The Prevention of Childhood Obesity Is a Priority: The Preliminary Results of the "EpPOI: Education to Prevent Childhood Obesity" Project.

BACKGROUND: The increase in childhood obesity rates represents a serious public health problem. The project "EpPOI: Education to prevent childhood obesity" is aimed at a multidisciplinary approach to raise awareness of the importance of preventing childhood obesity through lifestyle education. METHODS: Two actions by experts were performed: an intervention with children in schools and a meeting for both parents and school staff. Participants completed a questionnaire structured as a Likert scale. RESULTS: The sample size was 96 people, and awareness of the childhood obesity problem as well as the need for obesity prevention was high among respondents. We also found great interest among participants in having more information on pediatric nutrition and physical activity, with a positive correlation with age. Furthermore, the multivariate regression model configured interest in having more information on nutrition and physical activity as an independent and statistically significant predictor of awareness of childhood obesity as a current issue. CONCLUSIONS: The results highlight the need to act on childhood obesity through lifestyle prevention strategies early in life.

Adrenal Cushing's syndrome: diagnosis and management in a 10-year-old boy with Carney complex.

INTRODUCTION: ACTH-independent Cushing's Syndrome (CS) is very rare condition in children. Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of CS, which in most cases occurs in the context of Carney complex (CNC). CNC is an autosomal-dominantly inherited genetic syndrome, usually due to pathogenic variants of the PRKAR1A (regulatory subunit R1A of the protein kinase A) gene. The clinical picture is characterized by spotty skin pigmentation, cardiac, cutaneous and mammary myxomas, melanocytic schwannomas, endocrinopathies and tumours of the endocrine glands (mostly adrenal, pituitary and thyroid). CASE PRESENTATION: A 10-year-old boy first came to our Outpatient clinic due to severe obesity. During the first three months of follow-up the height growth rate was normal, but the response to dietary-behavioural indications was poor in term of weight loss. Later, 10 months after the last evaluation, there was evidence of significant worsening of obesity, growth failure, arterial hypertension and the occurrence of red skin striae at the trunk and root of the limbs. Endocrinological causes of obesity associated with growth failure were investigated. The circadian rhythm of cortisol, ACTH and cortisoluria were suggestive of ACTH-independent hypercortisolaemia. Iatrogenic causes were ruled out. Adrenal ultrasound and computer tomography initially indicated the presence of a nodule or hyperplasia of the medial arm of the left adrenal gland. Conversely, magnetic resonance imaging showed a significant increase in the global dimensions of the adrenals with a bilateral micronodular appearance. Considering the association between ACTH-independent hypercortisolism and PPNAD, a genetic investigation was performed, which found a pathogenic variant of the PRKAR1A gene. Patient started, and well tolerated, therapy with metyrapone during a two-year follow-up. The clinical picture has slightly improved, cortisoluria returned and remains within normal limits, but ACTH suppression persists. CONCLUSION: This is the first report on the clinical and biochemical effects of 2-year medical treatment with metyrapone of PPNAD-related hypercortisolaemia in a paediatric patient with CNC. Currently, there are no established protocols for the management of hypercortisolism in PPNAD and data are scarce especially in the paediatric field. Medical therapies may play a role in reducing the need, at least initially, for bilateral adrenalectomy. However, further studies are needed to clarify this aspect. In cases of CS due to PPNAD in which medical therapy was the initial approach, in the absence of clear clinical, auxological and biochemical improvements, metyrapone may have to be discontinued in favour of another approach, including surgery.

Retrospective Analysis of Fever in Pediatric Age: Our Experience over the Last 5 Years.

BACKGROUND: Fever is one of the most frequent symptoms highlighted during medical assistance. Due to this great impact, our study has the purpose of analyzing the demographic and laboratory characteristics of patients hospitalized in our center and identifying predictive markers to make the differential diagnosis between infectious and non-infectious fever. METHODS: Our population included 220 children, collected from January 2017 to August 2022, hospitalized for continuous fever (4 days or more in duration with at least one temperature peak ≥37.5 °C) and excluded cases of discharge against medical advice and/or transfer to other operating units. Demographic (mean age at the time of admission, frequency of hospitalization, and mean days of hospitalization), laboratory, and instrumental variables were analyzed in order to find correlation with fever etiology. RESULTS: Older age at the time of hospitalization, family history of periodic fever, fever lasting more than 8 days, and longer hospitalization are strongly associated with non-infectious fever, together with anemia, high platelet count, high CRP and ferritin, and hyponatremia at the time of admission. Paracetamol is the preferred antipyretic treatment. Echocardiogram has shown anomalies in patients with infectious fever, while ECG anomalies were detected in non-infectious fever. CONCLUSIONS: Our data underline the importance of predictive markers, such as clinical and laboratory parameters, to differentiate infectious from non-infectious fevers, but further studies are necessary.

Early adiposity rebound: predictors and outcomes.

Adiposity rebound (AR) refers to the second rise of the body mass index (BMI) curve that usually occurs between six and eight years of age. AR timing has a significant impact on patients' health: early AR (EAR), usually before the age of five, is considered to be the earliest indicator of obesity and its related health conditions later in life. Many studies have evaluated factors that can be predictors of EAR, and identified low birth weight and gestational weight gain as novel predictors of EAR, highlighting the role of the intrauterine environment in the kinetics of adiposity. Furthermore, children with breastfeeding longer than 4 months have been found to be less likely to have an EAR, whereas children born to advanced-age mothers, high maternal BMI had a higher risk of having an EAR. Some differences were found in the timing of AR in boys and girls, with girls being more likely to have EAR. The aim of this review is to answer the following three questions: 1) Which are the prenatal and perinatal factors associated with increased risk of EAR? Is gender one of these? 2) Which are the outcomes of EAR in childhood and in adulthood? 3) Which measures can be taken in order to prevent premature AR?

Growth impairment in children with atrophic autoimmune thyroiditis and pituitary hyperplasia.

BACKGROUND: Atrophic autoimmune thyroiditis (AAT) is a rare phenotype of autoimmune thyroiditis (AT) in pediatric age. AAT occurs without thyroid enlargement leading to a delay in its diagnosis. Growth impairment is infrequent in autoimmune thyroiditis, if timely diagnosed. Prolonged severe hypothyroidism is a rare cause of pituitary hyperplasia (PH) in childhood. Loss of thyroxine negative feedback causes a TRH-dependent hyperplasia of pituitary thyrotroph cells resulting in adenohypophysis enlargement. A transdifferentiation of pituitary somatotroph cells into thyrotroph cells could explain growth failure in those patients. METHODS: Twelve patients were retrospectively evaluated at five Italian and Polish Centres of Pediatric Endocrinology for height growth impairment. In all Centres, patients underwent routine clinical, biochemical and radiological evaluations. RESULTS: At the time of first assessment, the 75% of patients presented height growth arrest, while the remaining ones showed growth impairment. The study of thyroid function documented a condition of hypothyroidism, due to AT, in the entire cohort, although all patients had no thyroid enlargement. Thyroid ultrasound showed frankly atrophic or normal gland without goiter. Cerebral MRI documented symmetrical enlargement of the adenohypophysis in all patients and a homogeneous enhancement of the gland after the administration of Gadolinium-DPTA. Replacement therapy with levothyroxine was started and patients underwent close follow-up every 3 months. During the 12 months of follow-up, an improvement in terms of height growth has been observed in 88% of patients who continued the follow-up. Laboratory findings showed normalization of thyroid function and the control brain MRI documented complete regression of PH to a volume within the normal range for age and sex. CONCLUSIONS: This is the largest pediatric cohort with severe autoimmune primary hypothyroidism without goiter, but with pituitary hyperplasia in which significant growth impairment was the most evident presenting sign. AAT phenotype might be correlated with this specific clinical presentation. In youths with growth impairment, hypothyroidism should always be excluded even in the absence of clear clinical signs of dysthyroidism.

Early Assessment of Efficacy and Safety of Biologics in Pediatric Allergic Diseases: Preliminary Results from a Prospective Real-World Study.

BACKGROUND: Despite the increasing interest in biologics for the management of allergic diseases, sparse real-world data are still available in the pediatric population. This study aimed to evaluate the early real-life efficacy and safety of omalizumab for patients with moderate-to-severe asthma and chronic spontaneous urticaria (CSU), and Dupilumab for patients with moderate-to-severe atopic dermatitis (AD). METHODS: A prospective study enrolling children aged 6-18 years was designed to assess the efficacy and safety of biologic drugs at 16 weeks of treatment (T1). The effectiveness was measured using validated questionnaires (ACQ-5 for asthma, UAS7 for CSU, and EASI score for AD). Secondary outcome measures included reductions in inhaled corticosteroid (ICS) dosages, asthma-related hospitalizations/exacerbations, and quality of life (QoL) indicators (iNRS, sNRS, DLQI/cDLQI) for CSU and AD. Safety was expressed according to the descriptions of adverse events provided by EMA and FDA. RESULTS: The study cohort consisted of eighteen children (mean age 12.9 ± 3.4 years). The omalizumab treatment significantly reduced ACQ-5 and UAS7 scores (p = 0.002 and p < 0.001, respectively). In patients with asthma, decreased ICS dosage and hospitalization/exacerbation rates were observed. QoL parameters significantly improved in CSU and AD patients. No severe adverse events were reported for either treatment. CONCLUSIONS: Our findings validate omalizumab and dupilumab as effective and safe therapeutic options for managing moderate-to-severe allergic diseases in children and adolescents.

Growth Hormone Treatment to Final Height in Turner Syndrome: Systematic Review.

PURPOSE: Turner syndrome (TS) is the most common sex chromosomal abnormality found in female subjects. It is a result of a partial or complete loss of one of the X chromosomes. Short stature is a hallmark of TS. Attainment of adult height (AH) within the normal range for height within the general female population represents the usual long-term goal of growth hormone (GH) treatment. The aim of this systematic review was to understand the efficacy of GH therapy on AH of patients with TS. METHODS: The literature review yielded for analysis 9 articles published from 2010 to 2021. Using the data from this literature search, the goal was to answer 5 questions: (1) What is the efficacy of GH on AH of girls with TS?; (2) Is AH influenced by the age at initiation of GH treatment?; (3) What is the optimal dose of GH to improve AH?; (4) Can the timing of either spontaneous or induced puberty influence AH?; and (5) Can the karyotype influence AH in patients with TS? FINDINGS: GH therapy and adequate dose could enable patients with TS to achieve appropriate AH compared with the possible final height without therapy. The greatest increase in height during GH therapy occurs in the prepubertal years, and if therapy is continued to AH, there is no further increase. Furthermore, karyotype did not show a predictive value on height prognosis and did not affect the outcome of GH administration or the height gain in girls with TS. IMPLICATIONS: Even if GH therapy is safe, close monitoring is indicated and recommended. Further evidence is needed to understand what other parameters may influence AH in patients undergoing GH therapy.

Thyroid function in pediatric patients with juvenile idiopathic arthritis.

PURPOSE: Juvenile Idiopathic Arthritis (JIA) is a chronic inflammatory disease characterized by chronic synovitis, sometimes associated with fever, rash, pericarditis and uveitis. Limited data are available concerning autoimmune diseases associated with JIA in childhood. THE AIMS OF OUR STUDY WERE: (a) evaluating the thyroid function in a group of Italian children affected by JIA; (b) identifying which Autoimmune Thyroid Diseases (ATDs) are related to JIA in this population. METHODS: A population of 51 patients with JIA was investigated. Each patient enrolled was evaluated clinically (family history for Autoimmune Diseases (ADs), personal history and physical examination). In the sample were evaluated thyroid function, inflammation's index and anti-thyroid antibodies. RESULTS: The 68.6% (35) of our patients had the oligoarticular form, 27.5% (14) had the polyarticular one, 2% (1) had systemic onset and 2% (1) had undifferentiated arthritis. We focused our attention on the differences between the first two forms. We did not find any difference on the gender prevalence (p > 0.05). A higher presence of anti-TPO antibodies was found in the polyarticular form, with a significant difference with the oligoarticular one (p = 0.032). We researched the anti-hTG antibodies (p > 0.05) and ANA for each group (p > 0.05). We found a significant prevalence of family history for ADs in the polyarticular form (p < 0.05). CONCLUSION: Our findings show the necessity to focus on thyroid function in patients with JIA. Although the oligoarticular form is the most frequent, the polyarticular form shows a higher frequency of thyroid function's alteration. This suggests the need for specific attention in polyarticular form.

