Insulinaemia and insulin resistance in Caucasian general paediatric population aged 2 to 10 years: Associated risk factors.

BACKGROUND: The aim of this study is to determine values of insulinaemia, homeostasis model assessment (HOMA) index and quantitative insulin sensitivity check index (QUICKI) among a population of prepubertal Caucasian children, to analyse factors associated with insulin resistance (IR), and to study its association with cardiovascular risk factors. MATERIALS AND METHODS: Population-based study conducted on a randomly selected sample of prepubescent Caucasian subjects aged 2.00 to 9.99 years old. Anthropometric measurements, blood pressure, and fasting blood samples were obtained, including fasting glucose, triglycerides, High Density Lipoprotein (HDL)-cholesterol, and insulin. In addition, QUICKI and HOMA indices were calculated. Generalised additive models for location, scale and shape (GAMLSS) was used to calculate centiles curves and multivariate logistic regression analysis to assess factors associated with IR. RESULTS: A total of 654 subjects were included. Mean values obtained for insulinaemia, HOMA index, and QUICKI were 3.74 µIU/mL, 0.73, and 0.44, respectively, in the overall population and 3.32 µIU/mL, 0.64 and 0.46, respectively, in normal weight subjects. The main factor associated with IR was abdominal obesity (odds ratio [OR] 3.38 [95% CI 1.44-7.94] in the subgroup aged 2.00-5.99 years and OR 9.14 [3.42-24.41] for those aged 6.00-9.99 years). An increased risk of hyperglycaemia (P = 0.043), hypertriglyceridaemia (P < .001), and HDL < p10 (P = 0.021) was described among children aged 2.00 to 5.99 years with IR, and among those aged 6.00 to 9.99 years, IR was associated with an increased risk of hypertriglyceridaemia (P < .001). CONCLUSION: Abdominal obesity was the main factor associated with IR. Metabolic changes associated with IR seem to be present from early stages of life, which highlights the importance of the prevention, early diagnosis and treatment of obesity.

Iatrogenic Calcinosis Cutis Successfully Treated with Topical Sodium Thiosulfate.

Calcinosis cutis is a term used to describe a group of disorders in which calcium salt deposits form in the skin and subcutaneous tissue. We report a 6-year-old boy with hypoparathyroidism after thyroidectomy who was admitted to the hospital for severe hypocalcemia being treated with calcium gluconate intravenous infusion through peripheral veins. Within a few days we made a diagnosis of iatrogenic calcinosis cutis and treatment with 10% topical sodium thiosulfate was prescribed; complete resolution of lesions was achieved after 6 months, with no local or systemic adverse effects. Because of the lack of noninvasive alternatives and the good tolerance of the treatment, especially in childhood, we suggest the topical use of this drug as an option for this condition.

Reference values of serum transferrin receptor and sTfR/log ferritin index in healthy adolescents.

Adolescence is a period of increased iron requirements, which impact on iron status. The purpose of this research is to determine the reference intervals for serum transferrin receptor (sTfR) and sTfR/log ferritin index (sTfR-F index) in healthy adolescents, and their relation with iron parameters and erythropoiesis. A total of 253 healthy adolescents without overweight, aged 12 to 16 years, were selected in a cross-sectional study. Hemoglobin, red cell indices, reticulocyte hemoglobin content (rHb), reticulocytes, ferritin, transferrin saturation, erythrocyte protoporphirin, erythropoietin, C-reactive protein, sTfR, and sTfR-F index were measured. Changes in erythropoiesis and iron status in the age interval were observed and analyzed, and linear multiple regression was applied to identify the factors that determine the variability of sTfR and sTfR-F index. Mean values for sTfR and sTfR-F index were 1.32 ± 0.3 mg/L (95% CI, 1.3-1.36) and 0.9 ± 0.25 (95% CI, 0.87-0.93). The reference intervals were 0.84 to 1.97 mg/L and 0.51 to 1.44, respectively. sTfR and sTfR-F index values were significantly higher in boys (1.39 ± 0.3 vs. 1.23 ± 0.26 mg/L, P<0.0001 and 0.93 ± 0.37 vs. 0.86 ± 0.22, P<0.04) and decreased with age (P<0.0001 and 0.04, respectively). No changes were recorded in erythropoietin. Age, sex, pubertal status, and ferritin predicted 24.1% of sTfR variability and age, sex, pubertal status, transferrin saturation, rHb, erythrocytes, and reticulocytes predicted 15% of sTfR-F index variability.

Identification of a novel mutation in FGFR1 gene in mother and daughter with Kallmann syndrome.

