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Background: The aim of this multicenter observational real-world study was to investigate glycemic outcomes in children and adolescents with type 1 diabetes over the first 6-month use of MiniMed™ 780G. The secondary objective was to evaluate demographic and clinical factors that may be significantly associated with the achievement of therapeutic goals. Methods: Demographic, anamnestic, and clinical data of study participants were collected at the time of enrollment. Data on ambulatory glucose profile were acquired at 3 and 6 months after activating automatic mode. Aggregated glucose metrics and device settings of the entire study period were analyzed to identify predictors of optimal glycemic control, assessed by the concomitant achievement of time in range (TIR) >70%, coefficient of variation (CV)

The MiniMed™ 670G insulin pump was the first hybrid closed-loop (HCL) system available for clinical use. Data on metabolic outcomes in children, adolescents and young adults over the first 12 months with auto-mode use of this device are available, but no data with longer follow-up have been published. We aimed to assess the metabolic outcomes in children and adolescents using the MiniMed™ 670G for 24 months.

The use of technology offers recognized benefits to persons with diabetes. The aim of this study was to evaluate the organization of healthcare facilities, the composition of the diabetes team, and the use of Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitoring (CGM) in Italy.Diabetes care centers were asked to complete a web survey based on information collected in 2018. Sixty-one pediatric and 243 adult centers participated in the survey, accounting for 507,386 patients, mostly with type 2 diabetes (86.4%). Fifty-three percent of pediatric centers and 11% of adult centers reported a team composed of diabetologists, nurses, and psychologists. Overall, 13,204 patients (2.6%) were using CSII (95% with type 1 diabetes), and 28,936 (5.7%), were using CGM (74% with type 1 diabetes). When stratifying for the type of diabetes, 24% and 40.8% of patients with type 1 were using CSII and CGM, respectively, whereas low use of technology was reported for patients with type 2 and women with gestational diabetes. The percentage of adult and pediatric patients with type 1 diabetes on CSII and CGM was respectively 21% and 32%, and 35% and 57%.The spread of CGM and CSII increased in Italy between 2013 and 2018. However, the percentage of users is still lower than what is expected based on clinical indications for use of technology. The inadequate number of professionals in the diabetes care team and insufficient economic resources are relevant barriers to disseminating technology for diabetes management.

Wolfram syndrome 1 (WS1) is a rare neurodegenerative disease transmitted in an autosomal recessive mode. It is characterized by diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), and sensorineural hearing loss (D) (DIDMOAD). The clinical picture may be complicated by other symptoms, such as urinary tract, endocrinological, psychiatric, and neurological abnormalities. WS1 is caused by mutations in the WFS1 gene located on chromosome 4p16 that encodes a transmembrane protein named wolframin. Many studies have shown that wolframin regulates some mechanisms of ER calcium homeostasis and therefore plays a role in cellular apoptosis. More than 200 mutations are responsible for WS1. However, abnormal phenotypes of WS with or without DM, inherited in an autosomal dominant mode and associated with one or more WFS1 mutations, have been found. Furthermore, recessive Wolfram-like disease without DM has been described. The prognosis of WS1 is poor, and the death occurs prematurely. Although there are no therapies that can slow or stop WS1, a careful clinical monitoring can help patients during the rapid progression of the disease, thus improving their quality of life. In this review, we describe natural history and etiology of WS1 and suggest criteria for a most pertinent approach to the diagnosis and clinical follow up. We also describe the hallmarks of new therapies for WS1.

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Wolfram syndrome 1, a rare autosomal recessive neurodegenerative disease, is caused by mutations in the WFS1 gene. It is characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD), and other clinical manifestations such as urological and neurological disorders. Here we described the case of a patient with an atypical late-onset Wolfram syndrome 1 without DI. Our WS1 patient was a c.1620_1622delGTG (p.Trp540del)/c.124 C > T (p.Arg42*) heterozygous compound. The p.Arg42* nonsense mutation was also found in heterozygosity in his sister and niece, both suffering from psychiatric disorders. The p.Arg42* nonsense mutation has never been found in WS1 and its pathogenicity is unclear so far. Our study underlined the need to study a greater number of WS1 cases in order to better understand the clinical significance of many WFS1 variants.

