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Coexistence of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and Turner Syndrome (TS) is rare. We report a 6-year-old Portuguese girl with mosaic TS [45,XO(39)/47,XXX(21)] presented with premature pubarche at the age of 5 years. Laboratory findings showed elevated 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione and total testosterone, and sex-determining region Y (SRY) was negative. CYP21A2 gene analysis revealed two mutations (c.[844G>T]; [CYP21A2del]), consistent with the non-classical form of CAH. Complete deletion of CYP21A2 allele occurred de novo. At 6 years and 4 months, she presented accelerated growth velocity and hydrocortisone at the dose of 5 mg/m2/day was initiated. This case highlights the need to perform global examinations looking for virilization signs in TS patients follow-up. It also supports the reported genetic combination of TS and CAH. Therefore, CAH should be kept in mind in TS patients with SRY negative and virilization signs, even in the absence of short stature.

Objectives We intend to describe a case of McCune-Albright Syndrome (MAS), a rare disease characterized by fibrous dysplasia (FD), cutaneous hyperpigmentation and hyperfunctioning endocrinopathies (HFE). Case presentation We report the case of a 13-year-old male child who presented with a café-au-lait macule in the lumbosacral region and disabling polyostotic FD, requiring several surgical interventions and bisphosphonates from the age of 3 years (Y) + 9 months (M) due to persistent and severe pain. Hyperthyroidism (HT) became apparent at 5 Y + 1 M with a T3/T4 ratio greater than 20. Treatment with anti-thyroid drugs (ATD) was carried out for 7 Y and there was a progressive improvement in pain complaints 8 M after starting ATD, allowing treatment with pamidronate to be discontinued. Total thyroidectomy was performed at 12 Y + 5 M. Conclusions This is a case of MAS-associated HT that reflects the deleterious effect of thyroid hormone excess on FD, reinforcing the need of having a low threshold for suspicion of HFE that may arise.

Background Postprandial hyperglycemia is one of the biggest challenges in children with type 1 diabetes (T1D). Ultra-fast-acting aspartic insulin (faster aspart) has a quicker onset of action and an earlier maximum activity. The aim of this study is to analyze the impact of faster aspart in metabolic control of pediatric patients with T1D in a “real-world” setting. Methods Retrospective analysis of 60 pediatric patients with T1D who changed their insulin analogue to faster aspart. Anthropometric data, insulin doses, capillary and interstitial glucose recordings and average glycated hemoglobin before and after insulin analogue’s switch were obtained. After all population analyses, patients were analyzed separately according to the type of treatment, multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII), and according to age group. Results Faster aspart significantly improved metabolic control, increasing time in range (TIR) (42 vs.54%, respectively; P = 0.007) and decreasing time above range (TAR) (52 vs.40%, respectively; P = 0.009), without an increased time in hypoglycemia (7% before and after faster aspart’s introduction; P = 0.933). This was reassured in the adolescent years (n = 45), with an increase in TIR (37 vs. 47%, respectively; P = 0.034) and decrease in TAR (51 vs. 45%, respectively; P = 0.022). Patients on CSII (n = 47), also demonstrated an increase in TIR (38 vs. 50%, respectively; P = 0.010). The reduction of A1c was not statistically significant. Conclusion Although the advantage of faster aspart had already been demonstrated in pediatric patients under MDI, “real-world” studies, including patients under CSII, are still lacking. This study highlights the important impact of faster aspart on metabolic control in children with T1D, particularly among adolescents under CSII.

While data on the efficacy and safety of continuous glucose monitoring (CGM) exist across a broad age spectrum, it is limited in very young children with type 1 diabetes (T1D). We aimed to assess real-world data in this high-risk population, focusing on glycemic variability and metrics beyond HbA1c. A 12-month multi-national, prospective, observational, registry-based cohort study in children with T1D aged 1-7 years compared glucose control using real-time CGM and using fingerstick blood glucose monitoring (BGM) alone. The prespecified primary endpoint was a difference in coefficient of variation (CV) between the CGM users and BGM-only cohort. Among 227 individuals using insulin pumps (42% female, age 5.3 years), 175 were CGM and 52 were BGM-only users. The median (IQR) CV was 39.1% (36.6-41.9) among CGM and 46.8% (42.3-51.2) among BGM-only users (P

Objectives Since the beginning of the COVID-19 pandemic, there has been a consistent decrease in the number of admissions to the emergency department, leading to a delay in the diagnosis of several pathologies. The time from onset of symptoms to the diagnosis of Type 1 diabetes is highly variable. This treatment delay can lead to the appearance of ketoacidosis. Methods Retrospective study of inaugural Type 1 diabetes cases, from March 2016 to March 2021. The pandemic group was considered between March 2020 to March 2021, and the remaining period was considered as pre-pandemic. Clinical variables were analysed: duration of symptoms, weight loss and value of ketonemia and glycated haemoglobin on admission. The mean differences were considered statistically significant at p Results 103 inaugural episodes of Type 1 diabetes were registered. The pandemic group had a lower mean age when compared to pre-pandemic group, and 51.7% of the episodes had ketoacidosis with a higher relative risk of ketoacidosis and severe ketoacidosis, when compared the pandemic with pre-pandemic group, there was a longer symptom evolution time (34 vs. 20 days), greater weight loss occurred (9.5% vs. 6.3%), the pH and HCO3 − values were lower (7.30 vs. 7.36 and 16.43 vs. 20.71 mmol/L respectively) and ketonemia was higher (5.9 vs. 2.3 mmol/L). Conclusions The COVID-19 pandemic caused a delay in the diagnosis of Type 1 diabetes, greater length of disease, greater weight loss, higher ketonemia and lower pH and HCO3 −. There was greater ketoacidosis relative risk in pandemic group when compared to pre-pandemic group.

