Adrenocorticotropic Hormone Levels Research Articles

Effects of recreational SCUBA diving practiced once a week on neurohormonal response and myokines-mediated communication between muscles and the brain.

During physical activity, activation of muscular, endocrine, and nervous systems, results in intensive crosstalk between muscles and other organs, which enables response to physiological stress. In SCUBA diving, extreme environmental conditions represent an additional challenge for homeostasis maintenance, but underlying mechanisms are largely unknown. We aimed to contribute to the understanding of neurohormonal response and muscle-brain crosstalk by measuring the concentrations of the selected hormones secreted by the pituitary-target organ axis and myokines involved in the muscle-brain endocrine loop in recreational SCUBA (rSCUBA) divers. Fourteen male divers performed five open-water recreational dives (one per week, depth of 20-30 m, lasting 30 min, between 9 and 10 am), after a winter non-diving period of 5 months. Blood samples were collected immediately before and after the first, third, and fifth dives. Adrenocorticotropic hormone (ACTH), cortisol, thyroid-stimulating hormone (TSH), free thyroxine (fT4), prolactin, total testosterone, growth hormone (GH), insulin-like growth factor-1 (IGF-1), irisin, brain-derived neurotrophic factor (BDNF), S100B, glial fibrillary acidic protein (GFAP), and neuron-specific enolase (NSE) were measured using commercially available immunoassays. Cortisol and ACTH levels decreased after every dive, while total testosterone decreased only after the first dive. No significant changes in post-dive values, as well as the cumulative effect on any other measured hormone, were observed. Although irisin and BDNF levels decreased after the first and third dives, the fifth dive caused a significant increase in both myokines. Changes in IGF-1 levels were not observed. All three dives caused a significant increase in S100B levels. A statistically significant decrease in GFAP concentration was observed after every dive, while NSE pre-dive concentration declined over the studied period. The cumulative effect on myokine levels was reflected in a continuous decline in irisin and BDNF pre-dive levels throughout the studied period, but an increasing trend after the fifth dive was observed. Observed changes in myokines and hormone levels point to a specific response to rSCUBA practiced once a week, most likely due to extreme environmental conditions. Further studies on communication between muscles and other organ systems, particularly on the muscle-brain endocrine loop, are required for a deeper understanding of the adaptation mechanisms to this kind of physiological stress.

Risk factors for testicular adrenal rest tumors in pediatric patients with congenital adrenal hyperplasia

Testicular adrenal rest tumors (TARTs) predominantly occur in patients with congenital adrenal hyperplasia (CAH) and may interfere with the function of the testicles. This study aimed to identify the factors that contribute to the occurrence of TARTs in patients with CAH and influence their volume. This was a comparative cross-sectional study. Male patients aged 0-16 years with CAH were included. Weight, height, bone age determination, biochemical and androgenic profiles, and testicular ultrasound were performed. Patients were divided into those with and without TARTs and the between-group differences were assessed using the Mann-Whitey U test and Fisher's exact test. A ROC curve was created for serum ACTH levels to identify the cut-off point to diagnose TARTs. Variables that influenced the volume of the TARTs were identified using Spearman's correlation coefficient. TARTs were observed in seven (19.4%) of 36 male children with CAH. Of the patients with TARTs, 85.7% were pubertal. Serum concentrations of adrenocorticotropic hormone (ACTH) levels were significantly higher in patients with TARTs than in those without (309.0pg/mL vs. 45.2pg/mL; p=0.006). ACTH levels >200pg/mL were found to predict the presence of TARTs (sensitivity 85.7%; specificity 86.2%) (Figure). The factors found to correlate with TARTs volume were ACTH levels (coefficient 0.004; p=0.009) and the three-year average of serum testosterone levels (coefficient 9.64; p=0.003).] DISCUSSION: The main limitation of this study was the small sample size. However, an ACTH cut-off point to predict insufficient hormonal treatment and consequently the presence of TART had not been described. High ACTH (>200pg/mL) was found to be predictive insufficient hormonal treatment in patients with CAH. The three-year average of serum testosterone levels and ACTH concentrations were correlated with the volume of TARTs.

Synergistic antidepressant-like effect of n-3 polyunsaturated fatty acids and probiotics through the brain-gut axis in rats exposed to chronic mild stress