A Rare Case of Precocious Puberty in a Child with a Novel GATA-4 Gene Mutation: Implications for Disorders of Sex Development (DSD) and Review of the Literature.

BACKGROUND: Disorders/Differences of sex development (DSD) are often due to disruptions of the genetic programs that regulate gonad development. The GATA-4 gene, located on chromosome 8p23.1, encodes GATA-binding protein 4 (GATA-4), a transcription factor that is essential for cardiac and gonadal development and sexual differentiation. CASE DESCRIPTION: A child with a history of micropenis and cryptorchidism. At 8 years of age, he came under our observation for an increase in sexual pubic hair (pubarche). The laboratory parameters and the GnRH test suggested a central precocious puberty (CPP). Treatment with GnRH analogs was started, and we decided to perform genetic tests for DSD. The NGS genetic investigation showed a novel and heterozygous variant in the GATA-4 gene. DISCUSSION: In the literature, 26 cases with 46,XY DSD due to the GATA4 gene were reported. CONCLUSION: The novel variant in the GATA-4 gene of our patient was not previously associated with DSD. This is the first case of a DSD due to a GATA-4 mutation that develops precocious puberty. Precocious puberty could be associated with DSD and considered a prelude to hypogonadism in some cases.

Serum endocan as a predictive biomarker of cardiovascular risk in obese pediatric patients.

BACKGROUND: Endocan is a soluble dermatan sulfate proteoglycan (50 kDa) secreted by endothelial cells and expressed by dermal, coronary, pulmonary and adipose tissue microvasculature. It plays an important role in the pathogenesis of vascular disorders, inflammatory state, endothelium dysfunction and neoangiogenesis. Aims of the study were to compare fasting serum endocan levels between children with obesity and healthy controls and to investigate the relationships between endocan, body mass index (BMI) and other indices of cardiometabolic risk. METHODS: This single-center, observational, retrospective study included 19 pediatric patients with obesity aged 11.94 ± 0.52 years and 19 lean matched controls. Each patient underwent clinical and auxological examination and laboratory investigations including routine organs function tests and lipid profile. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Fasting endocan serum levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to healthy subjects, serum endocan levels were found to be significantly upraised in children with obesity. Endocan resulted significantly correlated with insulin levels (rho 0.47; p = 0.04); in addition, an association with HOMA-IR values with a trend toward the statistical significance (rho 0.43; p = 0.07) was found. No significant correlation with fasting blood glucose values and lipid serum levels was demonstrated. Although not statistically significant, a correlation between endocan and the presence and grading of liver steatosis on ultrasound (rho 0.51; p = 0.08 and rho 0.51; p = 0.08, respectively) was found. CONCLUSIONS: These findings confirm the association between endothelial damage and insulin resistance in children with obesity. Endocan could be used as a biomarker of early endothelial dysfunction in children with obesity and could be a valid predictor of future cardiovascular risk in adulthood.

Real-World Performance of First- Versus Second-Generation Automated Insulin Delivery Systems on a Pediatric Population With Type 1 Diabetes: A One-Year Observational Study.

