The potential of the Mediterranean diet to improve metabolic control and body composition in youths with Type 1 Diabetes Mellitus.

BACKGROUND: A chronic autoimmune disease with an increasing incidence rate, type 1 diabetes mellitus (T1DM) is typified by the degeneration of the pancreatic beta cells. Diabetes management is significantly impacted by nutrition. Although it has been demonstrated that following the Mediterranean diet (MD) improves metabolic control with type 2 diabetes in children and adults, its effects on children with T1DM have not received much attention. OBJECTIVE: Therefore, the purpose of this study was to assess whether adherence to Mediterranean diet is associated with better metabolic control and body composition in youths with Type 1 Diabetes Mellitus. The study recruited T1DM patients aged 6-18 years at Istanbul University Cerrahpasa Medical Faculty Hospital's Pediatric Endocrinology and Diabetes Outpatient Clinic for follow-up. METHODS: In addition to demographic variables, some anthropometric measurements, body composition and biochemical parameters such as: Trygliceride(TG), Total cholesterol (TC), High density lipoprotein cholesterol (HDL-C), Low density lipoprotein cholesterol (LDL-C), (Aspartate aminotransferase) AST, Alanine transaminase (ALT) and glycated hemoglobin (HbA1c) was analyzed. The time in range (TIR) is a value obtained from continuous glucose monitoring. KIDMED was used to assess the participants' adherence with the MD. RESULTS: Good adherence to the MD resulted in much larger height SDS than poor adherence. Poor adherence to MD resulted in higher body fat than moderate and good adherence. There is positivite correlation between TIR and KIDMED score. Adherence to MD is negatively associated with HbA1c. The regression anaylsis showed that a one-point rise in the KIDMED score would result in a 0.314-unit reduction in the HbA1c value (p < 0.01). CONCLUSIONS: In conclusion, this study found that adhering to MD led to improved anthropometric measurements, biochemistry, and diabetes outcomes. Awareness among children, adolescents with T1DM, and their parents about the benefits of MD compliance for glycemic and metabolic control should be raised.

Pteridine and tryptophan pathways in children with type 1 diabetes: Isoxanthopterin as an indicator of endothelial dysfunction.

AIM: Type 1 diabetes (T1D) and its complications are known to be associated with oxidative stress. Pteridine derivatives and indoleamine 2,3-dioxygenase (IDO) activity can be used as biomarkers in the evaluation of oxidative stress. In this study, our aim is to compare the concentrations of serum and urinary pteridine derivatives, as well as serum IDO activity, in children and adolescents diagnosed with T1D and those in a healthy control group. METHOD: A cross-sectional study was performed and included 93 patients with T1D and 71 healthy children. Serum and urine biopterin, neopterin, monapterin, pterin, isoxanthopterin, and pterin-6-carboxylic acid (6PTC) and serum tryptophan and kynurenine levels were analyzed and compared with healthy controls. High-performance liquid chromatography was used for the analysis of pteridine derivatives, tryptophan, and kynurenine. Xanthine oxidase (XO) activity, a marker of oxidative stress, was defined by measurement of serum and urine isoxanthopterin. As an indicator of indolamine 2,3-dioxygenase (IDO) activity, the ratio of serum kynurenine/tryptophan was used. RESULTS: Serum isoxanthopterin and tryptophan concentrations were increased, and serum 6PTC concentration was decreased in children with T1D (p=0.01, p=0.021, p<0.001, respectively). In children with T1D, IDO activity was not different from healthy controls (p>0.05). Serum neopterin level and duration of diabetes were weakly correlated (p=0.045, r=0.209); urine neopterin/creatinine and isoxanthopterin/creatinine levels were weakly correlated with HbA1c levels (p=0.005, r=0.305; p=0.021, r=0.249, respectively). Urine pterin/creatinine level negatively correlated with body mass index-SDS. (p=0.015, r=-0.208). CONCLUSION: We found for the first time that isoxanthopterin levels increased and 6PTC levels decreased in children and adolescents with T1D. Elevated isoxanthopterin levels suggest that the XO activity is increased in TID. Increased XO activity may be an indicator of vascular complications reflecting T1D-related endothelial dysfunction.

Natural history of ENPP1 deficiency: Nationwide Turkish Cohort Study of autosomal-recessive hypophosphataemic rickets type 2.

