Basal Serum Cortisol Concentrations Research Articles

Associations between immune competence phenotype and stress response in sheep

Immune competence in domestic sheep is gaining more attention in genetic selection programs that seek to enhance flock immunity and animal welfare. A goal of many programs is to identify behavioral phenotypes that indicate stress-coping strength, as well as disease resilience. The current study set out to explore the relationship between immune responsiveness, physiological stress, and behavioral response among sheep that had been selected for ‘low’ (LR) or ‘high’ (HR) response to cell-mediated and antibody-mediate reactivity to a clostridial vaccine. Multiparous ewes were placed in four experiments which exposed the animals to various threats including, dog presence, human proximity, visual isolation from flock, and physical restraint. To evaluate the consistency of behavioral phenotypes, all ewes were placed in the test circuit one year later. Basal body temperature (via iButton) and serum cortisol concentrations were collected prior to and after the circuit each year. Immune group (HR vs. LR) was not found to be related to behavioral performance during the dog, human, isolation, or restraint challenge. Immune group categorization was also unrelated to pre- and post-cortisol concentrations, and the change in cortisol concentrations during testing. There was a negative relationship identified between response to visual isolation and change in cortisol response during testing, indicating that sheep which were more active or agitated during visual isolation from the flock experienced less of an increase in serum cortisol levels and were perhaps experiencing a negative, high arousal state compared to less reactive sheep (e.g., freeze behavior) (χ2(4, N=99) = 42.72, P <0.0001). There was also a post hoc, positive relationship identified between weight measurements and immune group, such that individuals with greater body weight were more likely to be in the high immune responsiveness group (P= 0.01). Specifically, for every unit increase in weight, there was a ~49% chance of being categorized in the HR group. This is relevant for selection programs because producers that seek to enhance immune responsiveness and performance may be able to select sheep that carry a greater body mass, and while not found in the present study, could lead to greater flock immunity.

Association between childhood maltreatment and adult cortisol concentrations mediated through subjective health complaints.

Lower cortisol concentrations in adulthood were repeatedly associated with more severe childhood maltreatment. Additionally, childhood maltreatment was reported to promote health risk behavior, such as smoking or alcohol consumption, and to increase the risk of mental and somatic diseases during adulthood, such as major depressive disorders or obesity. The present study investigated if health risk behavior and disease symptoms in adults mediate the associations between past childhood maltreatment and present basal serum cortisol concentrations. Data from two independent adult cohorts of the general population-based Study of Health in Pomerania (SHIP-TREND-0: N = 3,517; SHIP-START-2: N = 1,640) was used. Childhood maltreatment was assessed via the Childhood Trauma Questionnaire (CTQ). Cortisol concentrations were measured in single-point serum samples. Health risk behavior and mental and physical symptoms were used as mediators. Mediation analyses were calculated separately for both cohorts; results were integrated via meta-analyses. In mediator-separated analyses, associations between childhood maltreatment and basal serum cortisol concentrations were partly mediated by depressive symptoms (BDI-II: βindirect effect = -.011, pFDR = .017, 21.0% mediated) and subjective somatic health complaints (somatic complaints: βindirect effect = -.010, pFDR = .005, 19.4% mediated). In the second step, both mediators were simultaneously integrated into one mediation model. The model replicated the mediation effects of the subjective somatic health complaints (whole model: βindirect effect = -.014, p = .001, 27.6% mediated; BDI-II: βindirect effect = -.006, p = .163, 11.4% mediated, somatic complaints: βindirect effect = -.020, p = .020, 15.5% mediated). The results support the hypothesis that the long-lasting effects of childhood maltreatment on the stress response system are partly mediated through self-perceived disease symptoms. However, no mediation was found for health risk behavior or physically measured mediators. Mediation models with multiple simultaneous mediators pointed to a relevant overlap between the potential mediators. This overlap should be focused on in future studies.