Background Adrenal insufficiency (AI) is a life-threatening disease characterized by deficient production of glucocorticoids and/or mineralocorticoids. It is caused by primary or secondary/tertiary adrenal failure. Prompt diagnosis and management are essential and may even be life-saving. Methods We retrospectively collected clinical, laboratory and radiological data from AI patients observed over 34 years (1984–2017) in a pediatric endocrinology department of a tertiary care hospital. Results Seventy AI patients were identified: 59% with primary adrenal insufficiency (PAI) and 41% with central adrenal insufficiency (CAI). PAI patients were diagnosed at 1.5 ± 4.4 years and followed for 11.6 ± 6.2 years; 85% had classical congenital adrenal hyperplasia (CAH) and 7% had autoimmune PAI. At presentation, 73% had hyponatremia and more than half had mucocutaneous hyperpigmentation, asthenia, anorexia, weight loss, nausea and vomiting. All the patients were treated with hydrocortisone and 90% were also on fludrocortisone. Regarding CAI patients, they were diagnosed at 5.4 ± 5.0 years and they were followed for 9.6 ± 6.4 years; craniopharyngioma was present in 31% of the cases and 14% had pituitary hypoplasia. Besides corticotropin, thyrotropin (93%), growth hormone (63%) and antidiuretic hormone (52%) were the most common hormone insufficiencies. The most frequent manifestations were hypoglycemia (34.5%), nausea/vomiting (27.6%) and infectious diseases (27.6%); all the patients were treated with hydrocortisone. Conclusions Despite medical advances, the diagnosis and management of AI remains a challenge, particularly in the pediatric population. Raising awareness and knowledge in medical teams and population about the disease is of crucial importance to improve clinical outcomes and to reduce disease morbidity/mortality.

Objective: To present a case of bilateral gynecomastia in a prepubertal boy with autism spectrum disorder, diagnosed with myotonic dystrophy type 1. Case description: A 12-year-old boy with autism spectrum disorder presented at a follow-up visit with bilateral breast growth. There was a family history of gynecomastia, cataracts at a young age, puberty delay, and myotonic dystrophy type 1. The physical examination showed that he had bilateral gynecomastia with external genitalia Tanner stage 1. Neurologic examination was regular, without demonstrable myotonia. The analytical study revealed increased estradiol levels and estradiol/testosterone ratio. After excluding endocrine diseases, the molecular study of the dystrophia myotonica protein kinase gene confirmed the diagnosis of myotonic dystrophy type 1. Comments: A diagnosis of prepubertal gynecomastia should include an investigation for possible underlying diseases. This case report highlights the importance of considering the diagnosis of myotonic dystrophy type 1 in the presence of endocrine and neurodevelopmental manifestations. RESUMO Objetivo: Apresentar o caso de um adolescente pré-púbere com ginecomastia bilateral e transtorno do espectro autista, diagnosticado com distrofia miotônica tipo 1. Descrição do caso: Adolescente do sexo masculino de 12 anos, com transtorno do espectro autista, observado em consulta de seguimento por crescimento mamário bilateral. O paciente tinha antecedentes familiares de ginecomastia, catarata em idade jovem, atraso pubertário e distrofia miotônica tipo 1. À observação física, apresentava ginecomastia bilateral estádio 1 de Tanner. O exame neurológico era normal, sem miotonia aparente. O estudo analítico mostrou níveis elevados de estradiol e da relação estradiol/testosterona. Após exclusão de causas endócrinas, o estudo molecular do gene DMPK confirmou o diagnóstico de distrofia miotônica tipo 1. Comentários: Perante um quadro de ginecomastia pré-púbere, deve-se excluir doenças subjacentes. Este caso reforça a importância de considerar o diagnóstico de distrofia miotônica tipo 1 na presença de manifestações endócrinas e do neurodesenvolvimento.

