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Abstract(s)
O presente trabalho integra o plano de estudos do Mestrado em Análises Clínicas da Faculdade de Farmácia da Universidade de Lisboa.
O estágio decorreu no Laboratório de Análises Clínicas Lumilabo (LACL) nas áreas de Pré-Analítica, Hematologia, Bioquímica, Microbiologia e Pós-Analítica e teve duração de seis meses. No relatório estão descritas as áreas de Pré-Analítica, Hematologia, Microbiologia e Pós-Analítica.
O estágio teve como objetivo aplicar e aprofundar os conhecimentos teóricos adquiridos nas aulas do Mestrado em Análises Clínicas, integrar a rotina diária do laboratório de análises e adquirir experiência profissional. No relatório de estágio estão descritos todas as etapas e os procedimentos realizados no LACL para a realização de análises clínicas desde o atendimento do doente até à emissão do boletim.
A monografia tem como tema “Glândula supra-renal: avaliação da hiperplasia congénita desde o feto até à idade adulta” e corresponde à segunda parte deste trabalho. As glândulas supra-renais são glândulas endócrinas que produzem hormonas esteroides como mineralocorticoides, glucocorticoides, precursores dos esteroides sexuais e androgénios em pequenas quantidades. Adicionalmente, as supra-renais também são responsáveis pela produção de catecolaminas, hormonas derivadas de aminoácidos.
O cortisol, também designado como hormona de stress, é o glucocorticoide mais abundante no Homem e apresenta como função a manutenção dos níveis de glicose no sangue em situações de stress, como por exemplo, luta ou fome prolongada, mobilizando as reservas proteicas e lipídicas do organismo.
A hiperplasia congénita da supra-renal (HCSR) é um grupo de distúrbios hereditários autossómicos recessivos causados por défices enzimáticos nas vias de produção de cortisol. A diminuição de produção cortisol aumenta os níveis da hormona adrenocorticotrópica, através de um sistema de feedback negativo, causando a constante estimulação do córtex adrenal. O excesso de estimulação do córtex resulta em hiperplasia da glândula e acumulação excessiva dos substratos da enzima deficitária. Cada tipo de défice enzimático específico dá origem a diferentes tipos de HCSR, do qual cada um origina uma combinação única de precursores elevados e produtos reduzidos ou ausentes.
O quadro clínico da HCSR depende da enzima na qual ocorre a mutação e do seu grau de atividade e pode levar a alterações na produção de glucocorticoides, mineralocorticoides e androgénios supra-renais. Durante o desenvolvimento fetal os níveis de androgénios são essenciais para a diferenciação sexual e alterações na sua produção são responsáveis pela formação de genitálias ambíguas nos fetos do género feminino.
O distúrbio de HCSR mais comum é devido à deficiência de 21-hidroxilase (21-OHD) causada por mutação no gene CYP21A2. Este distúrbio caracteriza-se por diminuição da produção de glucocorticoides e mineralocorticoides com excesso de produção de androgénios. Representa entre 90 a 95% dos casos totais da doença e é a causa mais comum de alterações de diferenciação sexual em recém-nascidos do sexo feminino. Neste trabalho será abordada somente a 21-OHD devido a sua elevada incidência.
A HCSR é classificada em forma clássica e forma não-clássica. A forma clássica apresenta uma deficiência enzimática severa na via de biossíntese do cortisol e excesso de androgénios supra-renais, que se manifesta na virilização dos fetos femininos no período pré-natal. A forma clássica pode ainda ser dividida em forma perdedora de sal e forma virilizante simples, dependendo da biossíntese da aldosterona. Já a forma não-clássica, corresponde a um défice enzimático moderado com ou sem virilização no período pós-natal.
Os diferentes tipos de HCSR podem ser distinguidos através de exames hormonais e genéticos. A falta de diagnóstico das formas mais graves de HCSR estão associadas a um risco elevado de morbilidade e mortalidade incluindo mortalidade no período neonatal.
