OBJECTIVE:Pediatric Graves' disease (PGD) is a rare autoimmune disorder. Predictors of remission after antithyroid drug (ATD) therapy have been described, but their applicability in pediatric populations remains inconsistent. This study aimed to identify clinical and biochemical factors associated with remission in PGD. SUBJECTS AND METHODS:Retrospective observational study of children diagnosed with Graves' disease at a tertiary hospital in Portugal (2001-2021), all initially treated with ATD. Demographic, clinical, and biochemical data at diagnosis, as well as treatment characteristics, were analyzed. The primary outcome was "In Remission". Secondary outcomes included "Remission Experienced" and "Disease Not Active ≥1 Month". Comparative analyses, logistic regression, and receiver operating characteristic (ROC) curves were applied. RESULTS:Among 45,000 pediatric patients, 36 had PGD (prevalence 0.08%). Median age at diagnosis was 13.7 years; 81% were female, and 78% were pubertal. Methimazole was prescribed in 81%. Mean initial treatment duration (ITD) was 35 months, and 47% of patients underwent definitive therapy. At data collection, 18% of patients were in remission. Longer ITD (>24 months) was associated with remission; the optimal cutoff ITD was 51 months. Smaller thyroid volume and TRAb levels at diagnosis correlated with "Disease Not Active ≥1 Month". Thyroid volume ≥2.5-fold the upper limit of normal (ULN) and TRAb ≥7.055-fold the ULN reduced the likelihood of disease inactivity. CONCLUSION:Prolonged ATD therapy, smaller thyroid volume, and lower TRAb levels at diagnosis were associated with favorable outcomes in PGD. The optimal ITD (≥51 months) supports extended ATD therapy. Larger multicenter studies are warranted to confirm these results.

Costello syndrome is a rare genetic disorder associated with developmental delay, short stature, and pubertal delay. However, a few cases of precocious puberty have been reported, reflecting the complex regulation of the hypothalamic-pituitary-gonadal axis affected by Harvey rat sarcoma viral oncogene homolog (HRAS) gene mutations. We present a case of a boy with Costello syndrome, heterozygous for a mutation in the HRAS gene, first seen in a pediatric endocrinology consultation at the age of nine years and seven months with central precocious puberty and short stature (-0.61 SD). The growth rate had accelerated from age seven years and six months. Pubarche and testicular enlargement began at age eight, and by nine years and seven months, the patient had reached Tanner stage V, with a testicular volume of 20 ml. Bone age was estimated to be 13 years. The brain magnetic resonance imaging (MRI) identified a Chiari type I malformation. At nine years and eight months, triptorelin treatment was initiated, leading to a reduction of pubic hair, stabilization of testicular volume, and a stature of -1.64 SD at the age of 13 years. Despite known factors influencing puberty, the precise physiological mechanisms behind its initiation remain unclear. This case provides valuable insights for understanding the genotype-phenotype relationship in Costello syndrome.

Objectives Subclinical hypothyroidism (SCH) is defined by elevated thyroid-stimulating hormone (TSH) levels (>5 mUI/L) and normal total and free thyroxine levels (fT4). There is ongoing debate over whether mild SCH should be treated. This study aims to assess the clinical course of normoponderal pediatric patients with SCH. Methods Retrospective study, involving normoponderal children and adolescents with SCH, followed at the Pediatrics Department of Hospital de Braga, from December 2007 to December 2022. Results We identified 47 children and adolescents with confirmed SCH. No sex predominance was found. The median age at diagnosis was 11 years. Most cases were idiopathic (59.6 %) and diagnosed during puberty (57.5 %). The majority (46.8 %) experienced spontaneous remission, while 38.3 % required levothyroxine (LT) therapy. Discharged patients were followed for a median of 25 months. No significant differences were seen in body mass index z-score, fT4 levels, heart rate, blood pressure, or lipid parameters. Significant differences were found in TSH levels and LT dosage. Thyroid peroxidase antibody (TPOAb) positivity was significantly correlated with SCH's natural history. Although initial TSH levels were not significantly associated with SCH's natural course, they predict treatment need. Individuals with initial TSH levels >6.47 mUI/L were more likely to require therapy. In the third year of follow-up, a significant strong negative correlation was found between TSH levels and high-density lipoprotein cholesterol. Conclusions SCH was self-limiting and benign in most cases. TPOAb positivity was a predictor of SCH's natural history, and the need for treatment was predicted by initial TSH levels.

