Plasma Adrenocorticotropic Hormone Concentrations Research Articles

Genotypic variation in the promoter region of the CRH-248 gene interacts with early rearing experiences to disrupt the development of the HPA axis in infant rhesus macaques (Macaca mulatta)

Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of conditions such as depression, anxiety disorders, and post-traumatic stress disorder. Early-life adversity and genetic variation can interaction to disrupt HPA axis regulation, potentially contributing to certain forms of psychopathology. This study employs a rhesus macaque model to investigate how early parental neglect interacts with a single nucleotide polymorphism within the promoter region of the corticotropin-releasing hormone (CRH-248) gene, impacting the development of the HPA axis. For the initial six months of life, 307 rhesus monkey infants (n = 146 females, n = 161 males) were either reared with their mothers (MR) in conditions emulating the natural environment (control group) or raised without maternal care in groups with constant or 3-hours daily access to same-aged peers (NR). Blood samples collected on days 30, 60, 90, and 120 of life under stressful conditions were assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. Findings revealed that NR subjects exhibited a significant blunting of both ACTH and cortisol concentrations. Notably, there was a gene-by-environment interaction observed for ACTH and cortisol levels, with NR subjects with the polymorphism displaying higher ACTH concentrations and lower cortisol concentrations. To the extent that these results generalize to humans, they suggest that early parental neglect may render individuals vulnerable to HPA axis dysfunction, a susceptibility that is modulated by CRH-248 genotype—a gene-by-environment interaction that leaves a lasting developmental signature.

Dysregulation of circadian clock gene expression patterns in a treatment-resistant animal model of depression.

Circadian rhythm (CR) disturbances are among the most commonly observed symptoms during major depressive disorder, mostly in the form of disrupted sleeping patterns. However, several other measurable parameters, such as plasma hormone rhythms and differential expression of circadian clock genes (ccgs), are also present, often referred to as circadian phase markers. In the recent years, CR disturbances have been recognized as an essential aspect of depression; however, most of the known animal models of depression have yet to be evaluated for their eligibility to model CR disturbances. In this study, we investigate the potential of adrenocorticotropic hormone (ACTH)-treated animals as a disease model for research in CR disturbances in treatment-resistant depression. For this purpose, we evaluate the changes in several circadian phase markers, including plasma concentrations of corticosterone, ACTH, and melatonin, as well as gene expression patterns of 13 selected ccgs at 3 different time points, in both peripheral and central tissues. We observed no impact on plasma corticosterone and melatonin concentrations in the ACTH rats compared to vehicle. However, the expression pattern of several ccgs was affected in the ACTH rats compared to vehicle. In the hippocampus, 10 ccgs were affected by ACTH treatment, whereas in the adrenal glands, 5 ccgs were affected and in the prefrontal cortex, hypothalamus and liver 4 ccgs were regulated. In the blood, only 1 gene was affected. Individual tissues showed changes in different ccgs, but the expression of Bmal1, Per1, and Per2 were most generally affected. Collectively, the results presented here indicate that the ACTH animal model displays dysregulation of a number of phase markers suggesting the model may be appropriate for future studies into CR disturbances.

Strongyle egg shedding and egg reappearance periods in horses with pituitary pars intermedia dysfunction

Pituitary pars intermedia dysfunction (PPID) is the most common endocrine disorder of older horses. Immune dysfunction in horses with PPID could increase susceptibility to infectious diseases, including strongyle infections; however, few data are available. The aim of this study was to determine if horses with PPID had increased strongyle faecal egg counts (FEC) compared with control horses, over a fourteen-week period in Victoria, Australia. Clinical signs and plasma adrenocorticotropic hormone (ACTH) concentrations were used to categorise horses into PPID (n=14) or control (n=31) groups. Faecal samples were collected for FEC determination prior to anthelmintic treatment, and fortnightly post-treatment for each horse. Generalised linear mixed modelling, using a gamma distribution, was used to compare differences between groups in the repeated measures study. The confounding variable of age was controlled for as a fixed effect. Following anthelmintic treatment, mean FEC was greater for the PPID group compared to the control group on day 56 (405 ± 756 eggs per gram [EPG] vs 40 ± 85 EPG, p=0.05) and day 70 (753 ±1598 EPG vs 82 ±141 EPG, p=0.04). There were no differences in mean FEC between groups on days 84 and 98. Cumulative FEC (day 14 to day 98) was significantly greater for the PPID horses than control horses (2118 ± 4016 EPG vs 798 ± 768 EPG, p<0.0001). Group egg reappearance period was shorter for PPID horses (day 56 post-anthelmintic treatment) compared to control horses (day 70) and 30% of the PPID horses reached a FEC threshold of >200 EPG on day 42, compared to 0% of control horses (p=0.02). These results suggest that the rate of a re-established patent infection between groups could be different due to a comprised immune response in PPID horses or differences in the host-parasite relationship regarding encysted stage larvae. However, despite differences between groups, some horses with PPID consistently had no detectable or low FEC (<200 EPG) during the study period. These findings highlight the importance of individual FEC monitoring to determine if anthelmintic treatment is required, in line with sustainable parasite management practices.