Serial changes in the concentrations of cortisol and thyroid hormones in Beagle dogs infected with Babesia rossi

An experimental infection using Babesia (B.) rossi was performed in healthy male Beagle dogs to assess the changes in endocrine variables during disease. Two dogs were infected with a low dose (LD) of parasite inoculum (104 parasites) and three dogs were infected with a high dose (HD) (108 parasites). Basal serum cortisol, thyroxine (T4), and thyrotropin (TSH) concentrations were measured every second day. Samples were analyzed using a solid- phase, competitive chemiluminescent enzyme immunoassay (Immulyte® 2000, Siemens). Variables were compared between groups and timepoints using linear mixed models. In both groups, the median cortisol concentration increased, whilst the median T4 concentration decreased after infection, with a return towards baseline concentration post treatment. The highest cortisol and the lowest T4 concentrations were reached at 96 h and 108 h post infection, respectively, in the HD group and slightly later at 108 and 144 h post-infection, respectively, in the LD group. A higher cortisol concentration with a more rapid increase, and a lower T4 concentration with a more rapid decline, were associated with disease severity and a higher dose of parasite inoculum. The TSH concentration remained within the reference interval throughout the study period. This study illustrated the temporal changes in endocrine parameters during experimental B. rossi infection and demonstrated that cortisol and T4 tracked the severity of disease, albeit in opposite directions.

Serum Cortisol and Its Correlation with Leucocyte Profile and Circulating Lipids in Donkeys (Equus asinus).

Simple SummaryThere are relatively few studies investigating serum cortisol levels in donkeys. The aim of this study was to evaluate basal cortisol values in donkeys, and its physiological role on the immune system and lipid levels in relation to age and pregnancy. The results showed that age did not influence cortisol levels while pregnancy increased its concentrations. Different correlations were found between cortisol, leucocyte types, and serum triglycerides depending upon age and pregnancy state. Although correlation is, of course, not equivalent to causation, we can hypothesize that the multiple functions of cortisol on the immune system and lipid metabolism vary across donkey lifespan and are related to physiological state.The values for basal serum cortisol concentrations of horses are available in many studies. However, there are limited data about serum cortisol in donkeys. The present study aimed to determine the baseline values for serum cortisol, to evaluate the influence of age and pregnancy on its levels, and to correlate its values with leucocyte profile, serum cholesterol, and triglycerides. Serum samples were collected from 97 healthy donkeys. Cortisol was analyzed by chemo-luminescent assay. The median and the 2.5th and 97.5th percentiles of serum cortisol measured and calculated in all donkeys were 5.64, 3.40, and 10.54 µg/dL, respectively. Females (n.91) were divided into three groups: Group A (young), Group B (adult), and Group C (pregnant at the 9th–11th months). The effect of age and physiological status was investigated by the Mann–Whitney test. Group C showed significantly higher levels than Group B (p < 0.05). Significant correlations were found in Group B with monocytes (r = 0.37, p < 0.01) and triglycerides (r = 0.30, p < 0.05), and in Group C with monocytes (r = 0.79, p < 0.01), basophils (r = 0.6, p < 0.05), and neutrophil/lymphocyte ratio (r = −0.63, p < 0.05). Higher cortisol values related to late pregnancy are also found in this species. These preliminary results provide evidence for a relationship between cortisol and the immune system as well as cortisol and lipid metabolism modulated by age and pregnancy when parameters are within normal values.

Sex differences in the association between basal serum cortisol concentrations and cortical thickness

BackgroundBasal cortisol concentrations vary between men and women. Likewise, previous findings suggest stress-related cortical thickness alterations. Thus, we aimed at elucidating sex differences in the association between serum cortisol concentrations and cortical thickness. MethodsData of 2594 participants (55.55% male; mean age = 53.55 years ± 13.17 years) of the general population were used to investigate sex differences in basal serum cortisol concentrations and associations of serum cortisol concentrations with global and regional cortical thickness. The validity of the results was tested by including sex hormone concentrations as a biological and childhood maltreatment and depressive symptoms as a psychological confounder. ResultsBasal serum cortisol concentrations were higher in men than in women (β = −0.158, t(2575) = -6.852, p = 9.056e-12). Sex differences in serum cortisol concentrations were diminished by including serum concentrations of testosterone, estrone, or estradiol in the models. In men but not in women, serum cortisol concentrations were inversely associated with the global cortical thickness (men: β = −0.064, t(1412) = -3.010, p = .003; women: β = −0.016, t(1131) = -0.607, p = .544). Additionally, these effects were observed in eleven cortical regions after adjusting for multiple testing. The associations were independent of childhood maltreatment and depressive symptoms. ConclusionSex differences in serum cortisol concentrations and the association between serum cortisol concentrations and cortical thickness suggest important sex-specific effects of stress on the brain. Future studies should integrate the interaction between the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis in sex-stratified analyses.