Ramsay Hunt Syndrome (RHS) arises due to the reactivation of the varicella-zoster virus (VZV) manifesting as peripheral facial paralysis (PFP), periauricular pain, vesicular eruptions in the external auditory canal and ear, and vestibulocochlear dysfunction. Although RHS is uncommon in children, it ranks as the second most prevalent cause of non-traumatic facial paralysis in childhood. Diagnosis hinges on clinical evaluation, and the recommended treatment involves a combination of high-dose corticosteroids and acyclovir. This case study focuses on a 13-year-old adolescent with right ear pain, without fever. Within four hours of admission to the emergency room (ER), the patient developed a vesiculobullous rash in the right auditory canal and exhibited signs of lower motor neuron-type facial paralysis. RHS was considered, prompting the initiation of treatment with acyclovir and prednisolone, resulting in progressive clinical improvement. This underscores the importance of thorough examination and prompt initiation of therapy in suspected cases of RHS. This approach enhances the recovery rate of facial nerve paralysis and positively influences the disease prognosis.

Objectives − This study aims to compare the clinical and analytical presentation of Central precocious puberty (CPP), considering age.Methods − An observational, cross-sectional study was conducted on children diagnosed with CPP at a level III hospital, between January 2002 and April 2022. Clinical, auxological, sociodemographic, laboratory, and imaging parameters were analyzed.Results − Out of the 52 children studied, the majority were girls (N=44). The median age of puberty onset in girls was 6.79 years and the mean age at first consultation of 8.13 years, with a significantly lower age at hospital referral (7.65 years; P=0.045) compared to boys. Idiopathic etiology was predominant in both. In girls, breast development appeared at older mean ages (P=0.009), while pubic hair growth and accelerated growth were associated with younger ages at puberty onset (P=0.021; P=0.018, respectively). Basal and peak levels of gonadotropin hormones were higher in girls, although not statistically significant. In girls, age at puberty onset correlated negatively with standard deviation of body mass index (P=0.023), while age at first consultation correlated positively with bone age (P<0.001), and was associated with younger ages at Gonadotropin-Releasing Hormone stimulation test (P=0.020).Conclusion − This study provides innovative and relevant findings that enhance understanding of CPP presentation according to age, thereby improving clinical management of this condition.

Introduction: Polycystic ovary syndrome (PCOS) is an endocrine disorder that can affect 3% to 11% of adolescents and is associated with the development of reproductive, metabolic, and psychological complications. Diagnosis of PCOS requires at least 2 of 3 criteria: ovulatory dysfunction, hyperandrogenism and polycystic ovaries. The basis of treatment is lifestyle measures (LSM), and pharmacological therapy may involve insulin-sensitizing drugs, anti-androgens and combined oral contraceptives (COC) Our aim was to assess the impact of therapy on the clinical and analytical profile of an adolescent population with PCOS. Methods: In this study were included 84 adolescents with their first appointment between 01/01/2012 and 1/07/2019. The variables analysed were ovulatory dysfunction, clinical and analytical hyperandrogenism, insulin resistance, lipid profile and body mass index (BMI), as well as the therapies used. An analysis of association was performed between treatment and clinical/analytical results. Results: In this cohort, we found 79.8% of ovulatory dysfunction, 100% of clinical/analytical hyperandrogenism, 67.9% of overweight/obesity, 42.9% of clinical insulin resistance and 23.8% of dyslipidaemia. There was regularization of the menstrual cycles in the adolescents who were undergoing pharmacological therapy (p=0.014), especially when using COC (p<0.001) and greater efficacy was associated with longer duration of treatment (p=0.005). However, COC was associated with a worse evolution of the lipid profile and BMI. Treatment directed to hyperandrogenism promoted a significant decrease in the values of dehydroepiandrosterone sulfate (p=0.004). The HOMA-IR evolved favorably with the use of LSM (p=0.026) and metformin (p=0.013). The LSM promoted an improvement in the BMI (p=0.007). Conclusion: The correct characterization of the clinical and analytical criteria of PCOS, as well as a thorough metabolic assessment, allow for the improvement of the therapeutic strategies to be adopted. There is a need to create protocols regarding diagnosis, therapy, and follow-up for adolescents with PCOS.