Bilateral Inferior Petrosal Sinus Sampling Without Lateralization Is Less Accurate for the Diagnosis of Cushing Disease.

During bilateral inferior petrosal sinus sampling (BIPSS), the side-to-side adrenocorticotropic hormone (ACTH) ratio, referred to as sampling lateralization, was used to predict pituitary adenoma localization. To investigate the potential different diagnostic accuracy of BIPSS for differentiating Cushing disease (CD) and ectopic ACTH secretory syndrome (EAS) patients with low lateralization (inferior petrosal sinus [IPS]:IPS ≤ 1.4) and high lateralization (IPS:IPS > 1.4). This single-center retrospective study (2011-2021) included (all patients had BIPSS results and confirmed pathologic diagnoses) 220 consecutive CD patients (validation set), 30 EAS patients, and 40 of the CD patients who had digital subtraction angiography (DSA) videos (discovery set). In the discovery set, the low-lateralization CD group (n = 11) had a higher median plasma ACTH concentration (62.2, IQR 44.7-181.0 ng/L) than the high-lateralization CD group (n = 29) (33.0, IQR 18.5-59.5, P = .013). Lower IPS to peripheral ratios were observed in the low-lateralization group during BIPSS, both before and after stimulation (P = .013 and P = .028). The sensitivity of BIPSS before stimulation in differentiating CD from EAS was lower in the low-lateralization group than the high-lateralization group (54.6% vs 93.1%, P = .003), as validated in the validation set. DSA videos revealed higher vascular area difference visible in the 2 sides of the pituitary in low lateralization (median 1.2 × 105 pixels, IQR 0.5-1.8) than the high-lateralization group (0.4 × 105 pixels, IQR 0.1-0.7, P = .008). The vascular area ratio of the 2 sides was also significantly higher in low (1.55, IQR 1.31-2.20) than high lateralization (1.19, IQR 1.07-1.35, P = .010). Our study suggested that low lateralization in CD patients may reduce the diagnostic sensitivity of BIPSS, which might be potentially associated with peripituitary vascular anatomy.

Adrenocorticotropic hormone secretion in response to anticipatory stress and venepuncture: The role of menstrual phase and oral contraceptive use

IntroductionOral contraceptives (OCs) are primarily known for their effects on the reproductive system, but they can also impact the hypothalamic–pituitary–adrenal (HPA) axis. The present study aimed to compare plasma adrenocorticotropic hormone (ACTH) responses to the anticipatory stress of participating in a scientific experiment and venepuncture in OC users versus naturally cycling (NC) women, with a focus on variations throughout the menstrual cycle. MethodsWe recruited 131 young women (average age 20.5) and obtained blood samples to measure plasma ACTH concentrations immediately after venepuncture and again after 15 min of group activities designed to facilitate interpersonal attachment and stress-buffering. ResultsACTH levels decreased in 70% of all participants throughout the group activities. A two-way repeated measures ANOVA highlighted a significant interaction between time and OC use, indicating differential changes in ACTH levels during social interaction between OC users and NC women. Further, the post-hoc analysis revealed that a period of stress-buffering group activities significantly decreased ACTH levels in NC women during menstrual and secretory phases, but not during the proliferative phase. In contrast, OC users did not display a decrease during group activities, regardless of the phase. ConclusionThis study underscores the influence of OC use on stress regulation, demonstrating that OCs not only modulate reproductive functions but also impact ACTH stress reactivity. Additionally, it emphasizes the importance of considering hormonal contraceptive use and menstrual cycle phases when assessing female stress responses.

