Plasma Adrenocorticotropic Hormone Research Articles

The Influence of Dietary Synbiotic on Agonistic Behavior, Stress, and Brain Monoamines via Modulation of the Microbiota–Gut–Brain Axis in Laying Hens

A complex system of neural pathways, collectively known as the microbiota–gut–brain (MGB) axis, interconnects the gut microbiota, the gastrointestinal system, and the brain along with its periphery. Previous studies have demonstrated that modulation of the MGB axis can influence stress-related behaviors such as anxiety. This connection becomes apparent in scenarios like agonistic behavior in laying hens, which is characterized by aggressive head and feather pecks, that can ultimately result in cannibalism and death. The objective was to examine the effects of a dietary synbiotic on agonistic behavior, plasma and brain monoamines, stress parameters, and cecal microbiota counts via modulation of the MGB axis. A total of 396 W36 Hy-Line laying hens were provided at random with a control (CON: basal diet) or treatment (SYN: basal diet supplemented with synbiotic) diet from 50 to 60 weeks old (nine pens/treatment, 22 birds/pen). Blood samples and video recordings (three consecutive days/week) were taken at 50 and 60 weeks. At 60 weeks, three hens/pen were euthanized for brain and cecal microbiota collection. Threatening, fighting, head, body, and feather pecking all occurred less frequently at 60 weeks in the SYN group (p < 0.05). Plasma corticosterone, adrenocorticotropic hormone, dopamine, and serotonin were significantly lower while tryptophan and 5-hydroxyindoleacetic acid were significantly higher in birds from the SYN group (p < 0.05). Significant differences in serotonin, 5-hydroxyindoleacetic acid, dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid were observed in the hypothalamus, hippocampus, and amygdala of the brain. Serotonin and dopamine turnover rates were significantly different in all three regions of the brain (p < 0.05). Cecal counts of Lactobacillus and Bifidobacterium were significantly higher in the SYN group (p < 0.05). Synbiotic supplementation resulted in many significant differences, indicating activation of the serotonergic systems and modulation of both the MGB axis and HPA axis with positive effects on welfare and stress.

478. Elevated Plasma Adrenocorticotropic Hormone (ACTH) Levels Correlate With Reduced Suicidal Thoughts in Psychiatric Patients Relative to Control Groups, Regardless of Depression Intensity

478. Elevated Plasma Adrenocorticotropic Hormone (ACTH) Levels Correlate With Reduced Suicidal Thoughts in Psychiatric Patients Relative to Control Groups, Regardless of Depression Intensity

Higher levels of plasma Adrenocorticotropic hormone (ACTH) are associated with lower suicidal ideation in depressed patients compared to controls and suicide attempters, independently from depression severity

IntroductionSuicidal ideation, an important risk factor for suicide attempts, has an unclear neurobiological basis and is potentially linked to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and immune-inflammatory systems. While inflammatory markers have been associated with suicide attempts and, to a lower extent suicidal ideation, the data on the role of a stress-response system is less robust, with most studies carried out with cortisol showing inconsistent results. The present study extends on the previous studies implicating stress-response and immune-inflammatory systems in suicidal thoughts and behaviours, focusing on the associations of several stress-response (adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone (DHEA)) and immune-inflammatory (C-reactive protein (CRP),interle ukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha)) with suicidal ideation severity in recent suicide attempters, patients with major depressive disorder, and non-psychiatric controls. MethodsThis observational study included 156 adults from three Vilnius hospitals, recruited into one of the three groups in equal parts: recent suicide attempters, patients with major depressive disorder in current depressive episode, and non-psychiatric controls. Measures included the Hamilton Depression Rating Scale (HDRS-17) and the Beck Scale for Suicide Ideation/Suicide Severity Index (BSS/SSI), alongside sociodemographic data, alcohol, tobacco use, and morning blood samples, measuring plasma ACTH, cortisol, DHEA, CRP, and IL-6. Data were analysed with non-parametric tests, Kendall's tau correlation, and multivariate linear regression adjusted for confounders. ResultsWe found a negative correlation between the plasma ACTH levels and suicidal ideation severity (tau = −0.130, p = 0.033), which was driven by the patients with major depressive disorder (tau = −0.237, p = 0.031). Suicidal ideation severity was also negatively correlated with TNF-alpha (tau = −0.231; p < 0.001), positively correlated with IL-6 (tau = 0.154, p = 0.015), and CRP levels (tau = 0.153, p = 0.015), but no differences were observed in group-stratified analyses. The association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder remained robust to adjustment for major confounders (adjusted for age, sex, education years, body mass index, smoking status, plasma CRP and PEth concentration (measuring chronic alcohol exposure), and antidepressant use) in the linear regression model (t = −2.71, p = 0.011), as well as additionally adjusting for depression severity (t = −2.99, p = 0.006). DiscussionThe present study shows an association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder, robust to adjustment for antidepressant use and depression severity. This finding highlights the potential role of ACTH, in elucidating the effects of stress and mental health disorders. Our findings underscore the importance of the HPA axis in the diagnosis and treatment of suicidal ideation in major depressive disorder and invite further research on interventions targeting this pathway.