Introduction: Hypoparathyroidism is characterized by low or inappropriately normal PTH production, hypocalcemia and hyperphosphatemia. Autosomal dominant hypocalcemia (ADH) type 1 is one of the genetic etiologies of this, caused by heterozygous activating mutations in the CASR gene. Some individuals fail to meet treatment goals despite standard therapy. Clinical Case: A 13-year-old male patient was admitted in the emergency department due to syncope during physical activity. There was no reference to seizures or other complaints. Standard screening for metabolic diseases revealed no changes at the 7th day of life and family history was unremarkable. There was a history of febrile seizures up to 5 years of age with several hospitalizations for diagnosis investigation that were inconclusive. Physical examination showed a positive Chvostek signal, without other changes. A basic workup revealed hypocalcemia 1.67mmol/L (NR: 2.19-2.66), hyperphosphatemia 3.06mmol/L (NR: 0.95-1.75), hypomagnesemia 0.62mmol/L (NR: 0.7-1.0), low 25Hydroxyvitamin D 8.7ng/mL (NR: >30ng/mL) and inappropriately low PTH 4.0pg/mL (NR: 16.0-87.0). Cranial computed tomography scan showed bilateral calcifications of the basal ganglia. Dual-energy x-ray absorptiometry revealed bone mineral density z-scores increased 15% in spine lumbar and decreased 7% in left femur. Cardiac ultrasound and electrocardiography were normal. The patient started therapy with intravenous calcium gluconate. During this treatment, he developed significant calcification of the peripheral veins at the site of administration, leading to intravenous therapy suspension. The dose of oral calcium, calcitriol and magnesium was gradually increased and sevelamer started to control hyperphosphatemia. Despite the optimization, the patient maintained hypocalcemia refractory to standard therapy. As a last resource strategy in therapeutic optimization, the patient started on rhPTH (1-34). Ever since, the patient has been clinically asymptomatic with biochemical stability and with a reasonable quality of life. At age 18, renal ultrasound revealed diffuse medullary nephrocalcinosis. The genetic testing revealed a novel variant c.368T>C p.(Leu123Ser) likely pathogenic in heterozygosity in the CASR gene, suggesting the diagnosis of ADH type 1. The patient′s mother did not give her consent for genetic study and patient’s father had already died with a diagnosis of acute leukemia. Conclusion: This case can be explained by the presence of a likely pathogenic variant in heterozygosity in the CASR gene that has been described in the medical literature that has not been identified in gnomAD population database, suggesting the diagnosis of ADH type 1. rhPTH (1-34) may be a treatment option for those individuals who are not well controlled on standard therapy, but long-term follow-up studies are needed to reinforce its safety.

Background Autosomal recessive axonal neuropathy with neuromyotonia is a recently described entity associated to the HINT1 gene, encoding histidine triad nucleotide-binding protein 1. Patient The authors report a Portuguese 16-year-old girl of Roma ethnicity, descendant of consanguineous parents, with progressive distal muscular atrophy and weakness, beginning at age 6. After several years of extensive investigation with inconclusive results, clinical myotonia was identified. Electrophysiologic studies revealed neuromyotonia associated with a severe chronic predominantly motor axonal neuropathy and homozygous mutation (c.334 C > A, p.H112 N) in HINT1 was detected. Conclusion This report emphasizes the late onset of clinical myotonia essential to the diagnosis.

Limbic encephalitis is a rare neurological disorder that may be difficult to recognize. Clinical features include memory impairment, temporal lobe seizures and affective disturbance. We report the case of a 10-year-old girl with type 1 diabetes mellitus that presented with seizures, depressed mood and memory changes. The diagnosis of glutamic acid decarboxylase 65 (GAD65) mediated limbic encephalitis relied on cerebral magnetic resonance imaging lesions and high serological and cerebrospinal fluid GAD65-antibodies titers. High-dose steroidal therapy was started with clinical improvement. Relapse led to a second high-dose steroid treatment followed by rituximab with remission. A correlation between serum GAD65-antibodies levels and symptoms was found, demonstrating GAD65-antibodies titers may be useful for clinical follow-up and immunotherapy guidance. This report raises awareness of this serious neurological condition that may be associated with type 1 diabetes, underlining the importance of an early diagnosis and prompt treatment for a better prognosis.

Summary Alternating between hyper- and hypo-thyroidism may be explained by the simultaneous presence of both types of TSH receptor autoantibodies (TRAbs) – thyroid stimulating autoantibodies (TSAbs) and TSH blocking autoantibodies (TBAbs). It is a very rare condition, particulary in the pediatric age. The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time. Many mechanisms may be involved in fluctuating thyroid function: hormonal supplementation, antithyroid drugs and levels of TSAbs and TBAbs. Frequent dose adjustments are needed in order to achieve euthyroidism. A definitive therapy may be necessary to avoid switches in thyroid function and frequent need of therapeutic changes. We describe an immune-mediated case of oscillating thyroid function in a 13-year-old adolescent. After a short period of levothyroxine treatment, the patient switched to a hyperthyroid state that was only controlled by adding an antithyroid drug. Learning points Autoimmune alternating hypo- and hyper-thyroidism is a highly uncommon condition in the pediatric age. It may be due to the simultaneous presence of both TSAbs and TBAbs, whose activity may be estimated in vitro through bioassays. The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time. The management of this condition is challenging, and three therapeutic options could be considered: I-131 ablation, thyroidectomy or pharmacological treatment (single or double therapy). Therapeutic decisions should be taken according to clinical manifestations and thyroid function tests, independent of the bioassays results. A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment. A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment.