Adrenal incidentaloma as a novel independent predictive factor for periodontitis.

PURPOSE: There are no data regarding periodontal derangements in patients with adrenal incidentalomas (AI). We assessed the frequency and severity of periodontitis in patients with AI [non-functioning adrenal incidentaloma (NFAI) and possible autonomous cortisol secretion (ACS)] and compared with individuals with normal adrenal. METHODS: A cross-sectional study evaluated thirty-five individuals with AI and 26 controls. NFAI and possible ACS diagnosis was based on the current guidelines: NFAI [cortisol levels after 1 mg dexamethasone suppression test (1 mg-DST) ≤ 1.8 µg/dL (≤ 50 nmol/L)]; possible ACS [cortisol levels after 1 mg-DST 1.9-5.0 µg/dL (51-138 nmol/L)]. Sociodemographic data were collected, and a full-mouth periodontal evaluation was performed. RESULTS: There was no significant difference between groups regarding age, sex, income, ethnicity, education level, smoking, body mass index, dysglycemia, and arterial hypertension. Patients with AI exhibited worse periodontal conditions than controls for the following periodontal clinical parameters: mean percentage of probing pocket depth (PPD) and clinical attachment level (CAL) ≥ 5 mm (p < 0.001 and p = 0.006, respectively). Patients with NFAI and possible ACS showed higher gingival bleeding index (p = 0.014), bleeding on probing (p < 0.001), and CAL (p < 0.001) means compared to controls. The frequencies of periodontitis were 72.7% in patients with NFAI, 84.6% in possible ACS, and 30.8% in controls (p = 0.001). Periodontitis was more severe in patients with possible ACS than NFAI and controls. Patients with NFAI and possible ACS exhibited odds ratio for periodontitis of 4.9 (p = 0.016) and 8.6 (p = 0.02), respectively. CONCLUSION: Patients with AI have higher frequency and severity of periodontitis than controls. The presence of AI was an independent predictive factor for periodontitis.

Developmental Programming of Capuchin Monkey Adrenal Dysfunction by Gestational Chronodisruption.

In the capuchin monkey (Cebus apella), a new-world nonhuman primate, maternal exposure to constant light during last third of gestation induces precocious maturation of the fetal adrenal and increased plasma cortisol in the newborn. Here, we further explored the effects of this challenge on the developmental programming of adrenal function in newborn and infant capuchin monkeys. We measured (i) plasma dehydroepiandrosterone sulphate (DHAS) and cortisol response to ACTH in infants with suppressed endogenous ACTH, (ii) plasma DHAS and cortisol response to ACTH in vitro, and (iii) adrenal weight and expression level of key factors in steroid synthesis (StAR and 3ß-HSD). In one-month-old infants from mothers subjected to constant light, plasma levels of cortisol and cortisol response to ACTH were twofold higher, whereas plasma levels of DHAS and DHAS response to ACTH were markedly reduced, compared to control conditions. At 10 months of age, DHAS levels were still lower but closer to control animals, whereas cortisol response to ACTH was similar in both experimental groups. A compensatory response was detected at the adrenal level, consisting of a 30% increase in adrenal weight and about 50% reduction of both StAR and 3ß-HSD mRNA and protein expression and the magnitude of DHAS and cortisol response to ACTH in vitro. Hence, at birth and at 10 months of age, there were differential effects in DHAS, cortisol production, and their response to ACTH. However, by 10 months of age, these subsided, leading to a normal cortisol response to ACTH. These compensatory mechanisms may help to overcome the adrenal alterations induced during pregnancy to restore normal cortisol concentrations in the growing infant.

Algorithm for Screening of Adrenal Function in Stable Patients with Cirrhosis.

