Eveline Gadelha Pereira Fontenele

The sitting height/height ratio for age in healthy and short individuals and its potential role in selecting short children for SHOX analysis.

Aims: To determine the presence of abnormal body proportion, assessed by sitting height/height ratio for age and sex (SH/H SDS) in healthy and short individuals, and to estimate its role in selecting short children for SHOX analysis. Methods: Height, sitting height and weight were evaluated in 1,771 healthy children, 128 children with idiopathic short stature (ISS), 58 individuals with SHOX defects (SHOX-D) and 193 females with Turner syndrome (TS). Results: The frequency of abnormal body proportion, defined as SH/H SDS >2, in ISS children was 16.4% (95% CI 10-22%), which was higher than in controls (1.4%, 95% CI 0.8-1.9%, p < 0.001). The SHOX gene was evaluated in all disproportionate ISS children and defects in this gene were observed in 19%. Among patients with SHOX-D, 88% of children (95% CI 75-100%) and 96% of adults had body disproportion. In contrast, SH/H SDS >2 were less common in children (48%, 95% CI 37-59%) and in adults (28%, 95% CI 20-36%) with TS. Conclusion: Abnormal body proportions were observed in almost all individuals with SHOX-D, 50% of females with TS and 16% of children considered ISS. Defects in SHOX gene were identified in 19% of ISS children with SH/H SDS >2, suggesting that SH/H SDS is a useful tool to select children for undergoing SHOX molecular studies.

Contaminantes ambientais e os interferentes endócrinos

The toxicity of various pollutants has been routinely investigated according to their teratogenic and carcinogenic effects. In the last few decades, however, many of such pollutants have been shown to adversely affect the endocrine system of human beings and other species. Currently, more than eleven million chemical substances are known in the world, and approximately 3,000 are produced on a large scale. Numerous chemical composites of domestic, industrial and agricultural use have been shown to influence hormonal activity. Examples of such chemical products with estrogenic activity are substances used in cosmetics, anabolizing substances for animal feeding, phytoestrogens and persistent organic pollutants (POPs). These agents are seen in residential, industrial and urban sewerage system effluents and represent an important source of environmental contamination. The International Programme on Chemical Safety (IPCS) defines as endocrine disruptors substances or mixtures seen in the environment capable of interfering with endocrine system functions resulting in adverse effects in an intact organism or its offspring. In this article the authors present a current literature review about the role of these pollutants in endocrine and metabolic diseases, probable mechanisms of action, and suggest paths of investigation and possible strategies for prevention and reduction of its possible damages.

Tumores testiculares bilaterais por hiperplasia congênita de restos adrenais

OBJECTIVES Testicular tumors are a rare condition associated with congenital adrenal hyperplasia (CAH), originated from intratesticular adrenal rest tumors, and they are rarely associated with malignant tumors. Their histological differentiation from Leydig-cell tumors is quite difficult, which would lead to inappropriate orchiectomies. Thus the objective of this report was to present this diagnostic dilemma. METHODS Reported the case of 16-yr-old boy with previous diagnosis of CAH with bilateral testicular enlargement who was recommended to be submitted to a bilateral orchiectomy. RESULTS Considering this findings, it was decided to treat conventionally with prednisone with significant reduction of testicular volume, and normalization of androgens levels. CONCLUSION This case shows the importance of intratesticular adrenal rest tumors in the differential diagnosis of testicular tumors. Cautious approach during investigation and treatment are recommended to avoid inappropriate orchiectomies.

A novel homozygous 1-bp deletion in the NOBOX gene in two Brazilian sisters with primary ovarian failure

PurposePrimary ovarian failure (POF) is characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women leading to infertility under the age of 40 years. POF is a heterogeneous disease with different causes, and several genes have been associated with the POF phenotype. Thus, Whole-exome sequencing (WES) was performed in a consanguineous family with two sisters affected by POF.MethodsAll exons of both sisters were massively sequenced by WES, and the segregation was confirmed by Sanger sequencing.ResultsThe novel homozygous c.1489delT variant in the NOBOX gene was identified in the two sisters with POF. Their parents were heterozygous carriers of this variant and, therefore, consistent with an autosomal recessive mode of inheritance. The c.1489delT NOBOX variant has not been previously reported in any public available databases (1000Genomes, 6500ESP/EVS, ExAC, and gnomAD). Furthermore, this variant was neither present in 387 Brazilian exomes control individuals nor in 200 fertile Brazilian women screened by Sanger sequencing.ConclusionWe report the first familial case of a novel homozygous NOBOX variant with an autosomal recessive mode of inheritance, thus allowing for a genetic diagnosis of primary ovarian failure.

Testosterone and Endocrine Disruptors: Influence of Endocrine Disruptors on Male Reproductive Tract

A wide variety of chemical compounds with endocrine disruptor (EDC) activity have been recognized for environmental control agencies worldwide, including pesticides, pollutants, and substances used in the production of plastics. Biomonitoring studies have identified the compounds in adults, children, pregnant women, and fetuses. EDCs are contributing to the increased prevalence of chronic diseases, including those related to the reproductive system. Initially, it was assumed that EDCs exert their adverse effects by binding to hormone receptors and transcription factors, but it is currently known that they may also alter the expression of enzymes involved in the steroid synthesis and/or catabolism or cause epigenetic changes. The true impact of endocrine disruptors on human health is difficult to assess because specific end points may be differentially affected at different ages. Humans are exposed to east hundreds of environmental chemicals and a major limitation of epidemiologic studies is that usually they measured the human exposure to a single EDC. The EDCs are an international problem and the public, the media, politicians, and governmental agencies should be educated on ways to avoid EDC exposure.