OBJECTIVE: Autosomal-recessive hypophosphataemic rickets type 2 (ARHR2) is a rare disease that is reported in survivors of generalized arterial calcification of infancy (GACI). DESIGN, PATIENTS AND MEASUREMENT: The objective of this study was to characterize a multicenter paediatric cohort with ARHR2 due to ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) deficiency and with a diagnosis of GACI or GACI-related findings. The clinical, biochemical and genetic characteristics of the patients were retrospectively retrieved. RESULTS: We identified 18 patients from 13 families diagnosed with ARHR2. Fifteen of the patients had an ENPP1 variation confirmed with genetic analyses, and three were siblings of one of these patients, who had clinically diagnosed hypophosphataemic rickets (HRs) with the same presentation. From nine centres, 18 patients, of whom 12 (66.7%) were females, were included in the study. The mean age at diagnosis was 4.2 ± 2.2 (1.6-9) years. The most frequently reported clinical findings on admission were limb deformities (66.6%) and short stature (44.4%). At diagnosis, the mean height SD was -2.2 ± 1.3. Five of the patients were diagnosed with GACI in the neonatal period and treated with bisphosphonates. Other patients were initially diagnosed with ARHR2, but after the detection of a biallelic variant in the ENPP1 gene, it was understood that they previously had clinical findings associated with GACI. Three patients had hearing loss, and two had cervical fusion. After the treatment of HRs, one patient developed calcification, and one developed intimal proliferation. CONCLUSION: ARHR2 represents one manifestation of ENPP1 deficiency that usually manifests later in life than GACI. The history of calcifications or comorbidities that might be associated with GACI will facilitate the diagnosis in patients with ARHR2, and patients receiving calcitriol and phosphate medication should be carefully monitored for signs of calcification or intimal proliferation.

Ovarian reserve in children with juvenile idiopathic arthritis using biologic disease-modifying anti-rheumatic drugs.

BACKGROUND/OBJECTIVES: The aim of the study is to assess the effect of juvenile idiopathic arthritis (JIA) and biologic disease-modifying anti-rheumatic drugs (bDMARDs) on ovarian reserve in children. MATERIALS AND METHODS: A cross-sectional study was performed from March 2021 to March 2022 and included 81 patients with JIA and 49 healthy children. Serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels were analyzed using electrochemiluminescence methods. RESULTS: The mean of current age (13.5 ± 3.2 vs. 14.4 ± 2.4 years), height standard deviation score (SDS) (- 0.35 ± 1.18 vs. - 0.44 ± 0.94), body mass index SDS (0.12 ± 1.33 vs. 0.25 ± 1.28), and the median weight SDS (- 0.13 (- 2.27-3.23) vs. - 0.52 (- 3.4-3.3)) were similar in JIA patients and controls (p > 0.05). Patients with JIA were divided into two groups according to their treatment regimens: treated with methotrexate (MTX) (biologic naive) (n = 32) and treated with MTX plus bDMARDs (n = 49). No significant differences were detected between the 3 groups regarding menarche age, menstrual cycle length, and flow duration (for all p > 0.05). The median serum concentration of AMH was 2.94 (1.12-7.88) ng/ml in the control group, 3.02 (0.36-8.54) ng/ml in the biologic naïve group, and 3.01 (0.99-8.26) ng/ml in the MTX plus bDMARD group. There were no significant differences between 3 groups according to serum AMH, FSH, LH, and estradiol levels (p > 0.05). CONCLUSION: Biologic DMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. Prospective studies with larger sample sizes are needed to confirm our findings and to evaluate the impact on the future fertility of patients. Key Points • Although biologic disease-modifying anti-rheumatic drugs (bDMARDs) are being game-changing treatment options in juvenile idiopathic arthritis, their effect on fertility and ovarian reserve is one of the most discussed issues. • In addition to treatment used, autoimmune diseases might also have a negative effect on fertility. • In this cross-sectional study, we found that anti-Mullerian hormone level of patients who were on bDMARDs, patients who were on methotrexate, and healthy controls were similar. • Our results suggest that bDMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment.

SARS-COV-2 infections in children: The role of fibrinogen in predicting diagnosis and severity: A retrospective cohort study.