INTRODUCTION: Type 1 diabetes is a chronic disease characterized by a selective loss of pancreatic ?-cells with a disproportionate recent increase at ages under 5-years old. Its etiology is multifactorial, to which immune factors contribute through pancreatic autoantibodies. Our main aim is to assess whether the type of pancreatic autoantibody influence the clinical symptoms, glycated hemoglobin and glycemia at diagnosis of type 1 diabetes in children diagnosed under ten-years of age.METHODS: Observational, retrospective and analytical study carried out with a total of 95 patients included. We compared two groups (aged ?60 months and >60 months) and each type of autoantibody (positive/negative) regarding demographic, immune, clinical and laboratory characteristics. The autoantibodies studied were islet cell autoantibodies (against cytoplasmic proteins in the ?-cell), antibodies to glutamic acid decarboxylase, anti-insulin and anti-zinc transporter 8. The impact of autoimmunity, glycated hemoglobin, gender and age on clinical and laboratory parameters of these children was analyzed.RESULTS: Children diagnosed over 60 months had a higher glycated hemoglobin value (p=0.005) and this laboratory parameter was the only one that showed an impact on the initial presentation as diabetic ketoacidosis (CI95%: OR=1.66;p=0.001). The value of glycemia at admission showed to be influenced negatively by age (?=--0.25;p=0.022) and positively by glycated hemoglobin (?=0.35;p=0.001). None of the autoantibodies evaluated seemed to interfere in the clinical and laboratory manifestations of type 1 diabetes.CONCLUSION: Demographic, clinical and laboratory characteristics showed no statistically significant differences between two groups of positive/negative pancreatic autoantibodies analyzed. It is crucial to develop further studies in the scope of autoimmunity that allow to structure potential immune phenotypes and assist in the discovery of new therapeutic targets.

Abstract Type 1 pseudohypoaldosteronism (PHA-1) is a rare genetic syndrome of unresponsiveness to aldosterone and presents in the neonatal period with hyperkalemia, hyponatremia and metabolic acidosis. The mortality rate can be high and multidisciplinary team is needed for optimal management and adequate growth and development of these patients. Many genotype-phenotype correlations remain uncertain, and the description of the evolution of cases can increase scientific knowledge about the psychomotor development and severity of the different mutations. We report the follow-up for the last 10 years of a patient, with previously unrecognized genetic findings identified. In addition, we reviewed the literature and compared it with other pediatric cases.

Introduction: Klinefelter syndrome is the most common sexual chromosome disorder in males and the most frequent cause of hypergonadotropic hypogonadism. The clinic is variable and there are no pathognomonic findings. There are several comorbidities associated with Klinefelter syndrome, being neurodevelopment and/or psychosocial disorders the most frequent. The aim of this study is to characterize the clinical manifestations and comorbidities associated with diagnosed cases and to optimize the diagnosis in pediatrics. Methods: Retrospective and descriptive study, including cases of Klinefelter syndrome diagnosed in the pediatric age, and followed at the pediatric endocrinology consultation of Hospital de Braga in the last 15 years. Results: We identified ten subjects with Klinefelter syndrome. The median age at diagnosis, excluding cases of prenatal diagnosis, was 7 years (minimum of 18 months and maximum of 16 years). The reasons for referral to pediatric endocrinology consultation were varied. In 3 cases, prenatal diagnosis was made after amniocentesis. Nine cases presented with a classic karyotype (47,XXY) and one case had arr(X)x2,(Y)y1 in the microarray. The most frequent characteristic on physical examination was small testes (at puberty age or in relation to the pubertal stage), with a mean volume of 6 mL (minimum 4 mL and maximum 15 mL, n=8/9), followed by bilateral cryptorchidism (3/10), gynecomastia (2/10) and micropenis (1/10). Neurodevelopmental and psychosocial disorders (6/10) were the most frequent associated comorbidities, followed by neurological manifestations (2/10), such as essential tremor. Analytically, 71% of patients had normal total testosterone levels and 29% had values below the lower limit for the pubertal stage. Testosterone replacement therapy was instituted in two cases (20%) at 14 and 15 years of age due to incomplete virilization, and no adverse reactions were described. Fertility preservation was not performed. Conclusion: The present analysis reinforces the previous knowledge of clinical and comorbidities associated with Klinefelter syndrome. The phenotypic variability and the small number of cases reinforce the underdiagnosis of Klinefelter syndrome and confirm that only knowledge allows a high index of suspicion for the diagnosis. This study emphasizes the need for a prompt diagnosis and multidisciplinary follow-up in order to minimize the associated morbidity and mortality.