INTRODUCTION AND AIMS: Adrenal insufficiency (AI) is common in patients with cirrhosis. We aimed to assess the presence of AI in stable patients with cirrhosis using the gold-standard insulin tolerance test (ITT) and to propose an algorithm for screening AI in these patients. MATERIAL AND METHODS: We studied 40 stable patients with cirrhosis. We determined the basal total (BTC) and peak cortisol (PTC) levels. Using the ITT, we defined AI as a serum PTC < 18 µg/dL at 30 min after insulin-induced hypoglycemia. We assessed the diagnostic accuracy of BTC in different stages of liver disease to discriminate between those with NAF and AI. RESULTS: Of the 40 patients, 24 (60%) presented with AI. Child-Pugh and MELD scores differed between the NAF and AI groups (Child-Pugh: NAF 7.2 ± 1.7 vs. AI 8.8 ± 2.4, p = 0.024 and MELD: NAF 9.9 ± 2.5 vs. AI 14.9 ± 6.3, p = 0.001). The BTC level was lower in patients with AI than in those with NAF (7.2 ± 2.4 vs. 12.5 ± 5.2, p < 0.001). A BTC value ≤ 10.0 µg/dL had a 96% sensitivity (negative predictive value: 90%) for identifying AI. This cutoff value (BTC ≤ 10.0 µg/dL) provided 100% specificity (positive predictive value: 100%) in patients with advanced liver disease (Child-Pugh ≥ 9 or MELD ≥ 12). CONCLUSION: An algorithm including the use of BTC and the severity of liver disease may be a useful and simple method for assessing adrenal function in stable patients with cirrhosis.

Maternal flaxseed diet during lactation changes adrenal function in adult male rat offspring.

Flaxseed (Linum usitatissimum L.) has been a focus of interest in the field of functional foods because of its potential health benefits. However, we hypothesised that maternal flaxseed intake during lactation could induce several metabolic dysfunctions in adult offspring. In the present study, we aimed to characterise the adrenal function of adult offspring whose dams were supplemented with whole flaxseed during lactation. At birth, lactating Wistar rats were divided into two groups: rats from dams fed the flaxseed diet (FLAX) with 25% of flaxseed and controls dams. Pups received standard diet after weaning and male offspring were killed at age 180 days old to collect blood and tissues. We evaluated body weight and food intake during development, corticosteronaemia, adrenal catecholamine content, hepatic cholesterol, TAG and glycogen contents, and the protein expression of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), 11-ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) and adrenaline ß2 receptor at postnatal day 180 (PN180). After weaning, pups from the FLAX group had a higher body weight (+10 %) and food intake (+10%). At PN180, the FLAX offspring exhibited higher serum corticosterone (+48%) and lower adrenal catecholamine ( - 23%) contents, lower glycogen ( - 30%), higher cholesterol (4-fold increase) and TAG (3-fold-increase) contents in the liver, and higher 11ß-HSD1 (+62%) protein expression. Although the protein expression of hypothalamic CRH was unaffected, the FLAX offspring had lower protein expression of pituitary ACTH ( - 34%). Therefore, induction of hypercorticosteronaemia by dietary flaxseed during lactation may be due to an increased hepatic activation of 11ß-HSD1 and suppression of ACTH. The changes in the liver fat content of the FLAX group are suggestive of steatosis, in which hypercorticosteronaemia may play an important role. Thus, it is recommended that lactating women restrict the intake of flaxseed during lactation.

Effects of neonatal inflammation on the inflammatory and oxidative profile during experimental sepsis in adult life.

The present study aimed to evaluate the long-term effects of neonatal inflammation on the inflammatory and oxidative profile during experimental sepsis in adult life. Neonatal Balb/c mice received different treatments on day 10: LPS i.p. injection (100g/kg) (nLPS) or saline i.p. injection (nSal). As adults, fear/anxiety behavior was evaluated in the elevated plus maze. The following week, saline solution or LPS was administered and, after 12h, serum (inflammatory cytokines), liver (mitochondrial complexes and oxidative stress) and adrenal gland samples (angiotensin II type 1 and 2 receptors) were collected. There was an increase in the fear/anxiety behavior in the nLPS group. Neonatal administration of LPS increased the mRNA expression of the AT1 receptor and decreased the mRNA expression of the AT2 receptor in the adrenal glands of males. The complexes II and II-III increased in the nLPS saline male group when compared to control. The LPS administration in adult females, regardless of the neonatal treatment, induced a decrease of the glutathione enzyme activity. There were no differences in the inflammatory cytokines. The results showed that neonatal inflammation influenced mitochondrial respiratory chain metabolism and angiotensin II receptors in a sex-dependent manner. Balb/c mice fear and anxiety behaviors in adulthood were programmed by early life inflammatory stress.

Adrenal response of male rats exposed to prenatal stress and early postnatal stimulation.

Stress in pregnant rats caused by chronic immobilization alters the pattern of secretion of corticosterone and modifies the hypothalamic-pituitary-adrenal axis (HPA) of the fetus. Early postnatal handling, however, may reverse the effects of increased secretion of corticosterone. We investigated the effects of prenatal stress and postnatal handling on the activity of the HPA axis of male offspring of stressed female rats. Male 90-day-old rats from four groups were investigated: prenatally stressed animals without postnatal handling, prenatally stressed animals with postnatal handling, unstressed control animals with postnatal handling, and unstressed control animals without postnatal handling. After sacrifice, the adrenal glands were weighed to determine the adrenal-somatic index. Apoptosis was evaluated by TUNEL assay and active caspase-3 expression. We found that the adrenal gland cortex:medulla ratio increased in animals with prenatal stress and that eventually the stress caused apoptosis. Handling newborns to simulate maternal activity ameliorated some of the negative effects of prenatal stress.

Short-term thyroid hormone excess affects the heart but does not affect adrenal activity in rats.

BACKGROUND: Hyperthyroidism (Hy) exerts a broad range of influences on a variety of physiological parameters. Its disruptive effect on cardiovascular system is one of its most remarkable impacts. Moreover, Hy has been clinically associated with stress - induced hyperactivation of the hypothalamic-pituitary-adrenal axis. OBJECTIVE: Evaluate the impact of short-term Hy on cardiac performance and adrenal activity of rats. METHODS: Induction of Hy in Wistar rats through injections of T3 (150 µg/kg) for 10 days (hyperthyroid group - HG) or vehicle (control group). The cardiovascular performance was evaluated by: echocardiography (ECHO); heart weight/body weight (mg/gr) ratio; contractility of isolated papillary muscles (IPM) and direct measurement of blood pressures. Adrenal activity was evaluated by adrenal weight/body weight (mg/gr) ratio and 24-hour fecal corticosterone (FC) levels on the, 5th and 10th days of T3 treatment. RESULTS: In HG, the ECHO showed reduction of the End Systolic and End Diastolic Volumes, Ejection, Total Diastolic and Isovolumic Relaxation Times, Diastolic and Systolic Areas and E/A ratio. Heart Rate, Ejection Fraction and Cardiac Output increased. The heart weight/body weight ratio was higher. Similarly, in IPM, the maximum rate of force decay during relaxation was higher in all extracellular calcium concentrations. Systolic blood pressure (SBP) levels were higher. (p ≤ 0.05). On the other hand, there was no difference in the adrenal weight/body weight ratio or in the 24-hour FC levels. CONCLUSIONS: Hy induces positive inotropic, chronotropic and lusitropic effects on the heart by direct effects of T3 and increases SBP. Those alterations are not correlated with changes in the adrenal activity.

Excesso de Hormônio Tireoidiano em Curto Prazo Afeta o Coração, mas não Afeta a Atividade Adrenal em Ratos / Short-Term Thyroid Hormone Excess Affects the Heart but Does not Affect Adrenal Activity in Rats

Fundamento: O hipertireoidismo (Hi) exerce um amplo leque de influências em diversos parâmetros fisiológicos. Seu efeito perturbador sobre o sistema cardiovascular é um de seus impactos mais importantes. Além disso, o Hi foi clinicamente associado com o estresse induzido pela hiperativação do eixo hipotalâmico-pituitário-adrenal. Objetivo: Avaliar o impacto do Hi de curto prazo sobre o desempenho cardíaco e a atividade adrenal de ratos. Métodos: A indução de Hi em ratos Wistar através de injeções de T3 (150 μg/kg) por 10 dias (grupo com hipertireoidismo - GH) ou veículo (grupo controle). O desempenho cardiovascular foi avaliado por: ecocardiograma (ECO); razão peso do coração/peso corporal (mg/gr); contratilidade de músculos papilares isolados (MPI) e mensuração direta da pressão arterial. A atividade adrenal foi avaliada pela razão peso adrenal/ peso corporal (mg/gr) e níveis de 24 horas de corticosterona fecal (CF) no 1º, 5º e 10º dias de tratamento com T3. Resultados: No GH, o ECO mostrou redução dos Volumes Finais Sistólico e Diastólico, Tempos de Ejeção, Relaxamento Isovolumétrico e Diastólico Total, Áreas Sistólicas e Diastólica e razão E/A. Aumentaram a frequência cardíaca, a fração de ejeção e o débito cardíaco. A razão peso corporal/peso do coração foi maior. Da mesma forma, nos MPI, a taxa máxima de degradação da força durante o relaxamento foi maior em todas as concentrações extracelulares de cálcio. Os níveis de pressão arterial sistólica (PAS) foram maiores. (p ≤ 0,05). Por outro lado, não houve diferença na razão peso das adrenais/peso corporal ou níveis de 24 horas de CF. ...

Background: Hyperthyroidism (Hy) exerts a broad range of influences on a variety of physiological parameters. Its disruptive effect on cardiovascular system is one of its most remarkable impacts. Moreover, Hy has been clinically associated with stress - induced hyperactivation of the hypothalamic-pituitary-adrenal axis. Objective: Evaluate the impact of short-term Hy on cardiac performance and adrenal activity of rats. Methods: Induction of Hy in Wistar rats through injections of T3 (150 µg/kg) for 10 days (hyperthyroid group - HG) or vehicle (control group). The cardiovascular performance was evaluated by: echocardiography (ECHO); heart weight/body weight (mg/gr) ratio; contractility of isolated papillary muscles (IPM) and direct measurement of blood pressures. Adrenal activity was evaluated by adrenal weight/body weight (mg/gr) ratio and 24-hour fecal corticosterone (FC) levels on the, 5th and 10th days of T3 treatment. Results: In HG, the ECHO showed reduction of the End Systolic and End Diastolic Volumes, Ejection, Total Diastolic and Isovolumic Relaxation Times, Diastolic and Systolic Areas and E/A ratio. Heart Rate, Ejection Fraction and Cardiac Output increased. The heart weight/body weight ratio was higher. Similarly, in IPM, the maximum rate of force decay during relaxation was higher in all extracellular calcium concentrations. Systolic blood pressure (SBP) levels were higher. (p ≤ 0.05). On the other hand, there was no difference in the adrenal weight/body weight ratio or in the 24-hour FC levels. Conclusions: Hy induces positive inotropic, chronotropic and lusitropic effects on the heart by direct effects of T3 and increases SBP. Those alterations are not correlated with changes in the adrenal activity. .

A chronic combinatory stress model that activates the HPA axis and avoids habituation in BALB/C mice.