Prevalence and characterization of hypoadrenocorticism in dogs with signs of chronic gastrointestinal disease: A multicenter study.

BackgroundDogs with hypoadrenocorticism (HA) frequently show signs of gastrointestinal disease (SGD). The prevalence of dogs presented for chronic SGD with HA is unknown.ObjectivesThe aims of this study were to determine the prevalence of HA in dogs with chronic SGD and to identify clinical and laboratory variables for HA in this population.AnimalsOne hundred fifty‐one dogs with chronic SGD.MethodsIn this multicentered prevalence study a standardized workup was performed in prospectively enrolled dogs with SGD > 3 weeks duration. Basal serum cortisol concentration was measured in every dog with ACTH stimulation test (ACTHST) if basal serum cortisol concentration was <3 μg/dL.ResultsBasal serum cortisol concentration was <3 μg/dL in 80/151 (53%) dogs, <2 μg/dL in 42/151 (28%) dogs, and < 1 μg/dL in 9/151 (6%) dogs. In 6/151 dogs HA was diagnosed based on ACTHST (stimulated serum cortisol concentration < 2 μg/dL), a prevalence of 4%. There was no difference in history, physical examination, and laboratory variables between dogs with HA and those with other causes of chronic SGD. In 4/6 dogs with HA, there was melena or hematochezia indicating gastrointestinal blood loss. Hyperkalemia, hyponatremia, or both was not observed in any dog.Conclusion and Clinical ImportanceThe prevalence of HA among dogs with chronic SGD is higher than in the general population. Based on these results, testing adrenal function should be performed as a standard screening test in dogs with chronic SGD to differentiate between HA and chronic enteropathies.

Basal serum cortisol concentration in very low birth weight infants

The aim of our study was to measure the basal serum cortisol concentration immediately after birth and to determine its association with perinatal factors and clinical outcomes in very low birth weight (VLBW) infants. Basal serum cortisol level was obtained within one hour after birth in inborn VLBW infants. The association between the basal serum cortisol level and perinatal and clinical outcomes was analyzed by comparing the groups with high versus low cortisol levels. In total, 80 infants were included. The median concentration of basal serum cortisol was 167nmol/L with an interquartile range of 98-298nmol/L. The basal serum cortisol concentration positively correlated with elapsed time from the last betamethasone dose. Low serum cortisol concentration was associated with antenatal corticosteroid therapy, low lactic acid level, and low leukocyte count at birth. Basal serum cortisol level was not associated with mortality and neonatal morbidities including hypotension and severe grade intraventricular hemorrhage. Both maternal corticosteroid therapy and perinatal distress may affect the basal serum cortisol concentration in VLBW infants early after birth.

Bioavailability and tolerability of nebulised dexamethasone sodium phosphate in adult horses.

Nebulisation of the injectable dexamethasone sodium phosphate (DSP) would offer an inexpensive way of delivering a potent corticosteroid directly to the lungs of horses with asthma. However, this approach would be advantageous only if systemic absorption is minimal and if the preservatives present in the formulation do not induce airway inflammation. To investigate the bioavailability of nebulised DSP and determine whether it induces airway inflammation or hypothalamic-pituitary-adrenal (HPA) axis suppression in healthy adult horses. Randomised crossover experiment. Dexamethasone sodium phosphate was administered to six healthy adult horses at a dose of 5 mg q. 24 h for 5 days via nebulised, or intravenous (i.v.) routes. Plasma dexamethasone concentrations were measured by UPLC/MS-MS to calculate bioavailability. Cytological examination of bronchoalveolar fluid was performed at baseline and after the last dose of DSP. A validated chemiluminescent immunoassay was used to measure basal serum cortisol concentrations. After nebulisation to adult horses, dexamethasone had a mean (±s.d.) maximum plasma concentration of 0.774 ± 0.215 ng/mL and systemic bioavailability of 4.3 ± 1.2%. Regardless of route of administration, there was a significant decrease in the percentage of neutrophils in bronchoalveolar lavage fluid over time. During i.v. administration, basal serum cortisol concentration decreased significantly from baseline to Day 3 and remained low on Day 5. In contrast, basal serum cortisol concentration did not change significantly during administration via nebulisation. Small sample size and short period of drug administration. Dexamethasone sodium phosphate administered via nebulisation had minimal systemic bioavailability and did not induce lower airway inflammation or HPA axis suppression in healthy horses.