ABSTRACT Objectives: Evaluate the celiac disease (CD) markers, within the scope of its screening, in a pediatric population with diagnosis of type 1 diabetes (T1D) at Hospital de Braga (HB) and determine the prevalence of CD in the sample. Reflect on CD screening algorithm applied in this pediatric population. Subjects and methods: Retrospective observational study with 94 patients diagnosed with T1D at age 10 years or younger, followed up at the HB Outpatient Diabetology Consultation, including those referred from other hospitals. Record of clinical information, IgA anti-transglutaminase and anti-endomysium and HLA DQ2/DQ8 haplotypes. Results: We obtained positive serological test for CD in 4 patients. This test had 100% sensitivity and specificity. The prevalence of CD was 4.3% (n = 4). Positive HLA screening in 84.6% of patients, with both sensitivity and negative predictive value of 100% and specificity of 16.67%. Diagnosis of CD was made on average 3.40 ± 3.32 years after the diagnosis of TD1. All cases of CD registered non-gastrointestinal manifestations, none had gastrointestinal symptoms. Conclusion: This study proved that there is a higher prevalence of CD in pediatric population with TD1, when compared to general population, and clarified the importance of CD screening. Furthermore, it was observed that serological screening for CD antibodies is an excellent screening test and HLA typing, although not the most suitable first line test, can be useful in excluding the possibility of patients with T1D developing CD.

Introduction: The use of rapid-acting insulin analogues in continuous subcutaneous insulin infusion as a treatment for type 1 diabetes is considered effective in improving glycaemic control and decreasing the risk of hypoglycaemia. Currently, the available analogues include aspart (Novorapid (R)), lispro (Humalog (R))and glulisine (Apidra (R)), as well as a new ultra-rapid insulin analogue, faster insulin aspart (Fiasp (R)).Objective was to compare the impact of different rapid-acting insulin analogues (Novorapid (R), Humalog (R),Apidra (R) and Fiasp (R)) used in continuous subcutaneous insulin infusion in the glycaemic control of children diagnosed with type 1 diabetes. Methods: Retrospective study including 98 patients diagnosed with type 1 diabetes at age 10 or younger under continuous subcutaneous insulin infusion treatment at Hospital de Braga's Outpatient Paediatric Endocrinology continuous subcutaneous insulin infusion Center. Results: Regarding the HbA1c values at 3 months, 6 months and 5 years after initiation of continuous subcutaneous insulin infusion, no statistically significant differences were observed between different insulin analogues used (p=0.396, p=0.155 and p=0.518, respectively). The HbA1c values obtained at 12 months and 2 years were significantly higher in Humalog (R) compared to Fiasp (R) (p=0.036 andp=0.019, respectively). At 3 years, the HbA1c value of patients with Humalog (R) was significantly higher than that of patients with Apidra (R) (p=0.019). The follow-up time for patients with Novorapid (R) was significantly longer than for those with Apidra (R) and Fiasp (R) (respectively, p=0.001 and p=0.023). Conclusion: Novorapid (R), Humalog (R) and Apidra (R) have similar efficiency in the glycaemic control of children with type 1 diabetes using continuous subcutaneous insulin infusion. Fiasp (R) may have benefit in the glycaemic control of these children, when compared with Humalog (R). However, it is necessary to conduct further studies, in paediatric age, on the use of this insulin in continuous subcutaneous insulin infusion.