BACKGROUND: The aim of this single-center observational study was to assess the real-world performance of first- and second-generation automated insulin delivery (AID) systems in a cohort of children and adolescents with type 1 diabetes over a one-year follow-up. METHODS: Demographic, anamnestic, and clinical data of the study cohort were collected at the start of automatic mode. Data on continuous glucose monitoring metrics, system settings, insulin requirements, and anthropometric parameters at three different time points (start period, six months, 12 months) were retrospectively gathered and statistically analyzed. RESULTS: Fifty-four individuals (55.6% of females) aged 7 to 18 years switching to AID therapy were included in the analysis. Two weeks after starting automatic mode, subjects using advanced hybrid closed-loop (AHCL) showed a better response than hybrid closed-loop (HCL) users in terms of time in range (P = .016), time above range 180 to 250 mg/dl (P = .022), sensor mean glucose (P = .047), and glycemia risk index (P = .012). After 12 months, AHCL group maintained better mean sensor glucose (P = .021) and glucose management indicator (P = .027). Noteworthy, both HCL and AHCL users achieved the recommended clinical targets over the entire study period. The second-generation AID system registered longer time spent with automatic mode activated and fewer shifts to manual mode at every time point (P < .001). CONCLUSIONS: Both systems showed sustained and successful glycemic outcomes in the first year of use. However, AHCL users achieved tighter glycemic targets, without an increase of hypoglycemia risk. Improved usability of the device may also have contributed to optimal glycemic outcomes by ensuring better continuity of the automatic mode activation.

Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies.

Introduction: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a rare monogenic disease determined by biallelic mutations in AIRE gene, which encodes a transcription factor essential for central immune tolerance. Classic diagnosis is determined by the presence of two of the main APECED clinical diseases: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison's disease. Non-endocrine autoimmunity, involving the liver, intestine, eyes, and kidneys, is generally reported in a minority of European patients, while American APECED patients have a higher tendency of developing organ-specific non-endocrine manifestations early in life. This observation led to the revision of the diagnostic criteria to permit earlier diagnosis based on the appearance of one classic triad symptom or one non-classical manifestation at a young age in the presence of IFNωAbs or AIRE mutations (Ferre-Lionakis criteria). Patients and methods: We analyzed the clinical, genetic, and autoantibody (Ab) profiles in a series of 14 pediatric Italian APECED patients with gastrointestinal manifestations (seven male and seven female patients). Ten patients presented hepatitis (APECED-associated hepatitis (APAH)), while seven were affected by constipation, diarrhea, and malabsorption. Four patients had developed APAH before classic triad symptoms. Results: Based on the age of appearance of non-endocrine manifestations including APAH and gastro-enteropathy, the Ferre-Lionakis criteria would have allowed an expedited diagnosis in 11/14 patients. Abs to tryptophan hydroxylase (TPHAb) and hepatic aromatic l-amino acid decarboxylase (AADC) were significantly associated with APECED patients of the present series. Abs to cP4501A2 were detectable in the serum of 4/8 patients with APAH, and Abs to cP4502A6 were detectable in 3/8 patients. AADC Abs tested positive in 5/7 patients, which is indicative of gastrointestinal dysfunction in APECED and TPHAb in 5/7 patients with gastrointestinal dysfunction. IFNAb was significantly associated with the syndrome. Conclusion: Although Ferre-Lionakis expanded criteria applied to the American cohorts of APECED patients would require validation in independent large cohorts of European patients, the results of this study emphasize the importance to evaluate the presence and the age of appearance of APAH and autoimmune enteropathy even in European cohorts for an earlier APECED diagnosis. An earlier APECED diagnosis would also allow the prevention of episodes of life-threatening hypocalcemic seizures and adrenal crisis, which are the main manifestations of undiagnosed APECED.

Prevalence and clinical features of severe diabetic ketoacidosis treated in pediatric intensive care unit: a 5-year monocentric experience.