A detailed protocol is described to induce chronic stress in BALB/c mice, which affects the hypothalamic-pituitary-adrenal (HPA) axis. The protocol is based on a combination of two mild physical stressors: restraint stress and forced swimming. Physical stressors were applied on an alternative schedule: one day restraint, next day swimming, during a 28-day period. Mice were sacrificed at days 7, 14, 21 and 28 and plasma was obtained. Optimized chromatographic system with electrochemical detection and a commercially available enzyme immunoassay kit were used to measure catecholamines [representative of the activation of the autonomic nervous system (ANS)] and corticosterone (representative of the activation of the HPA axis). Corticosterone levels increased in mice under stress and remained significantly higher in stressed mice compared to control animals throughout the experimental procedure, indicating that mice did not show habituation to the combined stress. In our experimental conditions, catecholamine levels were not useful as an index of stress. The stress model applied here provoked a steady activation of the HPA axis resulting in the constant secretion of corticosterone from the adrenal gland, which may prevent the activation of the ANS axis. The simple and economic stress model presented here affected the HPA axis but not the ANS of BALB/c mice and is useful for the study of metabolic stress-related gastric pathology and stress hormone secretion in mice.

Developmental plasticity of endocrine disorders in obesity model primed by early weaning in dams.

Early weaning is associated with changes in the developmental plasticity. Here, we studied the adipocytes morphology, adipokines expression or content in adipose tissue as well as adrenal and thyroid function of neonate and adult offspring primed by early weaning. After birth, lactating rats were divided into 2 groups: EW (early weaning)--dams were wrapped with a bandage to block access to milk during the last 3 days of lactation, and Control--dams whose pups had free access to milk throughout lactation (21 days). At postnatal day (PN) 21, EW pups had lower visceral and subcutaneous adipocyte area (-67.7% and -62%, respectively), body fat mass (-26%), and leptin expression in visceral adipocyte (-64%) but higher leptin expression in subcutaneous adipocyte (2.9-fold increase). Adrenal evaluations were normal, but neonate EW pups presented lower serum T3 (-55%) and TSH (-44%). At PN 180, EW offspring showed higher food intake, higher body fat mass (+21.6%), visceral and subcutaneous adipocyte area (both 3-fold increase), higher leptin (+95%) and ADRß3 (2-fold increase) content in visceral adipose tissue, and higher adiponectin expression in subcutaneous adipose tissue (+47%) but lower in visceral adipose tissue (-40%). Adult EW offspring presented higher adrenal catecholamine content (+31%), but no changes in serum corticosterone or thyroid status. Thus, early weaning primed for hypothyroidism at weaning, which can be associated with the adipocyte hypertrophy at adulthood. The marked changes in catecholamine adrenal content and visceral adipocyte ADRB3 are generally found in obesity, contributing to the development of other cardiovascular and metabolic disturbances.

Influence of the HPA axis on the inflammatory response in cutaneous wounds with the use of 670-nm laser photobiomodulation.

This study evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis in cutaneous wounds subjected to laser biomodulation. A total of 48 rats were divided into two groups: Group I (GI) with 24 adrenalectomized animals and Group II (GII) with 24 non-adrenalectomized animals. Each group was divided into two subgroups: the irradiated subgroup which laser was applied to four points at the edges of the wound (670 nm laser, 9 mW) and control subgroup. Rats in each subgroup were sacrificed at 24 or 72 h. Adrenal glands were only removed from GI rats. Three days after adrenalectomy, a cutaneous wound was made. An immunohistochemical analysis was performed using anti-CD45 and anti-CD8 antibodies. Flow cytometry was used to count T lymphocytes and their subpopulations in blood. Decreases in the number of CD45-positive inflammatory cells and in the total numbers of CD8- and CD45-positive cells were observed in histological sections of adrenalectomized animals subjected to laser biomodulation at 24h. Similar results were observed for distribution of total lymphocytes in blood (p<0.05). The action of 670 nm laser does not depend exclusively on HPA axis. It is believed that corticosteroid-promoting enzymes liberated in non-adrenal tissues may influence immune response under the influence of this type of phototherapy.

Cortisol levels and adrenal response in severe community-acquired pneumonia: a systematic review of the literature.

OBJECTIVES: Our aim was to review the literature on the prevalence and impact of critical-illness related corticosteroid insufficiency (CIRCI) on the outcomes of patients with severe community-acquired pneumonia (CAP). METHODS: We reviewed Cochrane, Medline, and CINAHL databases (through July 2008) to identify studies evaluating the adrenal function in severe CAP. Main data collected were prevalence of CIRCI and its mortality. RESULTS: We screened 152 articles and identified 7 valid studies. Evaluation of adrenal function varied, and most studies used baseline total cortisol levels. The prevalence of CIRCI in severe CAP ranged from 0% to 48%. Among 533 patients, 56 (10.7%) had cortisol levels of 10 µg/dL or less and 121 patients (21.2%) had cortisol levels of 15 µg/dL or less. In a raw analysis, there was no significant difference in mortality when patients with cortisol levels less than 10 µg/dL (8.6 vs 15.5%; P = .55) or less than 15 µg/dL (12.4 vs 16%; P = .38) were compared with those with cortisol above these levels. In the meta-analysis, relative risk for mortality were 0.81 (confidence interval, 0.39-1.7; P = .59; χ(2) = 1.04) for cortisol levels less than 10 µg/dL and relative risk was 0.67 (confidence interval, 0.4-1.14; P = .84; χ(2) = 1.4) for cortisol levels less than 15 µg/dL. CONCLUSIONS: A significant proportion of patients with severe CAP fulfilled criteria for CIRCI. However, CIRCI does not seem to affect the outcomes. Noteworthy, the presence of elevated cortisol levels is associated with increased mortality and may be useful as a prognostic marker in patients with severe CAP.

Adrenal function status in patients with paracoccidioidomycosis after prolonged post-therapy follow-up.

This study assessed adrenal function in patients with paracoccididioidomycosis who had been treated to determine a possible connection between high antibody titers and adrenal dysfunction attributable to persistence of the fungus in adrenal gland. Adrenal gland function was studied in 28 previously treated patients, 2 (7.1%) of whom were shown to have adrenal insufficiency and 7 (259%) who showed a below normal response to stimuli by adrenocorticotropic hormone. Paracoccidioides brasiliensis was detected in the adrenal gland from one of the patients with adrenal insufficiency. Although the study failed to demonstrate a significant difference between high antibody titers and low cortisol levels, the proportion of adrenal insufficiency detected and the subnormal response to adrenocorticotropic hormone confirmed that adrenal damage is an important sequela of paracoccidioidomycosis. Studies with a larger number of patients should be conducted to confirm the hypothesis of persistence of P. brasiliensis in adrenal gland after therapy.

Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression.

Depressive disorders, including major depression, are serious and disabling. However, the exact pathophysiology of depression is not clearly understood. Life stressors contribute in some fashion to depression and are an extension of what occurs normally. In this context, chronic stress has been used as an animal model of depression. Based on the hypothesis that metabolism impairment might be involved in the pathophysiology of depression, in the present work we evaluated the activities of mitochondrial respiratory chain complexes and creatine kinase in brain of rats subjected to chronic stress. After 40 days of mild stress, a reduction in sweet food ingestion was observed, as well as increased adrenal gland weight, when compared to control group. We also verified that control group gained weight after 40 days, but stressed group did not. Moreover, our findings showed that complex I, III and IV were inhibited in stress group only in cerebral cortex and cerebellum. On the other hand, complex II and creatine kinase were not affected in stressed group. Although it is difficult to extrapolate our findings to the human condition, the inhibition of mitochondrial respiratory chain by chronic stress may be one mechanism in the pathophysiology of depressive disorders.

The potential role of increased adrenal volume in the pathophysiology of obesity-related type 2 diabetes.