Background Hepatic glycogenosis is characterized by excessive glycogen accumulation in hepatocytes and represents a complication of poor controlled type 1 diabetes. It can be caused by excessive insulin doses or recurrent ketoacidosis episodes. Mauriac’s syndrome is a rare disease, which includes short stature, growth maturation delay, dyslipidemia, moon facies, protuberant abdomen, hepatomegaly with transaminase elevation. It has become even less common after the emergence of advances on diabetes treatment, but still exists. Recent reports described glycogenosis without the full spectrum of Mauriac’s syndrome in both adults and children with brittle diabetes. Clinical, laboratory and histological abnormalities are reversible with appropriate glycemic control. Case presentation We hereby report a case of 11-year-old male who presented with hepatic glycogenosis mimicking Mauriac’s syndrome. The patient was admitted at our Pediatric Diabetes Clinic for marked hepatomegaly, short stature and for the poor metabolic control. Blood investigations and liver tests excluded most of major causes of hepatopathy. A liver biopsy allowed us to make diagnosis of hepatic glycogenosis. To control hyperglycaemia, initially we titrated daily insulin dosage, and then intravenous insulin treatment was practiced with the consequent normalization of liver enzymes. Conclusion Mauriac’s syndrome should be considered in subjects with brittle type 1 diabetes and hepatomegaly.

Aim To compare nasal glucagon (NG) with intramuscular glucagon (IMG) for the treatment of insulin‐induced hypoglycaemia in Japanese patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). Materials and methods This phase 3, randomized, open‐label, two‐treatment, two‐period crossover non‐inferiority study enrolled Japanese adults with T1DM or T2DM on insulin therapy, with glycated haemoglobin levels ≤86 mmol/mol (≤10%). After ≥8 hours of fasting, hypoglycaemia was induced with human regular insulin (intravenous infusion). Patients received NG 3 mg or IMG 1 mg approximately 5 minutes after insulin termination. The primary endpoint was the proportion of patients achieving treatment success [plasma glucose (PG) increase to ≥3.9 mmol/L (≥70 mg/dL) or ≥1.1 mmol/L (≥20 mg/dL) increase from the PG nadir within 30 minutes of receiving glucagon]. Non‐inferiority was declared if the upper limit of the two‐sided 95% confidence interval (CI) of the mean difference in the percentage of patients achieving treatment success (IMG minus NG) was 2 patients were rhinalgia, increased blood pressure, nausea, ear pain and vomiting in the NG group, and nausea and vomiting in the IMG group. Conclusion Nasal glucagon was non‐inferior to IMG for successful treatment of insulin‐induced hypoglycaemia in Japanese patients with T1DM/T2DM, supporting use of NG as a rescue treatment for severe hypoglycaemia.

iNtrOdUctiON: type 2 diabetes (t2d) in adolescents has become an increasing health concern throughout the world and its prevention and screening should be implemented in pediatric care. as clinical features at presentation, in some cases can be similar to type 1 diabetes and family history can be in favor of a monogenic form of diabetes, it is pivotal for physicians to be aware of youth-onset T2D specificities to ensure an accurate diagnosis. EVIDENCE ACQUISITION: We conducted the first search in Medline, Embase, Web of Science, using different keywords and their compositions. The keywords used, also called “mesh” (MEdical Subject Headings) on PubMed, are the following: “type 2 diabetes” AND (“child*” OR “pediatr*” OR “adolesce*”) AND (“epidem*” OR “diagnos*” OR “treat*” OR “complication” OR “comorbidit*”). International review, systematic reviews and meta-analyses, randomized control trials and case reports published between May 2018 and February 2021 were considered, to identify publications that deal with the topic. No restrictions were applied regarding the published paper’s language. eVideNce sYNtHesis: the global increase of overweight and obesity can complicate the diagnostic process and makes it essential to apply a systematic approach to each new diagnosis. Microvascular complications may be present at the time of diagnosis and chronic complications are frequent and need to be screened regularly. regular screening of comorbidities should also be performed. childhood t2d should be followed up by pediatric diabetes units to avoid diagnostic errors and delay in care. cONcLUsiONs: a multidisciplinary approach, by an experienced team, is pivotal to provide treatment options targeting the unique needs of pediatric patients. treatment programs must include the whole family and address all the aspects of the care (lifestyle, pharmacological therapy, psychological aspects, complications and comorbidities). an organized process of transition to adult care is essential.