Investigation of breed differences in plasma adrenocorticotropic hormone concentrations among healthy horses and ponies

Plasma adrenocorticotropic hormone (ACTH) concentration is commonly measured to diagnose pituitary pars intermedia dysfunction (PPID). Several intrinsic and extrinsic factors affect ACTH concentrations, including breed. The objective of this study was to prospectively compare plasma ACTH concentrations among different breeds of mature horses and ponies. Three breed groups comprised Thoroughbred horses (n = 127), Shetland ponies (n = 131) and ponies of non-Shetland breeds (n = 141). Enrolled animals did not show any signs of illness, lameness or clinical signs consistent with PPID. Blood samples were collected 6 months apart, around the autumn equinox and spring equinox, and plasma concentrations of ACTH were measured by chemiluminescent immunoassay. Pairwise breed comparisons within each season were performed on log transformed data using the Tukey test. Estimated mean differences in ACTH concentrations were expressed as fold difference with 95 % confidence intervals (CI). Reference intervals for each breed group per season were calculated using non-parametric methods.In autumn, higher ACTH concentrations were found among non-Shetland pony breeds compared with Thoroughbreds (1.55 fold higher; 95 % CI, 1.35–1.77; P < 0.001), and in Shetland ponies compared with Thoroughbreds (2.67 fold higher; 95 % CI, 2.33–3.08; P < 0.001) and non-Shetland pony breeds (1.73 fold higher; 95 % CI, 1.51–1.98; P < 0.001). In spring, no differences were identified among breed groups (all P > 0.05). Reference intervals were similar among breed groups in spring, but upper limits for ACTH concentrations were markedly different between Thoroughbred horses and pony breeds in autumn. These findings emphasise that breed should be accounted for when determining and interpreting reference intervals for ACTH concentrations among healthy horses and ponies in autumn.

Intact GR dimerization is critical for restraining plasma ACTH levels during chronic psychosocial stress

Male C57BL/6N mice exposed to the chronic subordinate colony housing (CSC; 19 days) paradigm, a preclinically validated model of chronic psychosocial stress, are characterized by unaffected basal morning plasma corticosterone (CORT) concentrations despite adrenal and pituitary hyperplasia and increased adrenocorticotropic hormone (ACTH) plasma concentrations, compared with single-housed control (SHC) mice. However, as CSC mice are still able to show an increased CORT secretion towards novel heterotypic stressors, these effects might reflect an adaptation rather than a functional breakdown of general hypothalamus-pituitary-adrenal (HPA) axis functionality. In the present study we used male mice of a genetically modified mouse line, to investigate whether genetically-driven ACTH overexpression compromises adaptational processes occurring at the level of the adrenals during CSC exposure. Experimental mice carried a point mutation in the DNA binding domain of the glucocorticoid (GC) receptor (GR), attenuating dimerization of GR (GRdim), resulting in a congenially compromised negative feedback inhibition at the level of the pituitary.In line with previous studies, CSC mice in both the wild type (WT; GR+/+) and GRdim group developed adrenal enlargement. Moreover, compared with respective SHC and WT mice, CSC GRdim mice show increased basal morning plasma ACTH and CORT concentrations. Quantitative polymerase chain reaction (qPCR) analysis revealed neither a genotype effect, nor a CSC effect on pituitary mRNA expression of the ACTH precursor proopiomelanocortin (POMC). Finally, CSC increased anxiety-related behavior, active coping and splenocyte in vitro (re)activity in both WT and GRdim mice, while a CSC-induced increase in adrenal lipid vesicles and splenic GC resistance was detectable only in WT mice. Of note, lipopolysaccharide (LPS)-stimulated splenocytes of GRdim mice were resistant to the inhibitory effects of CORT.Together our findings support the hypothesis that pituitary ACTH protein concentration is negatively controlled by GR dimerization under conditions of chronic psychosocial stress, while POMC gene transcription is not dependent on intact GR dimerization under both basal and chronic stress conditions. Finally, our data suggest that adrenal adaptations during chronic psychosocial stress (i.e., ACTH desensitization), aiming at the prevention of prolonged hypercorticism, are protective only to a certain threshold of plasma ACTH levels.

A multi-targeted investigation of Deepwater Horizon crude oil exposure impacts on the marine teleost stress axis

The toxicity of the polycyclic aromatic hydrocarbons (PAHs) in Deepwater Horizon (DWH) oil is well-established, but a knowledge gap exists regarding how this combination of PAHs affects the vertebrate stress axis. We hypothesized that (1) marine vertebrates exposed to DWH PAHs experience stress axis impairment, and co-exposure to an additional chronic stressor may exacerbate these effects, (2) serotonin (5-hydroxytryptamine; 5-HT) may act as a secondary cortisol secretagogue in DWH PAH-exposed fish to compensate for impairment, and (3) the mechanism of stress axis impairment may involve downregulation of cyclic adenosine monophosphate (cAMP; as proxy for melanocortin 2 receptor (MC2R) functionality), total cholesterol, and/or mRNA expression of CYP1A and steroidogenic proteins StAR, P450scc, and 11β-h at the level of the kidney. We found that in vivo plasma cortisol and plasma adrenocorticotropic hormone (ACTH) concentrations in Gulf toadfish exposed to an environmentally relevant DWH PAH concentration (ΣPAH50= 4.6 ± 1.6 μg/L) for 7 days were not significantly different from controls, whether fish were chronically stressed or not. However, the rate of cortisol secretion by isolated kidneys after acute stimulation with ACTH was significantly lower in PAH-exposed toadfish compared to clean seawater (SW) controls. 5-HT does not appear to be acting as a secondary cortisol secretagogue, rather, PAH-exposed + stressed toadfish exhibited significantly lower plasma 5-HT concentrations than clean SW + stressed fish as well as a reduced sensitivity to 5-HT at the level of the kidney. There was a tendency for kidney cAMP concentrations to be lower in PAH-exposed fish (p = 0.069); however, mRNA expression of steroidogenic proteins between control and PAH-exposed toadfish were not significantly different and a significant elevation in total cholesterol concentration in PAH-exposed toadfish compared to controls was measured. Future work is needed to establish whether the slower cortisol secretion rate by isolated kidneys of PAH-exposed fish is detrimental, to determine the potential role of other secretagogues in compensating for the impaired kidney interrenal cell function, and to determine whether there is a reduction in MC2R mRNA expression or an impairment in the function of steroidogenic proteins.

Plasma marker ACTH, cortisol, and beta-endorphins profile on pregnant women as targeted marker of approach for antenatal depression

Background: Antenatal depression is a frequent mental disorder with much less attention, and most women remain undiagnosed. Altered hypothalamic-pituitary-adrenal (HPA)-axis function mediates maternal depressive symptoms and has been widely reported. The present research aimed to determine the plasma marker HPA-axis including Adrenocorticotropic hormone (ACTH), cortisol, and beta-endorphin, as a suitable representation of mental health in pregnancy by evaluating the psychometric properties. Methods: Therefore, we examined a case-control study of 216 Bontang pregnant women. Psychological measures were conducted during the 27th week of pregnancy, including the Patient Health Questionnaire-9 (PHQ-9) assessment and Depression Anxiety Stress Scale (DASS). Blood samples were collected for plasma ACTH, Cortisol, and beta-endorphins assay as a marker of the HPA axis profile. Data were analyzed Stata for Mac version 14 (StataCorp, USA). Results: our finding showed that DASS scores correlated with PHQ-9 (r=0.79), ACTH (r=0.22), and beta-endorphin (r=54). PHQ-9 score significantly related to ACTH (r=0.27), cortisol (r=0.36) and beta-endorphin (r=0.71). Women with the highest DASS score and PHQ-9 depression scores at 27 weeks of pregnancy had significantly lower baby birth weight (P=0.000) than those women whose stress improved to or normal state. Plasma ACTH, cortisol, and beta-endorphin concentrations were significantly higher in pregnant women with antenatal depression compared to normal pregnancy (p&lt;0.01). All effects remain without controlling unwanted pregnancy. Conclusion: Our study demonstrates a role for circulating ACTH in regulating maternal cortisol secretion and a significant correlation between the HPA-axis profile and antenatal depression at 27 weeks of pregnancy.

