Salivary Sex Steroid Levels in Infants and Their Relation with Infantile Colic.

Background: Hypothalamic-pituitary-gonadal axis is active during minipuberty, timing of which coincides with infantile colic. To the best of our knowledge, the relationship between these entities has not been investigated yet. Methods: Saliva samples were collected from 15- to 60-day-old term infants (n=139) between 9 am and 5 pm. Group 1 included infants with infantile colic (n=68, 54.4% female). Remaining healthy infants constituted Group 2 (n=71, 47.9% female). The salivary levels of estradiol (Esal) in females and testosterone (Tsal) in males were studied in duplicate by using the ELISA method. Results: The median (25th-75th centile) age and birth week for all infants were 33 (29-43) days and 39 (38.1-40) weeks, respectively. Levels of Tsal in males [Group 1, 73.35 (59.94-117.82) pg/mL vs Group 2, 77.66 (56.49-110.08) pg/mL, p=0.956] and Esal in females [Group 1, 3.91 (2.76-5.31) pg/mL vs Group 2, 4.03 (1.63-12.1) pg/mL, p=0.683] were similar among the groups. However, only in subjects with infantile colic (Group 1), Esal and body mass index (BMI) standard deviation scores of females were slightly correlated (Group 1, rs= 0.393, p=0.016 vs. Group 2, rs= 0.308, p=0.076) and there was a significant correlation between the sampling time and Tsal in males (Group 1, rs= 0.469, p=0.009 vs. Group 2, rs= -0.005, p=0.976). Conclusions: Random salivary sex steroid levels were similar among groups. However, only in subjects with infantile colic, salivary estradiol levels in females were positively correlated with BMI and salivary testosterone levels were higher later in the day among males. Thus, sex steroid production might be altered during minipuberty in subjects with infantile colic.

Clinical features, diagnosis and treatment outcomes of Cushing's disease in children: A multicenter study.

OBJECTIVE: Since Cushing's disease (CD) is less common in the paediatric age group than in adults, data on this subject are relatively limited in children. Herein, we aim to share the clinical, diagnostic and therapeutic features of paediatric CD cases. DESIGN: National, multicenter and retrospective study. PATIENTS: All centres were asked to complete a form including questions regarding initial complaints, physical examination findings, diagnostic tests, treatment modalities and follow-up data of the children with CD between December 2015 and March 2017. MEASUREMENTS: Diagnostic tests of CD and tumour size. RESULTS: Thirty-four patients (M:F = 16:18) from 15 tertiary centres were enroled. The most frequent complaint and physical examination finding were rapid weight gain, and round face with plethora, respectively. Late-night serum cortisol level was the most sensitive test for the diagnosis of hypercortisolism and morning adrenocorticotropic hormone (ACTH) level to demonstrate the pituitary origin (100% and 96.8%, respectively). Adenoma was detected on magnetic resonance imaging (MRI) in 70.5% of the patients. Transsphenoidal adenomectomy (TSA) was the most preferred treatment (78.1%). At follow-up, 6 (24%) of the patients who underwent TSA were reoperated due to recurrence or surgical failure. CONCLUSIONS: Herein, national data of the clinical experience on paediatric CD have been presented. Our findings highlight that presenting complaints may be subtle in children, the sensitivities of the diagnostic tests are very variable and require a careful interpretation, and MRI fails to detect adenoma in approximately one-third of cases. Finally, clinicians should be aware of the recurrence of the disease during the follow-up after surgery.

Aromatase Inhibitors May Increase the Risk of Cardiometabolic Complications in Adolescent Boys.