BACKGROUND: Diabetic ketoacidosis (DKA) is one of the most alarming concerns in the management of type 1 diabetes (T1D) in pediatric age. Prevalence of DKA at the onset of diabetes ranges from 30 to 40%. In selected cases of severe DKA, admission to pediatric intensive care unit (PICU) should be considered. METHODS: This study aims to assess the prevalence of severe DKA treated in PICU in our 5-year monocentric experience. Secondary outcome of the study was to describe the main demographical and clinical features of individuals who required admission to PICU. All clinical data were collected by retrospectively reviewing the electronic medical records of children and adolescents with diabetes hospitalized in our University Hospital from January 2017 to December 2022. RESULTS: During the study period, 103 children and adolescents were newly diagnosed with T1D. Among these, 51.5% presented clinical criteria for DKA and almost 10% needed to be treated in PICU. A higher rate of new T1D diagnoses was observed in 2021, as well as episodes of severe DKA being more frequent than in previous years. Due to severe clinical manifestations of DKA, 10 subjects (9.7%) with T1D onset needed to be treated in PICU. Of these, four children were younger than 5. The great majority came from a low household income and some of them had also immigrant background. The most common complication of DKA was acute kidney injury presented by four children. Other complications were cerebral edema, papilledema and acute esophageal necrosis. A 15-year-old girl had deep vein thrombosis (DVT) that evolved into multiple organ failure leading to death. CONCLUSIONS: Our findings demonstrated that severe DKA is still quite common in children and adolescents at T1D onset, especially in some areas such as Southern Italy. Public awareness campaigns should be increasingly promoted to facilitate the recognition of early symptoms of diabetes and to reduce morbidity and mortality related to DKA.

Mild COVID-19 in an APECED Patient with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and High Titer of Type 1 IFN-Abs: A Case Report.

Autoimmune-Poly-Endocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED), caused by mutations in the Autoimmune Regulator (AIRE) gene, is an autosomal recessive multi-organ autoimmunity syndrome usually defined by high serum titers of type I Interferon Autoantibodies (Type 1 IFN-Abs). These antibodies have recently been found in individuals in the general population who develop life-threatening Coronavirus Disease 2019 (COVID-19), but the significance of pre-existing Type 1 IFN-Abs in APECED patients with COVID-19 remains unclear. Previous reports of COVID-19 outcomes in APECED patients have been divergent, and protective roles have been proposed for female sex, age <26 years, and immunomodulatory medications including intravenous immunoglobulin (IVIg). We report the case of a 30-year-old male APECED patient who experienced a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with mild symptoms of fatigue and headache without respiratory distress and did not require hospitalization. He received a stress dose of hydrocortisone for adrenal insufficiency and continued on his baseline medications, including subcutaneous administration of Immunoglobulins (SCIgs) for chronic inflammatory demyelinating polyneuropathy (CIDP). Mild COVID-19 in a 30-year-old male patient with APECED and pre-existing Type 1 IFN-Abs was unexpected. Younger age and management of autoimmunity may have played a role.

Gastroparesis in Adolescent Patient with Type 1 Diabetes: Severe Presentation of a Rare Pediatric Complication.

Gastroparesis is a long-term complication of diabetes related to autonomic neuropathy. It is clinically characterized by delayed gastric emptying and upper gastrointestinal symptoms including early satiety, postprandial fullness, nausea, vomiting, and abdominal pain. Gastric emptying scintigraphy is the gold standard for the diagnosis as it reveals delayed gastric emptying. Therapeutic strategies include dietary modifications, improvement of glycemic control, and prokinetic drugs. Case descriptions of diabetic gastroparesis in pediatric age are very scarce. We hereby report the case of a 16-year-old adolescent with severe presentation of diabetic gastroparesis. She presented with recurrent episodes of nausea, vomiting and abdominal pain which led progressively to reduced oral intake and weight loss. Her past glycemic control had been quite brittle as demonstrated by several hospitalizations due to diabetic ketoacidosis and recurrent episodes of severe hypoglycemia. After the exclusion of infectious, mechanical, metabolic, and neurological causes of vomiting, a gastric emptying scintigraphy was performed, leading to the diagnosis of gastroparesis. Treatment with metoclopramide was started with progressive relief of symptoms. To improve glycemic control, insulin therapy with advanced hybrid closed loop system was successfully practiced. Pediatricians should seriously consider diabetic gastroparesis in children and adolescents with long-standing, poorly controlled diabetes.

