Cortisol and 17-a-hydroxy-progesterone levels in infants with refractory hypotension born at 30 weeks of gestation or less

Refractory hypotension is frequent in very low-birth weight infants, whose hypothalamic-pituitary-adrenal axis has been suggested to be immature. The objective of the present study was to evaluate basal cortisol and 17-a-OH-progesterone in the first 36 h of life in preterm infants with and without refractory hypotension (mean arterial blood pressure below the lower limit for gestational age throughout the study despite aggressive volume expansion and use of vasopressors). Thirty-five infants with £30 weeks of gestation and a birth weight £1250 g, with no postnatal use of corticosteroid or death in the first 48 h were studied. Mean arterial pressure was measured every 4 h during the first 48 h. Cortisol and 17-a-OH-progesterone were determined at 12 and 36 h and patients were divided into refractory hypotensive (N = 15) and control (N = 20) groups. The groups were not different regarding type of delivery, use of prenatal corticosteroid, requirement of mechanical ventilation, use of vasopressor drugs, morphine, fentanyl, prophylactic indomethacin, and mean sample timing. Although refractory hypotensive newborns were more immature, were smaller, suffered more deaths after 48 h of life and had a higher SNAPPE-2 score, their cortisol and 17-a-OH-progesterone levels were not different from controls at 12 h and at 36 h. The increase of cortisol in newborns with refractory hypotension 36 h after birth was significantly higher than in controls. Despite the fact that refractory hypotensive very low-birth weight neonates were submitted to a very stressful condition, their cortisol and 17-a-OH-progesterone levels were similar to controls.

Cortisol Awakening Response in Preschoolers and Depression Risk: Relations with Maternal History of Depression and Child Temperament

Increasing research suggests that elevations in the cortisol awakening response (CAR), the natural increase of cortisol 30 to 40 minutes after waking, may serve as a vulnerability marker for depression. However, existing studies have focused on adolescence and adulthood; very little is known about the CAR in early childhood and the factors that are associated with it. The current study aimed to examine the validity of the CAR as a potential early-emerging vulnerability marker for depression in a sample of preschool-age children. We examined associations between the CAR and two well-established risk factors for depression: maternal psychopathology and early child temperament (high negative emotionality (NE) and/or low positive emotionality (PE)). The sample consisted of 146 preschool-age children, of whom 71 (49.3%) had a biological mother with a history of depression and 65 (45.5%) had a biological mother with a history of anxiety. To assess the CAR, salivary cortisol samples were collected from the child upon waking, 30 and 45 minutes post-waking on two weekdays. Children’s CAR was examined as the total volume of cortisol secreted (AUCg) and the total increase in cortisol (AUCi) across waking. Evening cortisol was collected 30 minutes before bedtime. Child temperament was assessed using observational laboratory measures. Maternal depression and anxiety were assessed with clinical interviews. Associations with children’s CAR, as indicated by AUCg or AUCi, appeared to be specific to maternal current psychopathology and symptoms of anhedonia. Additionally, we observed significant interactions for both maternal lifetime and current depression and anxiety, in combination with child NE and PE, on elevated evening cortisol levels and flattened diurnal cortisol rhythms, indicating altered patterns of basal cortisol activity in offspring. Our study contributes to the limited but growing knowledge on the development of the CAR in preschool age children and as a marker of early risk. Findings suggest that there is a complex interplay between familial risk, affective vulnerability, and their joint effects on neuroendocrine dysfunction in young children, and highlight the need for future research to examine which aspects of the early diurnal rhythm predict the emergence of later depressive illness.