This work is part of the Master's Degree curriculum in Clinical Analysis at Faculdade de Farmácia da Universidade de Lisboa. The internship took place at Lumilabo's Clinical Analysis Laboratory (LACL) and lasted six months. The internship was in the areas of pre-Analytical stage, Hematology, Biochemistry, Microbiology and Post-Analytical stage. This report describes the areas of Pre- Analytical, Hematology, Microbiology and Post-Analytical. The internship aimed to apply and deepen the theoretical knowledge acquired in the Master's in Clinical Analysis classes, integrate the day-to-day of the clinical laboratory and acquire professional experience. The internship report describes all the steps and procedures performed at LACL to carry out clinical analyses, from patient care to issuing the report. The dissertation theme is “Adrenal gland: assessment of congenital hyperplasia from the fetus to adulthood” and corresponds to the second part of this work. The adrenal glands are endocrine glands that produce steroid hormones such as mineralocorticoids, glucocorticoids, sex steroid precursors and androgens in small amounts. They are also responsible for the production of catecholamines, which are hormones derived from amino acids. Cortisol, also known as the stress hormone, is the most abundant glucocorticoid in humans and has the function of maintaining blood glucose levels in stressful situations, such as in fighting or prolonged hunger situations, mobilizing protein and lipid reserves of the body. Congenital adrenal hyperplasia (HCSR) is a group of autosomal recessive disorders caused by enzyme deficits in the cortisol production pathways. Decreased cortisol production increases adrenocorticotropic hormone levels through a negative feedback system, causing constant stimulation of the adrenal cortex. Excessive stimulation of the cortex results in gland hyperplasia and excessive secretion of deficient enzyme precursors. The type of enzyme deficit defines the type of HCSR, each of which gives rise to a unique combination of elevated precursors and reduced or absent products. The clinical condition of HCSR depends on the enzyme in which the mutation occurs as well as the degree of activity. This can lead to alterations in the production of adrenal glucocorticoids, mineralocorticoids and androgens. During fetal development, androgen levels are essential for sexual differentiation and alterations in their production may lead to the formation of ambiguous genitalia in female fetuses. The most common HCSR disorder is due to 21-hydroxylase (21-OHD) deficiency caused by mutation in the CYP21A2 gene. This disorder is characterized by decreased production of glucocorticoids and mineralocorticoids with excess production of androgens. It represents between 90 and 95% of the total cases of the disease and is the most common cause of sexual differentiation alterations in female newborns. In this work, only 21-OHD will be addressed due to its high incidence. HCSR is classified into classic form and non-classic form. The classic form presents a severe enzyme deficiency in the cortisol biosynthesis pathway and an excess of adrenal androgens, which manifests itself in the virilization of female fetuses in the prenatal period. The classic form can be further divided into a salt wasting form and a simple virilizing form, depending on the aldosterone biosynthesis. On the other hand, the non-classic form corresponds to a moderate enzyme deficit with or without virilization in the postnatal period. The different types of HCSR can be distinguished through hormonal and genetic tests and the lack of diagnosis, of the most severe forms of HCSR, is associated with an increased risk of morbidity and mortality, including mortality in the neonatal period.
This work is part of the Master's Degree curriculum in Clinical Analysis at Faculdade de Farmácia da Universidade de Lisboa. The internship took place at Lumilabo's Clinical Analysis Laboratory (LACL) and lasted six months. The internship was in the areas of pre-Analytical stage, Hematology, Biochemistry, Microbiology and Post-Analytical stage. This report describes the areas of Pre- Analytical, Hematology, Microbiology and Post-Analytical. The internship aimed to apply and deepen the theoretical knowledge acquired in the Master's in Clinical Analysis classes, integrate the day-to-day of the clinical laboratory and acquire professional experience. The internship report describes all the steps and procedures performed at LACL to carry out clinical analyses, from patient care to issuing the report. The dissertation theme is “Adrenal gland: assessment of congenital hyperplasia from the fetus to adulthood” and corresponds to the second part of this work. The adrenal glands are endocrine glands that produce steroid hormones such as mineralocorticoids, glucocorticoids, sex steroid precursors and androgens in small amounts. They are also responsible for the production of catecholamines, which are hormones derived from amino acids. Cortisol, also known as the stress hormone, is the most abundant glucocorticoid in humans and has the function of maintaining blood glucose levels in stressful situations, such as in fighting or prolonged hunger situations, mobilizing protein and lipid reserves of the body. Congenital adrenal hyperplasia (HCSR) is a group of autosomal recessive disorders caused by enzyme deficits in the cortisol production pathways. Decreased cortisol production increases adrenocorticotropic hormone levels through a negative feedback system, causing constant stimulation of the adrenal cortex. Excessive stimulation of the cortex results in gland hyperplasia and excessive secretion of deficient enzyme precursors. The type of enzyme deficit defines the type of HCSR, each of which gives rise to a unique combination of elevated precursors and reduced or absent products. The clinical condition of HCSR depends on the enzyme in which the mutation occurs as well as the degree of activity. This can lead to alterations in the production of adrenal glucocorticoids, mineralocorticoids and androgens. During fetal development, androgen levels are essential for sexual differentiation and alterations in their production may lead to the formation of ambiguous genitalia in female fetuses. The most common HCSR disorder is due to 21-hydroxylase (21-OHD) deficiency caused by mutation in the CYP21A2 gene. This disorder is characterized by decreased production of glucocorticoids and mineralocorticoids with excess production of androgens. It represents between 90 and 95% of the total cases of the disease and is the most common cause of sexual differentiation alterations in female newborns. In this work, only 21-OHD will be addressed due to its high incidence. HCSR is classified into classic form and non-classic form. The classic form presents a severe enzyme deficiency in the cortisol biosynthesis pathway and an excess of adrenal androgens, which manifests itself in the virilization of female fetuses in the prenatal period. The classic form can be further divided into a salt wasting form and a simple virilizing form, depending on the aldosterone biosynthesis. On the other hand, the non-classic form corresponds to a moderate enzyme deficit with or without virilization in the postnatal period. The different types of HCSR can be distinguished through hormonal and genetic tests and the lack of diagnosis, of the most severe forms of HCSR, is associated with an increased risk of morbidity and mortality, including mortality in the neonatal period.
Description
Tese de mestrado, Análises Clínicas, 2021, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Estágio Glândula supra-renal Hiperplasia congénita da supra-renal Cortisol Esteróides