Minipuberty in born small for gestational age infants: A case control prospective pilot study.

PURPOSE: To evaluate minipuberty (MP) in small for gestational age (SGA) infants, both preterm and full-term, during the first year of life. METHODS: 33 SGA healthy newborns (group A), 21 of which full-term (subgroup A1) and 12 preterm (A2) were enrolled. Control group (B) consisted of 27 AGA, 17 full-term (subgroup B1) and 10 preterm (B2) infants. Growth parameters, FSH, LH, and Estradiol (E2) or Testosterone (T) serum levels were monitored at 3, 6, and 12 months. RESULTS: The gonadotropin surge reached greater increase of LH in males at 3 months and FSH in females at 3, 6 and 12 months (p < 0.001). In male infants: T at 3 months was higher in subgroup A2 vs A1(p = 0.001), and correlated negatively with gestational age (GA, p < 0.005), length and weight at birth (p < 0.05); LH was higher in subgroup B2 vs B1 at 6 months (p = 0.003), and in group A vs B at 12 months (p = 0.03). Females displayed higher E2 at 6 months in B2 vs B1 (p < 0.05), negatively correlated with GA and weight gain (p < 0.05); LH at 6 months was increased in A2 vs A1 (p = 0.03). Overall, preterm males displayed higher T at 3 months (p = 0.001), LH at 3, 6 and 12 months (p < 0.05), and LH/FSH ratio at 6 months (p = 0.001). Preterm females exhibited increased LH/FSH ratio at 3 and 6 months (p < 0.05). CONCLUSIONS: Irrespectively of GA, MP occurred with a typical sexual dimorphism and exhibited sex-specific correlations between hormones and perinatal parameters. SGA condition and prematurity seemed to enhance and protract MP over time in both sexes.

Clinical Peculiarities in a Cohort of Patients with Wolfram Syndrome 1.

Wolfram syndrome 1 is a rare, autosomal recessive, neurodegenerative, progressive disorder. Insulin-dependent, non-autoimmune diabetes mellitus and bilateral progressive optic atrophy are both sensitive and specific criteria for clinical diagnosis. The leading cause of death is central respiratory failure resulting from brainstem atrophy. We describe the clinical features of fourteen patients from seven different families followed in our Diabetes Center. The mean age at Wolfram syndrome 1 diagnosis was 12.4 years. Diabetes mellitus was the first clinical manifestation, in all patients. Sensorineural hearing impairment and central diabetes insipidus were present in 85.7% of patients. Other endocrine findings included hypogonadotropic hypogonadism (7.1%), hypergonadotropic hypogonadism (7.1%), and Hashimoto's thyroiditis (21.4%). Neuropsychiatric disorders were detected in 35.7% of patients, and urogenital tract abnormalities were present in 21.4%. Finally, heart diseases were found in 14.2% of patients. Eight patients (57.1%) died at the mean age of 27.3 years. The most common cause of death was respiratory failure which occurred in six patients. The remaining two died due to end-stage renal failure and myocardial infarction. Our data are superimposable with those reported in the literature in terms of mean age of onset, the clinical course of the disease, and causes of death. The frequency of deafness and diabetes insipidus was higher in our patients. The incidence of urogenital diseases was lower although it led to the death of one patient. Long-term follow-up studies including large patient cohorts are necessary to establish potential genotype-phenotype correlation in order to personalize the most suitable clinical approach for each patient.

Spinal cord compression as tumor onset: an unusual case report of Hodgkin lymphoma in a teenager.

