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Argentina: new method developed to diagnose endocrine diseases in pediatric patients

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Endocrine Deseases CEDIE CIBION CONICET María Eugenia Monge Gabriela Ropelato Dr. Ricardo Gutiérrez General Children's Hospital
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The methodology designed by CONICET specialists allows quantifying, from a small serum sample, eight steroid hormones relevant to the diagnosis of adrenal pathologies in infants. The procedure is already available at the Dr. Ricardo Gutiérrez General Children’s Hospital.

María Eugenia Monge and Gabriela Ropelato. Image credit: CONICET Photography/ Verónica Tello.
María Eugenia Monge and Gabriela Ropelato. Image credit: CONICET Photography/ Verónica Tello.

A research team from CONICET developed a sophisticated method to separate, detect and quantify eight steroid hormones relevant to the diagnosis of endocrine diseases, which are synthesized in the adrenal glands and gonads, in infant serum samples. It is a methodology that uses the ultra-high performance liquid chromatography technique coupled with the tandem mass spectrometry technique (UHPLC-MS/MS).

The new method, validated according to the guidelines indicated by the international guidelines of the Food and Drug Administration of the United States (FDA) and the European Medicines Agency (EMA), is now available to patients of the Dr. Ricardo Gutiérrez Children’s Hospital in the Autonomous City of Buenos Aires. The methodology was recently presented in an article published in the Journal of Mass Spectrometry and Advances in the Clinical Lab.

“The method we developed uses only 100 microliters of serum, a quarter of the volume required by immunoassays commonly used in clinical laboratories for the detection of steroid hormones. It should be borne in mind that while immunoassays require the analysis of a sample for each steroid to be quantified, our methodology allows the eight hormones to be quantified simultaneously in a single sample. Even two of the eight steroids that we were able to quantify using this method (pregnenolone and 17-hydroxypregnenolone) cannot be determined in any laboratory in Argentina, since there are currently no accessible commercial immunoassays,” said María Eugenia Monge, CONICET researcher at the Center for Research in Bionanosciences (CIBION; CONICET) and one of the leaders of the development.

María Eugenia Monge y Gabriela Ropelato in the lab, Image credit: CONICET Fotografía/ Verónica Tello
María Eugenia Monge y Gabriela Ropelato in the lab, Image credit: CONICET Fotografía/ Verónica Tello

The research team that carried out the development highlighted that this new method has a relevant application in the diagnosis and research of steroidogenesis disorders in children.

“Being able to evaluate which is the synthesis or metabolism pathway of the steroid hormone that is affected allows a more accurate diagnosis to be made and, consequently, to make therapeutic decisions based on scientific evidence,” said Gabriela Ropelato, CONICET researcher at the “Dr. César Bergadá” Endocrinological Research Center (CEDIE, CONICET-FEIEndocrinology Division, Ricardo Gutiérrez Children’s Hospital), head of the laboratory section of the Endocrinology Division of the Gutiérrez Hospital and another of the leaders of the work.

“In addition, the possibility of quantifying steroids that are not currently detected by immunoessays offered by clinical laboratories in Argentina will allow us to understand in greater depth the pathophysiological mechanisms that alter the health of children suffering from endocrine and metabolic disorders,” she added.

Currently, at the Gutiérrez Hospital, this procedure is used to perform a diagnostic confirmation and provide timely treatment to pediatric patients suffering from endocrine disorders, which have been previously detected by the Neonatal Screening Program. One of the pathologies that is sought to be identified early thanks to this type of study is renal hyperplasia, a disease that affects approximately one in 14 thousand newborn babies and can cause dehydration, vomiting, diarrhea, heart rhythm problems, precocious puberty and other complications in older children. In girls, symptoms may include ambiguous genitalia at birth or the development of pubic hair and severe acne during childhood.

María Eugenia Monge and Gabriela Ropelato in the laboratory, Photos: CONICET Photography/ Verónica Tello.
María Eugenia Monge and Gabriela Ropelato in the laboratory, Image credit: CONICET Photography / Verónica Tello.

The equipment used for this project is installed in the Translational Medicine Unit (UMT) of the Gutiérrez Children’s Hospital. The CEDIE staff who participated in this project under the direction of Ropelato, an expert in pediatric endocrinology, were responsible for taking the first steps for the development, as well as the selection of the clinical material that was used for the validation of the technique. The articulation with the team led by Monge, an international leader in mass spectrometry and metabolomics, ended up shaping the project and ensuring scientific rigor so that the new methodology could be validated according to international standards and transferred to the clinic.

“Through this development, now available in the public hospital, we bring more accurate and earlier measurements to infants; which enables safer and more timely clinical decisions,” the researchers concluded.

The first authors of the study were the CONICET researcher at the Faculty of Pharmacy and Biochemistry of the UBA, Manuela Martinefski, who did her postdoctoral work under Monge’s direction at CIBION, and the main professional of the CONICET Support Staff career Verónica Ambao (CEDIE). Also participating in the study were: CONICET researcher Rodolfo Rey (CEDIE), María Gabriela Ballerini (independent researcher at the GCBA) and María Eugenia Rodríguez, both from the Endocrinology Division on the Gutiérrez Hospital.

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