Clinical and Laboratory Characteristics of MODY (Maturity Onset Diabetes of Young) Cases, Genetic Mutation Spectrum and Phenotype-genotype Relationship.

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 antidiabetic 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.

Exploring Multiple Endocrinological Issues and Dysautonomia in a Rare Case: Hypoparathyroidism in MIRAGE Syndrome.

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.

Evaluation of quality of life in children with precocious puberty.

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.

Familial Clinical Heterogeneity of Medullary Thyroid Cancer with Germline RET S891A Protooncogene Mutation: 7-Year Follow-up with Successful Sorafenib Treatment.

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.

A Challenging Case of Ectopic ACTH Syndrome with Bronchial Carcinoid and Literature Review.

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.

Clinic Heterogeneity and Management of Pediatric Patients With Germline RET Proto-oncogene Mutation: Single-center Experience.

Inherited forms of medullary thyroid carcinoma (MTC) can cause serious problems in diagnosis and follow-up. Family screening is performed, and prophylactic thyroidectomy at an appropriate age can be life-saving. This study aimed to investigate the diagnostic, clinical, laboratory characteristics, and treatment methods of cases with rearranged during transfection ( RET) mutation in the childhood age group. Patients diagnosed with hereditary MTC and patients who were evaluated by detecting MTC and/or RET mutations in their families were included in this study. Nine cases from 6 families were included in the study. Seven patients were evaluated as a result of screening, whereas 2 patients, one of whom was MEN2B, were symptomatic. Prophylactic thyroidectomy was performed in 7 cases. Medullary microcarcinoma was found in all, and additional papillary thyroid carcinoma in one. An inoperable tumor was detected in one patient, and sorafenib treatment was applied. A very heterogeneous clinical presentation can be seen in a group of pediatric patients with RET mutation. In rare RET mutations, the genotype-phenotype relationship is still unclear, and different clinical pictures can be seen. Although prophylactic thyroidectomy is life-saving, it can cause iatrogenic hypothyroidism and hypoparathyroidism. Concomitant papillary microcarcinomas may occur in very young children with germline RET mutation.

Impact of the COVID-19 pandemic on diabetic ketoacidosis management in the pediatric intensive care unit.

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.

Evaluation of aggression level in adolescent girls with classical congenital adrenal hyperplasia.

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 11ß 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 11ß 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.

Clinical Characteristics and Treatment Outcomes of Children with Primary Osteoporosis.

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.

A National Multicenter Study of Leptin and Leptin Receptor Deficiency and Systematic Review.

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.

Evaluation of Abnormal Uterine Bleeding in Adolescents: Single Center Experience

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.

Clinical Profile of Parathyroid Adenoma in Children and Adolescents: A Single-Center Experience.

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.

Expanding the Phenotype of TRMT10A Mutations: Case Report and a Review of the Existing Cases

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.

Mitotically Active Follicular Nodule in Early Childhood: A Case Report with A Novel Mutation in the Thyroglobulin Gene.

Dyshormonogenesis 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 dyshormonogenesis, 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 due to congenital hypothyroidism since the neonatal period, and she had normal TSH levels. Genetic test revealed a novel compound heterogeneous mutation [c.2149C>T (p.R717*) (P.Arg717Ter) / c.5361_5362delCCinsG (p.H1787Qfs*3) (p.His1787GlnfsTer3)] in TG gene. She underwent total thyroidectomy for a thyroid nodule that was reported as Bethesda IV on 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/2mm2 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 emphasized 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 congenital hypothyroidism, 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 mortalities.

Hyperprolactinemia in children and adolescents and longterm follow-up results of prolactinoma cases: a single-centre experience.

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.

Difficulties in the diagnosis and management of eight infants with secondary pseudohypoaldosteronism.

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.

Evaluation of the etiological and clinical characteristics of pediatric central diabetes insipidus.

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.

The Effect of Growth Hormone Therapy on Cardiac Outcomes in Noonan Syndrome: Long Term Follow-up Results

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.

Fibroblast Growth Factor 21 Levels and Bone Mineral Density in Metabolically Healthy and Metabolically Unhealthy Obese Children

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.