The prednisolone suppression test in depression: Dose-response and changes with antidepressant treatment

Depressed patients have reduced glucocorticoid receptor (GR) function, as demonstrated by resistance to the suppressive effects of the synthetic glucocorticoid hormone, and GR agonist, dexamethasone. We have developed a suppressive test with prednisolone, a synthetic glucocorticoid that is similar to cortisol in its pharmacodynamics and pharmacokinetics, and binds to both the GR and the mineralocorticoid receptor (MR). We have found that depressed patients suppress normally to prednisolone, unless they are particularly non-responsive to treatment. In the present study, we evaluated 28 inpatients with treatment-resistant depression (TRD), and compared salivary cortisol secretion (at 0900 h, 1200 h and 1700 h) after placebo or after prednisolone (5 mg), before and after an inpatient treatment admission. Half of the patients (n = 14) reached treatment response. When comparing the assessment between admission and discharge, cortisol output after placebo fell (-26% of area under the curve; p = 0.024) while the output after prednisolone did not change. Moreover, there was no change in the response to prednisolone (percentage suppression) between admission at discharge, and this was not influenced by treatment response. Finally, we could confirm and extend our previously published data with prednisolone (5 mg), showing that depressed patients (n = 12) and controls (n = 12) suppressed equally to both 5 and 10 mg doses of prednisolone. This study suggests that the response to prednisolone is similar in depressed patients and controls at different doses of prednisolone, and does not change with symptomatic improvement. This is in contrast with findings, from us and others, using other measures of hypothalamic-pituitary-adrenal axis function, such as basal cortisol levels or the response to dexamethasone. Thus, we propose that the prednisolone suppression test may offer specific biological and clinical information, related to its action at both the GR and the MR. (C) 2010 Elsevier Ltd. All rights reserved.

Pain and distress reactivity and recovery as early predictors of temperament in toddlers born preterm

Background: Pain reactivity may reflect underlying mechanisms of constitutional aspects of temperament. Aim: To examine whether the neonatal biobehavioral reactivity and recovery responses from pain and distress, as well as the gestational age, the illness severity and the amount of painful procedures undergone the Neonatal Intensive Care Unit (NICU) stay, predict temperament later in toddlerhood, in vulnerable children born preterm. Study design: Prospective-longitudinal study. Subjects: Twenty-six preterm and very low birth weight infants followed from birth to toddlerhood. Outcome measures: Illness severity was assessed with the Clinical Risk Index for Babies (CRIB) score. The medical charts were reviewed prospectively for obtaining the amount of pain exposure in NICU. For assessing the behavioral and cardiac reactivity and recovery from pain and distress, the neonates were evaluated during routine blood collection in the NICU in the first 10 days of life. Pain and distress reactivity and recovery was measured using the Neonatal Facial Coding System score, the duration of crying. and the magnitude of average heart rate. At toddlerhood, mothers answered the Early Childhood Behavior Questionnaire. Results: Higher biobehavioral reactivity to pain and distress predicted higher temperamental Negative Affect, above and beyond gestational age, illness severity and amount of pain exposure in NICU. However, we did not find a predictive relation between gestational age, CRIB score and number of painful procedures undergone NICU and toddler`s temperament. Conclusions: The findings highlight the relevance of the neonatal individual characteristics of reactivity for identifying more vulnerable infants for future problems in biobehavioral regulation. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Attachment, Physiological and Familial Vulnerability in Childhood Obesity: an Interactive Multisystem Approach

The aims of the present study were to test the association between insecure attachment and basal cortisol and catecholamines levels in a sample of obese children. The role of familial vulnerability and gender was also investigated. Methods: Cortisol and catecholamines levels of 8- to 13-year olds obese children were measured. Self-report questionnaires were used to assess attachment pattern and current anxiety and depression, and parent-report questionnaires were used to assess attachment, current anxiety and depression and familial vulnerability. Linear regression analyses were performed for individuals that scored low versus high on parental internalizing problems, and for boys and girls, separately. Results: In the group with high parental internalizing problems, insecure attachment was significantly associated with reduced basal levels of cortisol, in boys (p=0.007, b= -0.861, R2= 73.0%). In the group with low parental internalizing problems, the association between insecure attachment and cortisol was not significant in either boys or girls, and it was negative in boys (p=0.075, b= -0.606, R2= 36.7%) and positive in girls (p=0.677, b= 0.176, R2= 3.1%) . Conclusions: Apparently, physiological risk factors for psicopathology in obesity are more evident in individuals with a high familial vulnerability. In addition, patterns of physiological risk for psicopathology in obesity are different in boys and girls. Therefore, it is important to take into account familial vulnerability and gender when investigating physiological risk factors for psycopathology in obesity. Insecure attachment in childhood may be a risk factor for obesity. Interventions to increase children's attachment security should examine the effects on children's weight.