Evaluation of Early Corticosteroid Therapy in Management of Pediatric Septic Shock in Pediatric Intensive Care Patients: A Randomized Clinical Study.

Septic shock is a major healthcare problem. Adrenal insufficiency (AI) in children with septic shock is a recognized complication, yet is controversial regarding its management and effect on mortality. According to the current guidelines, children with risk factors for AI should receive a stress dose of steroids in step 3 of treatment. This study aimed to evaluate and compare early corticosteroid therapy with the traditional use of steroids among pediatric septic shock patients. This prospective randomized interventional clinical study included 3 groups of patients (32 each) and was conducted in Alexandria University pediatric intensive care unit. By protocol, the first group received steroids in step 3 of the treatment according to the current international guidelines (group A), and the second group was managed as group A and was tested for AI by adrenal stimulation test using intramuscular adrenocorticotropic hormone (cosyntropin) (group B). The third group received steroids at the start of fluid therapy (group C). A fourth group (group D) was created by adding patients from groups A and B who needed corticosteroids in the third stage of therapy according to the international protocol in 1 group. All patients were evaluated for basal serum cortisol and plasma adrenocorticotropic hormone concentrations. The data showed a statistically significant shorter shock reversal time among patients receiving corticosteroids at the start of treatment compared with those who received it at the third step of treatment (P = 0.046); however, mortality was not statistically different among the groups. In addition, there was no superinfection in cases receiving early steroid therapy. Early use of corticosteroid in patients with septic shock might shorten the shock reversal time without increase in mortality or superinfection.

Effect of Suckling Systems on Serum Oxytocin and Cortisol Concentrations and Behavior to a Novel Object in Beef Calves.

We investigated differences between effects of natural- and bucket-suckling methods on basal serum oxytocin (OT) and cortisol concentrations, and the effect of OT concentration on affiliative and investigative behavior of calves to a novel object. Ten Japanese Black calves, balanced with birth order, were allocated evenly to natural-suckling (NS) and bucket suckling (BS) groups. Blood samples were collected at the ages of 1 and 2 months (1 week after weaning) calves, and serum OT and cortisol concentrations were measured using enzyme-linked immunosorbent assay and enzymeimmunoassay tests, respectively. Each calf at the age of 2 months (2 weeks after weaning) was released into an open-field with a calf decoy, and its investigative and affiliative behaviors were recorded for 20 minutes. In 1-month-old calves, the basal serum OT concentration (25.5±4.9 [mean±standard deviation, pg/mL]) of NS was significantly higher than that of BS (16.9±6.7) (p<0.05), whereas the basal cortisol concentration (5.8±2.5 [mean±standard deviation, ng/mL]) of NS was significantly lower than that in BS (10.0±2.8) (p<0.05). Additionally, a negative correlation was noted between serum OT and cortisol concentrations in 1-month-old calves (p = 0.06). Further, the higher serum OT concentration the calves had at 1 month old, the more investigative the calves were at 2 months old but not affiliative in the open-field with a calf decoy. Thus, we concluded that the natural suckling method from a dam elevates the basal serum OT concentration in calves, and high serum OT concentrations induce investigative behavior and attenuate cortisol concentrations.

Adrenal suppression in patients taking inhaled glucocorticoids is highly prevalent and management can be guided by morning cortisol.