The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in obesity and Type 2 diabetes (DM). The aim of the present study was to determine the adrenal volume in obese patients with DM in comparison to obese non-diabetic patients. Eleven diabetic obese and 19 non-diabetic obese women were sequentially invited to take part in the study. Computed tomography (CT) scan of the abdomen was performed to determine adrenal volume, visceral (VF) and sc fat (SCF). Daily urinary free cortisol (UFC) was used as a measure of integrated cortisol production. In the diabetic patients, hemoglobin A1c was measured as an index of metabolic control. Compared to nondiabetic controls, patients with diabetes had a significantly higher total adrenal volume (4.29+/-1.50 vs 2.95+/-1.64; p=0.03). A highly significant correlation was detected between VF and VF/SCF ratio and total adrenal volume in the whole group (r=0.36, p=0.04 and r=0.48, p=0.008, respectively). This study, therefore, suggests an association between abdominal obesity, enlarged adrenals and Type 2 diabetes. These findings support the hypothesis that an increased activity of the HPA axis in obese subjects may be involved in the pathogenesis of Type 2 diabetes.

Pituitary-adrenal dynamics after ACTH-secreting pituitary tumor resection in patients receiving no steroids post-operatively.

It has recently been suggested that the classical routine of glucocorticoid administration before and after transsphenoidal surgery (TSS) in Cushing's disease (CD) patients may not be necessary, since it is likely that peritumoral normal corticotrophs are not completely suppressed during this period. We compared the dynamics of ACTH and cortisol from a group of CD patients (cured and not cured), receiving no steroids post-operatively, with a control group of acromegalic patients who presented normal hypothalamic-pituitary-adrenal (HPA) axis. Blood samples for ACTH and cortisol determination were obtained immediately before, at the end of surgery and at 4, 8, 12, 16, 24, 48 and 72 h after surgery, in 8 cured CD patients (Group I), 9 not cured CD patients (Group II) and in 7 subjects with acromegaly (Group III) who presented normal HPA axis (control group). The mean ACTH level in Group I was significantly lower than in Group III from 4 to 12 h and lower than in Group II from 8 to 12 h post-operatively. The mean cortisol level in Group I was lower than in Groups II and III from 8 to 72 h after surgery. No difference in mean cortisol level was observed among Groups II and III during the evaluated period. The lowest cortisol value in Group II was 193 nmol/l (at 24 h after surgery) and in Group I patients, after 20 h post-operatively, the highest cortisol level was 165 nmol/l. Although all cured CD patients (Group I) presented serum cortisol level lower than 55 nmol/l until 72 h after surgery, none had significant complications related to adrenal insufficiency. Ours findings are in agreement with recent observations that there is probably no need for glucocorticoid administration until clinical and/or laboratorial data are suggestive of adrenal insufficiency. However, we have also shown that a subphysiological HPA axis response could be observed in cured CD patients after TSS, and a definitive conclusion about glucocorticoid management during and after this procedure could not be made on the ground of the few cases studied in the literature.

Hiperplasia adrenal macronodular independente de ACTH (AIMAH): aspectos clínicos e moleculares / Clinical and molecular aspects of the ACTH: independent bilateral macronodular adrenal hyperplasia

A AIMAH é caracterizada pela presença de macronódulos em ambas as adrenais, na ausência da estimulação do ACTH. Habitualmente, as manifestações clínicas aparecem somente após várias décadas de vida, provavelmente em função da baixa atividade esteroidogênica do tecido hiperplásico. Entretanto, em indivíduos assintomáticos cuja AIMAH foi descoberta acidentalmente, o eixo HHA já se encontra alterado. Estudos têm demonstrado que, na maioria dos casos de AIMAH, a secreção de cortisol é regulada de modo "aberrante" por hormônios como o GIP, AVP, catecolaminas, LH/hCG e serotonina, através de seus respectivos receptores, ectópicos ou eutópicos, porém aberrantemente acoplados à esteroidogênese. Os mecanismos moleculares responsáveis pela expressão ectópica dos receptores hormonais e/ou de seu acoplamento anormal à esteroidogênese adrenal ainda são pouco conhecidos. Embora a expressão aberrante destes receptores hormonais possa desempenhar um papel importante na iniciação da proliferação celular aumentada, bem como na esteroidogênese, é provável que eventos genéticos adicionais ocorram, envolvendo a regulação do ciclo celular, adesão e transcrição. Mutações no gene GNAS1 não associadas à síndrome de McCune-Albright podem ser encontradas em raros casos de AIMAH. Em alguns casos, a presença de receptor hormonal aberrante abre novas possibilidades de tratamento farmacológico específico do hipercortisolismo, seja isolado ou associado à adrenalectomia unilateral.