Avaliação do funcionamento do eixo HPA em deprimidos por meio de medidas basais: revisão sistemática da literatura e análise das metodologias utilizadas

Objetivo Realizar revisão sistemática da literatura para conhecer a atividade do eixo hipotálamo-pituitária-adrenal (HPA) em deprimidos considerando-se as medidas basais dos hormônios e analisar criticamente as metodologias utilizadas. Métodos Foi realizada busca de artigos nas bases de dados PubMed e SciELO. Na primeira base de dados, introduziram-se as palavras-chave “depressive disorder” e “HPA axis”, e na segunda utilizaram-se os termos “depression” ou “depressão” e “HHA” ou “HPA axis”. Optou-se por pesquisa realizada em humanos adultos, em inglês e português, do ano 2000 até 2011. Resultados Dos 27 artigos selecionados, obtiveram-se como resposta do eixo HPA tanto hiperatividade como atividade desregulada, hipoatividade ou não alteração. Tais resultados dependem das variáveis e dos hormônios estudados, do fluido coletado – plasma, urina, saliva, líquido cefalorraquidiano – do horário de coleta, do número de coletas, da análise estatística utilizada, do subtipo de doença depressiva, entre outros. Conclusão: Os resultados não apresentam consenso em relação à atividade do eixo HPA. Considerando as variáveis estudadas, o eixo HPA, na maioria das vezes, apresenta-se disfuncional na presença da depressão.

Teleost fish larvae adapt to dietary arachidonic acid supply through modulation of the expression of lipid metabolism and stress response genes

Dietary fatty acid supply can affect stress response in fish during early development. Although knowledge on the mechanisms involved in fatty acid regulation of stress tolerance is scarce, it has often been hypothesised that eicosanoid profiles can influence cortisol production. Genomic cortisol actions are mediated by cytosolic receptors which may respond to cellular fatty acid signalling. An experiment was designed to test the effects of feeding gilthead sea-bream larvae with four microdiets, containing graded arachidonic acid (ARA) levels (0·4, 0·8, 1·5 and 3·0 %), on the expression of genes involved in stress response (steroidogenic acute regulatory protein, glucocorticoid receptor and phosphoenolpyruvate carboxykinase), lipid and, particularly, eicosanoid metabolism (hormone-sensitive lipase, PPARα, phospholipase A2, cyclo-oxygenase-2 and 5-lipoxygenase), as determined by real-time quantitative PCR. Fish fatty acid phenotypes reflected dietary fatty acid profiles. Growth performance, survival after acute stress and similar whole-body basal cortisol levels suggested that sea-bream larvae could tolerate a wide range of dietary ARA levels. Transcription of all genes analysed was significantly reduced at dietary ARA levels above 0·4 %. Nonetheless, despite practical suppression of phospholipase A2 transcription, higher leukotriene B4 levels were detected in larvae fed 3·0 % ARA, whereas a similar trend was observed regarding PGE2 production. The present study demonstrates that adaptation to a wide range of dietary ARA levels in gilthead sea-bream larvae involves the modulation of the expression of genes related to eicosanoid synthesis, lipid metabolism and stress response. The roles of ARA, other polyunsaturates and eicosanoids as signals in this process are discussed.

