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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.

Obesity is a state of chronic inflammation. Data on IGF system are often discrepant, and their relationships with mediators of inflammation are unknown. Furthermore, changes in thyroid function have been reported. We aimed at investigating the changes in these systems, and verify any relationships among cytokines, IGF system, thyroid function and insulin-insensitivity. Fifty obese pre-pubertal children, and 55 normal-weight subjects comparable for age and sex were enrolled. Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, IL-6 and TNF-alpha were assayed. In obese children insulin, TSH and FT4 were measured also, and the HOMA-IR index was calculated. Increased IGF-II, IL-6 and TNF-alpha, and decreased IGFBP-1 and IGFBP-2 concentrations were found in obese compared to normal-weight children. The IGF-I/IGFBP-3 molar ratio was also reduced in the obese subjects. In the obese children with high HOMA-IR index, IGFBP-1 and -2 serum concentrations were significantly decreased compared with those with normal insulin sensitivity, and in the obese subjects with increased TSH, IGFBP-2 concentrations were lower, and IGFBP-3 levels were higher compared to their counterparts with normal TSH levels. Among the significant correlations, BMISDS was correlated with IGF-II, and TSH. IGF-II concentrations showed a positive relationship with IL-6. TSH was correlated with IGFBP-2 also. The data showed interactions among IL-6, IGF system, insulin sensitivity, and thyroid function with changes being related to the degree of obesity. Chronic inflammation in obese children was confirmed. Some of the changes in the IGF system could be a consequence of insulin resistance and could account also for later complications in obese subjects.

In a short girl with celiac disease and Hashimoto's thyroiditis (HT), suspicion of an associated pituitary lesion was suggested by the finding of a thyroid function pattern that was not compatible with HT-related hypothyroidism (low FT4 with normal TSH). This case report reinforces the view that the finding of a normal TSH in presence of a low FT4 should always alert pediatricians and raise suspicion of central hypothyroidism, even when a primary thyroid disease has been already identified. In this case TSH deficiency played a critical role in disclosing diagnosis of craniopharyngioma (CP). Therefore, the subsequent work-up was directed towards investigating pituitary function and morphology. Endocrinological investigations evidenced a picture of TSH and other pituitary hormone deficiency, whereas magnetic resonance imaging revealed an intrasellar CP. Therefore, in this case TSH deficiency played a key-role in disclosing CP diagnosis.

Clinical diagnosis in dysmorphology is made by the recognition of a specific pattern of malformations and through an analytic search for discrete features. We present our personal experience regarding the usefulness of hair morphology as a tool for diagnosis in some metabolic and malformation syndromes. These cases represent only a few illustrative examples; an exhaustive review of the topic can be found elsewhere.

The aim of this study was to investigate the influence of pre-treatment variables on subsequent insulin requirement (IR) and partial remission (PR) in children with insulin-dependent diabetes mellitus (T1DM). Sixty-seven children with newly diagnosed T1DM, admitted to our Clinic during a 3-year recruitment period, were longitudinally evaluated for 2 yr. Patients were characterized by sex, age, parental education, duration of symptomatic history at diagnosis, admission duration, ketoacidosis or absence of ketoacidosis and residual beta-cell activity. More than 80% of the children experienced a PR, which lasted more than 12 months in 41.7% and at least 24 months in 16.4% of cases. The prevalence of PR at different ages after T1DM onset was significantly lower in children diagnosed while younger than 5 years than in those diagnosed after 5 years. The mean duration of the remission period was 11.7 +/- 8.9 months, irrespectively of sex, duration of the symptomatic period preceding T1DM diagnosis, parental education, blood pH and base excess, HbA1c concentration and admission duration. Beta-cell residual function evaluated after glucagons stimulation test (basal and 6 min C-peptide) was statistically different in PR patients and in those who experienced no remission. Age at diagnosis was the only pre-treatment factor which, on stepwise regression analysis, affected both PR duration and IR at the end of follow-up. To conclude, honeymoon frequency and duration are strictly conditioned by both residual beta-cell function and IR at T1DM onset. Since IR is higher in younger subjects, early onset of T1DM can be considered the factor with the most detrimental influence on honeymoon incidence. Other pre-treatment variables have no significant impact on PR.