Band 34, Heft 11

Suppression of menstruation and/or ovarian function in adolescent girls may be desired for a variety of reasons. Numerous medical options exist. The choice of the appropriate modality for an individual patient depends on several factors based on differences in the efficacy of achieving menstrual suppression as well as in their side effect profiles. Adolescence is also a period of bone mass accrual in girls, and several of these modalities may negatively influence peak bone mass. This review focuses on the efficacy of achieving menstrual suppression and the effect on bone health of the various options through an overview of the current literature and also highlights areas in need of further research.

Objectives Longer-acting gonadotropin-releasing hormone analogs (GnRHa) have been widely used for central precocious puberty (CPP) treatment. However, the follow-up of patients after this treatment are still scarce. Our aim was to describe anthropometric, metabolic, and reproductive follow-up of CPP patients after treatment with leuprorelin acetate 3-month depot (11.25 mg). Methods Twenty-two female patients with idiopathic CPP were treated with leuprorelin acetate 3-month depot (11.25 mg). Their medical records were retrospectively evaluated regarding clinical, hormonal, and imaging aspects before, during, and after GnRHa treatment until adult height (AH). Results At the diagnosis of CPP, the mean chronological age (CA) was 8.2 ± 1.13 year, and mean bone age (BA) was 10.4 ± 1.4 year. Mean height SDS at the start and the end of GnRHa treatment was 1.6 ± 0.8 and 1.3 ± 0.9, respectively. The mean duration of GnRHa treatment was 2.8 ± 0.8 year. Mean predicted adult heights (PAH) at the start and the end of GnRH treatment was 153.2 ± 8.6 and 164.4 ± 7.3 cm, respectively (p<0.05). The mean AH was 163.2 ± 6.2 cm (mean SDS: 0.1 ± 1). All patients were within their target height (TH) range. There was a decrease in the percentage of overweight and obesity from the diagnosis until AH (39–19% p>0.05). At the AH, the insulin resistance and high LDL levels were identified in 3/17 patients (17.6%) and 2/21 patients (9.5%), respectively. The mean CA of menarche was 12.2 ± 0.5 years. At the AH, PCOS was diagnosed in one patient (4.8%). Conclusions Long-term anthropometric, metabolic, and reproductive follow-up of patients with CPP treated with longer-acting GnRHa revealed effectivity, safety, and favorable outcomes.

Objectives The aim of this study was to evaluate the resilience of girls with central precocious puberty (CPP) during treatment with a gonadotropin-releasing hormone agonist (GnRHa) and compare these results with their healthy peers. Methods The Connor–Davidson Resilience Scale (CD-RISC) is a self-report scale used to quantify resilience, which is divided into seven subgroups (hardiness, coping, flexibility, purpose, optimism, regulation of emotion and cognition (REC), and self-efficacy). Fifty-one girls with CPP receiving GnRHa treatment and 51 healthy controls were involved in the study. Anthropometric measurements were evaluated and CD-RISC was performed at least six months after the initiation of GnRHa treatment. Results There was no statistically significant difference between the anthropometric evaluations of girls with CPP and the control group. Similarly, the total score and subgroup scores of patients with CPP and the control group showed no statistically significant difference. In the correlation analysis, there was a weak negative correlation between height and flexibility (r =−0.314 p =0.025 ), height SDS and flexibility (r =−0.254 p =0.092 ), height SDS, and purpose (r =−0.285 p =0.058 ). Also, there was a weak negative correlation between REC and weight (r =−0.435 p =0.003 ), REC and weight SDS (r =−0.461 p =0.002 ) , REC and height (r =−0.269 p =0.077 ), REC and height SDS (r =−0.322 p =0.033 ), REC and BMI (r =−0.289 p =0.058 ), and REC and BMI SDS (r =−0.353 p =0.019 ). Conclusions The resilience of girls with CPP treated with GnRHa was found to be similar to their healthy peers. The early diagnosis of the disease and adequate treatment may decrease the discrepancy of somatic changes between girls with CPP and their peers, which may help them to overcome the stress of CPP and long-term treatment.