Fonction surrénalienne après bolus d'étomidate en chirurgie cardiaque: une étude rétrospective [Adrenal function after induction of cardiac surgery patients with etomidate: a retrospective study]

OBJECTIVE: A single bolus dose of etomidate decreases cortisol synthesis by inhibiting the 11-beta hydroxylase, a mitochondrial enzyme in the final step of cortisol synthesis. In our institution, all the patients undergoing cardiac surgery receive etomidate at anesthesia induction. The purpose of this study was to assess the incidence of adrenocortical dysfunction after a single dose of etomidate in selected patients undergoing major cardiac surgery and requiring high-dose norepinephrine postoperatively. STUDY DESIGN: Retrospective descriptive study in the surgical ICU of a university hospital. PATIENTS AND METHODS: Sixty-three patients presented acute circulatory failure requiring norepinephrine (>0,2 microg/kg/min) during the 48 hours following cardiac surgery. Absolute adrenal insufficiency was defined as a basal cortisol below 414 nmo/l (15 microg/dl) and relative adrenal insufficiency as a basal plasma cortisol between 414 nmo/l (15 microg/dl) and 938 nmo/l (34 microg/dl) with an incremental response after 250 microg of synthetic corticotropin (measured at 60 minutes) below 250 nmol/l (9 microg/dl). RESULTS: Fourteen patients (22%) had normal corticotropin test results, 10 (16%) had absolute and 39 (62%) relative adrenal insufficiency. All patients received a low-dose steroid substitution after the corticotropin test. Substituted patients had similar clinical outcomes compared to patients with normal adrenal function. CONCLUSION: A high incidence of relative adrenal failure was observed in selected cardiac surgery patients with acute postoperative circulatory failure.

Leptin inhibits directly glucocorticoid secretion by normal human and rat adrenal gland.

Different interactions have been described between glucocorticoids and the product of the ob gene leptin. Leptin can inhibit the activation of the hypothalamo-pituitary-adrenal axis by stressful stimuli, whereas adrenal glucocorticoids stimulate leptin production by the adipocyte. The present study was designed to investigate the potential direct effects of leptin to modulate glucocorticoid production by the adrenal. Human adrenal glands from kidney transplant donors were dissociated, and isolated primary cells were studied in vitro. These cells were preincubated with recombinant leptin (10(-10)-10(-7) M) for 6 or 24 h, and basal or ACTH-stimulated cortisol secretion was subsequently measured. Basal cortisol secretion was unaffected by leptin, but a significant and dose-dependent inhibition of ACTH-stimulated cortisol secretion was observed [down by 29 +/- 0.1% of controls with the highest leptin dose, P < 0.01 vs. CT (unrelated positive control)]. This effect of leptin was also observed in rat primary adrenocortical cells, where leptin inhibited stimulated corticosterone secretion in a dose-dependent manner (down by 46 +/- 0.1% of controls with the highest leptin dose, P < 0.001 vs. CT). These effects of leptin in adrenal cells are likely mediated by the long isoform of the leptin receptor (OB-R), because its transcript was found to be expressed in the adrenal tissue and leptin had no inhibitory effect in adrenal glands obtained from db/db mice. Therefore, leptin inhibits directly stimulated cortisol secretion from human and rat adrenal glands, and this may represent an important mechanism to modulate glucocorticoid levels in various metabolic states.

Environmental blue light prevents stress in the fish Nile tilapia

The present study aimed to test the effects of blue, green or white light on the stress response of the Nile tilapia, Oreochromis niloticus (L.). Each color was tested on two groups of isolated adult Nile tilapia (8 replicates each): one being subjected to confinement stress, and the other not (control). A different environmental color was imposed on each compartment by covering the light source with cellophane of the respective color (green or blue; no cellophane was used for white light). The intensity of green, white and blue lights was 250, 590 and 250 lux, respectively. Basal plasma cortisol levels were determined for each fish prior to the experimental procedures. The fish were confined by being displaced toward one side of the aquarium using an opaque partition for 1 h both in the morning and the afternoon of the two consecutive days of the test. At the end of this 48-h period, plasma cortisol levels were measured again. Basal cortisol levels (ng/ml) were similar for each group (ANOVA, F(2;42) = 0.77, P = 0.47). Thus, plasma cortisol levels were analyzed in terms of variation from their respective basal level. After confinement, plasma cortisol levels were not increased in fish submitted to a blue light environment. Thus, blue light prevents the confinement-induced cortisol response, an effect not necessarily related to light intensity.

