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Marked elevation of adrenal steroids, especially androgens, in saliva of prepubertal autistic children.

ABSTRACT: Autism is diagnosed on the basis of behavioral manifestations, but its biomarkers are not well defined. A strong gender bias typifying autism (it is 4-5 times more prevalent in males) suggests involvement of steroid hormones in autism pathobiology. In order to evaluate the potential roles of such hormones in autism, we compared the salivary levels of 22 steroids in prepubertal autistic male and female children from two age groups (3-4 and 7-9 years old) with those in healthy controls. The steroids were analyzed using gas chromatography-mass spectrometry and radioimmunoassay. Statistical analysis (ANOVA) revealed that autistic children had significantly higher salivary concentrations of many steroid hormones (both C21 and C19) than control children. These anomalies were more prominent in older autistic children and in boys. The levels of androgens (androstenediol, dehydroepiandrosterone, androsterone and their polar conjugates) were especially increased, indicative of precocious adrenarche and predictive of early puberty. The concentrations of the steroid precursor, pregnenolone, and of several pregnanolones were also higher in autistic than in healthy children, but cortisol levels were not different. Some steroids, whose levels are raised in autism (allopregnanolone, androsterone, pregnenolone, dehydroepiandrosterone and their sulfate conjugates) are neuroactive and modulate GABA, glutamate, and opioid neurotransmission, affecting brain development and functioning. These steroids may contribute to autism pathobiology and symptoms such as elevated anxiety, sleep disturbances, sensory deficits, and stereotypies among others. We suggest that salivary levels of selected steroids may serve as biomarkers of autism pathology useful for monitoring the progress of therapy.

SUBMITTER: Majewska MD

PROVIDER: S-EPMC4042015 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo determine the prognostic value of cortisol, Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone-sulfate (DHEAS), together with their ratios (cortisol/DHEA and cortisol/DHEAS), as independent predictors of mortality in septic patients.MethodsProspective cohort study of 139 consecutive patients with a diagnosis of severe sepsis or septic shock. Adrenal hormones were determined within the first 24 hours of the septic process. To determine and compare the predictive ability of each marker for the risk of unfavorable evolution (in-hospital, 28-day and 90-day mortality), ROC (Receiver Operating Characteristic) curves were constructed and the area under the curve (AUC) was determined. As measures of association, adjusted odds ratios (OR) with their 95% confidence intervals (95%CI) were estimated by unconditional logistic regression. Cortisol, DHEA and DHEAS results were compared to lactate, CRP, SOFA and APACHE II Scores.ResultsCortisol showed the best predictive ability, with AUCs of 0.758, 0.759 and 0.705 for in-hospital mortality, and 28-day and 90-day mortality, respectively; whereas AUCs for 28 days mortality for SOFA and APACHE II scores, and other biomarkers studied, such as Lactate or CRP, were 0.644, 0.618, 0.643 and 0.647, respectively. Associations between high cortisol levels (>17.5 μg/dL) and mortality were strong and statistically significant for in-hospital and 28-day mortality: adjusted ORs 10.13 and 9.45 respectively, and lower for long term mortality (90 days): adjusted OR 4.26 (95% CI 1.34-13.56), p trend 0.014. Regarding adrenal androgens, only positive associations were obtained for DHEAS and most of these positive associations did not yield statistical significance. Regarding Cortisol/DHEA and cortisol/DHEAS ratios, they did not improve the predictive ability of cortisol. The only exception was the cortisol/DHEAS ratio, which was the best predictor of mortality at 90 days (AUC 0.737), adjusted OR for highest cortisol/DHEAS ratio values 6.33 (95%CI 1.77-22.60), p trend 0.002.ConclusionBasal cortisol measured within the first 24 hours of the septic process was the best prognostic factor for in-hospital and 28-day mortality, even superior to the Sequential Organ Failure Assessment (SOFA) or Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. The cortisol/DHEAS ratio was an independent predictor of long-term mortality.

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Marked elevation of adrenal steroids, especially androgens, in saliva of prepubertal autistic children.

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