Diagnóstico Laboratorial da Síndrome de Cushing

Abstract

A suspeita clínica de síndrome de Cushing leva obrigatoriamente a uma avaliação laboratorial, baseada nas dosagens de cortisol e de ACTH. Entretanto as dosagens basais destes hormônios não são suficientes para confirmar o diagnóstico, sendo necessários testes dinâmicos que estimulem ou inibam o eixo hipotálamo-hipófise-adrenal (HHA). A adequada interpretação das dosagens requer o conhecimento dos princí-pios básicos da regulação do eixo HHA, o meio e a forma (ligada ou livre) onde o hormônio será quantificado, além das características dos ensaios empregados. Numa primeira fase do diagnóstico laboratorial, é feita a documentação do hipercortisolismo endógeno, através de dosagens salivares, urinárias ou séricas de cortisol, em amostras coletadas em horários apropriados e/ou após uso de dexametasona em doses baixas (1 mg). Numa segunda fase procede-se ao diagnóstico etiológico da síndrome de Cushing empregando-se basicamente dosagens de ACTH e de cortisol após uso de doses maiores de dexametasona. Muitas vezes a complexidade da patologia exige o uso de testes funcionais mais sofisticados, como o emprego de CRH, chegando até à necessidade de cateterismo do seio petroso inferior com coleta de amostras para a dosagem de ACTH. Apresentamos também o esquema utilizado na Divisão de Endocrinologia e Metabologia da Faculdade de Medicina de Ribeirão Preto para a confirmação da existência de sín-drome de Cushing e determinação de sua etiologia. ABSTRACTThe clinical suspicion of Cushing's syndrome leads to an obligatory laboratory evaluation, based on measurements of cortisol and ACTH. However, basal determination of these hormones is not sufficient to confirm the diagnosis, so that dynamic tests based on stimulation or inhibition of the hypothalamus-pituitary-adrenal axis (HPA) are necessary. An adequate interpretation of the laboratory results needs the understanding of the basic principles that regulate the HPA axis, the media and the form (bound or free) where the measurement will be perfomed, as well as the characteristics of the assays employed. The initial diagnostic phase, a documentation of the presence of endogenous hypercortisolism is done with the use of salivary, urinary or serum cortisol measurements, using samples collected with appropriate timing and/or after the use of low doses (1 mg) of dexamethasone. In a second phase we proceed to the etiologic diagnosis of Cushing's syndrome, using ACTH and cortisol measurements after higher doses of dexamethasone. The complexity of the syndrome frequently prompts the use of sophisticated functional tests, with the use of CRH and even samples collected during inferior petrosous sinus catheterization for the measurement of ACTH. We present the diagnostic scheme employed at the Division of Endocrinology and Metabolism of the Faculdade de Medicina de Ribeirão Preto for the confirmation

Limitations of Basal Cortisol in the Diagnosis of Cushing Syndrome

“…Cortisol is secreted in a pulsatile manner with a circadian rhythmicity; therefore, due to an overlap in similar values between normal subjects and CS patients, basal serum cortisol is not used for the diagnosis of CS (5,6). Even increased levels of morning basal serum cortisol have a low sensitivity for the diagnosis of CS (7).…”

Persistent glucocorticoid resistance in systemic lupus erythematosus patients during clinical remission

“…After 120 min of VLD-IV-DST, the concentration of cortisol was similar between groups, whereas the ACTH level was lower in the control group. Quantification of ACTH is characterized by known methodological difficulties owing to the sensitivity of the protein to heat and its instability in plasma (Castro and Moreira, 2002). The observed difference may also have been caused by sampling variability owing to the small number of cases in each group.…”

Primary pigmented nodular adrenocortical disease associated with Carney complex: case report and literature review

“…Otherwise, the ACTH values may be falsely found to be low and thereby induce diagnostic error. 9 PPNAD is a rare form of ACTH-independent Cushing's syndrome that may occur alone, but is found to be associated with CNC in 90% of the cases. 10 It is the most common endocrinal hyperactivity in these patients, and has been described in 25% of them.…”