Objective Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design Retrospective analysis of the Italian data set of patients with TNDM. Methods Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.

Cystic fibrosis related diabetes (CFRD) is a comorbidity of cystic fibrosis (CF) that negatively impacts on its clinical course. Prediabetes is an important predictor of either CFRD development and unfavorable prognosis of CF in both pediatric and adult patients. International guidelines recommend insulin only in case of CFRD diagnosis. Whether early detection and treatment of prediabetes may contribute to improve the clinical course of CF is still debated. A subgroup of pediatric diabetologists of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED) performed a systematic review of the literature based on predefined outcomes: impact of pre-diabetes on clinical outcomes and on the risk of developing CFRD; diagnosis of diabetes and pre-diabetes under 10 years of age; effectiveness of therapy on glycemic control, impact of therapy on pulmonary function and nutritional status. Thirty-one papers were selected for the analysis data presented in these papers were reported in tables sorted by outcomes, including comprehensive evidence grading according to the GRADE approach. Following the grading of the quality of the evidence, the entire ISPED diabetes study group achieved consensus for the Italian recommendations based on both evidence and clinical experience. We concluded that in patients with CF, prediabetes should be carefully considered as it can evolve into CFRD. In patients with CF and prediabetic conditions, after complete evaluation of the OGTT trend, glucometrics, glycemic values measured during pulmonary exacerbations and/or steroid therapy, early initiation of insulin therapy could have beneficial effects on clinical outcomes of patients with CF and prediabetes.

Background A retrospective observational study was conducted to assess the prevalence of maturity onset diabetes of the young (MODY) in a large paediatric population of Southern Italy newly diagnosed with diabetes. Clinical and genetic features of the identified MODY patients were also described. Methods Genetic testing was performed in children and adolescents newly diagnosed with diabetes who presented autoantibody negativity and fasting C-peptide levels ≥ 0.8 ng/mL. Patients with a low insulin daily dose and optimal glycaemic control after two years from diabetes onset were also investigated for monogenic diabetes, regardless of their autoimmunity status and/or C-peptide levels. Results A prevalence of 6.5% of MODY was found. In particular, glucokinase-MODY was the most common type of MODY. The mean age at diagnosis was 9.1 years. Clinical presentation and biochemical data were heterogeneous also among patients belonging to the same MODY group. Conclusions We found a relatively high prevalence of MODY among paediatric patients with a new diagnosis of diabetes in comparison to literature data. Our findings highlight that a more detailed clinical evaluation along with easier and less expensive approachability to genetic testing may allow diagnosing an increasing number of MODY cases. A correct, prompt diagnosis is crucial to choose the most appropriate treatment and offer adequate genetic counselling.

Aim: To evaluate the impact of a virtual educational camp (vEC) on glucose control in children and adolescents with type 1 diabetes using a closed-loop control (CLC) system. Materials and Methods: This was a prospective multicentre study of children and adolescents with type 1 diabetes using the Tandem Basal-IQ system. Insulin pumps were upgraded to Control-IQ, and children and their parents participated in a 3-day multidisciplinary vEC. Clinical data, glucose metrics and HbA1c were evaluated over the 12 weeks prior to the Control-IQ update and over the 12 weeks after the vEC. Results: Forty-three children and adolescents (aged 7-16 years) with type 1 diabetes and their families participated in the vEC. The median percentage of time in target range (70-180 mg/dL; TIR) increased from 64% (interquartile range [IQR] 56%-73%) with Basal-IQ to 76% (IQR 71%-81%) with Control-IQ (P&nbsp