BACKGROUND: Evaluating predictors of coronavirus disease 2019 (COVID-19) and severity among children may help clinicians manage the high rate of hospital admissions for suspected cases. OBJECTIVES: This study aimed to evaluate the demographic, clinical and laboratory characteristics of children during the pandemic, and determine the predictors of COVID-19 and moderate-to-severe disease. MATERIAL AND METHODS: This retrospective cohort study included all consecutive COVID-19 cases in patients aged <18 years who presented to the Pediatric Emergency Department at Haseki Training and Research Hospital (Istanbul, Turkey) between March 15 and May 1, 2020, and underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) analysis of oro-nasopharyngeal swabs (n = 1137). RESULTS: The frequency of SARS-CoV-2 PCR positivity was 28.6%. The COVID-19 (+) group presented with sore throat, headache and myalgia significantly more frequently than the COVID-19 (-) group. Multivariate logistic regression models showed independent predictors of SARS-CoV-2 positivity as follows: age, contact history, lymphocyte count <1500/mm3, and neutrophil count <4000/mm3. In addition, higher age, neutrophil count and fibrinogen levels were independent predictors of severity. The diagnostic cutoff value for fibrinogen (370.5 mg/dL) had a sensitivity of 53.12, specificity of 83.95, positive predictive value (PPV) of 39.53, and negative predictive value (NPV) of 90.07 for predicting severity. CONCLUSIONS: Symptomatology, whether alone or in combination with other approaches, may be an appropriate strategy to guide the diagnosis and management of COVID-19.

Temporary Thyroid Dysfunction and Catecholamine Excess Due to Mercury Poisoning in 6 Cases.

OBJECTIVE: Mercury poisoning is a condition with multiple-organ dysfunction that has effects on the central nervous system, gastrointestinal system, cardiovascular system, skin, lungs, and kidneys. It can be fatal or may result in sequelae such as neurological disturbances, if treated late or left untreated. The endocrinological effects of mercury exposure are not well-known. We aimed to evaluate patients with mercury poisoning. MATERIALS AND METHODS: A total of 6 cases of mercury poisoning from 3 families were included in the study. Clinical, laboratory, and follow-up data were recorded. RESULTS: Thyroid dysfunction was presented as high thyroid hormones and normal thyrotropin level (unsuppressed) in 5 cases (83.3%). On the other hand, pheochromocytoma-like syndrome was detected in 5 cases (83.3%) with hypertension. The 4 cases were the first to use methimazole for mercury poisoning due to tachycardia and hypertension despite antihypertensive treatment due to catecholamine excess and thyroid dysfunction. Hyponatremia was detected in 3 cases (50%). CONCLUSION: Mercury poisoning is difficult to diagnose because it is rare and presents with nonspecific physical and laboratory findings. Early diagnosis and providing appropriate treatment are essential in order to prevent sequelae. Mercury poisoning should be considered in patients with unexplained hypertension and tachycardia suggesting the involvement of thyroid hormones and catecholamines.

Reclassification of two germline DICER1 splicing variants leads to DICER1 syndrome diagnosis.

DICER1 syndrome is an inherited condition associated with an increased risk of developing hamartomatous and neoplastic lesions in diverse organs, mainly at early ages. Germline pathogenic variants in DICER1 cause this condition. Detecting a variant of uncertain significance in DICER1 or finding uncommon phenotypes complicate the diagnosis and can negatively impact patient care. We present two unrelated patients suspected to have DICER1 syndrome. Both females (aged 13 and 15 years) presented with multinodular goiter (thyroid follicular nodular disease) and ovarian tumours. One was diagnosed with an ovarian Sertoli-Leydig cell tumour (SLCT) and the other, with an ovarian juvenile granulosa cell tumour, later reclassified as a retiform variant of SLCT. Genetic screening showed no germline pathogenic variants in DICER1. However, two potentially splicing variants were found, DICER1 c.5365-4A>G and c.5527+3A>G. Also, typical somatic DICER1 RNase IIIb hotspot mutations were detected in the thyroid and ovarian tissues. In silico splicing algorithms predicted altered splicing for both germline variants and skipping of exon 25 was confirmed by RNA assays for both variants. The reclassification of the ovarian tumour, leading to recognition of the association with DICER1 syndrome and the characterization of the germline intronic variants were all applied to recently described DICER1 variant classification rules. This ultimately resulted in confirmation of DICER1 syndrome in the two teenage girls.

