Early Diagnosis of 46,XX Testicular Difference of Sexual Development: Unusual Presentation with Increased Nuchal Translucency.

INTRODUCTION: 46,XX testicular disorder of sexual development (DSD) may present prenatally as a mismatch between phenotype and karyotype. Enlarged nuchal translucency is an abnormal sign of many disorders. We present a first trimester fetus with increased nuchal translucency that was later determined to be a 46,XX testicular DSD. CASE PRESENTATION: A first-trimester pregnancy ultrasound revealed enlarged nuchal translucency. Chorionic villous sampling documented a 46,XX karyotype. Subsequent ultrasounds identified male external genitalia. FISH analysis documented a SRY gene translocation. At birth, the infant had normal male internal and external genitalia. CONCLUSIONS: 46,XX testicular DSD may present in the first trimester with an enlarged nuchal translucency.

Rare Coexistence of Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency and Turner Syndrome: A Case Report and Brief Literature Review

The coexistence of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and Turner syndrome (TS) is rare. We report on a 6-year-old Portuguese girl with mosaic TS [45,XO(39)/47,XXX(21)] presenting with premature pubarche at the age of 5 years. Laboratory findings showed elevated 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione and total testosterone, and her 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 with accelerated growth velocity and hydrocortisone at a 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-ups. 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.

Autoimmune Primary Adrenal Insufficiency in Children

Objective: Primary adrenal insufficiency (PAI) is a rare condition in children, and is potentially life-threatening. The most common cause is congenital adrenal hyperplasia, and autoimmune etiology is the most frequent acquired cause in this age group. Symptoms are usually non-specific and, when suspected, investigation should include adrenocorticotropin hormone (ACTH) and morning serum cortisol measurement and, in some cases, a cosyntropin test to confirm the diagnosis. Prompt treatment is essential to prevent an adverse outcome. Methods: We retrospectively collected clinical and laboratory data from adrenal insufficiency due to autoimmune adrenalitis, observed from 2015 to 2020 in a pediatric endocrinology department of a tertiary care hospital. Results: Eight patients were identified, seven males and one female, with age at diagnosis between 14 and 17 years. The symptoms at presentation ranged from non-specific symptoms, such as chronic fatigue and weight loss, to a severe presentation, with altered mental status and seizures. The median duration of symptoms was 4.5 months. The diagnosis was confirmed by serum cortisol and plasma ACTH measurement and all were confirmed to have autoimmune etiology (positive anti-adrenal antibodies). At diagnosis, the most common laboratory abnormality was hyponatremia. All patients were treated with hydrocortisone and fludrocortisone. One patient presented with evidence of type 2 autoimmune polyglandular syndrome. Conclusion: PAI is a rare condition in the pediatric age group. Due to non-specific symptoms, a high index of suspicion is necessary to establish a prompt diagnosis. Once an autoimmune etiology is confirmed, it is important to initiate the appropriate treatment and search for signs and symptoms of other autoimmune diseases during follow-up.

Effect of ultra-rapid insulin aspart on glycemic control in children with type 1 diabetes: the experience of a Portuguese tertiary centre.

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.

Ketoacidosis in new-onset type 1 diabetes: did the severity increase during the COVID-19 pandemic?

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<0.05. 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.

The spectrum of pediatric adrenal insufficiency: insights from 34 years of experience.

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.