INTRODUCTION: Aromatase inhibitors (AIs) are increasingly used in children and adolescents to augment adult height. The aim of this study was to investigate the effects AIs have on cardiac morphology, functions and their relation to several metabolic parameters in adolescent boys. METHODS: Three groups matched for sex (boys, n = 67), age (median age 13.5 years), weight, height, body mass index, and puberty stages were enrolled: (i) Group 1: 23 patients using AIs (only AI (n = 6) or in combination with growth hormone (GH) (n = 17)) for at least 6 months; (ii) Group 2: 22 patients using only GH, and (iii) Group 3: 22 healthy boys. Two-dimensional, M-mode conventional Doppler and tissue Doppler examinations of the left ventricle (LV) were performed. Bioelectrical bioimpedance analyses was conducted and follicle-stimulating hormone, luteinizing hormone, total testosterone, lipid, and hemogram parameters were obtained. RESULTS: Patients in Group 1 had significantly higher serum total testosterone (p < 0.001) and hemoglobin (p < 0.001) levels, fat free mass (p = 0.005), LV mass (LVM) (p = 0.002), as well as increased LV posterior wall diameter (LVPWD) (p = 0.002), interventricular septum diameter (IVSD) (p = 0.019), and myocardial systolic wave velocity (Sm) (p = 0.020) compared to the two other control groups. No significant differences were observed in terms of diastolic and systolic functions and lipid profiles (p > 0.05). There were positive correlations between total testosterone, hemoglobin levels, LVM, LVPWD and IVSD (p < 0.05). CONCLUSION: Increased LVM, LVPWD, IVSD and Sm of patients receiving AI therapy in comparison to the control groups, and the significant correlations of these parameters with total testosterone and hemoglobin levels were determined as potential side effects of AIs. These findings emphasize the need of routine cardiac follow-up in patients using AIs.

Anaemia-based screening for resistance to thyroid hormone alpha in children.

BACKGROUND: The hypothyroid phenotype associated with resistance to thyroid hormone alpha (RTH-α) is associated with a diverse clinical picture. On the other hand, thyroid-stimulating hormone (TSH) levels are normal. Free triiodothyronine (fT3) and free thyroxine (fT4) levels can also be normal; however, normo- or macrocytic anaemia is usually present in reported cases. Diagnosis is challenging and there is limited data regarding screening methods. OBJECTIVE: The study aimed to assess the efficiency of a screening strategy for RTH-α. SUBJECTS AND METHODS: Out of a total of 6540 children evaluated at the outpatient clinics of paediatric neurology over 2 years and who underwent complete blood count and thyroid function tests, 432 were found to have anaemia. Within this group, we identified 42 children without an underlying specific neurological aetiology who exhibited normo- or macrocytic anaemia, normal TSH levels, fT3 levels in the upper half of the normal range or high, and fT4 levels in the lower half of the normal range or low. We excluded one patient who had already been diagnosed with RTH-α and nine patients could not be reached. Subsequently, clinical evaluation, biochemical assessment, and THRA sequencing analysis were conducted on 32 children. The findings were compared with those of the known RTH-α patients in our unit. RESULTS: The median age of the patients was 5.7 (5.1-7.4) years, and 22 of them were males (69%). The main reasons for assessment in paediatric neurology clinics were autism spectrum disorder (n = 12, 38%), epilepsy (n = 11, 34%), and delay in developmental stages (n = 8, 25%). Constipation was present in five of the cases (16%), while the closure of the anterior fontanelle and tooth eruption were delayed in two cases (6%) and one case (3%), respectively. The median length/height and weight standard deviation (SD) scores were 0.3 [(-0.8)-(1.1)] and -0.1 [(-0.8)-(0.3)], respectively. The median fT3, fT4, and TSH levels were 4.6 (4.2-5.0) pg/mL, 0.9 (0.8-1.0) ng/dL, and 2.2 (1.8-3.1) uIU/mL, respectively. Thirteen of the patients (41%) had high fT3 levels, while none of them had low fT4 levels. The normo- or macrocytic anaemia rate was 47% (normocytic/macrocytic, n = 8/7) at the time of reassessment. Serum creatine kinase (CK) was elevated in five patients (16%; one had anaemia). None of the subjects had a pathological variant in THRA. Known RTH-α patients had significantly lower median height SD score, higher rates of delayed tooth eruption and closure of the anterior fontanelle, lower haemoglobin levels, and higher mean corpuscular volume (MCV) and CK levels as compared to those found without RTH-α. CONCLUSIONS: This approach found one known patient with RTH-α but did not reveal any new cases. Notably, normo- or macrocytic anaemia did not persist in nearly half of the screened patients. A screening strategy that takes clinical findings and prominent laboratory features suggestive of RTH-α into account could lower unnecessary genetic analysis of THRA in patients presenting with neurological problems.