Atypical thymic carcinoid associated with rapidly progressive symptoms of Cushing's syndrome in a child

Atypical thymic carcinoid in children is rare and its prognosis principally depends on the completeness of the surgical resection. We report a case of atypical thymic carcinoid with lymph node metastasis that had not been identified prior to surgery. An 8-year-old boy was referred because of Cushing's syndrome and a worsening of his symptom, which included facial edema, fatigue, and headache, over 3 weeks. Blood testing revealed high plasma cortisol and adrenocorticotropic hormone (ACTH), and chest computed tomography demonstrated two tumors in his anterior mediastinum, but no findings suggestive of lymph node metastasis. We suspected the presence of an ACTH-producing thymic carcinoid tumor; therefore, the patient underwent total thymectomy and dissection of his anterior mediastinal and bilateral deep cervical lymph nodes. Histopathological examination revealed an atypical carcinoid tumor and left cervical lymph node metastasis. The patients' plasma cortisol and ACTH concentrations decreased after surgery, and he was further treated with radiotherapy and combination chemotherapy. Thus, it is possible that the development of symptoms may indicate more rapid progression of atypical thymic carcinoid, and deep cervical lymphadenectomy is necessary for its complete resection.

Management of pituitary pars intermedia dysfunction in practice: A clinical audit

In horses/ponies with pituitary pars intermedia dysfunction (PPID), pergolide mesylate treatment, with monitoring of therapeutic response, is recommended by contemporaneous literature and equine endocrinologists. However, it is unknown whether these recommendations are adhered to in private practice. This clinical audit aimed to compare treatment and monitoring of PPID cases in veterinary practice against available recommendations. Case data and basal plasma adrenocorticotropic hormone (ACTH) concentrations from all equids tested for PPID between 2012 and 2016 from a single veterinary practice in the UK were obtained. Records were reviewed and information on treatment and monitoring over the subsequent 2–6 years was extracted and compared with published recommendations. After exclusions, the audit population was 480 animals (median age, 20 years). The most common presenting signs were laminitis and/or historical laminitis (51.2%) and hypertrichosis and/or delayed coat shedding (24.5%). Based on seasonally adjusted reference intervals for basal ACTH concentration, 51.7% (n = 248) of animals were classified as positive, 37.1% (n = 178) as negative and 11.3% (n = 54) as equivocal for PPID. Records were available for 459 animals; of which pergolide treatment was initiated in 78.7% (n = 185/235) of positive cases, 19.2% (n = 10/52) of equivocal cases and 6.4% (n = 11/172) of cases classified as negative. Overall, 87.2% (n = 129/148) of cases commenced treatment as per recommendations. Only 77.7% (n = 160/206) of pergolide-treated animals had documented PPID monitoring and of these, only 48.1% (n = 77/160) had follow-up basal ACTH testing in the first 1–3 months following diagnosis. The findings confirm that management of PPID in veterinary practice fell below contemporaneous recommendations, especially for monitoring.

Seasonal variation of endogenous adrenocorticotropic hormone concentrations in healthy non-geriatric donkeys in Northern California

Elevated plasma adrenocorticotropic hormone (ACTH) is often used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. The hormone naturally increases in the fall in horses, and donkeys have been found to have higher ACTH concentrations than horses. However, circannual variation of ACTH has not been assessed in donkeys. The objective of the study was to establish seasonal variation of basal plasma ACTH concentrations over the course of a year in clinically healthy, non-geriatric donkeys. It was hypothesized that donkey ACTH concentrations would be higher than those reported in horses without PPID in all seasons, and that, similarly to horses, ACTH concentrations would further increase in the fall months. Twenty-six healthy adult donkeys (10 standards, 16 miniatures), a median (range) of 6 (2–13) years of age, were included. Donkeys were housed at a single location. Serial plasma samples were obtained monthly for 12 months. Plasma ACTH concentrations were determined by immunoassay. Data are presented as median (range), with a P-value < 0.05 considered significant. ACTH concentrations were lowest in the winter and spring [12.8 (5.0–73.6) pg/ml and 12.5 (2.8–62.6) pg/ml, respectively], with an increase in the summer [53.2 (29.7–305.0) pg/ml], and peak in the fall [77.1 (12.4–319.0) pg/ml]. ACTH concentrations were highest in the month of September [122.0 (41.7–319.0) pg/ml]. Donkey ACTH concentrations were higher than equine reference ranges from May through November but showed similar circannual variation with dramatic increases in the fall months. Species-specific reference ranges are necessary for accurate interpretation of endocrinopathy screenings in donkeys.