OBJECTIVES: Congenital hypogonadotropic hypogonadism combined with anosmia or hyposmia is considered Kallmann syndrome (KS). It is often accompanied by bone defects. CASE PRESENTATION: Here, we report a girl and her mother with KS caused by a novel mutation in the fibroblast growth factor receptor 1 gene (FGFR1). Interestingly, the daughter presented syndactyly and oligodactyly of the feet. CONCLUSIONS: The presence of bone malformations in a KS patient should direct the geneticist towards a search for specific mutations in FGFR1. Our finding contributes to enrich the spectrum of FGFR1 mutations in patients with KS.

Hypoparathyroidism after thyroidectomy: A 20-year experience at a children's hospital.

INTRODUCTION: Hypoparathyroidism (HP) is the most common complication of total thyroidectomy and can be an emergency. OBJECTIVES: To describe the prevalence of HP after total thyroidectomy in children under 14 years of age, the variables related to its appearance and its clinical expression. PATIENTS AND METHODS: Retrospective study at a children's hospital in the last 20 years. HP was defined by the need to supplement calcium after the intervention and was considered permanent if it could not be suspended within 12 months. Fisher's statistical method of comparison of proportions. RESULTS: Thirty-nine children and adolescents (26 females) with an age range of 3.67-14.00 years. In 25 patients, the intervention was prophylactic and in 14 it was therapeutic; 14 suffered accidental excision of some parathyroid gland, but none more than two of them; 12 presented HP, of which 3 were permanent; 5 presented clinical symptoms; 1 of them was an emergency. The frequency of HP was 4/4 when 2 parathyroids were dissected, 2/10 when one was dissected, and 6/25 when none were dissected (p = 0.02). In the prophylactic interventions, it was 6/25 compared to 6/14 in the therapeutic ones (p = 0.29). The three cases of permanent HP were in children under 6 years of age, and it did not occur in any older children (p = 0.09). CONCLUSIONS: HP is a common and sometimes serious complication in children after total thyroidectomy. It can occur, and even be permanent, even if the intervention is prophylactic and parathyroid glands remain in situ. Younger age could be a risk factor.

Clinical practice guidelines for transsexual, transgender and gender diverse minors.

Some people, including minors, have a gender identity that does not correspond to the sex assigned at birth. They are known as trans* people, which is an umbrella term that encompasses transgender, transsexual, and other identities not conforming to the assigned gender. Healthcare units for trans* minors require multidisciplinary working, undertaken by personnel expert in gender identity, enabling, when requested, interventions for the minor and their social-familial environment, in an individualized and flexible way during the gender affirmation path. This service model also includes hormonal treatments tailored as much as possible to the individual's needs, beyond the dichotomic goals of a traditional binary model. This guide addresses the general aspects of professional care of trans* minors and presents the current evidence-based protocol of hormonal treatments for trans* and non-binary adolescents. In addition, it details key aspects related to expected body changes and their possible side effects, as well as prior counselling about fertility preservation.

Hypoparathyroidism after thyroidectomy: A 20-year experience at a children's hospital. / Hipoparatiroidismo postiroidectomía: experiencia de 20 años en un hospital infantil.

INTRODUCTION: Hypoparathyroidism (HP) is the most common complication of total thyroidectomy and can be an emergency. OBJECTIVES: To describe the prevalence of HP after total thyroidectomy in children under 14 years of age, the variables related to its appearance and its clinical expression. PATIENTS AND METHODS: Retrospective study at a children's hospital in the last 20 years. HP was defined by the need to supplement calcium after the intervention and was considered permanent if it could not be suspended within 12 months. Fisher's statistical method of comparison of proportions. RESULTS: Thirty-nine children and adolescents (26 females) with an age range of 3.67 to 14.00 years. In 25 patients, the intervention was prophylactic and in 14 it was therapeutic. Fourteen suffered accidental excision of some parathyroid gland, but none more than t2 of them. Twelve presented HP, of which 3 were permanent; 5 presented clinical symptoms; one of them was an emergency. The frequency of HP was 4/4 when 2 parathyroids were dissected, 2/10 when one was dissected, and 6/25 when none were dissected (P=.02). In the prophylactic interventions, it was 6/25 compared to 6/14 in the therapeutic ones (P=.29). The 3 cases of permanent HP were in children under 6 years of age, and it did not occur in any older children (P=.09). CONCLUSIONS: HP is a common and sometimes serious complication in children after total thyroidectomy. It can occur, and even be permanent, even if the intervention is prophylactic and parathyroid glands remain in situ. Younger age could be a risk factor.

Endocrine manifestations of central nervous system germ cell tumors in children. / Manifestaciones endocrinas de los tumores germinales del sistema nervioso central en niños.