Atypical Presentation and Course of ACTH-independent Cushing's Syndrome in Two Families.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare genetic disease mainly associated with Carney complex (CNC), which is caused by germline mutations of the regulatory subunit type 1A (RIα) of the cAMP-dependent protein kinase (PRKAR1A) gene. We report three cases suffering from CNC with unique features in diagnosis and follow-up. All cases had obesity and a cushingoid appearance and exhibited laboratory characteristics of hypercortisolism. However biochemical and radiological examinations initially suggested Cushing's disease in one case . All of the cases were treated surgically; two of them underwent bilateral adrenalectomy at once, one of them had unilateral adrenalectomy at first but required contralateral adrenalectomy after nine months. Contrary to what is usually known regarding PPNAD, the adrenal glands of two cases (case 2 and 3) had a macronodular morphology. Genetic analyses revealed pathogenic variants in PRKAR1A (case 1: c.440+5 G>A, not reported in the literature; cases 2 and 3: c.349G>T, p.V117F). One case developed Hodgkin lymphoma five year after adrenalectomy, this association was not previously reported with CNC. The findings of these families provide important information for a better understanding of the genetic pathogenesis, diagnosis, and clinical management of CNC. Hodgkin lymphoma may be a component of CNC.

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

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

Adverse Events Associated with COVID-19 Vaccination in Adolescents with Endocrinological Disorders: A Cross-Sectional Study

Objective: The aim was to evaluate the adverse events seen after Coronavirus disease-2019 (COVID-19) vaccination in pediatric patients with diagnosed endocrinological problems and to compare them with healthy controls. Methods: In this cross-sectional study, patients aged 12-18 years who attended a single department between January and May 2022 and were followed up for at least six months due to endocrine diseases, and healthy subjects in the same age group, all of whom had received a COVID-19 vaccine [BNT162b2 mRNA or inactivated vaccine] were included. Adverse events experienced after the vaccination were evaluated by questionnaire. Results: A total of 160 subjects (85 patients, 75 healthy controls) with a median (25-75p) age of 15.5 (14.1-16.9) years were included. The frequency of adverse events was higher in those vaccinated with the mRNA vaccine compared to the inactivated one after the first dose (p=0.015). The incidence of adverse events observed after the first and second doses of both COVID-19 vaccines was similar in the patient and control groups (p=0.879 and p=0.495, respectively), with local reactions being the most common. The frequency of adverse events was similar among the patients who did or did not receive any endocrinological treatment (p>0.05). The incidence and severity of systemic reactions were similar to those in healthy subjects for both vaccine doses, regardless of the underlying diagnosis, autoimmunity state, or treatment regimen used in patients with endocrine diseases. Conclusion: The incidence and severity of adverse events associated with COVID-19 vaccinations in adolescents with endocrinological disorders were similar to healthy subjects, in the early post-vaccination period.

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

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

The negative impact of levothyroxine treatment on urinary luteinizing hormone measurements in pediatric patients with thyroid disease.

Objectives: Previous studies suggest urinary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements by immunofluorometric assays (IFMA) as noninvasive alternatives to serum assays for puberty assessment. However, these studies excluded patients with other endocrine disorders and those taking medications. Besides, the recent discontinuation of IFMA manufacturing is a concern. We explored the utility of luminometric assays (LIA) for urinary gonadotropins and thyroid-stimulating hormone (TSH) determinations in euthyroid patients with thyroid pathologies. Methods: We used LIA and IFMA assays to measure serum and first-morning-voided (FMV) urine LH, FSH, and TSH concentrations in euthyroid patients with various thyroid disorders. Of the 47 euthyroid patients with normal serum TSH (S-TSH) levels, 14 were receiving levothyroxine therapy. Results: FMV total urinary LH (U-LH) concentrations correlated significantly with those measured in serum using either LIA (r=0.67, P<.001) or IFMA (r=0.83, P=.003) in patients not receiving levothyroxine treatment; however, no significant correlation could be detected in patients receiving levothyroxine regardless of the assay method (for LIA: r=0.50, P=.08 and IFMA r=0.44, P=.15). Urinary TSH (U-TSH) concentrations correlated poorly with those in serum in both the untreated and the treated groups (r=-0.13, P=.49, and r=-0.45, P=.11, respectively). Conclusion: FMV total U-LH determinations by LIA can be used to assess pubertal development in patients with thyroid pathology, provided the euthyroid patient is not on levothyroxine treatment. U-TSH measurements by LIA cannot replace invasive S-TSH measurements at least in patients with normal S-TSH levels. Further research may reveal the utility of U-TSH determinations in patients with elevated S-TSH levels.