BACKGROUND: Spinal cord compression (SCC) is an uncommon, severe complication of Hodgkin lymphoma (HL), occurring in 0.2% of cases at the onset and in 6% during disease progression. We present a teenager with SCC with clinical onset of HL; her pre-existing neurological abnormalities covered the presence of an epidural mass, which could have misled us. CASE PRESENTATION: A 13-year-old girl presented with a three-month history of lower back pain and degrading ability to walk. She suffered from a chronic gait disorder due to her preterm birth. A magnetic resonance imaging of the spine revealed an epidural mass causing collapse of twelfth thoracic vertebra and thus compression and displacement of the spinal cord. Histological examination with immunohistochemical analysis of the epidural mass demonstrated a classic-type Hodgkin lymphoma. Early pathology-specific treatment allowed to avoid urgent surgery, achieve survival and restore of neurological function. CONCLUSIONS: Children and adolescents with back pain and neurological abnormalities should be prioritized to avoid diagnostic delay resulting in potential loss of neurological function. SCC requires a prompt radiological assessment and an expert multidisciplinary management.

Pubertal induction in girls with Turner Syndrome.

Turner Syndrome (TS) is the most common female sex chromosome aneuploidy in females, and patients may present with hypergonadotropic hypogonadism due to gonadal dysgenesis. Timing and modalities of pubertal induction in these patients is still a matter of debate. Aim of this review was to focus on the latest update on pubertal induction in TS. Based on literature data, the following practical approach to this issue is recommended. Pubertal induction should begin between 11 and 12 years of age, starting with low doses of estradiol to preserve height potential. Transdermal 17ß-Estradiol (17ß-E2) could represent the first-choice induction regimen as it is more physiologic compared to an oral regimen and avoids the first-pass mechanism in the liver. In the case of poor compliance, administration of oral 17ß-E2 or ethinyl estradiol could be offered. Incremental dose increases, approximately every 6 months, can contribute to mimic normal pubertal progression until adult dosing is reached over a 2- to 3-year period. Progestin should be added once breakthrough bleeding occurs or after 2 to 3 years of estrogen therapy or if ultrasound shows a mature uterus with thick endometrium. Treatment needs to be individualized and monitored by clinical assessment in relation to patient compliance and satisfaction. Well-designed prospective randomized clinical trials aimed to identify the best estrogen regimen for pubertal induction in TS girls are needed.

Primary Adrenal Insufficiency in Childhood: Data From a Large Nationwide Cohort.

CONTEXT: Primary adrenal insufficiency (PAI) is a rare and potentially life-threatening condition that is poorly characterized in children. OBJECTIVE: To describe causes, presentation, auxological outcome, frequency of adrenal crisis and mortality of a large cohort of children with PAI. PATIENTS AND METHODS: Data from 803 patients from 8 centers of Pediatric Endocrinology were retrospectively collected. RESULTS: The following etiologies were reported: 85% (n = 682) congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD); 3.1% (n = 25) X-linked adrenoleukodystrophy; 3.1% (n = 25) autoimmune polyglandular syndrome type 1; 2.5% (n = 20) autoimmune adrenal insufficiency; 2% (n = 16) adrenal hypoplasia congenital; 1.2% (n = 10) non-21-OHD CAH; 1% (n = 8) rare syndromes; 0.6% (n = 5) familial glucocorticoid deficiency; 0.4% (n = 3) acquired adrenal insufficiency; 9 patients (1%) did not receive diagnosis. Since 21-OHD CAH has been extensively characterized, it was not further reviewed. In 121 patients with a diagnosis other than 21-OHD CAH, the most frequent symptoms at diagnosis were fatigue (67%), hyperpigmentation (50.4%), dehydration (33%), and hypotension (31%). Elevated adrenocorticotropic hormone (96.4%) was the most common laboratory finding followed by hyponatremia (55%), hyperkalemia (32.7%), and hypoglycemia (33.7%). The median age at presentation was 6.5 ± 5.1 years (0.1-17.8 years) and the mean duration of symptoms before diagnosis was 5.6 ± 11.6 months (0-56 months) depending on etiology. Rate of adrenal crisis was 2.7 per 100 patient-years. Three patients died from the underlying disease. Adult height, evaluated in 70 patients, was -0.70 ± 1.20 standard deviation score. CONCLUSIONS: We characterized one of the largest cohorts of children with PAI aiming to improve the knowledge on diagnosis of this rare condition.