INTRODUCTION: Central nervous system germ cell tumors need to be adequately diagnosed because their treatment is usually effective and they do not always require surgery. The study objectives are to describe the endocrine manifestations of these tumors and to compare the time of their onset to that of the occurrence of neurological and visual changes. PATIENTS AND METHODS: The medical histories of patients under 14 years of age seen at a pediatric endocrinology unit between 2000 and 2018 were reviewed. Wilcoxon and Fisher statistical tests were performed. RESULTS: We found 12patients (10 females) with an age at diagnosis of 9.4±1.7 years and a follow-up time of 5.5±3.0 years, 10with tumors in the sellar region, and each one with a pineal gland and a bifocal tumor. Clinical changes leading to diagnosis were neurological and/or visual in 9patients and hormonal in three. Seven patients diagnosed on the basis of neurological or visual symptoms had previously reported hormonal changes, giving us a total of 10 children at diagnosis (the most common diagnosis was central diabetes insipidus, found in 8). Endocrine symptoms had been present before diagnosis for 25.0±26.2 months, considerably longer than neuro-ophthalmological complaints (2.0±2.1 months, p=0.012). CONCLUSIONS: Almost all intracranial germ cell tumors have associated endocrine manifestations at diagnosis, with central diabetes insipidus the most common. Hormonal symptoms usually appear long before neuro-ophthalmological manifestations. Adequate clinical and endocrinological assessment may allow for an earlier diagnosis of these tumors.

Continuous glucose monitoring in insulin pump treated children.

INTRODUCTION: Insulin pump therapy aims to improve glycemic control and decrease the risk of hypoglycemia in type 1 diabetes. OBJECTIVE: To evaluate interstitial glucose levels and the frequency, duration and symptoms of hypo- and hyperglycemia through the use of a continuous glucose monitoring system (GGMS) in children and adolescents with insulin pump-treated type 1 diabetes, and to determine whether this monitoring method is well tolerated by these patients. PATIENTS AND METHOD: Thirteen patients (4 boys) with insulin pump-treated type 1 diabetes mellitus were monitored. Age was 10.6±3.5 (range, 3.2-13.6) years, diabetes duration was 5.0±3.2 years, pump therapy duration was 12.0±4.6 months, insulin dose was 0.99 ± 0.19 U/kg/day, and last hemoglobin A1c level was 7.1% ± 0.8%. The Minimed CGMS was used for 72 hours. RESULTS: A 3-year-old preschool child did not tolerate the CGMS. Interstitial glucose concentration was 187±40 mg/dl. Hypoglycemia (below 70mg/dl) accounted for 3.6% ± 5.6% of total time, while hyperglycemia (above 180 mg/dl) occurred 47.3% ± 17.4% of the time. No asymptomatic hypoglycemia episodes were detected. CONCLUSIONS: Insulin pump-treated children and adolescents showed an irregular interstitial glucose level and did not achieve normoglycemia. In our patients, adrenergic symptoms of hypoglycemia were preserved and the CGMS was generally well tolerated.

Long-term use of continuous subcutaneous insulin infusion compared with multiple daily injections of glargine in pediatric patients.

BACKGROUND: Studies comparing continuous subcutaneous insulin infusion (CSII) and glargine in pediatric patients are scarce and cover only 1 year follow up. Although short-term results are favorable for CSII, there is no clear evidence whether this therapy leads to a sustained improvement of glycemic control. OBJECTIVE: To evaluate long-term effects and safety of CSII versus multiple daily injections (MDI) of glargine over 2 years of treatment in children and adolescents. PATIENTS AND METHODS: 32 patients (aged 12.5 +/- 2.4 years; 19 females) with intensively treated type 1 diabetes mellitus were eligible. They were divided into two groups, virtually identical at study entry: eight on CSII and 24 on MDI of glargine. Variables at 0, 6, 12, 18 and 24 months were compared between groups by two-sided Mann-Whitney and Fisher tests. RESULTS: No significant differences were found between groups (CSII vs MDI) throughout the study period. At 24 months hemoglobin A1c was 7.70 +/- 0.64% vs 7.54 +/- 0.74% (p = 0.8); body mass index SDS was 0.33 +/- 0.74 vs 0.40 +/- 1.01 (p = 0.9); total daily insulin requirements were 0.95 +/- 0.10 vs 1.05 +/- 0.18 U/kg (p = 0.4), incidence of severe hypoglycemia was 0.00 +/- 0.00 vs 0.04 +/- 0.14 episodes/patient/year (p = 0.8); and incidence of ketoacidosis was 0.20 +/- 0.27 vs 0.04 +/- 0.14 episodes/patient/year (p = 0.2). CONCLUSION: CSII and MDI with glargine are equally effective and safe in pediatric patients at 2-year follow-up.