Maternal postnatal depression predicts altered offspring biological stress reactivity in adulthood

The offspring of depressed parents have been found to show elevated basal levels of the stress hormone cortisol. Whether heightened cortisol stress reactivity is also present in this group has yet to be clearly demonstrated. We tested whether postnatal maternal depression predicts subsequent increases in offspring biological sensitivity to social stress, as indexed by elevated cortisol reactivity. Participants (mean age 22.4-years) derived from a 22-year prospective longitudinal study of the offspring of mothers who had postnatal depression (PND group; n=38) and a control group (n=38). Salivary cortisol response to a social-evaluative threat (Trier Social Stress Test) was measured. Hierarchical linear modelling indicated that PND group offspring showed greater cortisol reactivity to the stress test than control group participants. Group differences were not explained by offspring depressive or anxiety symptoms, experiences of negative life events, elevated basal cortisol at age 13-years, subsequent exposure to maternal depression, or other key covariates. The findings indicate that the presence of early maternal depression can predict offspring biological sensitivity to social stress in adulthood, with potential implications for broader functioning.

Prolonged Physical Training Decreases mRNA Levels of Glucocorticoid Receptor and Inflammatory Genes

Background/Aims: Prolonged physical exercise induces adaptive alterations in the hypothalamic-pituitary axis, increasing cortisol metabolism, and reducing cortisol synthesis and glucocorticoid sensitivity. The mechanisms responsible for this relative glucocorticoid resistance remain unknown but may involve expression of genes encoding glucocorticoid receptor (GR) and/or inflammatory molecules of nuclear factor kappa B1 (NFkB1) signaling pathway and cytokines. This study aimed to determine the impact of prolonged physical training on the expression of genes involved in glucocorticoid action and inflammatory response. Methods: Normal sedentary male cadets of the Brazilian Air Force Academy were submitted to 6 weeks of standardized physical training. Eighteen of 29 initially selected cadets were able to fully complete the training program. Fasting glucose, insulin and cortisol levels, cytokine concentration and the expression of genes encoding GR, NFkB1, inhibitor of NFkB1 and IkB kinase A were determined before and after the training period. Results: Prolonged physical exercise reduced the basal cortisol levels and the percent cortisol reduction after dexamethasone. These findings were associated with a significant reduction in the mRNA levels of GR (6.3%), NFkB1 (63%), inhibitor of NFkB1 (25%) and IkB kinase A (46%) with concomitant reduction in cytokine concentrations (ELISA). Conclusions: Prolonged physical training decreases the glucocorticoid sensitivity and the mRNA levels of the GR gene combined with decreased mRNA of genes related to the NFkB pathway. Copyright (C) 2010 S. Karger AG, Basel

Caracterização comportamental endócrina das fases ontogenéticas de sagüi comum (Callithrix jacchus)

The use of animal models in biomedical research is ever increasing. Models that use primates might also have advantages in terms of low maintenance costs and availability of biological knowledge, thereby favoring their use in different experimental protocols. Many current stress studies use animal models at different developmental stages since biological response differs during ontogeny. The aims of this study were to perform a detailed characterization of the developmental stages of common marmosets (Callithrix jacchus), a very important animal model used in biomedical research. Ten subjects, 6 females and 4 males, were followed from birth to initial adult age (16 months). Behavioral and fecal collection for measurement of adrenal (cortisol) and sex (progesterone, estradiol and androgens) hormones took place twice a week during the first month of life and once a week for the remainder of the study. Behavior was observed for 30 minutes in the morning (0700-09:00h) and afternoon (12:00-14:00h). Behavioral profile showed changes during ontogeny, characterizing the 4 developmental stages and the respective phases proposed by Leão et al (2009).. Differentiation of developmental stages was considered using the onset, end, change and stabilization of the behavioral profile parental care (weaning and carrying), ingestion (solid food), affiliation (social grooming) and autogrooming, agonism (scent marking and piloerection) and play behavior and endocrine profile. Infant weaning and carrying terminated within the infantile stage and the peak of solid food ingestion was recorded in the infantile III phase. Receiving grooming was recorded earlier than grooming performed by the infant and autogrooming. The first episode of scent marking was recorded in the 4th week and it was the least variable behavior, in terms of its onset, which, in almost all animals, was between the 5th and 7th week of life. Solitary play and play with the twin started around the 7th week and play with other members of the group started 8 weeks later. Sex hormone secretion started to differ from basal levels between the 21st and 23rd week of life, in males and females, suggesting that puberty occurs simultaneously in both sexes. Basal cortisol, even at an early age, was higher in females than in males. However, cortisol was not correlated with the juvenile stage, as expected, since this stage corresponds to the transition between infancy and adult age and most behaviors are intensified by this time. The behavioral and endocrine profile of subadult animals did not differ from that of the adults. These results provide more detailed parameters for the developmental process of C. jacchus and open new perspectives for the use of experimental approaches focused on the intermediate ontogenetic phases of this species