[Long-term follow-up data of patients with Multiple Pituitary Hormone Deficiency]. / Seguimiento a largo plazo de pacientes con Deficiencia Hormonal Hipofisiaria Múltiple.

The deficiency of two or more pituitary hormones is called multiple pituitary hormone deficiencies (MPHD). Its prevalence is estimated to be about 1/8,000 worldwide. OBJECTIVE: To present the diagnosis processes, clinical findings, and long-term follow-up of patients with MPHD. PATIENTS AND METHOD: Between 1999 and 2015, patients diagnosed with MPHD were evaluated. Clinical presentation, anthropometry, imaging studies, and clinical evolution were analyzed. Hormone status was evaluated, including growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone/luteinizing hormone (FSH/LH), and prolactin (PRL). Data were assessed using the student's t-test and the Mann-Whitney U test. Spearman's correlation was used for correlations. A p-value < 0.05 was considered statistically significant. RESULTS: Forty-five patients were included; 55.6% were male, the mean age at presentation was 5.6 ± 3.9 (0-14.4) years, and the median bone age was 3.5 ± 2.3 (0.5-11) years. At admission, GH deficiency was found in 88.9% of the cases, TSH deficiency in 77.8%, ACTH deficiency in 33.3%, FSH/LH deficiency in 22.2%, and PRL deficiency in 17.8%. During the follow-up, 62% of the cases added other hormone deficiencies. The mean follow-up period was 9.18 ± 3.6 (3.02-17.2) years. CONCLUSION: Patients with MPHD have very different clinical presentations, with GH and TSH deficiency being the most common in this study. Additional hormonal deficiencies can occur even years after the initial diagnosis and our results demonstrate that genetic height potential is achieved with GH treatment.

Kidney Involvement in Pediatric COVID-19 Cases: A Single-Center Experience.

OBJECTIVE: The kidney is the second most commonly affected organ by severe acute respiratory syndrome coronavirus-2, characterized by hematuria, proteinuria, and acute kidney injury. There are few studies describing renal involvement in pediatric cases. MATERIALS AND METHODS: This retrospective study evaluated the prevalence of hematuria, proteinuria, and acute kidney injury in severe acute respiratory syndrome coronavirus-2-positive pediatric cases (1-18 years old) who visited emergency department between March and November 2020. Patients with urinary tract infections were excluded. An age-specific upper limit of reference interval was used to define "elevated serum creatinine" (greater than upper limit of reference interval) and acute kidney injury (>1.5 times upper limit of reference interval). RESULTS: A total of 228 patients were evaluated, median age was 12.7 years (interquartile range: 7.5; 16.1), and 51.3% were male. The prevalence of asymptomatic, mild, and moderate-to-severe disease was 12.7% (29/228), 77.2% (176/228), and 10.1% (23/228), respectively. The prevalence of hematuria, proteinuria, and elevated serum creatinine was 15.8% (36/228), 6% (14/228), and 3% (7/228), respectively. Kidney involvement (i.e., at least 1 of these findings) was 23.2% (53/228) and significantly higher in the moderate-to-severe disease (43.5%). None of the patients met the acute kidney injury criterion. In logistic regression analysis, female sex (odds ratio: 1.97, 95 CI%: 1.03; 3.70, P = .040) and fever (odds ratio: 2.28, 95% CI: 1.19; 4.36, P = .012) were independent predictors of kidney involvement. Three patients demonstrated a kidney presentation (macroscopic hematuria) on admission, and another patient was diagnosed with C3 glomerulonephritis during hospitalization. CONCLUSION: Kidney involvement was found about in 1 quarter of children with coronavirus disease 2019. Awareness and recognition of kidney involvement and follow-up are important in the management.

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

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

Catch-up Growth and Discontinuation of Fludrocortisone Treatment in Aldosterone Synthase Deficiency.