Introduction: Despite advances in the management of type 1 diabetes (T1D), there is an increasing incidence of skin reactions related to diabetes devices such as patch pumps and glucose sensors. Aim of the present study was to assess the prevalence of dermatological complications in pediatric patients with T1D using technological devices. Methods: Online survey regarding skin reactions related to the use of patch pumps and/or glucose sensors was administered to families of children and adolescents (0-17 years) with T1D. Data were collected on demographic characteristics, duration of diabetes, and clinical features of dermatological complications if present. Results: Our study population consisted of 139 patients (female 51.8%) aged 11.1 ± 3.3 years. More than half (51.1%) experienced skin reactions due to patch pumps or glucose sensors. Dermatological complications were mainly caused by continuous glucose monitoring (56.3% of total). Timing of appearance of dermatological reactions varied from a few days to several months after the introduction of the device. The application of hypoallergenic barrier bandages was the most frequently adopted measure to solve the issue. Conclusions: Our study confirmed high frequency of dermatological complications among pediatric patients with type 1 diabetes. Well-designed studies are awaited to provide clear recommendations to minimize the burden of skin issues related to technological devices.

Partial clinical remission (PCR) is a transitory period characterized by the residual endogenous insulin secretion following type 1 diabetes (T1D) diagnosis and introducing the insulin therapy. Scientific interest in PCR has been recently increasing, as this phase could be crucial to preserve functional beta cells after T1D onset, also taking advantage of new therapeutic opportunities. The aim of this study was to assess the frequency, duration and associated factors of PCR in children newly diagnosed with T1D. Our cohort study included 167 pediatric patients aged 13.8 &plusmn, 4.1 years. The association of clinical and laboratory factors with the occurrence and duration of PCR was evaluated via logistic regression and multivariable generalized linear model, respectively. PCR occurred in 63.5% of the examined patients. Patients who achieved the remission phase were significantly older, and they had lower daily insulin requirement compared with non-remitters. PCR was positively associated to body mass index (OR = 1.11, p = 0.032), pH value (OR 49.02, p = 0.003) and c-peptide levels (OR 12.8, p = 0.002). The average duration of PCR was 13.4 months, and older age at diagnosis was the only predictor factor. Two years after diagnosis remitter patients had lower HbA1c and daily insulin requirement.

Background: Glucose sensors consist of real-time continuous glucose monitoring (rtCGM) and intermittently scanned CGM (isCGM). Their clinical use has been widely increasing during the past 5 years. The aim of this study is to evaluate percentage of time in range (TIR) in a large group of children with type 1 diabetes (T1D) using glucose sensors with nonautomated insulin delivery systems, in a real-world setting. Methods: An 11-center cross-sectional study was conducted during January-May 2019. Children with T1D 1 year, treated with multiple daily injections (MDI) or nonautomated insulin pump (IP), were recruited consecutively. Clinical data, HbA1c measurement, and CGM downloaded data were collected by each center and included in a centralized database for the analysis. Glucose metrics of four treatment strategies were analyzed: isCGM-MDI, rtCGM-MDI, isCGM-IP, and rtCGM-IP. Results: Data from 666 children with T1D (51% male and 49% female), median age 12 years, diabetes duration 5 years, were analyzed. An rtCGM was used by 51% of the participants, and a nonautomated IP by 46%. For isCGM-MDI, rtCGM-MDI, isCGM-IP, and rtCGM-IP, the median TIR 70-180 mg/dL values were 49%, 56%, 56%, and 61% (P < 0.001), respectively; HbA1c 7.6%, 7.5%, 7.3%, and 7.3% (P < 0.001), respectively. Use of rtCGM was associated with significant lower time below target range 180 mg/dL and lower HbA1c. If there are no barriers, an upgrade of the treatment strategy with a higher performing technology should be offered to all children who do not achieve blood glucose metrics within the suggested range.