Hemoglobin A1C can differentiate subjects with GCK mutations among patients suspected to have MODY.

OBJECTIVES: The aim of this study is to determine the clinical and molecular characteristics enabling differential diagnosis in a group of Turkish children clinically diagnosed with MODY and identify the cut-off value of HbA1c, which can distinguish patients with GCK variants from young-onset type 1 and type 2 diabetes. METHODS: The study included 49 patients from 48 unrelated families who were admitted between 2018 and 2020 with a clinical diagnosis of MODY. Clinical and laboratory characteristics of the patients at the time of the diagnosis were obtained from hospital records. Variant analysis of ten MODY genes was performed using targeted next-generation sequencing (NGS) panel and the variants were classified according to American Collage of Medical Genetics and Genomics (ACMG) Standards and Guidelines recommendations. RESULTS: A total of 14 (28%) pathogenic/likely pathogenic variants were detected among 49 patients. 11 variants in GCK and 3 variants in HNF1A genes were found. We identified four novel variants in GCK gene. Using ROC analysis, we found that best cut-off value of HbA1c at the time of diagnosis for predicting the subjects with a GCK variant among patients suspected to have MODY was 6.95% (sensitivity 90%, specificity 86%, AUC 0.89 [95% CI: 0.783-1]). Most of the cases without GCK variant (33/38 [86%]) had an HbA1c value above this cutoff value. We found that among participants suspected of having MODY, family history, HbA1c at the time of diagnosis, and not using insulin therapy were the most differentiating variables of patients with GCK variants. CONCLUSIONS: Family history, HbA1c at the time of diagnosis, and not receiving insulin therapy were found to be the most distinguishing variables of patients with GCK variants among subjects suspected to have MODY.

Clinical course of primary empty sella in children: a singlecenter experience.

BACKGROUND: Various studies, mainly conducted in adults, have examined the hormonal axis in primary empty sella (PES), and reported various forms of pituitary deficiencies. We report our experience with PES in pediatric patients in terms of pituitary function, associated impairments, and responses to treatment. METHODS: We reviewed 10,560 cranial and 325 pituitary magnetic resonance imagings (MRIs) performed at our university hospital between January 2010 and December 2020 and identified patients with PES. Patients with additional abnormal MRI findings, a history of cranial surgery or radiotherapy, autoimmunity, long-term use of chemotherapeutic or immunosuppressive agents or incomplete diagnostic evaluation were excluded. Clinical, radiological and laboratory evaluations were recorded. RESULTS: The study included 17 patients [9 girls, 8 boys; median age 12.4 years (7.25, 4.3 - 17)]. The median size of the pituitary was 2 mm (0.7, 1.2 - 3). Based on age-dependent pituitary height measurements, fifteen (88%) patients had pituitary gland hypoplasia. Five patients presented with short stature, two had both pubertal delay and short stature, and one had pubertal delay. Nine patients presented with neurological symptoms such as headaches, tinnitus, tics, and dizziness. Five short patients had growth hormone deficiency. None of the patients had hyper- or hypoprolactinemia, adrenal insufficiency, hypothyroidism, or diabetes insipidus. There was statistically no significant association between the size of the pituitary gland and the severity of hypopituitarism (p = 0.42). CONCLUSIONS: The high incidence of pituitary dysfunctions ascertain that this entity should not be considered a normal variant but, should instead be carefully evaluated with appropriate basal and dynamic hormonal testing.

Efficacy of aromatase inhibitor therapy in a case with large cell calcifying Sertoli cell tumour-associated prepubertal gynaecomastia.