BACKGROUND: Aldosterone synthase deficiency (ASD) caused by mutations in the CYP11B2 gene is characterized by isolated mineralocorticoid deficiency. Data are scarce regarding clinical and biochemical outcomes of the disease in the follow-up. OBJECTIVE: Assessment of the growth and steroid profiles of patients with ASD at the time of diagnosis and after discontinuation of treatment. DESIGN AND METHOD: Children with clinical diagnosis of ASD were included in a multicenter study. Growth and treatment characteristics were recorded. Plasma adrenal steroids were measured using liquid chromatography-mass spectrometry. Genetic diagnosis was confirmed by CYP11B2 gene sequencing and in silico analyses. RESULTS: Sixteen patients from 12 families were included (8 females; median age at presentation: 3.1 months, range: 0.4 to 8.1). The most common symptom was poor weight gain (56.3%). Median age of onset of fludrocortisone treatment was 3.6 months (range: 0.9 to 8.3). Catch-up growth was achieved at median 2 months (range: 0.5 to 14.5) after treatment. Fludrocortisone could be stopped in 5 patients at a median age of 6.0 years (range: 2.2 to 7.6). Plasma steroid profiles revealed reduced aldosterone synthase activity both at diagnosis and after discontinuation of treatment compared to age-matched controls. We identified 6 novel (p.Y195H, c.1200 + 1G > A, p.F130L, p.E198del, c.1122-18G > A, p.I339_E343del) and 4 previously described CYP11B2 variants. The most common variant (40%) was p.T185I. CONCLUSIONS: Fludrocortisone treatment is associated with a rapid catch-up growth and control of electrolyte imbalances in ASD. Decreased mineralocorticoid requirement over time can be explained by the development of physiological adaptation mechanisms rather than improved aldosterone synthase activity. As complete biochemical remission cannot be achieved, a long-term surveillance of these patients is required.

A rare cause of salt-wasting in early infancy: Transient pseudohypoaldosteronism.

Three infants aged between 38 days and 43 days all presented with poor weight gain, hyponatremia, hyperkalemia, and were diagnosed as having urinary tract infections, which were accompanied by urinary tract malformations in our cases. Hydration and infection treatments were given. A few days after admission, hormonal studies revealed normal cortisol and 17-hydroxy progesterone levels and markedly high aldosterone levels, thus the patients were diagnosed as having transient pseudohypoaldosteronism. After the proper treatment was given, the transient pseudohypoaldosteronism resolved. In conclusion, when an infant with urinary tract infection or malformation has electrolyte abnormalities, pediatricians should consider the diagnosis of transient pseudohypoaldosteronism.

Authors' reply: the biologic importance of the vitamin D binding protein polymorphism in pediatric COVID-19 patients.

What is Known? • Vitamin D has multiple roles in the immune system that can modulate the body reaction to an infection • Vitamin D binding protein (DBP) is the key transport protein which, along with albumin, binds over 99% of the circulating vitamin D metabolites What is New? • Lower 25 OH vitamin D levels were associated with higher inflammation markers, suggesting an important role of vitamin D in the clinical course of COVID-19 in children and adolescents probably by regulating the systemic inflammatory response • Further studies are warranted to investigate the possible causal association of DBP levels and polymorphism with vitamin D status (total and bioavailable vitamin D) in COVID-19 patients.

Evaluation of the pathophysiological role of Fetuin A levels in adolescents with polycystic ovary syndrome.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is an endocrinopathy, in which hyperandrogenism and hyperinsulinism have both occurred. Fetuin-A, a natural inhibitor of tyrosine kinase, leads to insulin resistance. The aim was to evaluate the relationship between fetuin-A and hyperandrogenism and hyperinsulinism and the role of fetuin-A in the pathophysiology of PCOS. METHODS: Thirty-eight cases with PCOS and 40 healthy adolescents were included in the study. PCOS and controls were divided into obese/non-obese subgroups. LH, FSH, total and free testosterone (TT, FT), SHBG, androstenedione, DHEAS were measured in patients with PCOS. Fasting glucose, insulin, lipid profile, AST, ALT, HsCRP, and fetuin levels of PCOS patients and healthy controls were also measured. RESULTS: Fetuin-A levels were higher in PCOS patients than in controls. In the obese-PCOS group, when compared to non-obese PCOS patients; the levels of SHBG and HDL were low while cholesterol, LDL, triglyceride, HOMA-IR, FT, FAI, and HSCRP levels were high, but Fetuin-A levels were similar. In the obese-PCOS group, fetuin-A levels were higher than in obese-controls. HOMA-IR and fetuin-A levels were higher in non-obese PCOS patients than in non-obese controls. In the PCOS group, fetuin-A was positively correlated with TT, FT, FAI and androstenedione and negatively correlated with SHBG. Regression analysis demonstrated that FT, SHBG, and androstenedione significantly predicted fetuin-A levels (R2=54%). In non-obese PCOS patients and controls, fetuin-A was positively correlated with insulin and HOMA-IR. CONCLUSIONS: These results suggest a relationship between androgen levels and fetuin-A in PCOS cases, independent of insulin resistance, and may shed light on further studies.