Objectives There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic–pituitary–gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups. Methods Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group. Results After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group’s basal AMH level; AMH response to GnRH stimulation was not different (p>0.05). Conclusions In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups.

Background Apoptosis antigen 1/FAS receptor (APO1/Fas) signaling in endothelial cells plays a significant role in angiogenesis while increased mean platelet volume (MPV) is an important marker for platelet activation. We investigated the possible correlation between APO1/Fas and both metabolic parameters and platelet activity (indicated by the MPV) in a healthy pediatric population. Methods One hundred and eighty-five children, aged 5–17 years old, were enrolled in the study. The participants were divided into subgroups according to their age and body mass index percentile (BMI%). APO1/Fas was measured by enzyme-linked immunosorbent assay (ELISA) and MPV by the MEK-6410K. Results Eighty-one children (43.8%) had excess weight, which was more prevalent in children ≤9 years of age. Sixty-five children (35.1%) exhibited a predisposition for metabolic syndrome. A negative correlation was found between APO1/Fas and predisposing factors for metabolic syndrome: Glucose, cholesterol, uric acid, low-density lipoprotein (LDL), and triglycerides. In contrast, a positive correlation was found between APO1/Fas and C-reactive protein (CRP). Receiver operating characteristic (ROC) analysis showed a predisposition to metabolic syndrome when APO1/Fas was <78.46 pg/mL. A negative correlation was also observed between APO1/Fas and MPV. MPV was also positively correlated with predisposing factors for metabolic syndrome: BMI%, glucose, cholesterol, uric acid, LDL, and negatively with high-density lipoprotein. Conclusions APO1/Fas expression is associated with a lower predisposition to metabolic syndrome may be through endothelial homeostasis, the induction of apoptosis of cells involved in atherosclerosis, and platelet activity. It may also enhance CRP-mediated noninflammatory clearance of apoptotic cells. Early monitoring of all the components of metabolic syndrome in overweight children is important in order to prevent metabolic and cardiovascular complications.

Objectives Children with Down syndrome (DS) have a higher risk for obesity. Adiponectin plays a crucial role in obesity-related cardiometabolic comorbidities. The study aimed to explore whether body adiposity indicators, the frequency of metabolic syndrome (MetS) and its components, serum adiponectin and insulin resistance indices as well as the validity of serum adiponectin as a biomarker for MetS are different in prepubertal obese-DS children compared to matched obese-controls. Methods Cross-sectional study included 150 prepubertal children classfied into three groups; obese-DS (n=50), obese-control (n=50) and normal-weight-control (n=50). Participants were evaluated for waist-circumference (WC), body adiposity, serum triglycerides, HDL-C, adiponectin and Homeostasis-Model-Assessment of Insulin-Resistance (HOMA-IR). MetS was defined using modified Adult Treatment Panel III-criteria. Results Obese-DS had significantly higher WC, %body fat, total-fat mass, trunk-fat mass, trunk/appendicular-fat mass ratio, triglycerides, insulin and HOMA-IR and significantly lower HDL-C values compared to obese-control. Higher prevalence of MetS and its components were observed in obese-DS that was evident at younger age. Adiponectin was significantly lower in obese-DS compared with obese-control and in obese-DS children with MetS compared to obesecontrol with MetS. The decrease in adiponectin with increasing grades of obesity was pronounced in obese-DS. Adiponectin exhibited strong correlations with body adiposity, several MetS components and HOMA-IR in obese-DS. Adiponectin performed better as a biomarker for MetS among obese-DS (AUC=0.808) than obese-control (AUC=0.674). Conclusions Prepubertal obese-DS displayed excess body adiposity with pronounced central fat distribution, atherogenic lipid profile and higher insulin resistance compared to matched obese-control. Adiponectin performed better as potential biomarker of MetS in obese-DS than obese-control.