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.

Electroacupuncture regulates gut microbiota to reduce depressive-like behavior in rats.

Growing studies show that gut microbiota is closely associated with depression. Acupuncture treatment could regulate the gut microbiota of many diseases. Here, we aim to observe the effect of electroacupuncture (EA) on gut microbiota in rats that showed depressive-like behavior. The rats were randomly divided into normal group, chronic unpredictable mild stress model (CUMS) group, CUMS + electroacupuncture (EA) group, and CUMS + sham-electroacupuncture (Sham) group. The CUMS+EA rats were treated with EA stimulation at bilateral Zusanli (ST36) and Tianshu (ST25) acupoints for 2 weeks (0.7 mA, 2/100 Hz, 30 min/day). The rats in the sham EA group were treated with the same conditions without inserting needles and electrical stimulation. Behavioral tests were conducted by forced swimming test (FST), open field test (OFT), and sucrose preference test (SPT) to assess depression-like behavior in rats. The relative abundance of intestinal bacteria in rat feces was detected by 16S rRNA analysis. The expression of calcitonin-gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), somatostatin (SST), and adrenocorticotropic hormone (ACTH) in serum was detected by ELISA kit, and VIP, CGRP, and SST in the colon were detected by qRT-PCR and Western blot. Chronic unpredictable mild stress model rats exhibited depressive-like behaviors and had differential abundance vs. control rats. CUMS significantly decreased the relative abundance of Bifidobacterium and Streptococcus at the genus level, CGRP in plasma (p < 0.05), and significantly increased the intestine propulsion rate, the mRNA and protein expression of VIP, SST, and mRNA in the colon, and ATCH in plasma (p < 0.05). EA rats with microbial profiles were distinct from CUMS rats. EA markedly reduced the depressive-like behaviors, significantly increased the intestine propulsion rate, the relative abundance of Bacteroidetes, Proteobacteria, and Actinobacteria at the phylum level, Bifidobacterium and Streptococcus at the genus level, and VIP and CGRP in plasma (p < 0.05), and significantly decreased Firmicutes, the ratio of Firmicutes to Bacteroidetes at the phylum level, ACTH and SST in plasma, and SST mRNA in the colon (p < 0.05). The antidepressant effect of EA at ST36 and ST25 is related to regulating intestinal flora and the neurotransmitter system. Our study suggests that EA contributes to the improvement of depression, and gut microbiota may be one of the mechanisms of EA effect.

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.

Is high salt intake inducing obesity via production of cortisol? A novel working hypothesis and pilot study.

