BACKGROUNDOvotesticular Difference of Sex Development (OT DSD) is a rare condition characterized by histologic demonstration of ovarian and testicular tissue in the same individual. Descriptions in literature usually do not include long term follow-up data.OBJECTIVESThe aim of this study is to describe clinical, biochemical and histological findings, as well as long term outcomes (including onset and progression of puberty) in patients with OT DSD.RESULTSIn a retrospective study of 31 patients, findings include predominantly male gender assignment at the time of referral (54.8%) and subsequent female gender of rearing (54.8%). The most frequent karyotype was 46,XX (58.1%). Ovotestis was the most frequent gonad (48.4%) Puberty could be evaluated in 20 patients, being spontaneous in 12 of them. Four patients with partial gonadectomy in infancy were able to enter female puberty spontaneously.CONCLUSIONIt was observed that patients who preserved gonadal tissues were able to enter puberty spontaneously.
Globally it is estimated that over 1 million children and adolescents have Type 1 diabetes with large variations in incidence between different contexts. Health systems need to provide a variety of elements to ensure appropriate diabetes care, such as service delivery; healthcare workforce; information; medical products and technologies; financing and leadership and governance. Describing these elements between Geneva, Switzerland, a high-income country with high spending on healthcare and a large density of doctors, and low- and middle-income countries this article aims to highlight the global inequality of diabetes care. Type 1 diabetes can serve as a litmus as we move towards the centenary of the discovery of insulin and beyond as there is a need for a global movement to ensure that innovation in the management of diabetes benefits the whole diabetes community and not just a select few.
The negative consequencies of diabetes treatment are traditionally regarded as caused by a disastrous treatment rather than adverse events of the insulin preparations. However, hypoglycemia, changes at the injection site (lipatrophy, lipoma), insulin allergy, obesity and increased risk of certain forms of cancer can easily be regarded as adverse events of the drug, and needle-phobia, psychological problems, increased risk of suicide are adverse events related to insulin and its administration. Also macroangiopathy and even microangiopathy to some extent can be regarded as adverse events as the most crucial part of the treatment of Type 1 diabetes is the insulin treatment. There is still room for improvments of insulin as a drug. We need insulins with more predictable absorption and kinetics, leading to more stable near-normal blood glucose, less risk of hypoglycemia, less effect in periphery and more effect on the liver, and less risk of vascular complications, obesity, cancer.
For the increasing number of type 1 diabetes in Japan, after 1960, a greater supply of insulin was required, accordingly the availability of insulin gradually improved, The National Health Insurance approved self-injections of insulin at home in 1981. Afterwards, intensive insulin treatment with short -acting insulin and intermediate -acting insulin became widely used. Recombinant rapid -acting insulin analog was introduced in 1986 and long -acting insulin analog was introduced in 2003. In recent years, basal -bolus insulin regimens using these insulin analogs have become popular in children and adolescents with type 1 diabetes in Japan, which can improve the metabolic state and quality of life. This also will contribute to prevent the occurrence and progression of micro- and macro -vascular complications later in life.
For people with type 1 diabetes, achieving optimal glycemic control requires use of intensive insulin therapy. To achieve this goal individuals are required to become proficient in accurately determining the appropriate amount of insulin needed to address a variety of situations throughout the day while considering numerous influencing factors. They also need to perform multiple tasks a day such as counting carbohydrates to accurately determine the required premeal bolus. There is also a need to periodically adjust insulin dosing as insulin sensitivity varies considerably over time. Sophisticated advanced technologies are being used by growing numbers of individuals to manage diabetes. However, despite innovations in glucose monitoring technologies and new insulin formulations, many of these individuals are not achieving their glycemic goals. The new technologies provide ample amount of valuable diabetes related data that may complicate even further the insulin dosing decision making for people with diabetes as well as for the health care providers. Mobile health, digital tools and decision support systems can help to increase accurate, timely insulin dosing and insulin titration and holds the potential to improve glycemic control to a wide range of individuals with diabetes. The emerging mobile toolbox for insulin dosing adjustments that will be reviewed in this paper includes insulin management Apps; diverse range of Apps to guide insulin adjustments such as in times of physical activity and eating; data management systems which enable visualization and analysis of insulin and glucose data of various devices; real-time alarms and glucose prediction Apps that help to prevent hypoglycemia and hyperglycemia events; various bolus calculators for meal time dosing; sophisticated decision support algorithms for people using insulin pump, multiple insulin injections and closed loop systems for real-time and retrospective insulin dosing adjustments.