Objectives Iodine deficiency and excess both cause thyroid dysfunction. Few data describe the relationship between iodine status and outcomes of congenital hypothyroidism (CH) in iodine-sufficient areas. We investigated urinary iodine (UI) concentration and its relationship with the clinical course of CH. Methods We reviewed and retrospectively analyzed patients with positive newborn screening (NBS) for CH from January 2012 to June 2019 in Japan, obtaining UI and UI-urine creatinine ratio (UI/Cr), serum TSH, free T 4 , free T 3 and thyroglobulin (Tg) at the first visit, TSH at NBS, levothyroxine (LT4) dose, and subsequent doses. A UI value of 100–299 μg/L was considered adequate. Results Forty-eight patients were included. Median UI and UI/Cr were 325 μg/L and 3,930 µg/gCr, respectively. UI was high (≥300 μg/L) in 26 (54%) and low (≤99 μg/L) in 11 (23%). LT4 was administered to 34 patients. Iodine status was not related to the need for treatment. We found a U-shaped relationship between Tg and UI/Cr. Patients with high Tg (≥400 ng/mL) and abnormal UI levels required significantly lower LT4 doses (≤20 µg/day) at three years of age. Even if they showed severe hypothyroidism initially, they did not need subsequent dose increments. Conclusions Abnormal UI levels with Tg elevation were associated with lower LT4 dose requirements. The evaluation of iodine status and Tg concentrations were considered useful in patients suspected of CH.

Objectives We aimed to compare plasmapheresis and medical apheresis as lipid-lowering therapies in children with familial lipoprotein lipase (LPL) deficiency. Methods The data of 13 patients who were followed up after a diagnosis of LPL deficiency were retrospectively analyzed. Plasma triglyceride, cholesterol, amylase, and lipase values and complications were recorded before and after each patient underwent plasmapheresis or medical apheresis. Results The mean follow-up period of the patients was 99.64 ± 52.92 months in the medical apheresis group and 118 ± 16.97 months in the plasmapheresis group. While the mean triglyceride level before plasmapheresis was 1,875.38 ± 547.46 mg/dL, it was 617 ± 228.28 mg/dL after plasmapheresis. While the mean triglyceride level before medical apheresis was 1,756.86 ± 749.27 mg/dL, it was found to be 623.03 ± 51.36 mg/dL after medical apheresis. Triglyceride levels were decreased by 59.62% with medical apheresis and 65.57% with plasmapheresis. The cost of treatment for medical apheresis was found to be lower compared to plasmapheresis 296.93 ± 29.94 Turkish lira (USD 43.34 ± 4.01) vs. 3,845.42 ± 156.17 Turkish lira (USD 561.37 ± 20.93; p<0.001). Conclusions Although there is no standardized strategy for the acute treatment of hypertriglyceridemia due to LPL deficiency, medical apheresis is a safe and effective treatment with a low risk of side effects. Unlike plasmapheresis, medical apheresis can be performed in any center, which is another important advantage of the procedure.

Objectives Hypotonia, lethargy, eczema, alopecia, conjunctivitis, ataxia, hearing loss, optic atrophy, cognitive retardation, and seizures can occur in patients with biotinidase deficiency, and it is inherited as autosomal recessive. The aim of this study was to evaluate the cases followed up with the diagnosis of biotinidase deficiency in our unit, in terms of clinical, biochemical and genetic analyses. Methods A total of 112 cases followed up in our centre with the diagnosis of biotinidase deficiency between August 2018–September 2020 were included in the study. Data were collected retrospectively. Results A total of 112 cases (55.4% male, mean age: 2.2 ± 2.8 years) diagnosed with biotinidase deficiency were evaluated. Diagnoses were made by newborn screening in 90.2% of the cases, by family screening in 4.5%, and by investigating symptoms in 5.4%. The most frequently (27.5%) detected mutations were c.1330G>C (p.D444H)/c.1330G>C (p.D444H) homozygous mutation, followed by (13.0%) c.1330G>C (p.D444H)/c.470G>A (p.R157H) compound heterozygous mutation, and (13.0%) c.470G>A (p.R157H)/c.470G>A (p.R157H) homozygous mutation. Biotinidase enzyme levels were found to be higher in patients with the p.D444H homozygous mutation than patients with other mutations. Biotin treatment was started in all patients with enzyme deficiency. Conclusions Since the treatment is inexpensive and easily available, it is vital to detect this disease before symptom onset, especially findings related to the central nervous system, hearing and vision loss. In patients diagnosed with enzyme deficiency, the diagnosis should be definitively confirmed by genetic analysis.

Objectives The prevalence of hyperuricemia, a common disorder, has been increasing. Moreover, the association between obesity, serum uric acid levels, and cardiometabolic markers in children is unclear. Therefore, this study aimed to analyze the inter-relationships between these factors in a sample of children aged 6–12 years. Methods We evaluated 764 children and stratified them according to their body mass index (BMI). Blood pressure and uric acid, creatinine, lipid, and glycemic profiles were evaluated, and the estimated glomerular filtration rate (eGFR) and the homeostatic model assessment for insulin resistance (HOMA-IR) index were calculated. Results There was a significant linear trend of increasing systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), total cholesterol, low-density lipoprotein cholesterol (LDLc), uric acid, insulin levels, and HOMA-IR index values corresponding with overweight and obese groups; however, high-density lipoprotein cholesterol (HDLc) levels decreased with increasing obesity. The mean creatinine level and eGFR were similar across all BMI groups. Uric acid levels were significantly correlated with BMI ( r =0.527), waist circumference ( r =0.580), SBP ( r =0.497), DBP ( r =0.362), TG ( r =0.534), total cholesterol ( r =0.416), LDLc ( r =0.286), HDLc ( r =−0.248), insulin ( r =0.613), and HOMA-IR index ( r =0.607). Multiple regression analyses showed that BMI (B=0.071; SE=0.012; p<0.001), TG (B=0.004; SE=0.001; p<0.001), LDLc (B=0.003; SE=0.001; p=0.006), and insulin (B=0.066; SE=0.007; p<0.001) (R 2 =0.460) were significant predictors of increased uric acid levels and explained 46% of the variability in uric acid in these children. Conclusions Our findings suggest that overweight or obese children are more likely to have higher uric acid levels. Moreover, several cardiometabolic risk factors were strongly associated with high uric acid levels.

Objectives The purpose of this study was to review our success rate performing the histrelin implant procedure in clinic without sedation. Methods A retrospective study was performed for histrelin implant procedures done at our institution from 2008 to 2020. Wilcoxon rank-sum test or Fisher’s exact test was utilized to identify significant differences (p<0.05). Results A total of 73 patients underwent 184 histrelin implant procedures from 2008 to 2020. In the past few years, there has been a decrease in procedures for precocious puberty and an increase for gender dysphoria. The majority of procedures were performed in clinic without sedation (82%). The only risk factor associated with requiring sedation was younger age (median 9 vs. 10 years; p<0.003). Complications (i.e. implant fracture or need for counter-incision) were noted in 10 of the procedures (5%). The only risk factor identified for a procedural complication during implant removal/replacement was interval time from insertion (21 vs. 13 months; p<0.01). The only documented wound problem reported was dermatitis in 1 patient (no suture granuloma, dehiscence, or implant extravasation). Conclusions Procedural refinements and distraction therapy have enabled us to perform the majority of procedures in clinic without sedation. In our experience, procedural difficulty and complications appear to increase with prolonged implant duration. Histrelin implantation is increasingly being performed for gender dysphoria.

