NKX2.1-Related Disorders: a novel mutation with mild clinical presentation.

Background: A highly variable phenotype characterized by thyroid, respiratory and neurological defects has been reported in an already established group of disorders namely NKX2.1-related disorders. We describe here the case of an infant with a novel mutation of the NKX2.1 gene characterized by mild clinical presentation. Aim of the study was to elucidate the genotype-phenotype correlation in our patient. Methods: We performed genetic analysis of the NKX2.1 gene in an infant with no neonatal respiratory distress and near-normal results at neonatal screening test for congenital hypothyroidism, choreoathetosis, ataxia and delayed independent walking. Results: A novel mutation of the NKX2.1 gene has been identified, that is responsible for a mild framework of congenital hypothyroidism and neurological symptoms. Conclusions: The frequency of congenital hypothyroidism cases associated with NKX2.1 mutations is expected to be higher in a subgroup of patients, selected according to the neurological presentation. In these patients the analysis of NKX2.1 mutational status is recommended

46, XX DSD due to androgen excess in monogenic disorders of steroidogenesis: Genetic, biochemical, and clinical features

The term ‘differences of sex development’ (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, or anatomical sex. Disorders of steroidogenesis comprise autosomal recessive conditions that affect adrenal and gonadal enzymes and are responsible for some conditions of 46, XX DSD where hyperandrogenism interferes with chromosomal and gonadal sex development. Congenital adrenal hyperplasias (CAHs) are disorders of steroidogenesis that mainly involve the adrenals (21-hydroxylase and 11-hydroxylase deficiencies) and sometimes the gonads (3-beta-hydroxysteroidodehydrogenase and P450-oxidoreductase); in contrast, aromatase deficiency mainly involves the steroidogenetic activity of the gonads. This review describes the main genetic, biochemical, and clinical features that apply to the abovementioned conditions. The activities of the steroidogenetic enzymes are modulated by post-translational modifications and cofactors, particularly electron-donating redox partners. The incidences of the rare forms of CAH vary with ethnicity and geography. The elucidation of the precise roles of these enzymes and cofactors has been significantly facilitated by the identification of the genetic bases of rare disorders of steroidogenesis. Understanding steroidogenesis is important to our comprehension of differences in sexual development and other processes that are related to human reproduction and fertility, particularly those that involve androgen excess as consequence of their impairment

Central Precocious Puberty: Treatment with Triptorelin 11.25 mg

Background. Few data are available on quarterly 11.25 mg GnRH analog treatment in central precocious puberty (CPP). Aim. To assess the efficacy of triptorelin 11.25 mg in children with CPP. Patients. 17 patients (16 females) with CPP (7.9 ± 0.9 years) were treated with triptorelin 11.25 mg/90 days. Methods. Gonadotropins, basal-, and GnRH-stimulated peak, gonadal steroids, and pubertal signs were assessed at preinclusion and at inclusion visit, 3 months, 6 months, and 12 months of treatment. Results. At 3, 6, and 12 months, all patients had suppressed LH peak (<3 IU/L after GnRH stimulation), as well as prepubertal oestradiol levels. Mean LH peak values after GnRH test significantly decreased from 25.7 ± 16.5 IU/L at baseline to 0.9 ± 0.5 IU/L at M3 (P < 0.0001); they did not significantly changed at M6 and M12. Conclusions. Triptorelin 11.25 mg/90 days efficiently suppressed the pituitary-gonadal axis in children with CPP from first administration

Influence of Hashimoto thyroiditis on the development of thyroid nodules and cancer in children and adolescents

It is unclear whether patients with Hashimoto thyroiditis (HT) are predisposed to develop thyroid nodules and/or thyroid cancer. The objective of our study was therefore to assess the prevalence of thyroid nodules and/or cancer in patients with HT and to look for possible prognostic factors. A retrospective survey of 904 children/adolescents with HT (709 females, 195 males) regularly followed in nine Italian centers of pediatric endocrinology was performed. Median period of follow-up was 4.5 years (1.2 to 12.8 years). We evaluated free T4, TSH, thyroid peroxidase antibody (TPOAb), thyroglobulin antibodies, and thyroid ultrasound yearly. One hundred seventy-four nodules were detected, with an annual incidence rate of 3.5%. Ten nodules were malignant (8 papillary and 2 papillary follicular variant), giving a 5.7% prevalence of cancer among patients with nodules. The severity of hypo-echogenity at ultrasound, TPOAb, and free T4 serum concentrations were predictive for the appearance of new nodules. Furthermore, a positive correlation was observed between TPOAb titer and the development of thyroid cancer. In conclusion, HT seems to influence the development of thyroid nodules, but not cancer in children and adolescents

Effect of initial levothyroxine dose on neurodevelopmental and growth outcomes in children with congenital hypothyroidism

We designed a multicentre open prospective randomized trial to evaluate the risk-benefit profile of two different initial treatment schemes with levothyroxine (L-T4), 10-12.5 μg/kg/day vs 12.6-15 μg/kg/day, on growth and neurodevelopmental outcomes in children with congenital hypothyroidism (CH) detected by neonatal screening to identify the best range dose to achieve optimal neurocognitive development

Are Patients with Polycystic Ovarian Syndrome Ideal Candidates for Oocyte Donation?

Background. The use of donated oocytes for in vitro fertilization treatment in patients with ovarian failure is universally recognized. But would patients with polycystic ovarian syndrome (PCOS) be a good choice for egg donation programs? Objective. Comparing the pregnancy rates of egg receptors from donor patients diagnosed with PCOS to receptors from donors without PCOS. Design. Retrospective cohort study. Methods. A total of 234 patients who had undergone egg reception program were separated into two groups: Group I, receptors from PCOS donors ( = 36); Group II, receptors from donors without PCOS ( = 198). Medical records were reviewed and the fertilization, implantation, and pregnancy rates were calculated. Results. PCOS patients had an average of 3.23 more oocytes retrieved, but there were no differences in the number of mature oocytes that were used for donation between the groups. We also observed that the number of transferred embryos was also not significantly different, as well as the fertilization and implantation rates. The clinical pregnancy rates were not significantly different: 28% and 26% in Group I and Group II, respectively. Conclusions. Women with PCOS should not be excluded from egg donation programs

Current Knowledge on Endocrine Disrupting Chemicals (EDCs) from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting

Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic

Micropolíticas: devir, cooperação dissonante e experiência pura

This article traces the definition of the concept of micropolitics in a singular perspective of Critical Semiotics. It seeks supplements in the theories of Deleuze and Guattari to think of it as an underlying force to alliances that produce zones of becoming. Regarding the propositions of Rolnik and Guattari, it proposes the understanding of micropolitics as a process of dissonant cooperation among subjects positioned in distinct subjectivities, a process that makes these existential models deterritorialize themselves. Concerning the phenomenal characteristics of this process, it uses the thought of James and Lapoujade to understand that micropolitics is produced and intensified based on what these thinkers called pure experience.O artigo traça um percurso de definição do conceito de micropolítica em uma visada singular da Semiótica Crítica. Busca suplementos nas teorizações de Deleuze e Guattari para pensá-la enquanto força subjacente a alianças que produzem zonas de devir. Em relação às proposições de Rolnik e Guattari, projeta a compreensão da micropolítica enquanto processo de cooperação dissonante entre sujeitos posicionados em subjetividades distintas, processo que faz esses modelos existenciais desterritorializarem-se. Já considerando as características fenomênicas desse processo, recorre ao pensamento de James e de Lapoujade para compreender que a micropolítica é produzida e intensificada a partir do que esses filósofos chamaram de experiência pura