Almost a century ago, the first insulin was produced by Banting, Best, MacLeod and Collip in Toronto, thereby enabling life-saving treatment for people with diabetes. Since then, there have been many advancements in insulin production and development of new insulin analogues. In this article, we reflect on the rich heritage of Sanofi and its predecessor, Hoechst, in insulin production and development, from being one of the first companies to produce insulin in Europe in 1923, to modern-day insulin analogues and integrated care solutions at present-day Sanofi.
Childhood obesity is a considerable worldwide health problem and a major risk factor for several chronic diseases. Fat rich diets result in altered serum levels of lipids, cytokines and hormonal factors, which influence skeletal acquisition and promote microstructural and mechanical behavior changes in bone, especially to bone quality and quantity. However, the possible longterm implications of high-fat diets in childhood are controversial. Despite not fully understood, multiple signaling pathways which support bone tissue homeostasis are altered under hyperlipidic conditions, including RANKL/RANK/OPG, PPAR-γ/Alox5/5-LO, leptin/IGF-I/AGE, ApoE/Lrp-1, Thy-1, IL-6, TNFα, calcium, vitamin D and K metabolism. Moreover, the expression of reactive oxygen species is also modified. Considering the importance of this subject, the aim of this review was to explore the mechanisms of bone formation affected by obesity during childhood during childhood.
Pheochromocytomas/paragangliomas (PCCs/PGLs) are rare neuroendocrine tumors, developed from chromaffin cells derived from the neural crest. From a genetic point of view PCCs/PGLs are divided as sporadic cases, and inherited cases as part of hereditary (familial) syndromes. While the majority is benign, up to 26% of PCCs/PGLs will undergo malignant transformation. Validated prognostic pathological parameters for malignant PCCs/PGLs are still lacking. Signaling that follows the interactions between IGFs and their receptor/s in tumor cells received extensive attention when investigating the role of IGF1R in cancer. Increased IGF1R expression has been shown during progression to metastatic phenotypes and associated with worse prognosis in several types of cancer. In this review we provide evidence supporting a role for the IGFs system on PCC/PGL tumor biology and malignant behavior, endocrine actions to sustain tumor phenotype as well as heterotypic interaction´s regulation by IGF1, encouraging further research for targeted therapeutic options for these tumors.
Glucose dysregulation (GD), a feature of growth hormone excess, in the setting of acromegaly is well known by clinicians. However, less well known is that GD may be a feature of growth hormone deficiency. The fact that either ends of the spectrum of growth hormone (excess or deficiency) can be associated with diabetes mellitus is unique and clinicians should especially recognize that impaired glucose tolerance and even diabetes mellitus may develop in individuals predisposed to having growth hormone deficiency.
Frasier syndrome (FS), a rare disease caused by inherited or de novo mutation in Wilm's Tumor suppressor gene 1 (WT1), is characterized by slow progressive nephropathy, XY gonadal dysgenesis (XY-DSD), and increased risk for gonadal tumors. Early childhood (1-6 years) nephropathy progresses with age to refractory nephrotic syndrome, and end-stage renal failure in late adolescence, when delayed puberty and/or primary amenorrhea are clinically evident. We report a unique case of FS presenting initially with primary amenorrhea at 16 years, without previous or concomitant renal damage. Only subsequently she developed an extremely late-onset nephropathy. Genetic analysis revealed the IVS9 + 5 G>A mutation in intron 9 of the WT1 gene. This clinical presentation and review of WT1 literature highlights the importance of considering FS in the differential diagnosis of patients with 46,XY disorders of Sexual development, even without nephropathy. Furthermore, the identification WT1 gene mutation prior to evident renal dysfunction indicates an immediate and close surveillance of renal function enabling an optimal and timely medical response.