OBJECTIVES: Large cell calcifying Sertoli cell tumours (LCCSCTs) are one of the infrequent causes of prepubertal gynaecomastia. Most of these tumours are in the content of Peutz-Jeghers syndrome (PJS) or other familial syndromes (Carney complex). CASE PRESENTATION: Here, we report a long-term follow-up of an 8.5-year-old prepubertal boy with a diagnosis of PJS, who presented with bilateral gynaecomastia, advanced bone age and accelerated growth velocity, and were found to have bilateral multifocal testicular microcalcifications. As the findings were compatible with LCCSCT, anastrozole was initiated. Gynaecomastia completely regressed and growth velocity and pubertal development were appropriate for age during follow-up. Testicular lesions slightly increased in size. After four years of medication, anastrozole was discontinued but was restarted due to the recurrence of gynaecomastia after six months. CONCLUSIONS: Testicular tumour should be investigated in a patient with PJS who presents with prepubertal gynaecomastia. When findings are consistent with LCCSCT, aromatase inhibitors may be preferred in the treatment.

Association between thyroid autoimmunity and antidepressant treatment-emergent mania in pediatric mood disorders.

Risk factors associated with antidepressant treatment-emergent mania(ATEM) are poorly characterized in child and adolescent populations. To identify better biomarkers, we aimed to explore whether thyroid autoimmunity is associated with ATEM in pediatric mood disorders. We enrolled two groups of pediatric mood disorders, those with ATEM+ (n = 29) and those with ATEM- controls (n = 31). All diagnoses were made according to structured interviews by the clinicians. Autoimmune thyroiditis (anti-thyroid peroxidase antibodies [TPO-abs] and thyroid function (thyroid-stimulating hormone [TSH] and free thyroxin [FT4]) were assessed. Logistic regression was used to explore the relationship between TPO-abs seroprevalence and ATEM+ while controlling for covariates. Group comparisons showed that the patient with ATEM+ had significantly higher seroprevalence and titer of TPO-abs compared to ATEM- controls. In logistic regression analysis adjusting for age, gender, Tanner stage, body mass index, antipsychotic treatments, smoking status and family history of thyroid disorder, the seroprevalence of TPO-abs (>60 U/mL) was significantly associated with ATEM+ (OR = 3.67, 95% confidence interval [CI] = 1.2-11.1, p = 0.022). Our findings demonstrated that seroprevalence and titer of TPO-abs in pediatric mood disorders are associated with ATEM+ status. TPO-abs could potentially serve as a biomarker when assessing the risk of ATEM in the child and adolescent population.

Has the Frequency of Precocious Puberty and Rapidly Progressive Early Puberty Increased in Girls During the COVID-19 Pandemic?

Objective: Early puberty is development of secondary sex characteristics earlier than the expected normal age range. We subjectively observed an increased frequency of early puberty during the Coronavirus disease-2019 (COVID-19) lockdown and aimed to show the clinical, demographic characteristics of the cases and the change in its incidence. Methods: Female patients with central precocious puberty (CPP, n=28) and rapidly progressive early puberty (RPEP, n=61), presenting to our clinic before (January 2019-March 2020) and during the COVID-19 pandemic (April 2020-June 2021) were included. Results: Among 28 CPP cases, six (21%) presented before the pandemic lockdown, whereas 22 (79%) were diagnosed during the COVID-19 pandemic lockdown. While RPEP was seen in 16 (26%) patients before the pandemic, 45 (74%) patients were diagnosed during the lockdown period. Presentation with menarche was seen in 15 RPEP patients; two (13%) were in the prepandemic period and 13 (87%) were in the lockdown period. Chronological age, bone age, bone age to chronological age ratio, height, weight, and body mass index standard deviation scores of patients with RPEP and CPP were similar between the prepandemic and pandemic period. Conclusion: In this cohort, the frequency of CPP and RPP cases were significantly (p<0.001) increased during the COVID-19 pandemic, possibly due to environmental changes.

Atypical comorbidities in a child considered to have type 1 diabetes led to the diagnosis of SLC29A3 spectrum disorder.

INTRODUCTION: SLC29A3 spectrum disorder is an autosomal, recessively inherited, autoinflammatory, multisystem disorder characterized by distinctive cutaneous features, including hyperpigmentation or hypertrichosis, hepatosplenomegaly, hearing loss, cardiac anomalies, hypogonadism, short stature, and insulin-dependent diabetes. CASE PRESENTATION: Herein, we report a 6-year-old boy who presented with features resembling type 1 diabetes mellitus, but his clinical course was complicated by IgA nephropathy, pure red cell aplasia, and recurrent febrile episodes. The patient was tested for the presence of pathogenic variants in 53 genes related to monogenic diabetes and found to be compound heterozygous for two SLC29A3 pathogenic variants (p. Arg386Gln and p. Leu298fs). CONCLUSION: This case demonstrated that SLC29A3 spectrum disorder should be included in the differential diagnosis of diabetes with atypical comorbidities, even when the distinctive dermatological hallmarks of SLC29A3 spectrum disorder are entirely absent.