The effect of month and breed on plasma adrenocorticotropic hormone concentrations in equids

Use of plasma adrenocorticotropic hormone (ACTH) concentrations for the diagnosis of PPID in equids requires awareness of other factors that might influence ACTH concentrations, including breed and time of year. This study was designed to investigate effects of breed on plasma ACTH concentrations and potential interactions between breed and time of year. Ten breeds were selected from a laboratory database containing data on plasma ACTH concentrations. Breeds represented were Arabians, Cobs, Connemara ponies, donkeys, Irish Sports horses, New Forest ponies, Shetland ponies, Thoroughbreds, Warmbloods and Welsh breeds. Multivariable analysis was used to determine the effects of month and breed on plasma ACTH concentrations.A circannual pattern of ACTH concentration was documented, with a nadir in April and a peak in September. Arabian horses and donkeys had significantly higher ACTH concentrations than some other breeds, primarily from May to November, whereas in Shetland ponies and Welsh breeds, relatively higher ACTH concentrations only occurred from July to November. The annual increase in plasma ACTH appeared to commence in late April/early May in response to increasing daylight and decreased again promptly after the late September equinox as daylength fell below 12 h per day. Inter-breed differences in plasma ACTH were substantial and indicated that breed and time of year should be considered when interpreting plasma ACTH concentrations in equids suspected for PPID.

Dexmedetomidine in the Program of Multimodal Low-opioid Anesthesia During Laparoscopic Surgery in Urology

Dexmedetomidine, a highly selective α2-adrenergic agonist, has become a valuable component of low-opioid multimodal anesthesia, providing sedative, anxiolytic and analgesic effects. The objective: to evaluate the effectiveness of using dexmedetomidine in a multimodal low opioid anesthesia program for laparoscopic renal surgery. Materials and methods. 55 patients who underwent laparoscopic renal surgery under two types of general anesthesia were included. All patients underwent surgery under general anesthesia with tracheal intubation. Induction: intravenous propofol 2 mg/kg, fentanyl 1.5–2 μg/kg, atracurium 0.6 mg/kg. Anesthesia maintenance: sevoflurane (MAC – 1.44±0.25 vol.%). In group 1 analgesia was provided with fentanyl 3.89±2.1 μg/kg/h. Multimodal low-opioid anesthesia with fentanyl 2.38±1.01 μg/kg/h combined with dexmedetomidine 0.7 μg/kg/h was used in group 2. The efficacy of antinociceptive protection was assessed by the dynamics of changes in the levels of stress hormones, hemodynamic parameters, and blood glucose concentrations. Results. The total average doses of fentanyl used during the entire period of anesthesia were: 369.23±16.42 μg in group 1, 272.41±10,98 μg in group 2 (p&lt;0.001). In patients of the control group 1, an increase in the plasma concentration of adrenocorticotropic hormone by 111.86% (p&lt;0.01) from 25.7±2.1 pg/ml to 54.45±5.43 pg/ml was recorded (the study was conducted before the start of surgery and after the end of the operation), which was accompanied by a statistically significant increase cortisol concentration from 371.0±32.32 nmol/l to 562.72±45.37 nmol/l (by 51.67%) (p&lt;0.01). In patients of the second group (dexmedetomidine group), an intraoperative increase in the plasma concentration of adrenocorticotropic hormone was recorded from 26.25±2.3 pg/l to 46.88±2.36 pg/l (by 78.59%) (p&lt;0.01), which was accompanied by a statistically insignificant intraoperative increase in cortisol concentration from 393.51±25.0 nmol/l to 436.37±34.92 nmol/l – only by 10.89% (p&gt;0.05). Blood glucose concentrations in the early postoperative period in the both groups were 6.79±0.31 mmol/l and 6.29±0.24 mmol/l, respectively (p&gt;0.05). Hemodynamic parameters and BIS, which was maintained within 44±6.4%, indicated the adequacy of anesthesia and analgesia in both groups. Conclusions. The use of dexmedetomidine in multimodal low-opioid anesthesia for laparoscopic renal surgery provides the greatest antinociceptive protection and reduces the stress response to surgery.