Objectives To analyze the determinants of UPP consumption among children and adolescents with type 1 diabetes mellitus. Methods Cross-sectional study at a reference hospital for the treatment of diabetes in Rio de Janeiro, Brazil. The sociodemographic, anthropometric, dietary, and clinical factors associated with the percentage of total energy intake (TEI) consumed in the form of UPP were investigated. Food consumption was assessed by 24 h recall and the foods were classified according to the degree of processing as described in the NOVA classification, after which the TEI of each food group was calculated. Multiple linear regression was adopted in the analysis, and associations with p<0.05 were considered significant. Results The study included 120 children and adolescents with a mean age of 11.74 ± 2.88 years, 53.3% female. Body mass index z -score was 0.65 (± 0.89) and 31.7% (n=38) were overweight. The average total energy consumption was 1,756.38 kcal (± 518.38). The mean percentage of TEI from UPP was 24.2% ± 17.9, meaning that 425.59 kcal (± 380.15) of all calories ingested came from such foods. The independent variables associated with the percentage of ultra-processed foods (UPP) in TEI were: per capita household income up to one the minimum wage ( β : −22.03; CI 95% −35.24 to −8.82); and parents/guardians schooling of the up to nine years in formal education ( β : 19.86; CI 95% 8.27–31.45). Conclusions Lower household income and fewer years in formal education seem to determine a preference for UPP over fresh and minimally processed foods. Highlights – Lower household income and education of parents/guardians seem to result in a preference for ultra-processed foods over fresh and minimally processed foods. – Low education may result in reduced adherence to treatment of children and adolescents with T1DM and may cause difficulty in understanding medication use and nutritional treatment focused on healthy eating.

Objectives Children with antibody positive type 1 diabetes mellitus (type 1 diabetes) are at an increased risk of developing celiac disease (CD) which suggests a common autoimmune basis with both high-risk human lymphocyte antigen (HLA) and non-HLA factors playing a role in the pathophysiology. We aim to describe the prevalence, immune profile, and clinical characteristics of children with CD who have type 1 diabetes mellitus in Qatar. Methods All children (aged 0–18 years) attending a regional diabetes clinic with antibody positive type 1 diabetes were screened for CD. Measurement of tissue transglutaminase IgA and IgG as well as anti-endomysial antibody, was done, clinical details about the birth history, family history of diabetes and CD, age of onset, and ethnicity were collected. Results Out of the 1,325 children with antibody positive type 1 diabetes, 54 were identified to have CD on screening and then confirmed on small bowel biopsy. The prevalence of CD in the type 1 diabetes childhood population in Qatar is 4.07%. CD and type 1 diabetes were more prevalent in the Qatari children (n=32) as compared to non-Qatari (n=22) and occurred mostly in the age group 6–10 years. The most common type 1 diabetes antibodies in children with CD were glutamic acid decarboxylase and insulin autoantibody. Twelve subjects were asymptomatic for CD symptoms and picked up only on screening. Conclusions The prevalence of CD in children with type 1 diabetes in Qatar is comparable to reports from around the world. Many children were asymptomatic and thus routine screening is recommended.

Objectives Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterised by isolated glucocorticoid deficiency. Melanocortin receptor 2 (MC2R) mediates the functions of adrenocorticotropic hormone (ACTH) in the adrenal cortex. MC2R accessory protein (MRAP) is a transmembrane protein involved in the trafficking of MC2R to the cell surface. Mutations in MC2R and MRAP genes cause FGD type 1 and 2. In the present case series, we evaluate the clinical characteristics and long-term follow-up of six cases with FGD due to mutations in MC2R and MRAP . Case presentation Data of six cases with FGD (five with mutations in MC2R and one with a mutation in MRAP ) who were being followed at our paediatric endocrine centre was evaluated. Diagnosis of FGD was considered in case of elevated ACTH and inappropriately low cortisol level, and exclusion of other aetiologies. The main presenting complaints were hyperpigmentation and hypoglycaemic convulsion in all cases. During a follow-up period of 26–115 months, one patient with homozygous 560delT mutation in MC2R , one female with G226R mutation in MC2R and one female with IVS3ds+1delG mutation in MRAP had a neurodevelopmental delay (NDD), while the other three patients had normal neurodevelopment. Conclusions FGD patients due to MC2R and MRAP mutations with early diagnosis and compliance to the hydrocortisone therapy had normal neurodevelopment, while delay in diagnosis and poor compliance was associated with severe hypoglycaemic convulsions and subsequent complications NDD.