Aims to assess the prevalence of cardiovascular risk factors (CVRFs) and to identify the variables associated with CVRFs in a cohort of children and adolescents with Type 1 Diabetes. Methods 2,021 subjects, 2-18 year-old, were recruited in 17 Italian Pediatric Diabetes Centers. Anthropometric, blood pressure, biochemical (HbA1c, lipid profile, ACR), insulin therapy, physical activity level, smoking and family socio-economic status data were collected. CVRFs prevalence and their distribution were analyzed according to age and binary logistic regression was performed with positivity for at least one major CVRF (BMI-SDS>+2SD, blood pressure>90th percentile, LDL cholesterol>100 mg/dl) as dependent variable and age, duration of illness, gender, HbA1c and physical activity, as independent variables. Results The prevalence of CVFRs not at the recommended target was respectively: 32.5% one CVRF, 6.7% two CVRFs and 0.6% three CVRFs, with no significant differences across the 3 age groups (2-10, 10-15, 15-18 years). In the total sample, HbA1c and inadequate physical activity were associated with a higher probability of having at least one major CVRF. This probability was associated with physical activity in the 2-10-year-old group, with physical activity and HbA1c in the 10-15-year-old group and with HbA1c only in subjects older than 15 years. Conclusions More than 30% of subjects had at least a major CVRF. Early detection of CVRFs may be useful to enforce the therapeutic intervention in this subgroup, in order to reduce the risk to develop cardiovascular complications. This article is protected by copyright. All rights reserved.

Aims Aim of our observational study was to assess the prevalence of allergic contact dermatitis among children and adolescents with type 1 diabetes who use technological devices for diabetes treatment and its management. Secondary outcome was to identify possible clinical and/or demographic variables that could be associated to contact dermatitis. Methods Among a total of 215 patients using insulin pumps and/or glucose sensors followed-up at our Pediatric Diabetes Centre between January and September 2018, 64 patients were enrolled and 42 (19 male and 23 female) completed the study. Demographic and clinical features of the study population were statistically analysed. All the patients underwent patch testing with specific allergens belonged to resin and acrylate classes. Results Eighteen patients experienced skin reactions suggestive of allergic contact dermatitis, demonstrating a prevalence of 8.4%. None of the demographic or clinical variables were associated to skin reactions. Colophonium was the most identified sensitizing allergen (87.5% of the cases). Conclusions The rate of sensitization to allergens included into diabetes devices among pediatric patients is higher than commonly assumed. Well-designed studies are needed to better investigate the association between type 1 diabetes and allergic contact dermatitis. Moreover, we suggest that manufactures should supply detailed information about adhesives in order to avoid dermatological complications and consequently a worsening of disease management and patients’ quality of life.

We studied 45 patients with Wolfram syndrome 1 (WS1) to describe their clinical history and to search for possible genotype–phenotype correlations. Clinical criteria contributing to WS1 diagnosis were analyzed. The patients were classified into three genotypic classes according to type of detected mutations. WS1 prevalence in Italy is 0.74/1,000,000. All four manifestations of DIDMOAD were found in 46.7% of patients. Differently combined WS1 clinical features were detected in 53.3% of patients. We found 35 WFS1 different mutations and a novel missense mutation, c.1523A>G. WS1 patients were homozygotes or compound heterozygotes for WFS1 mutations except for 2 heterozygote patients (4.5%). Each genotypic group exhibited a different age onset of DM, D, and DI but not of OA. Genotypic Group 2 patients manifested a lower number of clinical manifestations compared to Groups 1 and 3. Moreover, genotypic Group 1 patients tended to have a shorter survival time than the other groups. No differences were found regarding type of clinical pictures. Our study suggested that molecular WFS1 typing is a useful tool for early assessment of clinical history, follow-up, and prognosis of WS1.

Maturity onset diabetes of the young (MODY) accounts for up to 4% of all cases of diabetes in pediatric patients. MODY is usually characterized by autosomal dominant inheritance, impaired insulin secretion, and an average age at diagnosis of 18–26 years. Mutations in the hepatocyte nuclear factor 1-alpha (HNF1A), glucokinase, hepatocyte nuclear factor 4-alpha, and hepatocyte nuclear factor 1-beta genes are the mutations most frequently observed in cases of MODY. We herein report a case of HNF1A-MODY characterized by an early onset of diabetes. Genetic investigations revealed a de novo heterozygous substitution, N237D (HNF1A c.709A>G), in exon 3 of the HNF1A gene. Our case supports the hypothesis that de novo mutations are more frequent than expected. This recent evidence may suggest that conventional clinical diagnostic criteria for MODY should be revised and personalized according to the individual patient. Electronic Supplementary Material The online version of this article (10.1007/s13300-019-0633-3) contains supplementary material, which is available to authorized users.