ContextUp to 3% of US and UK populations are prescribed glucocorticoids (GC). Suppression of the hypothalamo–pituitary–adrenal axis with the potential risk of adrenal crisis is a recognized complication of therapy. The 250 μg short Synacthen stimulation test (SST) is the most commonly used dynamic assessment to diagnose adrenal insufficiency. There are challenges to the use of the SST in routine clinical practice, including both the staff and time constraints and a significant recent increase in Synacthen cost.MethodsWe performed a retrospective analysis to determine the prevalence of adrenal suppression due to prescribed GCs and the utility of a morning serum cortisol for rapid assessment of adrenal reserve in the routine clinical setting.ResultsIn total, 2773 patients underwent 3603 SSTs in a large secondary/tertiary centre between 2008 and 2013 and 17.9% (n=496) failed the SST. Of 404 patients taking oral, topical, intranasal or inhaled GC therapy for non-endocrine conditions, 33.2% (n=134) had a subnormal SST response. In patients taking inhaled GCs without additional GC therapy, 20.5% (34/166) failed an SST and suppression of adrenal function increased in a dose-dependent fashion. Using receiver operating characteristic curve analysis in patients currently taking inhaled GCs, a basal cortisol ≥348 nmol/l provided 100% specificity for passing the SST; a cortisol value <34 nmol/l had 100% sensitivity for SST failure. Using these cut-offs, 50% (n=83) of SSTs performed on patients prescribed inhaled GCs were unnecessary.ConclusionAdrenal suppression due to GC treatment, particularly inhaled GCs, is common. A basal serum cortisol concentration has utility in helping determine which patients should undergo dynamic assessment of adrenal function.

Gender difference in adrenal sensitivity to ACTH is abolished in type 2 diabetes.

ObjectiveDysfunction of the hypothalamus–pituitary–adrenal (HPA) axis has been implicated in type 2 diabetes (T2D). The aim of this study was to investigate the impact of T2D and gender on the HPA axis.MethodsSynthetic ACTH (1 μg) was administered to 21 subjects with T2D (age 62 (54–70) years, 11 men/ten women, HbA1c 49±2 mmol/mol, treated with diet or oral antidiabetic drugs) and 38 controls (age 58 (41–67) years, 20 men/18 women). Fasting basal B-glucose, serum cortisol, insulin, IGF1 and IGFBP1 concentrations were measured, and sampling for all but IGF1 was repeated 30, 60, and 90 min after ACTH injection. Patients took 0.25 mg dexamethasone at 2200–2300 h and returned the next morning for the measurement of serum cortisol concentration.DesignCross-sectional study.ResultsPatients with T2D had similar fasting serum cortisol, IGF1 and IGFBP1 concentrations; however, serum cortisol concentration after administration of dexamethasone did not differ between the groups. Healthy women exhibited higher peak cortisol levels compared with healthy men (675±26 vs 582±21 nmol/l, P=0.014), while the peak levels were equally high in men and women with T2D, resulting in a higher peak level in men with T2D compared with healthy men (691±42 vs 582±21 nmol/l, P=0.024). Serum cortisol concentration after administration of dexamethasone did not differ between the groups, nor did IGF1 and IGFBP1.Novelty of the findingsSome studies have previously indicated disturbed regulation of the hypothalamus–pituitary–adrenal (HPA) axis in subjects with type 2 diabetes (T2D); however, much remains unknown in this area. To the best of our knowledge, this is the first study to show that the gender difference in the adrenal response to ACTH (with greater reactivity in women) is abolished in T2D. While the clinical implications cannot be determined by this paper, it is known that gender differences exist in the pathogenesis and complications of T2D. Thus, our findings suggest that further research into gender differences in the HPA axis is warranted.ConclusionsGender differences in adrenal response to ACTH were abolished in T2D. Men with T2D had a higher peak cortisol compared with controls. Further studies are needed to elucidate the clinical implications.