Problem statement: Ramsay Hunt syndrome is characterized by peripheral facial palsy and eruptions in external ear reportedly due to the reactivation of latent varicela zoster virus in the sensory ganglia of facial nerve. Our purpose is to describe a case of this syndrome accompanied by the Neurology Service of Nova Iguacu General Hospital. Approach: A 60-year old female patient sought the emergency room due to a complaint because she was not able to close her left eye, followed by a drift of the labial fold to the right as well as a sensation of "burning eyes" for the last three days. She also referred vertigo and bilateral hypoacusis, more intensely felt on the left side. Results: Physical examination showed a left facial palsy with a vesicular eruption in the left external auditory canal, ear lobe and neck on that side. Her taste sensation was decreased on the anterior 2/3 of the tongue, a negative rinne test, a positive weber test indicating a neurossensorial hearing loss, ataxia in walking, a Romberg sign and an abnormal fukuda pace test, however the CT scan was normal. Conclusion: The diagnosis is basically clinical, in turn, treatment is controversial. In addition to clinical findings, the diagnosis is confirmed by the presence of viral DNA in the involved tissue and vesicular exudate, as assessed by polymerase chain reaction. Ramsay Hunt syndrome involves severe dysfunction, with poorer facial nerve prognosis than in Bell’s palsy. Some studies suggest that treatment with prednisone and acyclovir may improve outcome, although a prospective randomised treatment trial remains to be undertaken.

Introduction: Type 1 diabetes is one of the autoimmune diseases associated with celiac disease. The prevalence of celiac disease in type 1 diabetes patients is ten times higher than in the general population. This study aimed to characterize the predisposition and diagnosis of celiac disease in children with type 1 diabetes diagnosed under 6 years of age. Methods: We conducted a retrospective study of children with type 1 diabetes diagnosed under 6 years. between January 2009 and November 2019. All children were observed at the Pediatric Department of the Hospital de Braga, a reference centre for continuous insulin infusion treatment throughout the Minho region. The following human leukocyte antigen were screened: DR3-DQ2, DR5-DQ7, DR7-DQ2 and DR4-DQ8. Predisposition to celiac disease was assumed in case of positivity for DR3-DQ2 and/or DR4-DQ8 and/or DR7-DQ2 combined with DR5-DQ7. Immunoglobulin A and anti-transglutaminase or anti-endomysium antibody or immunoglobulin G (in case of immunoglobulin A deficiency) assays were performed. Given the suspicion of celiac disease, upper digestive endoscopy with biopsy was performed. Results: Positivity for human leukocyte antigen-DQ2/DQ8 was found in 71% (25/35) of the screened cases and two cases of celiac disease were later diagnosed (classification: Marsh3b). There was a female predominance (72%) in the cases with predisposition to celiac disease but without significant association. Median age was higher in the group with predisposition to celiac disease (47 months versus 42 months, p> 0.05). In this group, 5 cases had personal history of autoimmune thyroiditis and 2 cases had family history of autoimmune disease (autoimmune thyroiditis and celiac disease). Conclusion: The percentage of risk human leukocyte antigen found is lower than that described in literature. Seventy one per cent of the patients screened for human leukocyte antigen had a genetic predisposition and 5,7% (2/35) were diagnosed with celiac disease. There was no celiac disease diagnosis in the human leukocyte antigen negative group.

Introduction: Congenital hypothyroidism is the most common congenital endocrine disease. Late diagnosis and treatment results in mental retardation and irreversible neurological damage. The objective was to characterize patients with congenital hypothyroidism and evaluate clinical outcomes and diagnostic reassessment. Methods: Retrospective and observational study, using data of the clinical processes of patients, currently under follow-up at the pediatric endocrinology unit of a tertiary hospital not considered a reference center. Results: Twenty-two patients with a median age of 7.5 years (minimum 4 months; maximum 17 years) were included. Twelve patients (54.5%) were female. The median TSH measurement at diagnosis was 201.5 mU/mL (minimum 13.4; maximum 934) and the age at the start of treatment was 12.5 days (minimum 7; maximum 285). Only one patient was not identified in the neonatal screening. Ultrasound revealed thyroid dysgenesis in 70% (n=14) and only one patient performed thyroid scintigraphy. Pro-longed jaundice was the most frequent sign at diagnosis. Of the total, 27.3 % (n=6) have associated congenital abnormalities and 18.2% (n=4) have family history of thyroid disease. After a diagnostic reassessment at 3 years old, two patients were reclassified as transient congenital hypothyroidism. None of the patient had growth disorders. Ten patients underwent a formal assessment of psychomo-tor development, and of these, five patients had abnormalities. No association was found between: the presence of signs/symptoms at diagnosis and the initial TSH value (p=0.694) neither with ultrasound findings (p=0.285) and between the initial TSH value and findings on thyroid ultrasound (p=0.706). The presence of abnormalities in psychomotor development did not show any association with the age at which treatment was started (p=0.740) nor with the initial TSH value (p=0.140). Conclusion: In this cohort of patients, the data are mostly consistent with those in the literature. It was possible to achieve the goal of adequate growth. Contrary to that described in other studies, psychomotor changes did not seem to be related to delayed initiation of therapy. They also identified the need for greater uniformity in follow-up.