Aim: To evaluate the incidence of insulin pump and infusion set failures in a cohort of children and adolescents with type 1 diabetes during a 1-year follow-up. Materials and Methods: Insulin pump breakdown and infusion set failures were prospectively registered in a cohort of 1046 children and adolescents from 25 tertiary pediatric diabetes centres (50% male, mean age 12.2 ± 4.1 years), with type 1 diabetes from the age of 6.7 ± 3.6 years, and using an insulin pump from the age of 3.3 ± 2.2 years. Results: An average rate of 4.5 failures/person-year was registered; the incidences (events per person-year) for each failure were 8.4 for hyperglycaemia episodes solved with infusion set change, 7 for bubbles, 2.8 for kinking, 2.4 for bleeding, 2 for set dislodge, 2 for pump blockage, 1.9 for tunnelling, 1.8 for lipohypertrophy, and 0.3 for infection. At multivariate analysis significant association between HbA1c and lipohypertrophy (P < 0.0028) was shown. Analysis by age group (11 years) showed a higher frequency of bubbles, hyperglycaemia episodes and lipohypertrophy in preschoolers; tunnelling and pump blockage were more frequent in adolescents. Aspart was associated with a lower risk of bubbles and hyperglycaemia whereas glulisine was associated with a higher risk of lipohypertrophy and pump blockage. The usage of oblique cannula was associated with a low risk of all failures except infections. Conclusions: This prospective 1-year study on a large cohort of Italian children and adolescents with type 1 diabetes using insulin pump therapy showed a low total failure rate, highlighting the importance of continuous education to reduce failures. Lipohypertrophy was the only issue associated with a worsening of metabolic control.

We conducted a retrospective survey in pediatric centers belonging to the Italian Society for Pediatric Diabetology and Endocrinology. The following data were collected for all new-onset diabetes patients aged 0–18 years: DKA (pH < 7.30), severe DKA (pH < 7.1), DKA in preschool children, DKA treatment according to ISPAD protocol, type of rehydrating solution used, bicarbonates use, and amount of insulin infused. Records(n=2453)of children with newly diagnosed diabetes were collected from 68/77 centers (87%), 39 of which are tertiary referral centers, the majority of whom (n=1536, 89.4%) were diagnosed in the tertiary referral centers. DKA was observed in 38.5% and severe DKA in 10.3%. Considering preschool children, DKA was observed in 72%, and severe DKA in 16.7%. Cerebral edema following DKA treatment was observed in 5 (0.5%). DKA treatment according to ISPAD guidelines was adopted in 68% of the centers. In the first 2 hours, rehydration was started with normal saline in all centers, but with different amount. Bicarbonate was quite never been used. Insulin was infused starting from third hour at the rate of 0.05–0.1 U/kg/h in 72% of centers. Despite prevention campaign, DKA is still observed in Italian children at onset, with significant variability in DKA treatment, underlying the need to share guidelines among centers.

Primary gonadal failure may occur in most individuals with Turner syndrome (TS). Since ovaries in TS girls undergo premature apoptosis and cryopreservation of ovarian tissue is now feasible, it would be useful to identify a reliable marker of ovarian reserve in these patients. We planned to evaluate ovarian function in a group of TS patients by measuring both traditional markers and inhibin B and to compare these results with those of a control group.We enrolled 23 patients with TS and 17 age-matched healthy girls. The median age of our TS patients was 17.6 years. Three out of the 23 patients (13%) showed spontaneous pubertal development and regular menstrual cycles; the remaining 20 (86.9%) presented with primary amenorrhea.The median level of inhibin B in the TS patients with primary amenorrhea was 42 pg/mL and did not differ significantly among the different subgroups in relation to karyotype. The median inhibin B level in the control group was significantly higher than in the TS girls with primary amenorrhea (83 vs. 42 pg/mL, pTS patients with primary amenorrhea have significantly lower levels of inhibin B than TS girls with spontaneous puberty and healthy controls. Inhibin B does not correlate with follicle-stimulating hormone/luteinizing hormone. If our results are confirmed in further studies, inhibin B could become a first-line screening test for assessing ovarian reserve and a longitudinal marker of the possible decline of ovarian function in TS.