The association between vitamin D levels and the clinical severity and inflammation markers in pediatric COVID-19 patients: single-center experience from a pandemic hospital.

Vitamin D has an immunomodulating property that regulates the inflammatory response. In this study, the aim was to evaluate the relationship between vitamin D levels and clinical severity and inflammation markers in children and adolescents with COVID-19. The clinical and laboratory records of 103 pediatric cases with COVID-19, whose vitamin D levels had been measured, were retrospectively reviewed. The cases were divided into groups according to their clinical severity (asymptomatic, mild, and moderate-to-severe) and vitamin D levels. The moderate-to-severe clinical group had significantly higher inflammation markers (CRP, procalcitonin, fibrinogen, D-dimer) and a lower lymphocyte count compared to both the mild and asymptomatic groups. The 25 OH vitamin D levels were also significantly lower (p < 0.001), and the ratio of vitamin D deficiency was 70.6% in the moderate-to-severe group. The vitamin D-deficient group had a significantly higher age and fibrinogen levels while also having a lower lymphocyte count compared to the insufficient and normal groups. The 25 OH vitamin D level was correlated positively with the lymphocyte count (r = 0.375, p = <0.001), and negatively with age (r = -0.496, p = <0.001), CRP (r = -0.309, p = 0.002) and fibrinogen levels (r = -0.381, p = <0.001). In a logistic regression analysis, vitamin D deficiency, D-dimer, and fibrinogen levels on admission were independent predictors of severe clinical course.Conclusion: This study revealed an association between vitamin D deficiency and clinical severity, in addition to inflammation markers in pediatric COVID-19 cases. Prophylactic vitamin D supplementation may be considered, especially in the adolescent age group. What is Known: • • The pathology of COVID-19 involves a complex interaction between the SARS-CoV-2 and the immune system. Hyperinflammation/cytokine storm is held responsible for the severity of the disease. • Vitamin D has multiple roles in the immune system that can modulate the body reaction to an infection. What is New: • • Clinically more severe group had significantly lower vit D levels and significantly higher inflammation markers. • Lower 25 OH vit D levels were associated with higher inflammation markers, suggesting an important role of vitamin D in the clinical course of COVID-19 in children and adolescents probably by regulating the systemic inflammatory response.

Clinical Characteristics and Growth Hormone Treatment in Patients with Prader-Willi Syndrome

Objective: To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey. Methods: The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated. Results: The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. GH treatment was started in 40% at a mean age of 4.7±2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, body mass index (BMI) standard deviation (SDS) remained unchanged. Conclusion: The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. GH treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start.

Long-term Clinical Follow-up of Patients with Familial Hypomagnesemia with Secondary Hypocalcemia

Objective: Familial hypomagnesemia with secondary hypocalcemia (HSH) is an autosomal recessive disease caused by a mutation in the transient receptor potential melastatin 6 (TRPM6) gene and is characterized by selective magnesium malabsorption. Affected cases are usually diagnosed during infancy and usually present with seizures due to hypocalcemia and hypomagnesemia. Irreversible neurological deficits and arrhythmias can be observed without appropriate treatment. The aim was to evaluate the long-term follow-up of patients with genetically confirmed HSH. Methods: A total of six patients with HSH, two of whom were siblings, were included. Age at diagnosis, clinical, laboratory and follow-up data on admission were recorded. All 39 exons of the TRPM6 gene and flanking exon-intron junctions from genomic DNA were amplified and sequenced in all cases. Results: The median (range) follow-up duration was 12.1 (7.6-21.7) years. All cases were diagnosed in infancy. Four different mutations, three of which had not been previously reported, were detected in the TRPM6 gene. Treatment compliance was good and there were no severe complications in the long-term follow-up of cases. However, mental retardation, specific learning difficulty and attention deficit/hyperactive disorder were observed as comorbidities. Conclusion: Of the four different TRPM6 mutations in this small cohort, three had not been previously reported. The long-term prognosis of HSH appears to be good, given early diagnosis and good treatment compliance. This long-term follow-up and prognostic data and the three novel mutations will contribute to the published evidence concerning this rare condition, HSH, and it is hoped will prevent negative outcomes.