Evidence is growing that high salt intake is an independent risk factor for obesity, but the mechanisms are unknown. Our novel working hypothesis is that high salt intake drives cortisol production, which in turn, drives obesity. The current study aimed to demonstrate an acute cortisol response following a single high salt meal. Eight participants (age 30.5 ± 9.8 years [mean ± SD], 50% female), consumed high salt (3.82 g; 1529 mg sodium) and low salt (0.02 g; 9 mg sodium) meals in a randomized cross-over design. Urinary and salivary cortisol and plasma adrenocorticotropic hormone (ACTH) demonstrated order effects. When high salt was given second, there was a peak above baseline for urinary cortisol (26.3%), salivary cortisol (9.4%) and plasma ACTH (4.1%) followed by a significant decline in each hormone (treatment*time, F[9, 18] = 2.641, p = 0.038, partial η2 = 0.569; treatment*time, F[12, 24] = 2.668, p = 0.020, partial η2 = 0.572; treatment*time, F[12, 24] = 2.580, p = 0.023, partial η2 = 0.563, respectively), but not when high salt was given first (p > 0.05 for all). These intriguing findings provide partial support for our hypothesis and support a need for further research to elucidate the role of high salt intake in cortisol production and, in turn, in the aetiology of obesity. ACTRN12623000490673; date of registration 12/05/2023; retrospectively registered.

Glucocorticoid-induced adrenal insufficiency after therapy with intravenous methylprednisolone in patients with moderate-to-severe and active Graves' orbitopathy: assessment with a low-dose corticotropin test.

We aimed to assess adrenal function following treatment of moderate-to-severe and active Graves' orbitopathy (GO) with intravenous methylprednisolone (IVMP) in weekly pulses in a cumulative dose of 4.5 or 7.5g. We evaluated the impact of IVMP pulses on adrenal reserve using a low-dose (1μg) ACTH stimulation test (LDT) for the first time. In this prospective study we evaluated adrenal function in 21 patients with moderate-to-severe and active GO treated with 12 weekly IVMP pulses according to the European Group on Graves' Orbitopathy (EUGOGO) recommendations. We assessed serum cortisol, plasma adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone sulfate (DHEA-S) levels before the 1st and 12th IVMP pulse. We performed dynamic testing using LDT before the 12th IVMP pulse in all patients. In those who failed LDT, adrenal function was reassessed with LDT and the overnight metyrapone test after 4-7weeks. Two patients failed to achieve serum cortisol levels ≥ 18.1μg/dL at 30 and 60min in LDT and were diagnosed with glucocorticoid-induced adrenal insufficiency (GC-induced AI). They were recommended to take hydrocortisone in situations of acute stress. Both patients were reassessed within 4-7weeks after treatment cessation and showed an adequate response in LDT and overnight metyrapone test. We observed a statistically significant decrease in DHEA-S levels (p = 0.004) before the 12th IVMP pulse compared to baseline in all patients. For the first time, our research shows that administering IVMP in 12 weekly pulses can result in GC-induced AI. We suggest that patients should undergo careful evaluation for GC-induced AI, including LDT, after therapy with IVMP according to EUGOGO guidelines. Screening for altered adrenal reserve could prevent life-threatening complications, particularly during acute stress situations.

O-03 Adrenalectomy for Cushing's syndrome during pregnancy

Abstract Introduction Cushing's syndrome (CS) is rare in pregnancy because CS itself is a cause of anovulatory infertility due to excess cortisol secretion. Moreover it is also difficult to diagnose CS in pregnancy because placental production of corticotropin releasing and adrenocorticotropic hormone (ACTH), increased maternal production of estrogen induced corticosteroid binding globulin leads to physiological hypercortisolism during pregnancy. So physicians face a clinical overlap in many features of CS such as weight gain, fatigue, edema, hypertension, hyperglycemia, stretch marks, mood changes that can also be attributed to pregnancy. Thus their coexistence represents a diagnostic challenge. Herein we report a case of CS that was diagnosed and successfully treated during pregnancy. Clinical Case A 43-year-old gravida 3 female was consulted at the 21st week of gestation with persistent high blood pressure and hyperglycemia for a month. She had an obstetric history of 2 spontaneous first term abortion, 2 healthy labor 18 years ago and she was healthy after. She was in such a depressive mood that she was consulted with psychiatry many times. On physical examination edema, proximal weakness of lower extremities and hirsutism (modified Ferriman–Gallwey score of 9) was detected. Initial laboratory tests were all within normal range except potassium level (2.7 mmol/L), the results were not consistent with preeclampsia and there was a suspicious adrenal mass detected on ultrasound. She was currently receiving high dose antihypertensive treatment with methyldopa, calcium channel blockers, rapid acting and detemir insulin for diabetes and i.v. potassium replacement. We ruled out conns syndrome with normal plasma aldosterone renin ratio and found catecholamine levels normal. Hormonal analyses revealed with high plasma cortisol levels, increased nocturnal cortisolemia, a suppressed plasma ACTH and dehydroepiandrosterone sulfate level and distinctly elevated 24-hour urinary cortisol greater than 3-fold the upper normal reference range. Non contrast magnetic resonance imaging demonstrated a 47×32 mm left adrenal mass. Laparoscopic adrenalectomy was performed in the 26th week of gestation and the following histopathology revealed an adrenocortical adenoma. Antihypertensive medication was progressively reduced, glycemic control and hypokalemia reversal were achieved. She was followed up with appropriate glucocorticoid replacement. At 34 weeks of gestation, after sudden labor pain and regular uterine contractions a 2586 g male infant with Apgar scores of 8 was born by cesarean section. They were discharged in good health. Conclusion CS should be kept in mind especially in the case of hypertension and diabetes that started before the 20th gestational age. Analysis of the urinary free cortisol level and circadian rhythm of cortisol is necessary to diagnose. Despite the diagnostic challenge we can achieve better maternal and fetal outcomes with proper management.Figure 1.Non-contrast magnetic resonance imaging of the patient Table 1.Patient's laboratuary test results Table 2.Patient's laboratory test results

Hypothalamic-Pituitary-Adrenal Axis Activity in SARS-CoV-2 Infected Noncritically Ill Hospitalized Patients.

This study determined the baseline hypothalamic-pituitary-adrenal axis hormonal levels and their associated factors in noncritically ill hospitalized patients with coronavirus disease 2019 (COVID-19). This cross-sectional study was carried out in 91 noncritical RT-PCR-confirmed COVID-19 patients (aged 18 to 65 years) recruited consecutively from the COVID unit of two tertiary care hospitals over a period of six months. After the screening, relevant history and physical examinations were done, and blood was drawn between 07:00 am to 09:00 am in a fasting state to measure serum cortisol and plasma adrenocorticotropic hormone (ACTH) by chemiluminescent microparticle immunoassay. Of 91 patients, 54, 26, and 11 had mild, moderate, and severe COVID-19, respectively. Median values of serum cortisol (p = 0.057) and plasma ACTH (p = 0.910) were statistically similar among the severity groups. Considering a cortisol cut-off of 276 nmol/L (<10 μg/dL), the highest percent of adrenal insufficiency was present in severe (27.3%), followed by mild (25.9%) and least in the moderate (3.8%) COVID-19 cases. Using the cortisol/ACTH ratio >15, only 6.6% had enough reserve. The adrenocortical response was compromised in a significant percentage of noncritically ill hospitalized patients with COVID-19, with the highest percentage of adrenal insufficiency present in severely infected cases. The HPA axis parameters of serum cortisol, plasma ACTH and cortisol/ACTH were similar across the severity of noncritical patients with COVID-19.

Efficacious Primary Pasireotide Therapy in a Case of a Large Invasive Adrenocorticotropin-secreting Pituitary Tumor

Abstract A 41-year-old woman presented with a headache, diplopia, weight gain, moon face, and central obesity. Her plasma adrenocorticotropin (ACTH) level was 25.5 pmol/L (116 pg/mL) (normal range, 1.6-13.9 pmol/L [7.2-63.3 pg/mL]), serum cortisol level was 397.3 nmol/L (14.4 µg/dL) (normal range, 195.1-540.7 nmol/L [7.1-19.6 µg/dL]), and urinary free cortisol was 413.9 nmol/day (150.3 µg/day) (normal range, &amp;lt;221.5 mmol/day [&amp;lt;80.3 µg/day]). ACTH-dependent hypercortisolism was present, with cortisol suppression using a high-dose dexamethasone suppression test. Cushing disease was diagnosed and a contrast-enhanced magnetic resonance imaging scan demonstrated a 36-mm pituitary tumor with right cavernous sinus invasion. Before surgery, 20 mg pasireotide long-acting-release was initiated, and her symptoms rapidly improved. After 1 month, obvious tumor shrinkage was observed, ACTH and cortisol levels decreased, and diplopia resolved; therefore, we continued medical therapy. After 11 months, her ACTH and cortisol levels normalized, and most of the tumor had disappeared. The clinical course in this case suggests that pasireotide may be useful for preoperative treatment and primary medical therapy, at least in some patients with Cushing disease caused by a large tumor predicted to have difficulty achieving remission by surgery.

FRI203 A Case Of Pseudoadrenal Tumor Mimicking Left Adrenal Pheochromocytoma

Abstract Disclosure: A. Tanabe: None. E. Sugito: None. H. Kajio: None. Approximately 50% of adrenal incidentalomas are non-functional cortical adenomas, and 25% are adrenocortical hormone-secreting adenomas and pheochromocytomas. Adrenocortical carcinomas, and pheochromocytomas which have malignant potential, need to be differentiated and removed even if the tumors are hormonally inactive. In addition to these adrenal origin tumors, anatomic structures and tumors that develop in tissues neighboring the adrenal glands (pseudoadrenal tumors) may be confused with primary adrenal tumors. The larger the tumor, the more difficult it is to determine continuity with the adrenal glands. Herein we report a patient with gastrointestinal stromal tumor (GIST) that mimicked a left adrenal pheochromocytoma. A 47-year-old man was diagnosed with a left adrenal incidentaloma at 40 years of age. The tumor had irregular margins and grew from 18 mm to 30 mm in maximum diameter over 7 years. The mass appeared to be in the tip of the lateral limb of the left adrenal gland and was located between the left adrenal gland and the posterior wall of the stomach. The patient had no abnormal findings other than general obesity. The blood pressure was 106/72 mmHg with antihypertensive agents. The plasma corticotropin and cortisol concentrations were normal and suppressed normally after a 1-mg overnight dexamethasone suppression test. The plasma aldosterone concentration and renin activity were increased with angiotensin receptor blocker and diuretic therapy. The 24-h urine fractionated metanephrines levels were at the upper limit of the reference range. Because the tumor showed unenhanced computed tomography (CT) attenuation of 40-50 Hounsfield units, hormonally-inactive adrenocortical carcinoma or pheochromocytoma had to be differentiated. I-123-metaiodobenylguanidine (I-123-MIBG) scintigraphy showed tumor avidity consistent with a pheochromocytoma. A laparoscopic left adrenalectomy was performed; however, no tumor was present in the resected specimen. Abdominal CT postoperatively showed that the tumor remained intact and appeared to connect to the posterior wall of the stomach. A laparotomy was performed and the tumor was removed. The tumor was localized to the intraperitoneal space and isolated from the posterior wall of the stomach. The pathological diagnosis was a GIST. Although it has been reported that I-123-MIBG may accumulate in tumors other than neuroendocrine tumors, reports on GISTs are rare. Lessons learned from our case include the importance of clinicians need to be aware of the limitations of diagnostic imaging studies in diagnosing non-functioning adrenal incidentalomas, which require a pathologic analysis for the final diagnosis. Moreover, clinicians need to provide patients with sufficient informed consent when deciding on treatment strategies. Presentation: Friday, June 16, 2023

Hippocampal Dynamic Functional Connectivity, HPA Axis Activity, and Personality Trait in Bipolar Disorder with Suicidal Attempt

Introduction: Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associated with suicide-related personality traits. The objective of our study was to clarify this. Methods: Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA), and 40 without SA, and 35 healthy controls (HCs). The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results: BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression, and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. Conclusion: These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits.

Inhibitory action of B-type natriuretic peptide on adrenocorticotropic hormone in patients with acute coronary syndrome.

In addition to the classical actions of hemodynamic regulation, natriuretic peptides (NPs) interact with various neurohumoral factors that are deeply involved in the pathophysiology of cardiovascular diseases. However, their effects on the hypothalamic-pituitary-adrenal (HPA) axis, which is activated under acute high-stress conditions in acute coronary syndrome (ACS), remain largely unknown. We investigated the impact of plasma B-type NP (BNP) on plasma adrenocorticotropic hormone (ACTH)-cortisol levels during the acute phase of ACS ischemic attacks. The study population included 436 consecutive patients with ACS for whom data were collected during emergency cardiac catheterization. Among them, biochemical data after acute-phase treatment were available in 320 cases, defined as the ACS-remission phase (ACS-rem). Multiple regression analyses revealed that plasma BNP levels were significantly negatively associated with plasma ACTH levels only during ACS attacks (P < 0.001), but not in ACS-rem, whereas plasma BNP levels were not significantly associated with plasma cortisol levels at any point. Accordingly, covariance structure analyses were performed to clarify the direct contribution of BNP to ACTH by excluding other confounding factors, confirming that BNP level was negatively correlated with ACTH level only during ACS attacks (β = -0.152, P = 0.002), whereas BNP did not significantly affect ACTH in ACS-rem. In conclusion, despite the lack of a significant direct association with cortisol levels, BNP negatively regulated ACTH levels during the acute phase of an ACS attack in which the HPA axis ought to be activated. NP may alleviate the acute stress response induced by severe ischemic attacks in patients with ACS.NEW & NOTEWORTHY BNP negatively regulates ACTH during a severe ischemic attack of ACS in which hypothalamic-pituitary-adrenal axis ought to be activated, indicating an important role of natriuretic peptides as a mechanism of adaptation to acute critical stress conditions in humans.

Factitious cushing's syndrome with unusual presentation: a case report and literature review.

A 40-year-old female patient who worked as a registered nurse presented with clinical features of CS but denied any exogenous corticosteroid use. The endocrine workup revealed that the patient had a high 24h urinary-free cortisol collection before admission. Subsequent evaluations showed low levels of morning cortisol and plasma adrenocorticotropic hormone along with a suppressed overnight low-dose dexamethasone suppression test, leading to an investigation of hypercortisolism. Unexpectedly, subsequent testing showed a normal 24h urinary-free cortisol level. Additionally, the patient was diagnosed with panhypopituitarism, the radiological investigations showed normal pituitary and adrenal glands. Despite consistently denying the use of corticosteroids, it was finally discovered that the patient had been surreptitiously taking prednisone and receiving multiple dexamethasone injections over the past few months. The patient received treatment through a gradual prednisone tapering regimen, accompanied by comprehensive psychiatric evaluation and management. This case underscores the exceptional rarity of factitious CS and emphasizes the importance of considering it as a potential differential diagnosis in hypercortisolism cases, particularly when the patient's medical history contradicts investigative findings. Furthermore, it highlights the criticality of adopting a multidisciplinary approach to investigate patients whose clinical presentation aligns with factitious CS.

Adrenal Hemorrhaging in a Patient with Severe Obstructive Sleep Apnea Syndrome with Elevated Plasma ACTH Levels.

Adrenal hemorrhaging (AH) is a rare condition characterized by bleeding into the suprarenal glands. A 62-year-old man with untreated obstructive sleep apnea syndrome (OSAS) was admitted to our hospital complaining of abdominal stiffness. He was diagnosed with left-sided AH and underwent adrenalectomy. Pre- and post-surgery, elevated plasma adrenocorticotropic hormone (ACTH) levels were observed. However, Cushing's syndrome and adrenal insufficiency were negative, and nasal continuous positive airway pressure (CPAP) normalized the plasma ACTH levels. Elevated ACTH levels are reportedly present in patients with OSAS. ACTH may be associated with the development of AH through the change in blood supply and other mechanisms.