The prevalence of neonatal hyperthyroidism (HN) due to maternal Graves Disease (GD) ranges from 0.1 to 2.7%. It may occur in pregnant women with the following: active DG, after treatment with radioactive iodine, anti-thyroid or thyroidectomy or with a previous child with hyperthyroidism. The aim of our observational study was to evaluate the follow-up of infants born to mothers with GD at a Tertiary Hospital prior to the implementation of a follow-up protocol. This was a retrospective observational study using data from the medical records of mothers with a diagnosis of GD and their newborns from January 2013 until May 2018. Newborns were divided into two groups: high and low risk for NH according to maternal TRAb, third trimester treatment and signs of fetal hyperthyroidism. We identified 31 newborns, 58% female; 87% high risk. In none of the newborns was umbilical cord blood collected. In the high risk group, 22% had thyroid function evaluation at day-1, one patient presented with hyperthyroidism and 82% were asymptomatic. Considering the cases with an insufficient blood sample for analysis, 9 consultations would have been spared. We found a significant delay in obtaining the high-risk group results which would have spared 10 appointments. A positive correlation was found between age at outpatient clinic discharge and the number of appointments and the maternal TRAb titer. The correct surveillance of pregnancy and newborns with identification of those at high risk is essential to avoid unnecessary consultations and blood analyses that increase parental anxiety and hospital costs. Consequently, a multidisciplinary protocol was created to standardize the approach. La prevalencia del hipertiroidismo neonatal (HN) debido a la enfermedad de Graves (EG) materna varía del 0,1 al 2,7%. Puede ocurrir en mujeres embarazadas con EG activa, después del tratamiento con yodo radioactivo, antitiroideo o tiroidectomía, o en las que ya tienen un hijo con hipertiroidismo. El objetivo de nuestro estudio observacional fue evaluar el seguimiento de los bebés nacidos de madres con EG en un hospital terciario previamente a la implementación del protocolo de seguimiento. Estudio observacional retrospectivo, utilizando datos de los registros médicos de madres con diagnóstico de EG y sus recién nacidos desde enero del 2013 hasta mayo del 2018. Estos se dividieron en dos grupos: alto y bajo riesgo de HN según thyrotropin stimulating receptor antibodies (TRAb) materno, tratamiento del tercer trimestre y signos de hipertiroidismo fetal. Identificamos 31 recién nacidos, 58% niñas; 87,1% de alto riesgo. Ninguno de ellos recolectó sangre del cordón umbilical. En el grupo de alto riesgo, 22% tuvo evaluación de la función tiroidea en el día uno, un paciente presentó hipertiroidismo y 81,5% era asintomático. Considerando los casos en los que la muestra de sangre era insuficiente para el análisis, se habrían ahorrado nueve consultas. Encontramos un retraso significativo en la obtención de los resultados del grupo de alto riesgo, que habría ahorrado 10 citas. Se identificó una correlación positiva entre la edad al alta de la consulta externa y el número de citas y el título de TRAb materno. La vigilancia correcta del embarazo y de los recién nacidos con identificación de las personas de alto riesgo es esencial para evitar consultas y análisis innecesarios que aumentan la ansiedad de los padres y los costos hospitalarios. Fue posible elaborar un protocolo multidisciplinario para estandarizar el enfoque.

Gonadal dysgenesis (GD) is a disorder of sexual development (DSD) characterized by defective or incomplete formation of the gonads (ovary or testis) due to either structural or numerical modifications of the sex chromosomes or due to mutations in the genes responsible for gonadal development. Two cases of unrelated phenotypically female patients are presented, a complete GD and a partial GD. Both cases were diagnosed with premalignant lesions at a prepubertal age. Even at very young ages there is a high tumor risk, which reiterates the importance of early diagnosis of suspected cases, in order to better characterize and guide this patients. To prevent the development of malignancy, a gonadectomy is recommended, as close as possible to the diagnosis.