Initial neutrophil/lymphocyte and lymphocyte/monocyte ratios can predict future insulin need in newly diagnosed type 1 diabetes mellitus.

OBJECTIVES: The exact mechanism of partial clinical remission in type 1 diabetes mellitus (T1DM) has not been elucidated yet. The severity of the inflammation at the time of diagnosis may affect the occurrence or duration of this phase. We aimed to investigate the relationship between hematological inflammatory parameters at the time of diagnosis in T1DM and (i) daily insulin requirement during the follow-up and (ii) the presence of partial clinical remission period, which was determined according to insulin dose-adjusted HbA1c levels. METHODS: A single-center retrospective study was conducted, including children who were diagnosed with T1DM, were positive for at least one autoantibody, and were followed up for one year in our clinic between 2010 and 2020. RESULTS: Sixty-eight patients (55.9% female, 64.7% prepubertal) were included in the study, whose mean age was 8.4 ± 4.2 years. A total of 38 patients (55.9%) had partial clinical remission. None of the initial hematological indices were associated with the occurrence of partial remission. Initial neutrophil/lymphocyte ratio (NLR) and derived-NLR (d-NLR) levels were significantly lower (p=0.011 and 0.033, respectively) and lymphocyte/monocyte ratio (LMR) levels were significantly higher (p=0.005) in patients who showed an insulin requirement of <0.5 IU/kg/day at the 3rd month after diagnosis. CONCLUSIONS: Initial hematological parameters were not found as a predictor of partial clinical remission period in T1DM in children. However, a lower NLR and d-NLR, or a higher LMR at the time of diagnosis can be used as an indicator of a low daily insulin need at the 3rd month of T1DM.

The effect of leisure boredom and A1C level on diabetes eating problems in adolescents with type 1 diabetes.

PURPOSE: Eating out of boredom, the changes in daily routine, physical inactivity and longer exposure to screens have made glycemic control difficult at home during the COVID-19 pandemic among adolescents with Type 1 Diabetes Mellitus. Adolescents with diabetes are at higher risk of developing eating problems than are their healthy peers. The aim of this study is to examine the effects of leisure time boredom and A1C level on eating problems in adolescents with Type 1 Diabetes Mellitus. DESIGN AND METHODS: A descriptive, correlational, and cross-sectional design was used in this study. The study was conducted in Turkey, with the participation of 173 adolescents diagnosed with Type 1 Diabetes Mellitus. Convenience sampling was used to recruit patients from pediatric endocrinology outpatient clinics of hospitals. RESULTS: It was determined that the diabetes eating problems of adolescents with Type 1 Diabetes were mostly affected by the level of leisure time and A1C, respectively. In the overall model, 58% (F = 4119.701, p < .001) of the factors affecting diabetes eating problems could be explained by the level of leisure boredom and A1C level. CONCLUSION: It has been found that the adolescents with diabetes with high A1C levels and who cannot use their leisure time and have boredom are more at risk in terms of diabetes eating problems. PRACTICE IMPLICATIONS: It should be determined how the adolescents with diabetes spend their lesiure time by diabetes health care team, which should be supported to develop leisure time skills. Effective use of leisure time and strategies to cope with boredom should also be included in diabetes education.