Pulsatile Subcutaneous Hydrocortisone Replacement in Primary Adrenal Insufficiency.

Pulsatile endogenous cortisol secretion is critical for physiological glucocorticoid gene signaling. Conventional glucocorticoid replacement therapy does not mimic endogenous cortisol pulsing in primary adrenal insufficiency. In an open-labeled, two-week, nonrandomized cross-over study of five patients with adrenal insufficiency (Addison's disease in two, bilateral adrenalectomy in one, and congenital adrenal hyperplasia in two patients) we compared pulsatile and continuous cortisol pump treatment and conventional oral glucocorticoid therapy with respect to 24-h serum corticosteroid levels and plasma adrenocorticotropic hormone (ACTH). Pulsed pump restored ultradian rhythmicity as demonstrated by five peaks of serum (all patients) and subcutaneous tissue cortisol (four patients). Morning subcutaneous cortisol and cortisone were higher in continuous and pulsed pump treatment than in oral therapy despite nearly similar serum cortisol levels in all treatment arms. ACTH was within the physiological range during pulsed pump treatment in all patients except for slightly elevated levels in the morning hours 04:00-08:00 h. During oral therapy, ACTH was very high in patients with Addison's disease and suppressed in patients with congenital adrenal hyperplasia. In conclusions, mimicking endogenous cortisol rhythmicity by ultradian subcutaneous infusion of cortisol is feasible. It was superior to both continuous pump and oral therapy in maintaining normal ACTH levels throughout the 24-h cycle. Our results demonstrate a low free cortisol bioavailability on thrice daily oral replacement therapy compared to both types of subcutaneous infusion.

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.

AMBULATORY BLOOD PRESSURE MONITORING BEFORE AND AFTER TREATMENT IN SECONDARY FORMS OF HYPERTENSION

Objective: Studies using ambulatory blood pressure (BP) monitoring (ABPM) have reported that in some secondary forms of hypertension the normal nocturnal BP decrease is blunted. Design and method: The aim of our study was to compare the nocturnal BP decrease in patients with secondary hypertension before and after treatment. ABPM was performed using the validated Meditech ABPM-06. ABPM readings were obtained at 30-minute intervals for 24-hour in patients with secondary hypertension before and after treatment. The diagnosis of secondary hypertension was based on the history and laboratory data: plasma and urinary electrolytes, renal function, calcium-phosphorus system, the renin-angiotensin-aldosterone system, urinary free cortisol, suppressibility of cortisol after 1 mg dexamethasone, plasma adrenocorticotropic hormone, plasma D4 androstenedione, plasma dehydroepiandrosterone sulphate, plasma 17-alpha hydroxyprogesterone, plasma testosterone, and urinary metanephrine. BP decrease were studied in the following groups: 42 patients with primary aldosteronism (19 men and 23 women; mean age, 44±12 years), 25 patients with adrenal pheochromocytoma (11 men and 14 women; mean age, 42±13 years), and 55 patients with Cushing's syndrome (18 men and 37 women, mean age, 43±13 years). Results: Average systolic/diastolic BP decrease was: before 2/1 mmHg and after 8/6 mmHg treatment in patients with primary aldosteronism. Average systolic/diastolic BP decrease was: before 4/5 mmHg and after 9/12 mmHg treatment in patients with adrenal pheochromocytoma. Average systolic/diastolic BP decrease was: before 3/2 mmHg and after 11/9 mmHg treatment in patients with Cushing's syndrome. All differences in systolic/diastolic BP decrease were statistically significant, with a P value &lt;.001 Conclusions: The results of our study confirm that secondary causes of hypertension lead to a reduced decrease in blood pressure during sleep. After proper treatment reduction in nighttime BP normalizes. A detailed analysis of ABPM can lead us to find the accurate etiology of hypertension.

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.