Vitamin D is important for skeletal growth, bone mineralization and dental health. Vitamin D deficiency is reported in many countries, may have several causes and can cause rickets in children. A guideline with recommendations of vitamin D supplementation to prevent nutritional rickets was published recently. The vitamin D receptor is present in many cells of the body including cells of the immune system. Many studies have been published on associations between vitamin D deficiency and extra skeletal effects, mainly without proof of causality in intervention studies. This review aims to summarize available evidence of the skeletal and extra-skeletal effects of vitamin D. For the extra-skeletal effects there is proof that vitamin D supplementation can prevent acute respiratory infections in children with vitamin D deficiency and can reduce the rate of asthma exacerbations requiring corticosteroids in children with vitamin D deficiency. The evidence of benefit of vitamin D supplementation is too limited for pediatric patients with other infectious, inflammatory, and autoimmune diseases.
Finding multiple familial patients with Hashimoto thyroiditis in our clinic a search in the literature confirms that genetic factors, in addition to environmental factors, seem involved in the etiology of this disease.
Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder, caused by deficiency of α-L-iduronidase, and consequent accumulation of dermatan and heparan sulfates. Severity of the disease ranges from mild (Scheie) to moderate (Hurler-Scheie) to severe (Hurler or MPS-IH). A prominent clinical manifestation of MPS-IH is dysostosis multiplex, a constellation of skeletal abnormalities. We performed a retrospective review comparing manifestations of dysostosis multiplex in patients presenting with MPSIH and relevant animal models. Dog, cat and mouse models of MPS-IH are extensively studied to better understand the pathology of the disease. While all animal models display certain characteristics of human MPSIH, species-specific manifestations must be considered when evaluating skeletal abnormalities. Moreover, some skeletal abnormalities emerge at species-specific developmental stages, e.g. thoracolumbar kyphosis is an early manifestation in humans, while it appears late in the mouse model. The choice of the appropriate diagnostic test is of importance to avoid misleading conclusions.
Skeletal dysplasias are the disorders of the skeletal and cartilaginous tissues. Short stature is the hallmark presentation. Achondroplasia is the commonest skeletal dysplasia. Growth hormone (GH) has been widely used in children with achondroplasia. Various studies have shown 1st year increase in height velocity is about 2-3cm. Apart from achondroplasia, studies have also shown positive effect of GH in hypochondroplasia children. However, in hypochondroplasia GH treatment seems to give better results when administered at puberty. Other forms of skeletal dysplasias are rare, so no conclusion on GH use in such patients can be drawn.
Recent epidemiological surveys performed in Australia, USA and Israel demonstrate that Rotavirus vaccination correlates with an attenuated prevalence and/or incidence of early childhood diabetes (T1D). Other studies failed to confirm the above.
Hypoglycemia remains a significant cause of morbidity in infants and children. Up to 50% of children with hypoglycemic disorders suffer from neurodevelopmental deficits, as a consequence of delays in the diagnosis and inadequate treatment. Recent advances in the field have resulted in new therapies and improved outcomes. To review these advances and have a dialogue regarding controversies in the field, the Fourth International Hyperinsulinism Symposium, sponsored by the Children's Hospital of Philadelphia was held in Philadelphia, Pennsylvania on September 5-6, 2019. The symposium faculty, leaders in the field of hyperinsulinism and hypoglycemia, presented 25 plenary lectures on all aspects of these disorders. Additionally, a mini-symposium on neonatal hypoglycemia closed out the conference. Objectives of the symposium were to: 1. Describe the clinical manifestations, genetics and natural history of congenital hyperinsulinism 2. Review recent advances in the medical and surgical management of hyperinsulinism 3. Discuss current controversies and management options of neonatal hypoglycemia.
