos syndrome (SS) is characterized by overgrowth, distinctive facial appearance, and learning disability. It is caused by heterozygous mutations, including deletions of NSD1 located at chromosome 5q35. While advanced bone age can occur in some cases, precocious puberty (PP) has only been reported in three cases previously. Here, we reported a case of SS diagnosed in the infancy period with central PP. The discovery of potential factors that trigger puberty is one of the central mysteries of pubertal biology. Depot gonadotropin-releasing hormone analogs constitute the first-line therapy in central PP (CPP), which has proven to be both effective and safe. In our cases, leuprolide acetate at maximum dose was not successful in controlling pubertal progression, and cyproterone acetate (CPA) was added to therapy, with successful control of pubertal progression. In some specific syndromes with PP, such as SS, treatment can be challenging. CPA may be an asset for effective treatment.

Objectives: Central diabetes insipidus (CDI) is a rare but important disease of varying etiology that poses challenges in diagnosis and follow-up. Identifying diagnostic difficulties in patients with CDI will help ensure an optimal approach to their management and follow-up. This study aimed to characterize the clinical and etiological characteristics of CDI in pediatric patients., Methods: We analyzed the admission and follow-up data of CDI patients aged 0-18 years who were followed in our center between 2010 and 2019., Results: The study included 56 patients with a mean age at diagnosis of 7.92 ± 5.11 years and symptom duration of 8.65 ± 21.3 months. The patients were grouped by etiology into those with organic causes, such as structural anomalies, tumors, and trauma (group 1, n=41) and other causes (group 2, n=15). The prevalence of idiopathic CDI was 16%. At least one pituitary hormone deficiency was detected in 60.7%, the most common being thyroid stimulating hormone deficiency. Patients in group 1 had a higher mean age at diagnosis, shorter symptom duration, and higher frequency of other pituitary hormone deficiencies compared to group 2. Additionally, germinoma was detected 1 year subsequent to normal MRI findings at diagnosis and another patient was diagnosed with Langerhans cell histiocytosis (LCH) 5 years after diagnosis. All patients responded well to replacement therapies, but two patients with germinoma died during follow-up., Conclusions: In the pediatric age group, intracranial organic pathologies are an important etiology of CDI, and despite a short symptomatic period, determining the cause may be challenging and prolonged. Patients presenting at a young age with a long history of symptoms and no other pituitary hormone deficiency are unlikely to have organic CDI. However, organic causes such as LCH should be evaluated at all ages. Patients with idiopathic disease are candidates for further etiological studies, and repeated cranial imaging is important during follow-up., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

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.

Background: Type 1 pseudohypoaldosteronism (PHA1) is a rare condition characterized by the resistance of the kidney to the effect of aldosterone. Secondary PHA1 is a syndrome that is most often related to urinary tract anomalies (UTAs) and/or urinary tract infections (UTIs). A similar pattern of electrolyte impairment is seen in congenital adrenal hyperplasia (CAH) and secondary PHA1, and CAH is a condition that requires urgent treatment. In our study, eight patients aged between 15 days and 8 months (seven males and one female) were included in the evaluation. It was aimed to evaluate cases of secondary PHA1 in our clinic and to identify the problems encountered in diagnosis and follow-up., Methods: The records of the patients who presented to our hospital between February 2010 and 2021 were retrieved and retrospectively scanned., Results: In all cases, hyponatremia, hyperkalemia, hyperaldosteronism, and hyperreninemia were detected. Other biochemical and hormonal tests were normal. Leukocytosis was detected in urine analysis, and urine cultures were productive. UTA was detected in five cases. Nine episodes of PHA1 occurred in eight patients and fungal infections were responsible for causing two episodes. Four episodes of PHA1 needed mineralocorticoid treatment. On the third day, serum electrolytes normalized. Fludrocortisone treatment was continued for 1 week. In one case, UTIs were repeated with PHA1, but in the follow-up, there were no additional problems., Conclusions: Secondary PHA1 should be kept in mind when hyponatremia and hyperkalemia are seen, especially in infants aged under 3 months or older, up to 8 months, who present with non-specific symptoms. Fungal infections should not be forgotten in UTI etiology because PHA1 episodes can be initiated. If CAH is suspected, mineralocorticoid treatment should be rapidly initiated.

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