Environmental blue light prevents stress in the fish Nile tilapia

The present study aimed to test the effects of blue, green or white light on the stress response of the Nile tilapia, Oreochromis niloticus (L.). Each color was tested on two groups of isolated adult Nile tilapia (8 replicates each): one being subjected to confinement stress, and the other not (control). A different environmental color was imposed on each compartment by covering the light source with cellophane of the respective color (green or blue; no cellophane was used for white light). The intensity of green, white and blue lights was 250, 590 and 250 lux, respectively. Basal plasma cortisol levels were determined for each fish prior to the experimental procedures. The fish were confined by being displaced toward one side of the aquarium using an opaque partition for 1 h both in the morning and the afternoon of the two consecutive days of the test. At the end of this 48-h period, plasma cortisol levels were measured again. Basal cortisol levels (ng/ml) were similar for each group (ANOVA, F(2;42) = 0.77, P = 0.47). Thus, plasma cortisol levels were analyzed in terms of variation from their respective basal level. After confinement, plasma cortisol levels were not increased in fish submitted to a blue light environment. Thus, blue light prevents the confinement-induced cortisol response, an effect not necessarily related to light intensity.

Sindrome di cushing nel cane: Nuove prospettive diagnostiche e terapeutiche

La sindrome di Cushing (SC) è una delle endocrinopatie più comuni nel cane. La diagnosi richiede l'integrazione di anamnesi, segnalamento, segni clinici, esami ematobiochimici, test endocrini specifici e diagnostica per immagini . Nel corso degli anni diversi sono i principi attivi testati per la terapia della SC del cane. In passato, il mitotane è stato il farmaco più utilizzato, sebbene il suo uso risulti complicato e non privo di potenziali effetti collaterali. Recentemente, il trilostano ha dimostrato di essere un trattamento efficace per il controllo dei sintomi ed è stato approvato per tale uso nel cane. Al fine di testare metodiche non invasive per la diagnosi di SC nel cane abbiamo valutato le concentrazioni di cortisolo nel pelo (HCC) .Queste risultavano significativamente più elevate nei cani con SC rispetto ai cani sani e malati. Questo test può essere quindi considerato una procedura diagnostica non invasiva in cani con un elevato sospetto di SC. Inoltre, a causa della difficile reperibilità dell’ACTH esogeno sono state valutate le concentrazioni di cortisolo basale come strumento di monitoraggio in cani con SC trattati con trilostano. Tuttavia la singola valutazione del cortisolo basale non rappresenta un parametro efficace ed accurato per il monitoraggio della terapia con trilostano. Sono stati inoltre valutati i fattori prognostici in cani con SC alla diagnosi. L' iperfosfatemia è risultata un riscontro comune nei cani SC, rappresentando un fattore prognostico negativo. La terapia chirurgica non è una procedura di routine nella SC del cane, tuttavia abbiamo descritto l'approccio di ipofisectomia transsfenoidale in un Galgo spagnolo di 8 anni con SC . Il cane è stato sottoposto per due volte ad ipofisectomia transsfenoidale che ha permesso di rimuovere completamente il macroadenoma ipofisario. In conclusione, questi studi ci hanno permesso di indagare alcuni aspetti patogenetici, clinici e diagnostici della SC del cane.