Only few studies have focused on neurosensory hearing function of patients with congenital hypothyroidism (CH) identified by CH screening programs and treated early and, therefore, this issue remains still controversial. The aim of this study was to ascertain whether an early and adequate replacement treatment may be able to prevent sensorineural hearing loss in 32 screened children with CH and no associated risk factors for neuro-otologic alterations. These patients were recruited according to highly selective criteria aiming to preliminarily exclude the negative interference of both treatment variables and other underlying risk factors. All the selected patients underwent, at a median age of 15.4 years, an audiologic investigation, which evidenced a mild and subclinical hearing loss in 25% of them. The poorest hearing scores were recorded in the individuals with athyreosis and in those with absence of distal femur bony nucleus at CH diagnosis. The prevalence of hearing impairment was significantly higher in CH patients than in 32 age-matched control subjects with no CH (χ2 = 6.3, p In light of these findings, we concluded that: a) 25% of CH patients detected by CH screening may show, at a median age of 15.4 years, a mild and subclinical hearing impairment, despite early and adequate replacement treatment; b) the risk of hearing loss is higher in CH young patients than in age-matched control subjects without CH; c) the risk of hearing loss is closely associated with the severity of CH; d) this risk is particularly relevant in the children with pre-natal onset of hypothyroidism.

Type 2 and monogenic diabetes are emerging causes of diabetes in youths. Among 1244 Italian patients

Aim of this commentary is to summarize the salient literature news on the relationships between autoimmune thyroid diseases (ATDs) and either Down syndrome (DS) or Turner syndrome (TS). According to literature reports both Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are more frequent in children with DS or TS than in those without these chromosomopathies. An up-regulation of proinflammatory cytokines might be responsible for the enhanced susceptibility of TS children to ATDs, whereas a dysregulation of immune system may favor the development of ATDs in DS. In TS children biochemical presentation of HT is less severe than in peer controls. In both DS and TS GD picture at the time of diagnosis is not significantly different than in the pediatric general population. The evolution over time of GD in DS and TS does not differ from that observed in the pediatric general population, whereas the evolution of HT in both TS and DS is more severe than in girls without these chromosomopathies. Conclusions: The association with TS or DS is able to affect both epidemiology and course of ATDs by conditioning: a) an increased susceptibility to these disorders; b) a less severe biochemical presentation and a more severe evolutive pattern of HT in TS girls; c) a more severe biochemical presentation and evolution of HT in DS patients.

Since the original description, there have been only few epidemiological studies of Wolfram syndrome (WS).Aims of the present paper are to ascertain WS prevalence and expression in a district of North-eastern Sicily, i.e. a geographic area where consanguineous unions are not very unusual.Prevalence rates of WS in the Messina district were calculated by taking into consideration both the total population (653,737) and the populations included within the 0-30 year age range (202,681). We estimated the relative prevalence of WS among patients with youth-onset insulin-dependent diabetes mellitus (DM) who are currently aged under 30 years (256).Global WS prevalence in our district is 1:54,478, whereas prevalence among individuals under 30 is 1:16,890 and relative prevalence among patients with juvenile-onset insulin-dependent DM is 1:22.3. When compared with the patients with insulin-dependent DM of Messina district, WS patients did not exhibit significant differences in terms of biochemical features at DM onset, whereas age at DM diagnosis was significantly earlier in WS group.(a) WS prevalence is not so infrequent as generally expected; (b) in our series, DM presented before 10 years in 11/12 patients and ten cases have already developed all the four peculiar manifestations of WS by 26 years; (c) 9/12 patients exhibited a homozygous frameshift/truncation mutation (Y454_L459del_fsX454), which is the one most frequently found also in patients from other Italian regions; (d) age at DM diagnosis was significantly earlier in WS group than in the patients with insulin-dependent DM of Messina district.