Effects of endurance training only versus same-session combined endurance and strength training on physical performance and serum hormone concentrations in recreational endurance runners

This study investigated the effects of endurance training only (E, n = 14) and same-session combined training, when strength training is repeatedly preceded by endurance loading (endurance and strength training (E+S), n = 13) on endurance (1000-m running time during incremental field test) and strength performance (1-repetition maximum (1RM) in dynamic leg press), basal serum hormone concentrations, and endurance loading-induced force and hormone responses in recreationally endurance-trained men. E was identical in the 2 groups and consisted of steady-state and interval running, 4-6 times per week for 24 weeks. E+S performed additional mixed-maximal and explosive-strength training (2 times per week) immediately following an incremental running session (35-45 min, 65%-85% maximal heart rate). E and E+S decreased running time at week 12 (-8% ± 5%, p = 0.001 and -7% ± 3%, p < 0.001) and 24 (-13% ± 5%, p < 0.001 and -9% ± 5%, p = 0.001). Strength performance decreased in E at week 24 (-5% ± 5%, p = 0.014) but was maintained in E+S (between-groups at week 12 and 24, p = 0.014 and 0.011, respectively). Basal serum testosterone and cortisol concentrations remained unaltered in E and E+S but testosterone/sex hormone binding globulin ratio decreased in E+S at week 12 (-19% ± 26%, p = 0.006). At week 0 and 24, endurance loading-induced acute force (-5% to -9%, p = 0.032 to 0.001) and testosterone and cortisol responses (18%-47%, p = 0.013 to p < 0.001) were similar between E and E+S. This study showed no endurance performance benefits when strength training was performed repeatedly after endurance training compared with endurance training only. This was supported by similar acute responses in force and hormonal measures immediately post-endurance loading after the training with sustained 1RM strength in E+S.

Basal serum cortisol concentration as a screening test for hypoadrenocorticism in dogs.

BackgroundMeasurement of basal serum or plasma cortisol concentration is used as a screening test for hypoadrenocorticism in dogs, but is not well characterized.ObjectivesTo evaluate the sensitivity and specificity of basal serum cortisol to detect hypoadrenocorticism in a population of dogs with a clinical suspicion of hypoadrenocorticism.AnimalsFour hundred and fifty dogs with nonadrenal gland illness and 14 dogs with naturally occurring hypoadrenocorticism were included.MethodsRetrospective case‐control study. The records of all dogs having had an ACTH stimulation test performed between January 2005 and September 2011 at the University of Bristol were reviewed. Dogs were included if the test was performed as a screening for hypoadrenocorticism. The sensitivity and specificity of basal serum cortisol concentration to detect dogs with hypoadrenocorticism were calculated using 2 cut‐offs and compared to the gold standard ACTH stimulation test.ResultsUsing a cut‐off of ≤2 μg/dL (≤55 nmol/L), the sensitivity and specificity of basal cortisol to detect hypoadrenocorticism were 100% and 63.3%, respectively, whereas for a cut‐off of ≤1 μg/dL (≤28 nmol/L), the sensitivity and specificity were 85.7% and 91.8%, respectively.Conclusions and Clinical ImportanceMeasurement of basal serum cortisol is useful as a screening test for hypoadrenocorticism in dogs using a cut‐off of ≤2 μg/dL (≤55 nmol/L), and the disease is unlikely with a basal serum cortisol >2 μg/dL (>55 nmol/L). A basal serum cortisol ≤2 μg/dL (≤55 nmol/L) cannot be used to diagnose hypoadrenocorticism, and an ACTH stimulation test should be performed in these cases.

Temperament can be an indicator of feedlot performance and carcass merit in beef cattle (2014)

Cattle producers historically have selected for docile temperaments simply for management convenience because calmer animals are conducive to safe environments for their peers as well as their handlers. As many producers would acknowledge, however, there seems to be a relationship between temperament and cattle health, and calmer cattle tend to frequent the working chute for treatment of disease less often. Positive correlations have been found in cattle between temperament traits (chute scores, pen scores, and chute exit velocities) and cortisol concentration in the blood, suggesting that more excitable cattle are easily stressed (Curley et al., 2006; Cooke et al., 2009). Curley et al. (2007) also found that easily excitable animals sustain elevated cortisol concentrations for a longer duration and have greater pituitary and adrenal responses following a stressor than calm cattle. Temperamental cattle have significantly higher mean temperament responses at all points (Oliphint, 2006). Higher basal serum cortisol concentrations may suggest that easily excitable cattle are chronically stressed (Curley et al., 2007), possibly resulting in a compromised immune system, illness, and decreased fat and protein deposition. This study was conducted to further investigate the relationships between cattle temperament (measured by chute score and exit velocity), immunological factors, and a range of economically relevant performance traits.