Hypocortisolism in a dog caused by bilateral pheochromocytoma

AbstractWe present a 12‐year‐old French bulldog with muscle weakness, epigastric pain, weight loss, high systolic blood pressure and cardiac arrhythmias. Physical and laboratory examination revealed no abnormalities. On a computed tomography scan, severely enlarged adrenals were found, and endocrine and biochemical evaluations excluded hypercortisolism and hyperaldosteronism. Urinary metanephrine and normetanephrine/creatinine ratios were elevated, compatible with a diagnosis of pheochromocytoma. Symptomatic treatment with phenoxybenzamine was started and resulted in normalisation of a systolic blood pressure and reduction of arrhythmias. However, the onset of anorexia, vomiting and clinical deterioration prompted exploration of the adrenocortical reserve through an adrenocorticotropic hormone stimulation test, which confirmed glucocorticoid deficiency. Mineralocorticoid deficiency was ruled out by normal plasma aldosterone concentration and renin activity. Finally, an elevated endogenous plasma adrenocorticotropic hormone concentration defined the primary origin of the hypocortisolism. Clinical resolution occurred with prednisolone supplementation. This is the first report of hypocortisolism in a dog caused by a bilateral pheochromocytoma.

Effect of early or late blood sampling on thyrotropin releasing hormone stimulation test results in horses.

BackgroundDiagnosis of pituitary pars intermedia dysfunction (PPID) using the thyrotropin‐releasing hormone (TRH) stimulation test requires blood collection 10 minutes after TRH injection; it is unknown if small differences in timing affect test results.ObjectiveTo determine whether early or late sampling results in a significant (≥10%) difference in plasma adrenocorticotropic hormone (ACTH) concentration compared to standard 10‐minute sampling.AnimalsTwenty‐four healthy adult horses with unknown PPID status.MethodsIn this prospective study, subjects underwent a single TRH stimulation test, with blood collected exactly 9 minutes (early), 10 minutes (standard), and 11 minutes (late) after injection. ACTH was measured by chemiluminescent immunoassay. Two aliquots of the 10‐minute plasma sample were analyzed separately to assess intra‐assay variability. Data were reported descriptively and bias was calculated using Bland‐Altman plots. Significance was set at P = .05.ResultsMinor variability was observed between the paired 10‐minute sample aliquots (range, 0%‐6%; median 3%). Overall variability of early or late samples compared to the corresponding paired (average) 10‐minute standard concentration ranged from 0% to 92% (median 10%). Seventy‐five percent of horses (18/24) tested had at least 1 early or late reading that differed by ≥10% from its corresponding 10‐minute standard concentration, and 21% of horses (5/24) would have a different interpretation of testing result with either early or late sampling. Incidence of ≥10% variability was independent of PPID status (P = .59).Conclusions and Clinical ImportancePrecise timing of sample collection is critical to ensure accurate assessment of PPID status given the observation of significant variability associated with minor alterations in timing of sample collection.

Basal plasma adrenocorticotrophic hormone concentration for diagnosing pituitary pars intermedia dysfunction in horses: Comparative analysis of two systematic reviews

Basal plasma adrenocorticotrophic hormone concentration for diagnosing pituitary pars intermedia dysfunction in horses: Comparative analysis of two systematic reviews

FTY720 (Fingolimod), a modulator of sphingosine-1-phosphate receptors, increases baseline hypothalamic-pituitary adrenal axis activity and alters behaviors relevant to affect and anxiety