Multinodular goiter in children: treatment controversies.

BACKGROUND: Multinodular goiter (MG) is very common in adults. MG may occur in children in some exceptional circumstances. The objective of this study was to examine two cases of MG in children who relapsed soon after surgery and to discuss the treatment options in pediatric ages. METHODS: Two girls consulted for euthyroid colloid goiter, uninodular goiter and bilateral MG. They were intervened by hemithyroidectomy and total thyroidectomy, respectively, due to the existence of local symptoms. RESULTS: Goiters reappeared 3 years after intervention in both cases. They already appeared as bilaterally MG, and patients underwent a total thyroidectomy, in one case after 1 year of treatment with levothyroxine (LT4). CONCLUSIONS: MG treatment remains controversial. There is an increasing trend to a more radical surgery decreasing recurrence risk. Treatment with LT4 may be tested but it is rarely effective. Regardless of the therapeutic option, these children should be followed up and they should know about the possibility of goiter regeneration and the need for reintervention.

Guía clínica de atención a menores transexuales, transgéneros y de género diverso / Clinical practice guidelines for transsexual, transgender and gender diverse minors

Algunas personas, también las menores de edad, tienen una identidad de género que no se corresponde con el sexo asignado al nacer. Se les conoce como personas trans*, que es el término paraguas que engloba transgénero, transexual y otras identidades no conformes con el género asignado. Las unidades de asistencia sanitaria a menores trans* requieren un trabajo multidisciplinario, realizado por personal experto en identidad de género, que permita, cuando así lo soliciten, intervenciones para el menor y su entorno sociofamiliar, de forma individualizada y flexible durante el camino de afirmación de género. Este modelo de servicio también incluye tratamientos hormonales adaptados en la medida de lo posible a las necesidades del individuo, más allá de los objetivos dicotómicos de un modelo binario tradicional. Esta guía aborda los aspectos generales de la atención profesional de menores trans* y presenta el protocolo actual basado en evidencia de tratamientos hormonales para adolescentes trans* y no binarios. Además, detalla aspectos clave relacionados con los cambios corporales esperados y sus posibles efectos secundarios, así como el asesoramiento previo sobre preservación de la fertilidad. (AU)

Some people, including minors, have a gender identity that does not correspond to the sex assigned at birth. They are known as trans* people, which is an umbrella term that encompasses transgender, transsexual, and other identities not conforming to the assigned gender. Healthcare units for trans* minors require multidisciplinary working, undertaken by personnel expert in gender identity, enabling, when requested, interventions for the minor and their social–familial environment, in an individualized and flexible way during the gender affirmation path. This service model also includes hormonal treatments tailored as much as possible to the individual's needs, beyond the dichotomic goals of a traditional binary model. This guide addresses the general aspects of professional care of trans* minors and presents the current evidence-based protocol of hormonal treatments for trans* and non-binary adolescents. In addition, it details key aspects related to expected body changes and their possible side effects, as well as prior counselling about fertility preservation. (AU)

Discordant Genotypic Sex and Phenotype Variations in Two Spanish Siblings with 17α-Hydroxylase/17,20-Lyase Deficiency Carrying the Most Prevalent Mutated CYP17A1 Alleles of Brazilian Patients.

17α-hydroxylase/17,20-lyase deficiency is a rare form of congenital adrenal hyperplasia caused by mutations in CYP17A1. Two phenotypic female sisters, aged 17 and 15 years and with 46,XY and 46,XX karyotypes, respectively, presented with primary amenorrhea and absent secondary sexual characteristics. The elder sib also presented with high blood pressure. Both patients had elevated levels of ACTH, gonadotropins, progesterone, corticosterone, and deoxycorticosterone, and reduced levels of estradiol, testosterone, androstenedione, 17-OH-P, DHEA-S, cortisol, aldosterone, and renin activity. The CYP17A1 gene was sequenced, and polymorphic haplotypes were further analyzed in the Spanish family and in Brazilian patients. The 2 sisters were compound heterozygous for p.Arg362Cys and p.Trp406Arg mutations, previously described as the most prevalent mutations in Brazilian families of Spanish (p.Trp406Arg) or Portuguese (p.Arg362Cys) origin. Analysis of polymorphisms in CYP17A1 suggested that the paternal allele with p.Arg362Cys may share a common origin with the Brazilian carriers, while the maternal allele with p.Trp406Arg did not. Hydrocortisone and sex hormone replacement therapy was initiated in both patients. In conclusion, one CYP17A1 mutation (p.Arg362Cys) may share a common ancestry in Brazilian and our present Spanish patients, while p.Trp406Arg may have arisen separately. The elder patient (46,XY) developed a more severe phenotype and a poorer response to estradiol replacement therapy.