Adrenocortical Carcinoma in a Dog with Incomplete Excision Managed Long-term with Metastasectomy Alone

A 10 yr old bichon frise presented with a 3 mo history of polyuria, polydipsia, and hind limb weakness. Serum biochemistry revealed persistent hypokalemia. A left adrenal gland mass with right adrenal atrophy was detected ultrasonographically. Basal serum cortisol concentration was at the low end of normal (30 nmol/L; reference range, 30-140 nmol/L) and adrenocorticotropic hormone (ACTH)-stimulated cortisol concentration was low (199 nmol/L; reference range, 220-470 nmol/L). Basal serum 17-α-OH progesterone concentration was also low (0.03 ng/mL; reference range, 0.06-0.30 ng/mL), but the aldosterone concentration 2 hr after the ACTH stimulation was elevated (> 3,000 pmol/L; reference range, 197-2,103 pmol/L). A left adrenalectomy and nephrectomy were performed. Histopathology revealed an adrenocortical zona glomerulosa carcinoma. Surgical excision was considered incomplete; however, clinical signs resolved. Two years later, basal and ACTH-stimulated aldosterone concentrations were elevated. Computed tomography demonstrated a mass effect in the liver. The left lateral and left medial hepatic lobes were removed. Histopathology confirmed metastatic endocrine carcinoma. The patient was stable 1,353 days postsurgically (when this report was prepared). This is the first case report of a metastatic adrenal carcinoma that was successfully managed surgically for > 3 yr.

Blunted serum and enhanced salivary free cortisol concentrations in the chronic phase after aneurysmal subarachnoid haemorrhage—is stress the culprit?

Spontaneous aneurysmal subarachnoid haemorrhage (SAH) is a cause of stroke, which constitutes a severe trauma to the brain and may lead to serious long-term medical, psychosocial and endocrinological sequelae. Adrenocorticotrophic hormone deficiency, which is considered to occur in up to 20% of all survivors, is a possible consequence of bleeding. Moreover, preliminary data suggest that a poor psychosocial outcome in SAH survivors is linked to alterations in cortisol secretion. Despite these findings, investigation of diurnal cortisol profiles and the cortisol awakening response (CAR) in chronic SAH patients has not been done so far. In this study, basal serum cortisol and salivary cortisol concentration profiles were investigated in 31 SAH patients more than 1 year after the acute event and in 25 healthy controls. Additionally, low-dose dexamethasone (DEX) suppression tests were conducted, and sensitivity to stress was measured with a psychometric questionnaire (NeuropatternTM). Although significantly higher salivary cortisol concentrations were observed on waking in SAH patients (p = 0.013, ANOVA), without a CAR change, total serum cortisol concentrations were blunted, but only in patients with high levels of perceived stress (SAH high stress: 337 nmol/l, SAH low stress: 442 nmol/l, controls: 467 nmol/l; Controls vs. SAH high stress p = 0.018). DEX suppression of cortisol secretion was not significantly different between patients and controls. The results indicate that total (serum) and free (salivary) cortisol concentrations give different information about cortisol availability in patients after aneurysmal SAH. Enhanced free cortisol concentrations may reflect a meaningful biological coping mechanism in SAH patients.

Cytomegalovirus-Induced Adrenal Insufficiency in a Renal Transplant Recipient

Cytomegalovirus (CMV) is an important pathogen in organ-transplant recipients. There have been frequent reports of CMV-induced adrenal insufficiency in patients with human immunodeficiency virus infection. Herein, we report CMV-induced renal insufficiency in a renal transplant recipient. A 24-year-old woman had gradual onset of weakness, anorexia, nausea, hypotension, and skin hyperpigmentation at 5 months after renal transplantation. The immunosuppression regimen included cyclosporine, mycophenolate mofetil, and corticosteroid (prednisolone, 5 mg/d). Recent history included acute CMV infection, which was treated with ganciclovir. Basal serum cortisol concentration was 4 μg/dL, and stimulated serum cortisol concentration was less than 10 μg/dL. All clinical signs and symptoms and hypotension gradually improved after the oral prednisolone dose was increased to 10 mg/d. Clinicians must be aware of the possibility of CMV-induced adrenal insufficiency in renal transplant recipients. The condition may be symptomatic despite low-dose prednisolone therapy.