Clitoromegaly caused by ovarian stimulation in a preterm newborn: ovarian hyperstimulation syndrome of preterm babies.

BACKGROUND: Preterm ovarian hyperstimulation syndrome (POHS) is an uncommon disorder characterized by prematurity, hypogastric and upper leg swelling, high serum estradiol and gonadotropin levels, and ovarian cysts. Immaturity of the gonadal axis is accepted as the cause. But still, other etiological factors are suspected. CASE: A preterm baby who was born at 24 gestational weeks was referred to our clinic for ambiguous genitalia on day 118 of life. Labia majora and clitoris was edematous. Clitoris length was 1.5 cm. On laboratory evaluation: 17OH-Progesterone: 1.84 ng/ml, dehydroepiandrosterone sulphate (DHEA-S): 139 µg/dl, total testosterone (T.T): 88 ng/dl, luteinizing hormone (LH): 22.5 mIU/l, Follicle stimulating hormone (FSH): 15.7 mIU/l, estradiol (E2): 447 pg/ml. Karyotype analysis was 46, XX. There was a 25x14x12 mm ovarian cyst detected on ultrasound. On follow-up, E2 levels and cyst size increased, and there was 4 mm pericardial effusion on echocardiography at the time. CONCLUSION: In this paper, we present a case with POHS and to discuss possible pathophysiological mechanisms and treatment. This is the first case of POHS developing pericardial effusion.

Serum Fetuin-A and Insulin Levels in Classic Congenital Adrenal Hyperplasia.

Androgens play a pivotal role in non-reproductive organs such as the kidney, heart, liver, and pancreas. As androgen receptors are expressed in pancreatic and liver cells, excess testosterone can result in hypersecretion of insulin and fetuin-A, a protein produced in the liver. The expression of fetuin-A, a natural inhibitor of tyrosine kinase activity in muscle and liver, leads to insulin resistance. In addition, insulin and fetuin-A levels are thought to be affected by drugs such as glucocorticoids (GCs) and fludrocortisone. However, whether fetuin-A and insulin levels are affected by androgens and GCs in patients with classic congenital adrenal hyperplasia (CAH) is unknown. This cross-sectional study included 56 CAH patients and 70 controls. Analyses were stratified by sex and prepubertal/pubertal status to control for potential changes in serum metabolic/inflammatory markers associated with the production of sex steroids. Fasting blood glucose, insulin, triglyceride, total cholesterol, high density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, fetuin-A, and high-sensitivity C-reactive protein (hs-CRP) levels were measured in blood samples. In addition, 17α-hydroxyprogesterone, androstenedione, total testosterone, free testosterone, and dehydroepiandrosterone sulfate levels were measured before medication was administered. Insulin and fetuin-A levels were significantly higher in CAH patients than in controls. The unfavourably high levels of these substances exhibited a positive correlation with total and free testosterone. Regression analysis revealed that fetuin-A and free testosterone were the only independent predictors of the insulin level, while insulin and free testosterone levels significantly predicted the fetuin-A level (R2=42.7% and 59.8%). Differences were also observed in triglyceride and hs-CRP levels between the pubertal and prepubertal groups. We conclude that serum fetuin-A and insulin levels may be associated with androgens in CAH patients.

Alterations of Tear Film and Ocular Surface in Children with Type 1 Diabetes Mellitus.

Purpose: To investigate whether diabetes mellitus (DM) affects ocular surface of children with well-controlled type 1 DM.Methods: Sixty-five diabetic patients and 55 age-matched controls enrolled to study. Detailed ocular surface assessment including, ocular surface disease index (OSDI) questionnaire, tear film break-up time (TBUT) analysis, Schirmer test, and conjunctival impression cytologic analysis were performed.Results: Schirmer test and TBUT results were significantly lower in DM group than controls (p = 0.001, for all). OSDI scores of all participants were within normal range. Impression cytology analysis showed grade 0 changes in all participants and there was no difference between groups for goblet cell density (p > 0.05). The TBUT results were significantly associated with duration of DM (r = -0.309, p = 0.036).Conclusion: Diabetic children without symptoms, signs, and definite diagnosis of dry eye still had lower TBUT and Schirmer test results than controls; however, impression cytology analysis was similar in both groups.