FTY720 (fingolimod) is an analog of sphingosine, a ubiquitous sphingolipid. Phosphorylated FTY720 (FTY720-P) non-selectively binds to sphingosine-1-phosphate receptors (S1PRs) and regulates multiple cellular processes including cell proliferation, inflammation, and vascular remodeling. We recently demonstrated that S1PR3 expression in the medial prefrontal cortex (mPFC) of rats promotes stress resilience and that S1PR3 expression in blood may serve as a biomarker for PTSD. Here we investigate the effects of FTY720 in regulating the stress response. We found that single and repeated intraperitoneal injections of FTY720 increased baseline plasma adrenocorticotropic hormone (ACTH) and corticosterone concentrations. FTY720 reduced social anxiety- and despair-like behavior as assessed by increased social interaction time and reduced time spent immobile in the Porsolt forced swim test. In blood, FTY720 administration reduced lymphocyte and reticulocyte counts, but raised erythrocyte counts. FTY720 also reduced mRNA of angiopoietin 1, endothelin 1, plasminogen, TgfB2, Pdgfa, and Mmp2 in the medial prefrontal cortex, suggesting that FTY720 reduced vascular remodeling. The antidepressant-like and anxiolytic-like effects of FTY720 may be attributed to reduced vascular remodeling as increased stress-induced blood vessel density in the brain contributes to behavior associated with vulnerability in rats. Together, these results demonstrate that FTY720 regulates baseline HPA axis activity but reduces social anxiety and despair, providing further evidence that S1PRs are important and novel regulators of stress-related functions.

The Effects of At-Birth Adoption on Atypical Behavior and Anxiety: A Nonhuman Primate Model

Adopted children tend to show an increased risk for a variety of psychopathological outcomes, even when adoption occurs at birth, which some suggest is a result of nonrandom assignment of adoptees and parents. This study uses a nonhuman primate model, in which adoptions were randomly assigned, to investigate the behavioral and physiological outcomes associated with at-birth adoption. Immediately following birth, rhesus monkey infants were randomly assigned to be reared by either their biological mother (n= 113) or by an unrelated, lactating, adoptive mother (n= 34). At 6 months of age, infant behavior and physiology were assessed during a stressful series of mother-infant separations. Four years later, stress-related behaviors were measured following confrontation by an unfamiliar intruder, an ecologically meaningful stressor. When compared to infants reared by their biological mothers, adopted infants exhibited more behavioral withdrawal and higher plasma adrenocorticotropic hormone (ACTH) concentrations in response to separation. These behavioral differences persisted 4 years later during a stressful intruder challenge, with adoptees exhibiting more behavioral withdrawal, stereotypies, and impulsive approaches of the potentially aggressive intruder. Compared to infants reared by their biological mothers, adopted infants exhibited more behavioral inhibition, impulsivity, and higher ACTH concentrations, even when subjects were randomly assigned to be adopted or to remain with their biological mother. To the extent that these findings generalize to humans, they suggest that the overall risk for psychopathology in adopted individuals persists even after random assignment to adoption conditions.

Relationship between endogenous plasma adrenocorticotropic hormone concentration and reproductive performance in Thoroughbred broodmares.

BackgroundPituitary pars intermedia dysfunction (PPID) is an endocrine disorder the clinical signs of which include infertility, but few reports have examined the relationship between PPID and reproductive performance in broodmares.Hypothesis/ObjectiveBroodmares with infertility of unknown etiology were screened for PPID using baseline endogenous plasma ACTH concentrations, and its relationship with subsequent reproductive performance was analyzed.AnimalsSixty‐seven Thoroughbred broodmares.MethodsAdrenocorticotropic hormone concentrations were measured in autumn. The broodmares were divided into 3 groups based on endogenous plasma ACTH concentration (low, <50 pg/mL; intermediate 50‐100 pg/mL; and high >100 pg/mL) as recommended by the Equine Endocrinology Group. We compared these results with those of other blood tests, clinical examinations, subsequent conception, and frequency of normal delivery.ResultsThe numbers of horses per group (percentage) were 22 (32.8%), 20 (29.9%), and 25 (37.3%). The mean ± SD ages (years) were 11.1 ± 3.4, 12.1 ± 4.5, and 13.0 ± 4.3, with no significant difference among groups. Mean ± SD plasma cortisol concentrations (μg/dL) were 4.0 ± 1.6, 7.1 ± 1.4, and 7.6 ± 1.9, with the intermediate and high ACTH groups having significantly higher results than the low ACTH group (P < .001). Conception rates were 77.3%, 89.5%, and 56.5% and normal delivery rates were 77.2%, 84.2%, and 43.5% with the percentage of each significantly lower in the high ACTH group (P = .02, P = .008, respectively).Conclusions and Clinical ImportanceThe study group of infertile broodmares may include horses with PPID. The reproductive performance of the high ACTH group was significantly lower than the other groups. Early diagnosis and treatment of infertile broodmares by screening plasma ACTH concentrations could help improve reproductive performance.