Hypothalamic‐Pituitary‐Adrenal Axis Dysfunction in Hospitalized Neonatal Foals

Transient hypothalamic-pituitary-adrenal (HPA) axis dysfunction occurs frequently in critically ill humans and impacts survival. The prevalence and impact of HPA axis dysfunction in critically ill neonatal foals are not well characterized. (1) HPA axis dysfunction occurs in hospitalized neonatal foals, and is characterized by inappropriately low basal serum cortisol concentration or inadequate cortisol response to exogenous adrenocorticotropic hormone (ACTH); (2) hospitalized foals with HPA axis dysfunction have more severe disease and are less likely to survive than hospitalized foals with normal HPA axis function. Seventy-two hospitalized foals and 23 healthy age-matched foals. Basal ACTH and cortisol concentrations were measured and a paired low-dose (10 microg)/high-dose (100 microg) cosyntropin stimulation test was performed at admission in hospitalized foals. HPA axis dysfunction was defined as (1) an inappropriately low basal cortisol concentration or (2) an inadequate increase in cortisol concentration (delta cortisol) after administration of cosyntropin, with cut-off values for appropriate basal and delta cortisol concentrations determined from results obtained in healthy age-matched foals. Forty-six percent of hospitalized foals had an inappropriately low basal cortisol concentration and 52% had an inadequate delta cortisol concentration after administration of the 100 microg dose of cosyntropin. An inadequate delta cortisol response to the high (100 microg) dose of cosyntropin was significantly correlated with shock and multiple organ dysfunction syndrome in hospitalized foals, and with decreased survival in a subgroup of septic foals. HPA axis dysfunction occurs frequently in hospitalized neonatal foals, and negatively impacts disease severity and survival.

Pheochromocytoma with Subclinical Cushing’s Syndrome Caused by Corticomedullary Mixed Tumor of the Adrenal Gland

A 54-yr-old woman was referred to our hospital because of an incidentally discovered left adrenal mass. Although she had mild hypertension and diabetes, she had no signs of excessive production of either catecholamines or adrenocortical steroids. Her 24-h urine metanephrine, normetanephrine, and vanillylmandelic acid levels were 1700 g, 9000 g, and 25.8 mg, respectively. Although the basal serum cortisol concentration was normal, the diurnal rhythm was absent and the 0800 h cortisol level did not suppress with the 1-mg overnight dexamethasone suppression test (10.9 g/dl). Her basal corticotrophin concentration was 8 pg/ml. Abdominal computed tomography (CT) showed heterogeneous mass, and T2-weighted magnetic resonance imaging (MRI) showed high-intensity mass in the left adrenal gland (Fig. 1, A and B). A I-metaiodobenzylguanidine scan revealed uptake within the tumor (Fig. 1C). After adequate adrenergic -receptor blockade, a left adrenalectomy was performed. The patient developed adrenal insufficiency after surgery and required glucocorticoid replacement therapy for 18 months. Both her hypertension and diabetes were improved. Histopathological examination revealed that the tumor consisted of two different types of lesions: pheochromocytes and adrenocortical cells (Fig. 2A). Cells that were morphologically consistent with pheochromocytoma and adrenocortical cells were confirmed by immunostaining for chromogranin A and P450c21 (compare Fig. 2, B and C). Pheochromocytomas and adrenocortical adenomas derive from distinct origins. Therefore, a single adrenal tumor that produces both catecholamines and cortisol is rare and termed a corticomedullary mixed tumor (1–5); it may be found incidentally as a pheochromocytoma with subclinical Cushing’s syndrome as in the present case. Acknowledgments