Skeletal demineralization and mineral metabolism derangement are well-recognized features of untreated celiac disease (CD). Although treatment with a gluten-free diet appears to prevent bone loss while correcting skeletal demineralization in childhood, there is evidence that bone mineral density does not return to normal in celiacs diagnosed in adulthood. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, and ligand of receptor activator of NFkB (RANKL) are involved in the process of bone turnover and have been implicated in the pathogenesis of osteoporosis and other metabolic bone diseases. We measured OPG, RANKL, bone mineral density (BMD), and biochemical markers of bone turnover in 32 adult female premenopausal celiac patients on a gluten-free diet, and thirty age-matched healthy women. We correlated the OPG/RANKL ratio with the severity of bone loss. Celiac patients had a mean BMD lower than controls in lumbar spine and in the femoral neck. Serum levels of bone alkaline phosphatase (BAP, marker of bone formation), and urinary excretion of telopeptides of type I collagen (a marker of bone resorption) were significantly higher than in controls. Serum OPG and RANKL levels were significantly higher in CD patients than in controls, while the OPG/RANKL ratio was significantly lower in CD patients than in controls and was positively correlated with BMD at the spine. The role of elevated OPG in CD patients is unclear, but it might represent a compensatory mechanism against other factors that promote bone damage. Further studies are required to assess a possible therapeutic potential of osteoprotegerin in optimally treated celiacs with persistent osteopenia.

Context Primary adrenal insufficiency (PAI) is a rare and potentially life-threatening condition, 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 AI; 2% (n=16) Adrenal Hypoplasia Congenital; 1.2% (n=10) CAH non 21-OHD; 1% (n=8) rare syndromes; 0.6% (n=5) Familial Glucocorticoid Deficiency; 0.4% (n=3) acquired AI; 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 different from 21-OHD CAH, the most frequent symptoms at diagnosis were fatigue (67%), hyperpigmentation (50.4%), dehydration (33%) and hypotension (31%). Elevated ACTH (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 length 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 patients years. Three patients died for the underlying disease. Adult height, evaluated in 70 patients, was -0.70±1.20 SDS. Conclusions we characterized one of the largest cohorts of children with PAI aiming to improve the knowledge on diagnosis of this rare condition.

Introduction: Necrobiosis lipoidica (NL) is a rare chronic granulomatous dermatitis that usually appears in the lower extremities. It affects about 0.3–1.2% of diabetic patients, the majority of whom have type 1 diabetes. The etiology and pathogenesis of this disorder are still unclear. NL is characterized by skin rash that usually affects the shins. The average onset is 30 years, with females being affected more commonly. There are very few reported cases of necrobiosis lipoidica in children. Case report: We report a case of a 16 year old girl affected by type 1 diabetes mellitus (15 years disease duration) who developed an erythematous nodular rash on the lower extremities and interscapular area. In the suspect of necrobiosis lipoidica, a skin biopsy was performed (lower extremities and interscapular area). The microscopic evaluation of the pretibial lesions was suggestive of necrobiosis lipoidica. The smaller lesions in the interscapular area showed signs of perivascular dermatitis which could be consistent with early stages of necrobiosis lipoidica. Local treatment with tacrolimus determined a progressive improvement of the lesions. Conclusion: In patients with T1DM, diagnosis of NL of the lower legs is usually unequivocal. However, diagnosis may be more challenging in the presence of lesions with recent onset and/or atypical clinical presentation and unusual site. In these cases, NL must always be taken in consideration in order to avoid misdiagnosis, wrong/late treatment decisions and progression to ulceration.

The prevalence of diabetes is increasing. Improved glucose control is fundamental to reduce both long-term micro- and macrovascular complications and short-term complications, such as diabetic ketoacidosis and severe hypoglycemia. Frequent blood glucose monitoring is an essential part of diabetes management. However, almost all available blood glucose monitoring devices are invasive. This determines a reduced patient compliance, which in turn reflects negatively on glucose control. Therefore, there is a need to develop noninvasive glucose monitoring devices that will reduce the need of invasive procedures, thus increasing patient compliance and consequently improving quality of life and health of patients with diabetes.