Objectives To describe the case of a 12-year-old girl with a rare plurihormonal pituitary macroadenoma secreting prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), and alpha subunit (α-SU). Case presentation The patient experienced recurrent headaches and progressing loss of vision in one eye. During the examination, abnormalities such as tall stature, coarse facial features, enlarged feet and hands, tachycardia, hand tremor, hyperhidrosis, galactorrhea, and goiter were observed. Head magnetic resonance imaging (MRI) revealed a solid tumor in the anterior and middle cranial fossa, measuring 80 × 50 × 55 mm. A stereotactic biopsy revealed plurihormonal Pit-1 positive pituitary adenoma secreting PRL, GH, and TSH. A pituitary hyperfunction with PRL, GH, TSH, and α-SU excess was diagnosed. The patient was successfully treated pharmacologically with dopamine agonists and somatostatin analogue, and a decrease of tumor volume (30%) was achieved. Conclusions When neurosurgery is not possible, long-term pharmacological treatment of plurihormonal pituitary macroadenoma can be a safe and relatively effective alternative.

Objectives We report a case of an infant with nephrogenic diabetes insipidus (NDI) diagnosed by the measurement of serum copeptin. There is only one study that previously evaluated the use of copeptin measurement in a pediatric patient. Case presentation We present a 10-month-old child with polyuria–polydipsia syndrome (PPS) and hypernatremia that could not support water restriction due to increased risk of dehydration and worsening of his condition. Therefore, plasma measurement of copeptin allowed the diagnosis of NDI. Conclusions The water deprivation test (WDT) is considered the gold standard for diagnosis in PPS. However, WDT has serious limitations regarding its interpretation. Furthermore, the WDT can cause dehydration and hypernatremia, especially in young children. Therefore, the measurement of plasma copeptin seems to be a promising method to perform an earlier, safer, and accurate investigation of PPS. Up to now, our study is the second to report the usefulness of copeptin in children.

Objectives Hypomagnesemia 1, intestinal (HOMG1) is characterized by neurological symptoms that occur due to hypocalcemia and hypomagnesemia and caused by mutations in the TRPM6 . Most of the identified variants in TRPM6 lead to premature termination: nonsense, frameshift, deletion, and splice site mutations. Case presentation Herein, we report a 1.5 month-old case who presented with convulsion due to hypocalcemia and hypomagnesemia in the early infancy. Sequencing of TRPM6 revealed a novel homozygous synonymous variant [c.2538G > A (p.Thr846Thr)] in the last codon of exon 19, which is most likely to affect the splicing. We report a novel homozygous synonymous variant in the TRPM6 leading to HOMG1, expanding the mutational spectrum. Conclusions Synonymous mutations that were previously considered as harmless should be evaluated at the nucleotide level, keeping in mind that they may affect splicing and cause to the disease.

Objectives Childhood osteoporosis is an uncommon condition that usually develops secondary to underlying disease states. Idiopathic juvenile osteoporosis or early onset osteoporosis is a rare cause of primary osteoporosis in childhood associated with mutations in “bone fragility” genes. Case presentation The index case presented with upper back pain and was detected to have multiple vertebral fractures. Further workup for the cause revealed a homozygous benign mutation in low-density lipoprotein receptor-related protein 5, which was also detected in the mother who remained asymptomatic till presentation. The child was successfully treated with intravenous zoledronate. Conclusions The case report describes the management approach and four-year follow-up of the child.