Low Complement C1q/TNF-related Protein-13 Levels are Associated with Childhood Obesity But not Binge Eating Disorder

Objective: C1q/tumor necrosis factor-related proteins (CTRPs) are recently described members of the adipokine family. CTRP-13, a new member of this family, has been shown to increase insulin sensitivity and had an anorexigenic effect on food intake in experimental studies. The aim was to investigate serum CTRP-13 levels in children with obesity, and its relationship with other adipokines, metabolic parameters, or binge eating disorder (BED). Methods: A cross-sectional study was conducted with 105 pubertal children attending a single center. Clinical (metabolic syndrome, BED) and biochemical (glucose, insulin, lipids, leptin, adiponectin, CTRP-13 levels) parameters were assessed. Results: Sixty children with obesity [24 males (40%); median age 14.7 (13.0-16.4) years] and 45 healthy controls [15 males (33.3%); median age 15.2 (14.1-16.5) years] were included. Serum adiponectin and CTRP-13 levels were significantly lower in children with obesity than controls (7.1 vs 20.1 µg/mL, p<0.001; 64.7 vs 103.8 ng/mL, p<0.001, respectively). CTRP-13 levels correlated negatively with body mass index (Spearman rho=-0.230, p=0.018) and positively with high-density lipoprotein-cholesterol levels (Spearman rho=0.218, p=0.026). There was no significant difference in serum CTRP-13 concentrations in terms of the presence of metabolic syndrome or BED. Conclusion: Childhood obesity seems to be causing dysregulation in adipokine production and function, including the down-regulation of CTRP-13. The positive correlation between CTRP-13 and HDL-C levels suggested a possible effect of this adipokine on lipid metabolism. Thus CTRP-13 may be a novel biomarker for dyslipidemia in childhood obesity.

Inactivating NHLH2 variants cause idiopathic hypogonadotropic hypogonadism and obesity in humans.

Metabolism has a role in determining the time of pubertal development and fertility. Nonetheless, molecular/cellular pathways linking metabolism/body weight to puberty/reproduction are unknown. The KNDy (Kisspeptin/Neurokinin B/Dynorphin) neurons in the arcuate nucleus of the hypothalamus constitute the GnRH (gonadotropin-releasing hormone) pulse generator. We previously created a mouse model with a whole-body targeted deletion of nescient helix-loop-helix 2 (Nhlh2; N2KO), a class II member of the basic helix-loop-helix family of transcription factors. As this mouse model features pubertal failure and late-onset obesity, we wanted to study whether NHLH2 represents a candidate molecule to link metabolism and puberty in the hypothalamus. Exome sequencing of a large Idiopathic Hypogonadotropic Hypogonadism cohort revealed obese patients with rare sequence variants in NHLH2, which were characterized by in-silico protein analysis, chromatin immunoprecipitation, and luciferase reporter assays. In vitro heterologous expression studies demonstrated that the variant p.R79C impairs Nhlh2 binding to the Mc4r promoter. Furthermore, p.R79C and other variants show impaired transactivation of the human KISS1 promoter. These are the first inactivating human variants that support NHLH2's critical role in human puberty and body weight control. Failure to carry out this function results in the absence of pubertal development and late-onset obesity in humans.

Diagnostic Value of Bilateral Petrosal Sinus Sampling in Children with Cushing Disease: A Multi-center Study

Objective: Although the sensitivity and specificity of bilateral inferior petrosal sinus sampling (BIPSS) were shown to be quite high in adult patients, pediatric studies are limited in number and have conflicting results, since BIPSS is much less commonly performed in children. The aim of this study was to assess the role of BIPSS in the detection and accuracy of lateralization of pituitary adenomas in pediatric patients with Cushing disease (CD) and its possible advantage over other diagnostic methods. Methods: This was a multicenter, nationwide, web-based study. The diagnostic value of BIPSS in 16 patients, aged between four and 16.5 years with a confirmed diagnosis of CD, was evaluated retrospectively. The sensitivity and specificity of BIPSS and magnetic resonance imaging (MRI) were calculated, and compared statistically. Results: Standard tests, except for morning cortisol level, were effective in proving the presence of Cushing syndrome. While MRI findings were consistent with microadenoma in eight cases (50%), CD presence and lateralization was successfully predicted in 14 of 16 patients using BIPSS. BIPSS compared with MRI examination was significantly more accurate, both in pre-stimulation and post-stimulation results (p=0.047 and p=0.041, respectively). BIPSS showed a significantly higher sensitivity (92.8%) than MRI in detecting the pituitary source of adrenocorticotropic hormone secretion. Conclusion: These results suggest that BIPSS is superior to MRI for diagnostic work-up to confirm the diagnosis of CD. Moreover, in line with previous studies, BIPSS was shown to provide better information about adenoma location, which is vital for possible surgical intervention.