Nature of changes in adrenocortical function in chronic hyperleptinemic female rats.

Neonatal treatment of rats with monosodium L-glutamate, which destroys hypothalamic arcuate nucleus neuronal bodies, induces several metabolic abnormalities; as a result, rats develop a phenotype of pseudoobesity. This study was designed to explore, in the monosodium L-glutamate-treated female rat, the influence of chronic hyperleptinemia on adrenal cortex functionality. For this purpose, we evaluated in control and hypothalamic-damaged rats: (a) in vivo and in vitro adrenocortical function, (b) adrenal leptin receptor immunodistribution and mRNA expression, and (c) whether the inhibitory effect of leptin on adrenal function remains. Our results indicate that, compared to normal counterparts, pseudoobese animals displayed (1) hyperadiposity, despite being hypophagic and of lower body weight, (2) in vivo and in vitro enhanced adrenocortical response to ACTH stimulation, (3) an in vitro adrenal fasciculata-reticularis cell hyper-sensitivity to ACTH stimulus, (4) hyperplasia of their adrenal zona fasciculata cells, and (5) adrenal fasciculata-reticularis cell refractoriness to the inhibitory effect of leptin on ACTH-stimulated glucocorticoid production due, at least in part, to decreased adrenal leptin receptor expression. These data further support that increased hypothalamo-pituitary-adrenal axis function, in the adult neurotoxin-lesioned female rat, is mainly dependent on the development of both hyperplasia of adrenal zona fasciculata and adrenal gland refractoriness to leptin inhibitory effect. Our study supports that adrenal leptin resistance could be responsible, at least in part, for enhanced glucocorticoid circulating levels in this phenotype of obesity.

The effect of social rank on the physiological response during repeated stressful handling in Zebu cattle (Bos indicus).

Although the order of entry to a handling chute is related to social rank, it is still not clear what the consequences are for Zebu cattle of occupying different ranks when being exposed repeatedly to a stressful handling procedure. Eighteen Brahman cows were observed for 243 h to obtain information on social interactions. From that information, indices of success in displacing other individuals of the herd were calculated to reflect social status of each cow. One week after behavioral observations, the cows were forced 19 times to enter a handling chute where they were palpated and 7 ml of blood was collected from their caudal vein. To have an adrenal activity profile along the experimental period, five blood samples (Days 2, 6, 10, 15, and 19) were chosen for cortisol determination. On each sampling day, the average time in the chute, the order of entry, and a value of entrance consistency were calculated. On average, the high-ranking cows entered the chute before the medium- and low-ranking cows. Medium-ranking cows showed higher consistency when entering the race than high- and low-ranking cows. Low-ranking cows had significantly lower cortisol levels than the other two groups since the second sample (Day 6 in the race), and had higher cortisol levels the first time handled than at subsequent sampling days. It is suggested that low-ranking cows adopt a passive strategy that allows them to have a better control over the stressful event, while high-ranking cows respond with higher cortisol levels perhaps because of the need to become aroused to deal with challenges. It was concluded that the herd (a) habituated to repeat handling in a squeeze chute and (b) low-ranking cows responded with lower cortisol concentration to handling.