N-3 polyunsaturated fatty acids (PUFA) and probiotics have antidepressant-like effects, but the underlying mechanisms are unclear. We hypothesized that n-3 PUFA combined with live and dead probiotics synergistically improves depression by modulating the hypothalamic-pituitary-adrenal (HPA) axis and serotonergic pathways through the brain-gut axis. Rats were randomly divided into seven groups (n = 8/group): nonchronic mild stress (CMS) with n-6 PUFA, CMS with n-3 PUFA, n-6 PUFA, live probiotics, dead probiotics, n-3 PUFA, and live probiotics, and n-3 PUFA and dead probiotics. Diets of n-6 and n-3 PUFA and oral supplementation of live and dead probiotics were provided for 12 weeks, and CMS was performed for the last 5 weeks. N-3 PUFA and probiotics improved depressive behaviors and modulated the brain and gut HPA axis by synergistically increasing glucocorticoid receptor expression and decreasing corticotropin-releasing factor expression and blood levels of adrenocorticotropic hormone and corticosterone. N-3 PUFA and probiotics upregulated the brain serotonergic pathway through serotonin levels and expression of brain-derived neurotrophic factor, phosphorylated cAMP response binding protein, and 5-hydroxytryptamine 1A receptor while downregulating the gut serotonergic pathway. Furthermore, n-3 PUFA and probiotics increased the abundance of Ruminococcaceae, brain and gut short chain fatty acid levels, and occludin expression while decreasing the expression of tumor necrosis factor-α, interleukin-1β, and prostaglandin E2 and blood lipopolysaccharides levels. There was no significant difference between the live and dead probiotics. In conclusion, n-3 PUFA and probiotics had synergistic antidepressant-like effects on the HPA axis and serotonergic pathways of the brain and gut through the brain-gut axis.

Pituitary hypoadrenocorticism and hypothyroidism after immunochemotherapy followed by salvage surgery for lung cancer: a case report

BackgroundImmune checkpoint inhibitors (ICIs) have been shown to prolong the survival of patients with non-small cell lung cancer (NSCLC) and have allowed complete resection for advanced lung cancer. However, immune-related adverse events (irAEs) have been recognized as concerning side effects of ICIs.Case presentationA 62-year-old man visited our hospital because of fever, dyspnea, and anorexia. A tumor was found in the right hilum of the lung. It compressed the left atrium and was also thought to be invading the esophagus and a vertebral body. A bronchoscopic biopsy revealed squamous cell carcinoma of the lung (cT4N2M0-IIIB). We thought that a complete resection was impossible because of the N2 status of the tumor and because it had invaded several organs. Radiotherapy was thought to be contraindicated because of the patient’s marked emphysema. Therefore, we administered 4 courses of pembrolizumab plus carboplatin plus nab-paclitaxel immunochemotherapy.After immunochemotherapy, the tumor was downstaged to ycT2bN0M0-IIA and was determined to be acceptable for salvage surgery. A right lower lobectomy and systematic dissection of the mediastinal lymph nodes were performed. The histopathological examination of the resected specimen found that the proportion of the remaining tumor cells was 5%, indicating achievement of a major pathologic response.On postoperative day 79, the patient visited the emergency room because of anorexia. Blood tests showed hyponatremia, hypoglycemia, and eosinophilia. The serum thyroid hormone and thyroid-stimulating hormone levels were low and high, respectively. A corticotropin-releasing hormone stimulation test revealed levels of adrenocorticotropic hormone and cortisol far below the normal ranges. We speculated that the patient had developed pituitary hypoadrenocorticism and hypothyroidism as irAEs associated with ICI treatment. We administered hydrocortisone and levothyroxine, with improvement in the patient’s appetite and normalization of the patient’s serum sodium level. The patient has been receiving ongoing supplementation with oral hydrocortisone and levothyroxine and is doing well 11 months after surgery.ConclusionsThe increasing numbers of patients treated with perioperative ICIs might lead to increasing numbers of patients who develop perioperative irAEs. Careful attention should be paid to the possible development of irAEs during the perioperative management of patients undergoing surgery for lung cancer.

The Association of the Hypothalamic-Pituitary-Adrenal Axis with Appetite Regulation in Children with Fetal Alcohol Spectrum Disorders (FASDs)

Prenatal alcohol exposure causes growth impairment and a wide range of developmental, physical, and cognitive disorders in children, collectively referred to as fetal alcohol spectrum disorders (FASDs). In the course of FASDs, abnormalities can also affect eating behavior and nutritional status, but these problems have received little attention. Therefore, the aim of our study was to determine the levels of hormones involved in the action of the hypothalamic-pituitary-adrenal axis: proopiomelanocortin (POMC), cortisol, and adrenocorticotropic hormone (ACTH), in the serum of patients with FASDs. To our knowledge, none of these hormones studied have yet been evaluated in FASDs to date. We investigated 62 FASD patients and 23 healthy controls by applying an enzyme-linked immunosorbent method (ELISA). Fasting POMC levels were significantly lower in patients with FASDs (10.97 vs. 18,57 ng/mL, p = 0.039) compared to controls. However, there were no differences in cortisol concentrations. Additionally, the sex and subgroup status (fetal alcohol syndrome (FAS), neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE), and FASD risk) did not affect hormone levels. POMC was positively correlated with some clinical parameters such as age, BMI percentile, carbohydrate biomarkers, and ACTH. A positive correlation was observed between ACTH and cortisol levels, as well as ACTH and cholesterol levels. Data analysis showed no HPA axis abnormalities in the form of elevated serum cortisol and ACTH levels. Differences in POMC concentration may indicate the involvement and/or impairment of central nervous system structures in hormonal alterations in FASD individuals, caused by prenatal alcohol exposure. Hormonal dysregulation in FASDs can contribute to reduced growth and development, as well as many other disturbed processes, including neurological/neurodevelopmental dysfunctions. Further insightful studies involving a larger group of patients are needed to determine the potential impact of the measured hormones.

High-Fat Diet Exacerbates Stress Responsivity in Juvenile Traumatic Brain Injury.

Abstract Traumatic brain injury (TBI) is one of the leading causes of death for children in the United States. Juveniles are more likely to sustain TBIs than most other age groups, and TBI has been shown to result in increased anxiety and stress behaviors. In addition, the hypothalamic-pituitary-adrenal (HPA) axis has previously been shown to become dysregulated after a TBI. Further, many children consume diets high in saturated fats and refined sugars, which are also connected to alterations in HPA axis function and behavior disorders. The goal of the current study was to identify a potential relationship between high-fat diet (HFD) consumption and TBI on HPA axis function in juvenile rats. In the present study, male juvenile Long-Evans rats were fed either a combination of an HFD with a high-fructose corn syrup solution or a standard chow diet. On post-natal Day 30, subjects sustained either a sham TBI or a TBI via the Closed-Head Injury Model of Engineered Rotational Acceleration (CHIMERA). Subjects participated in a trial of the open field test (OFT) following injury. In addition, some rats performed in an acute restraint stress test. All subjects were euthanized 7 days post-injury. Brain and blood plasma samples were collected for use in real-time polymerase chain reaction (RT-PCR), immunohistochemistry, and corticosterone or adrenocorticotropic hormone (ACTH) assays. Immediately following TBI, injured juveniles had increased time to righting and walking, with HFD-fed TBI rats having increased time to walking over Chow-fed TBI rats. HFD-fed TBI rats had a reduced number of entries to the center of the OFT, in addition to reduced time spent in the center compared with HFD Sham controls and Chow TBI rats. During the acute restraint stress test, HFD-fed TBI rats had elevated pre-stress ACTH and corticosterone and post-stress ACTH levels. Pre-stress ACTH levels were significantly elevated in HFD TBI compared with Chow TBI. Further, pre-stress ACTH:corticosterone ratios were elevated in HFD TBI compared with Chow TBI. cFos immunoreactivity in the paraventricular nucleus (PVN) of the hypothalamus following the acute restraint stress test was elevated in HFD-fed TBI rats. HFD TBI rats had greater activation of cFos in the PVN compared with Chow TBI. In addition, RT-PCR showed significantly reduced expression of relevant HPA axis genes, NR3C1, NR3C2, and CRHR2, in the hypothalamus of TBI subjects compared with Sham subjects. Further, AVP and CRHR2 in the hypothalamus were significantly reduced in HFD TBI compared with Chow TBI. These results offer evidence that TBI paired with high-fat diet consumption can cause HPA axis dysfunction, resulting in more anxiety-like behaviors.

Hypothalamo-Pituitary-Adrenal Axis in Depressive Disorders and Treatment Resistance

Background: hypothalamo-pituitary-adrenal (HPA) axis plays an important role in the pathogenesis of depression. Patterns of HPA functioning depend on both biologic factors and psychological background, which, taken together, may increase the risk of depression later on. Objective: to analyze scientific publications on pathophysiology of depression, linked to HPA disruption, assess causal relationship between hypercorticism and depression, role of hypercorticism in clinical symptoms and course of depressive disorder.Material and methods: according to the key words “hypercortiсism”, “depression disorder”, “cortisol”, “treatment resistant depression”, “Cushing’s syndrome”, “Сushing’s disease”, a search was conducted for publications in databases Medline/ PubMed, Scopus, Web of Science, RSCI and other resources.Conclusion: there is a high comorbidity between depressive disorders and HPA axis abnormalities, including endocrine disorders with both increased and decreased cortisol secretion. Hypercorticism related to Сushing’s disease or Cushing’s syndrome is often associated with irreversible mental disorders, especially anxiety and depressive disorders, which persist after normalization of cortisol levels. Depressive patients are characterized by persistently elevated cortisol levels and their non-supression in the 1 mg dexamethasone suppression test (DST); however, sometimes they have reduced cortisol secretion. The possible pathophysiology mechanisms of hypercorticism are discussed. Beside hypercorticism, increased level of adrenocorticotropic hormone (ACTH) and decreased secretion of ACTH after CRH stimulation are demonstrated. It has been demonstrated that elevation of cortisol levels may precede the development of depression and as such can be used as marker of increased depression risk. Hypercorticism in patients with depression may promote its increased severity and transform ation of depressive symptoms. Persistent hypercorticism and non-supression of cortisol in DST are predictors of poor outcomes. HPA dysfunction seems to play an essential role in evolvement of treatment resistant depression. There is data on the efficacy of drugs modifying HPA activity for amelioration of affective disorders and psychotic symptoms in patients with depression. Further research into HPA functioning in patients with depression are needed to clarify pathogenetic mechanisms and development of newer treatment approaches to depression.

Effects of electroacupuncture on perioperative anxiety and stress response in patients undergoing surgery for gastric or colorectal cancer: Study protocol for a randomized controlled trial.

Perioperative anxiety is one of the main psychological stresses experienced by patients who undergo cancer surgery. The surgery itself inevitably causes a stress response characterized by activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Both the perioperative anxiety and surgical stress response lead to increased levels of catecholamines and prostaglandins, which may be related to perioperative suppression of antimetastatic immunity and tumor-promoting alterations in the microenvironment. Hence, we designed this clinical trial to investigate the effect of electroacupuncture in reducing perioperative anxiety and surgical stress response. This is a randomized, single-center, parallel, and controlled clinical trial. Seventy-eight participants between the ages of 35 and 85 with gastric or colorectal cancer who plan to undergo tumorectomy will be randomly divided into an electroacupuncture group and a control group. The primary outcome will be the six-item short form of the State-Trait Anxiety Inventory score. The secondary outcomes will be the Amsterdam Preoperative Anxiety and Information Scale score; levels of plasma cortisol, adrenocorticotropic hormone, interleukin-6, and tumor necrosis factor-α; first exhaust time after surgery; postoperative quality of the recovery-15 score, numeric rating scale for pain score; and dosage of postoperative analgesics. Cumulative studies revealed the efficacy of various types of acupuncture therapy with regard to reducing the anxiety and stress response caused by surgery. We expect that the results of this trial will provide high-quality clinical evidence for the choice of perioperative acupuncture for patients undergoing cancer surgery. https://www.chictr.org.cn, identifier ChiCTR200003 7127.

Three cases of immune-related hypopituitarism after atezolizumab-bevacizumab treatment for hepatocellular carcinoma.

We herein report three cases of immune-related hypopituitarism after atezolizumab-bevacizumab treatment for hepatocellular carcinoma (HCC). Case 1 was a man in his 60s with hepatitis C-related liver cirrhosis. He had been diagnosed with HCC and undergone surgical resection. However, HCC recurred 17months after surgery. After 13 cycles of atezolizumab-bevacizumab therapy, general fatigue, appetite loss, and muscle weakness appeared. The plasma levels of adrenocorticotropic hormone (ACTH) and cortisol were decreased. He was diagnosed with central adrenal insufficiency associated with hypopituitarism. Glucocorticoid therapy rapidly improved his symptoms. Case 2 was a man in his 70s with HCC associated with non-alcoholic steatohepatitis (NASH). After eight cycles of atezolizumab-bevacizumab therapy, general fatigue, appetite loss, and muscle weakness appeared. Hyponatremia and eosinophilia were observed. He was also diagnosed with hypopituitarism, and glucocorticoid therapy rapidly improved his symptoms. Case 3 was a man in his 60s with HCC associated with alcoholic liver cirrhosis. After 10 cycles of atezolizumab-bevacizumab therapy, hypopituitarism developed. In these cases, the presence of hyponatremia and/or eosinophilia was useful for making a diagnosis. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody is reported to be likely to induce hypophysitis two to three months after its administration. In contrast, anti-programmed cell death 1 (PD-1) antibody is likely to induce hypopituitarism six to seven months after its administration. These three patients treated with anti-programmed death ligand 1 (PD-L1) antibody developed hypopituitarism six to nine months later, close to the condition with anti-PD-1 antibody administration. Although immune-related hypopituitarism after atezolizumab-bevacizumab treatment is rare, we should be alert for hypopituitarism developing during atezolizumab-bevacizumab treatment.

Testicular Adrenal Rest Tumor

A 17-year-old boy with a history of classic congenital adrenal hyperplasia (CAH) secondary to 21-α hydroxylase deficiency on treatment with hydrocortisone and fludrocortisone presented to the endocrinology clinic with bilateral painful testicular masses. Previous urologic evaluation revealed no evidence of hydrocele or epididymitis. Semen analysis showed azoospermia. Physical examination demonstrated Tanner stage V and normal phallus; the left testicle measured approximately 8 cm, and the right testicle measured 7 cm in largest diameter (Fig. 1 and 2). Laboratory evaluation showed the following: (1) alfa-fetoprotein level, 1.4 (reference range, 0.0-10.0) ng/mL; (2) human chorionic gonadotropin level, <0.1 (reference range, 0.0-1.0) mU/mL; (3) total testosterone level, 541 (reference range, 250-1100) ng/dL; (4) follicle-stimulating hormone level, 11.4 (reference range, 1.5-12.4) mU/mL; (5) luteinizing hormone level, 1.7 (reference range, 1.7-11) mU/mL; (6) adrenocorticotropic hormone level, 86 (reference range, 6-50) pg/mL; and (7) inhibin A level, <1 (reference range, <21) pg/mL.Fig. 2The left testicle measuring approximately 8 cm in largest diameter.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Scrotal ultrasound revealed markedly enlarged testes (60 mL and 70 mL) with hyperemia and no discrete masses, findings consistent with testicular adrenal rest tumor (TART) (Fig. 3). Partial orchiectomy confirmed the diagnosis. TARTs are firm bilateral painful masses originating near the rete testes developed in men with poorly controlled classic 21-α hydroxylase deficiency under the influence of chronically elevated adrenocorticotropic hormone levels. In recent studies, an overall prevalence of 40% (14%-89%) has been reported in patients with classic CAH.1Engels M. Span P.N. van Herwaarden A.E. Sweep F.C.G.J. Stikkelbroeck N.M.M.L. Claahsen-van der Grinten H.L. Testicular adrenal rest tumors: current insights on prevalence, characteristics, origin, and treatment.Endocr Rev. 2019; 40: 973-987Crossref PubMed Scopus (53) Google Scholar Ultrasonography is the most sensitive method of diagnosis. This condition is the most common cause of infertility in male patients with CAH. Although surgery can relieve the pain associated with the mass, it does not lead to increased testosterone production and improved fertility. Intensified glucocorticoid therapy is sometimes, but not always, effective in decreasing TART size and restoring fertility.2Claahsen-van der Grinten H.L. Otten B.J. Stikkelbroeck M.M. Sweep F.C. Hermus A.R. Testicular adrenal rest tumours in congenital adrenal hyperplasia.Best Pract Res Clin Endocrinol Metab. 2009; 23: 209-220Crossref PubMed Scopus (111) Google Scholar Routine physical examination along with annual ultrasound screening is recommended for early detection of the disease. The importance of good medication compliance was discussed with the patient, and the dosage of glucocorticoids was increased. The plan was to proceed with microdissection of testicular sperm extraction with cryopreservation in case fertility is not achieved by medical approach. The authors have no multiplicity of interest to disclose.

Rosuvastatin Potentiates Gonadotropin-Lowering Effects of Metformin in Postmenopausal Women: A Pilot Study

Introduction: Metformin reduces elevated levels of FSH and LH. In some studies, gonadotroph secretory function was inhibited by statins. The aim of the present study was to investigate whether statin therapy modulates the impact of metformin on hypothalamic-pituitary-gonadal axis activity in postmenopausal women. Methods: The study population included 60 postmenopausal women with prediabetes, 40 of whom, because of high cardiovascular risk, received rosuvastatin (20–40 mg daily). One group of rosuvastatin-treated women (group A, n = 23) and all statin-naïve patients (group B, n = 20) were matched for age, glucose homeostasis markers, and gonadotropin levels. Over the entire study period (6 months), these women received metformin. The third group (group C) included 17 rosuvastatin-treated women refusing metformin treatment. We assessed baseline and follow-up plasma lipids, glucose homeostasis markers, and concentrations of FSH, LH, thyrotropin, prolactin, adrenocorticotropic hormone (ACTH), insulin-like growth factor-1, estradiol, progesterone, and anti-Müllerian hormone (in selected patients). Results: Fifty-three women (18 in groups A and B and 17 in group C) completed the study. At study entry, rosuvastatin-treated and statin-naïve women differed in levels of total cholesterol, LDL-cholesterol, and ACTH. In statin-naïve women, metformin reduced FSH levels and tended to reduce LH levels. In rosuvastatin-treated women, metformin decreased FSH and LH levels, and both effects were stronger than in statin-naïve women. Although observed in both groups, the impact on glucose homeostasis markers was more pronounced in individuals not receiving statin therapy. Metformin treatment did not affect circulating levels of lipids, thyrotropin, prolactin, ACTH, insulin-like growth factor-1, estradiol, and anti-Müllerian hormone. In group C, plasma lipids, glucose homeostasis markers, and hormone levels remained at a similar level throughout the study period. Conclusion: The obtained results indicate that statin therapy may enhance gonadotropin-lowering effects of metformin.

Familial Glucocorticoid Deficiency Presenting with Tonic-Clonic Seizure: A Case Report

Familial glucocorticoid deficiency (FGD) is a rare cause of adrenal insufficiency in children. The condition can present with features of low cortisol and high adrenocorticotropic hormone (ACTH). Late diagnosis can be associated with high morbidity and high mortality rates. The presented case was a three-year-old Saudi girl who presented with dehydration and seizures as a complication of hypoglycemia. The initial examination and investigations revealed hyperpigmentation and normal arterial blood pressure. The lab investigation and genetic study revealed hypoglycemia, metabolic acidosis, low serum cortisol: 53 nmol/L (N: 140-690 nmol/L), normal androgens: 0.65 nmol/L (N: 0.5-2.4 nmol/L) and aldosterone: 50 pgmL (N: 2-200 pg/mol), and normal serum electrolytes. The ACTH level was more than 2000 pg/mL. A genetic study indicated a homozygous likely variant in the nicotinamide nucleotide transhydrogenase (NNT) gene, consistent with a genetic diagnosis of autosomal recessive glucocorticoid deficiency type 4. No mutations were found regarding MC2R, MRAP, and TXNRD2. The child was started on hydrocortisone, initially at 100 mg/m2/dose IV and then 100 mg/m2/day divided to q 6 hr. The dose was gradually decreased to 15 mg/m2/day PO BID, with clinical improvement and normalization of the serum ACTH level. The autosomal recessive glucocorticoid deficiency, a variant of FGD type 4, is a very rare condition that may lead to high rates of mortality when the diagnosis and treatment occur late. Therefore, early diagnosis and treatment is essential for good outcomes.

Efficacy of suspended moxibustion stimulating Shenshu (BL23) and Guanyuan (CV4) on the amygdala-HPA axis in rats with kidney-deficiency symptom pattern induced by hydrocortisone.

To investigated the effects of suspended moxibustion stimulating Shenshu (BL23) and Guanyuan (CV4) acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney- deficiency symptom pattern (KYDS). Sixty male Sprague Dawley rats were randomly divided into a control group ( 12) and an experimental group ( 48). Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model. The 48 rats successfully modeled were then randomly divided into a model group (model, 12), a carbenoxolone intraperitoneal injection group (CBX, 12), a moxibustion group (moxi, 12), and a moxi + CBX group ( 12). In the moxi, the Shenshu (BL23) and Guanyuan (CV 4) acupoints were treated with moxibustion for 14 d. After treatment, measures were taken of serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), and corticotropin-releasing hormone (CRH). The expression of mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs), 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1), CRH, and ACTH in the rats' amygdala, hypothalamus, or pituitary (as appropriate) was detected. Data were analyzed using one-way analysis of variance. Compared with those of the control group, the serum levels of CRH, ACTH, and CORT; the mRNA and protein expressions of MR, GR, and 11β-HSD1 in the amygdala; the mRNA and protein expressions of 11β-HSD1 in the hypothalamus; the CRH mRNA expression in the amygdala and hypothalamus; and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased (0.05 or 0.01). After treatment with moxibustion, all the aforementioned observation indices except for 11β-HSD1 mRNA expression were ameliorated compared with those in the model group (0.05 or 0.01). Suspended moxibustion can effectively improve the serum levels of ACTH, CRH, and CORT and can up-regulate the mRNA and protein expressions of MR, GR, 11β-HSD1, CRH, and ACTH in the amygdala and hypothalamus of KYDS rats. This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.

Epileptik ensefalopatide kullanılan adrenokortikotropik hormonun kemik mineral metabolizması ve adrenal yolak üzerine kısa dönem etkilerinin değerlendirilmesi

Background: We aimed to investigate the short-term effects of adrenocorticotropic hormone (ACTH) treatment on the adrenal pathway and bone metabolism in patients with epileptic encephalopathy.&#x0D; Methods: Two groups with 16 patients and 16 controls were formed. Before the treatment, all patients and controls were tested for bone and adrenal metabolism. Twenty doses of ACTH therapy were given to the patient group over 3 months. The tests on the patient group were repeated 1 month after the end of the treatment.&#x0D; Results: In the patient group, serum calcium, phosphorus and parathyroid hormone levels increased significantly after treatment compared with before treatment. Comparing the bone metabolism of the patient and control groups, urinary calcium/creatinine ratio was higher before treatment; serum phosphorus level, bone-specific alkaline phosphatase level and the urinary calcium/creatinine ratio were higher after treatment in the patient group. In the evaluation of the adrenal pathway, no significant differences were found between fasting serum glucose, sodium, potassium, cortisol and ACTH levels before and after treatment and in the comparison of the patient and control groups.&#x0D; Conclusion: Our study investigated the short-term effect of ACTH on the adrenal pathway and bone metabolism. The results show that ACTH treatment did not have a negative effect on the adrenal pathway in the early period but, its effects on bone metabolism have not been adequately clarified.

Exposure to dipentyl phthalate in utero disrupts the adrenal cortex function of adult male rats by inhibiting SIRT1/PGC-1α and inducing AMPK phosphorylation.

Di-n-pentyl phthalate (DPeP) is an endocrine-disrupting phthalate plasticizer. The objective of this study was to investigate the effect of DPeP on adrenocortical function in adult male rats following in utero exposure. DPeP (0, 10, 50, 100, and 500 mg/kg/day) was administered by gavage to pregnant Sprague-Dawley rats from gestational day 14 to 21. The morphology and function of the adrenal cortex in 56-day-old male offspring were studied. DPeP at 100 and 500 mg/kg/day significantly reduced serum aldosterone levels and at 500 mg/kg/day markedly reduced corticosterone and adrenocorticotropic hormone levels. DPeP at 10-500 mg/kg markedly reduced the thickness of zona glomerulosa without affecting the thickness of zona fasciculata. DPeP significantly downregulated the expression of Agtr1a, Mc2r, Scarb1, Cyp11a1, Hsd3b1, Cyp21, Cyp11b1, Cyp11b2, Nr5a1, Nr4a2, and Bcl2 genes as well as their proteins. DPeP at 500 mg/kg/day significantly increased phosphorylated AMPK, while DPeP at 100 mg/kg/day and higher doses reduced phosphorylated AKT1 and total SIRT1 level. DPeP at 100 and 500 μM markedly induced reactive oxygen species and apoptosis in H295R cells after 24 h of culture. In conclusion, in utero exposure to DPeP disrupts adrenocortical function of the adult male offspring by (1) increasing AMPK phosphorylation and decreasing AKT1 phosphorylation and SIRT1 levels, (2) reducing adrenocorticotropic hormone levels, and (3) possibly inducing oxidative stress and apoptosis.

Radical Cystectomy as a Cause of an Increased Neuroendocrine Response

The present study compared the neuroendocrine response in patients undergoing conventional cystectomy with two postoperative pain management techniques: epidural analgesia (EA) and intermittent opioid analgesia (IOA) on adrenocorticotropic hormone (ACTH), cortisol, glucose levels for 48 hours. We hypothesize that appropriate analgesic regime can attenuate stress response reaction. Forty-four patients scheduled for radical conventional cystectomy were assigned to one of the two study groups: group A (n=22) with EA, group B (n=22) with IOA. The surgical stress factor induced significant hypothalamic-pituitary-adrenal (HPA) axis responses in both groups. The ACTH and cortisol levels were higher than baseline for both groups, but more significantly in group B. Blood glucose level was elevated few hours after the surgical intervention and was back to baseline level by the following morning. The results suggest that EA might have more advantages associated with reduced postoperative pain and attenuated neuroendocrine response when open access is the preferred operative technique. There is a need of randomized multicentre trials to evaluate the quality of life, the survival and the role of pain management at least 12 months after radical cystectomy.

Glucocorticoid-sensitive period of corticotroph development-Implications for mechanisms of early life stress.

Corticotrophs are intermediaries in the hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in stress response in vertebrates. The HPA axis displays an intricate mode of negative feedback regulation, whereby the peripheral effector, cortisol inhibits the secretion of its upstream regulator, adrenocorticotropic hormone (ACTH) from proopiomelanocortin (POMC)-expressing cells in the pituitary. While the feedback regulation of the HPA axis is well characterized in the adult organism, the effect of feedback regulation on the development of corticotrophs is poorly understood. Here, we studied the effect of glucocorticoids on the development of POMC-expressing cells in the zebrafish pituitary. The development of POMC cells showed a steady increase in numbers between 2-6 days post fertilization. Inhibition of endogenous glucocorticoid synthesis resulted in an increase in POMC cell number due to reduced developmental feedback inhibition of cortisol on POMC cells. Conversely, addition of exogenous dexamethasone at a critical developmental window led to a decrease in corticotroph cell number, mimicking greater feedback control due to increased cortisol levels. Finally, developmental dysregulation of ACTH levels resulted in impaired anxiety-like and stress-coping behaviours. Hence, we identified a sensitive developmental window for the effect of glucocorticoids on corticotrophs and demonstrate the downstream effect on stress-responsive behaviour.

Changes of adrenocorticotropic hormone rhythm and cortisol circadian rhythm in patients with depression complicated with anxiety and their effects on the psychological state of patients.

Objective: This work was to explore the rhythm of adrenocorticotropic hormone (ACTH) and cortisol in patients with depression and anxiety and their effects on mental state. In this work, with depression complicated with anxiety patients as the A-MDD group (n = 21), and depression without anxiety symptoms as the NA-MDD group (n = 21). Firstly, data features were extracted according to the electroencephalo-graph (EEG) data of different patients, and a DR model was constructed for diagnosis. The Hamilton Depression Scale 24 (HAMD-24) was employed to evaluate the severity, and the ACTH and cortisol levels were detected and compared for patients in the A-MDD group and NA-MDD group. In addition, the psychological status of the patients was assessed using the Toronto Alexithymia Scale (TAS). As a result, the AI-based DR model showed a high recognition accuracy for depression. The HAMD-24 score in the A-MDD group (31.81 ± 5.39 points) was statistically higher than the score in the NA-MDD group (25.25 ± 5.02 points) (P < 0.05). No visible difference was found in ACTH levels of patients in different groups (P > 0.05). The incidence of cortisol rhythm disorder (CRD) in the A-MDD group was much higher (P < 0.05). The differences in TAS scores between the two groups were significantly statistically significant (P < 0.01). In conclusion, the AI-based DR Model achieves a more accurate identification of depression; depression with or without anxiety has different effects on the mental state of patients. CRD may be one of the biological markers of depression combined with anxiety.

Hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system in adulthood PTSD and childhood maltreatment history.

Accumulated evidence shows that psychological trauma and posttraumatic stress disorder (PTSD) are associated with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis. Besides the HPA axis hormones, recent evidence suggests that the renin-angiotensin-aldosterone (RAA) system and genetic factors may be involved in trauma/PTSD as well as in HPA axis regulation. This study attempted to better understand the HPA axis function in relation to PTSD and childhood maltreatment by simultaneously examining RAA system and genetic polymorphisms of candidate genes. Here we studied 69 civilian women with PTSD and 107 healthy control women without DSM-IV-based traumatic experience. Childhood maltreatment history was assessed with the Childhood Trauma Questionnaire. PTSD severity was assessed with the Posttraumatic Diagnostic Scale. Functional disability was assessed with the Sheehan Disability Scale. HPA axis was examined by measuring blood levels of cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone-sulphate (DHEA-S). RAA system was examined by measuring blood renin and aldosterone levels. The FKBP5 rs1360780 and CACNA1C rs1006737 polymorphisms were genotyped. No significant differences were seen between patients and controls in any of the five hormone levels. DHEA-S levels were significantly negatively correlated with overall PTSD severity (p = 0.003) and functional disability (p = 0.008). A two-way analysis of variance with diagnostic groups and genotypes as fixed factors revealed that patients with the rs1006737 A-allele had significantly lower DHEA-S levels than patients with the GG genotype (p = 0.002) and controls with the A-allele (p = 0.006). Childhood maltreatment history was not significantly correlated with any of the five hormone levels. These results were generally unchanged after controlling for the potentially confounding effect of age, depression, and anxiety. Our findings suggest that lower DHEA-S levels could indicate more severe subtype of PTSD, the association of which might be partly modified by the CACNA1C polymorphism.

Functional changes in the hypothalamic-pituitary-adrenal axis after successful cardiopulmonary resuscitation

Abstract Background Cardiac arrest (CA) is a terminal event that results in a range of pathophysiological changes in the body, most notably, systemic ischemia-reperfusion injury. The hypothalamic-pituitary-adrenal (HPA) axis is an important neuroendocrine system that modulates adrenocortical hormone release. This study was designed to investigate the changes in HPA-related hormone levels after successful cardiopulmonary resuscitation (CPR) and to explore possible etiologies to provide a basis for relevant clinical research. Methods We collected the clinical data of 96 patients with CA admitted to the Emergency Department of Beijing Chaoyang Hospital, Capital Medical University, between January 2016 and May 2017. Serum samples were collected 6, 24, and 72 hours after restoring spontaneous circulation (ROSC). The data were compared with those of the healthy control group (n = 50). An enzyme-linked immunosorbent assay (ELISA) was performed to measure copeptin, adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), and total cortisol. Demographic data were collected for both groups. For the CPR group, clinical data and the end-of-study cerebral performance category (CPC) were analyzed. Patients were followed up through day 28. Death or survival after day 28 was used as the study endpoint. Simple values were expressed as medians and quartiles or ratios (%) for statistical analysis. Continuous variables are expressed as mean ± standard deviation. Categorical variables were expressed as frequencies and percentages. The mean values of normally distributed measurement data were analyzed using 1-way analysis of variance (ANOVA) for among-group comparisons and the least significant difference (LSD) test for between-group comparisons. SPSS v17 (SPSS, Chicago, IL, USA) was used for statistical analysis, and P &lt; 0.05 was considered statistically significant. Results No significant between-group differences were observed in terms of age or sex. The 28-day mortality rate in the CPR group was 71%. ACTH and CRH levels were significantly lower in the CPR group than in the healthy control group (P &lt; 0.001). Copeptin and cortisol levels 6 hours after ROSC were significantly higher in the CPR group than in the healthy control group (P &lt; 0.001). No significant changes in any indicator were observed over time (6, 24, and 72 hours after ROSC) (P &gt; 0.05). The CPC score was 1–2 (good cerebral performance group) in 13 patients, 3–4 (poor cerebral performance group) in 17 patients, and 5 (brain death or clinical death) in 66 patients. Patients with significantly declining ACTH and CRH levels had higher CPC scores (P &lt; 0.05); however, no significant differences were found in other indicators (P &gt; 0.05). Conclusion After post-CA ROSC, ischemia-reperfusion injury may cause brain damage and HPA axis damage and dysfunction, the severity of which is associated with CPC score.