Adrenocorticotropic Hormone Levels Research Articles

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.

Stress biomarkers in individuals with fibromyalgia syndrome: a systematic review with meta-analysis.

Evidence suggests an involvement of hypothalamic-pituitary-adrenal (HPA) axis dysregulation in the development and maintenance of fibromyalgia syndrome (FMS). However, studies on the stress response via the HPA-axis in individuals with FMS show conflicting results. To better understand the relationship between FMS and HPA-axis dysregulation, we (1) systematically summarized the current level of evidence on HPA biomarkers in individuals with FMS compared with individuals without and (2) evaluated whether FMS is associated with a specific pattern of HPA dysregulation. The main outcome measures were cortisol, adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), epinephrine, and norepinephrine. A systematic search of MEDLINE, EMBASE, and PsychMed yielded 47 studies eligible for meta-analysis, including 1465 individuals with FMS and 1192 FMS-free controls. No main effect of FMS was found on altered levels of blood cortisol, ACTH, CRH, and epinephrine. Compared with controls, salivary and urinary cortisol levels were decreased in individuals with FMS, whereas blood levels of norepinephrine were increased. However, heterogeneity of data was high with significant evidence for publication bias. Overall, the data are compatible with association of FMS with adrenocortical hypofunction in the presence of increased sympathetic tone. However, the data are partially contradictory, so it must be assumed that the data are highly dependent on the respective study designs, patient samples, and analytical methods and do not necessarily demonstrate an abnormal HPA-axis function in FMS.

GLUCOCORTICOIDS AND MINERALOCORTICOIDS IN BLOOD PLASMA AS MARKERS FOR THE EARLY DIAGNOSIS OF ADRENAL CORTEX TUMORS

Summary: Aim: assessment of the pituitary-adrenal and renin-aldosterone systems state in patients with various types of adrenocortical adenomas. Object and methods: in 35 patients with adrenocortical adenomas, the hormonal status was evaluated by a direct quantitative immunoenzymatic analysis. The levels of glucocorticoids (cortisol) and mineralocorticoids (aldosterone) were determined. The levels of adrenocorticotropic hormone (ACTH) and renin were assessed by immunochemical methods using monoclonal antibodies specific for ACTH and renin. Results: increasing level of the cortisol against the background of a decreasing level of the ACTH in patients with cortisol-producing adrenocortical adenomas was revealed. In patients with aldosterone-producing adenomas, aldosteronism develops against the background of an unchanged level of renin and an increase in the aldosterone-renin ratio. Conclusions: the occurrence of hormone-dependent adenomas in the adrenal cortex disrupts the functioning of the pituitary-adrenal and renin-aldosterone systems, which serves as a criterion for the early diagnosis of adrenocortical adrenal adenomas.

Prophylactic Effects of Hemp Seed Oil on Perimenopausal Depression: A Role of HPA Axis.

Hemp seed, the dried fruit of Cannabis sativa L. (Moraceae), has been extensively documented as a folk source of food due to its nutritional and functional value. This study evaluated the antidepressant effect of hemp seed oil (HSO) during its estrogen-like effect in Perimenopausal depression (PMD) rats induced by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS). Female SD rats (SPF, 10 weeks, sham operated group, ovariectomy (OVX) model group, ovariectomy - chronic unpredictable mild stress (OVX-CUMS) group, HSO + OVX-CUMS group, fluoxetine (FLU) + OVX-CUMS group, n=8) were subjected to treatment with HSO (4.32 g/kg) or fluoxetine (10 mg/kg) for 28 days (20 mL/kg by ig). Sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), estrogen receptor α (ERα) and estrogen receptor β (ERβ) expression, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol (CORT), adrenocorticotropic hormone (ACTH), corticotropin releasing hormone (CRH), norepinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5HIAA) levels are measured to evaluate the function of the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-adrenal (HPA) axis. The results showed that OVX-CUMS significantly decrease sucrose preference rate in SPT, increase immobility time in FST and OFT, and decrease movement distance and stand-up times in OFT. HSO treatment significantly improves depression-like behaviors, upregulates the expression of ERα and ERβ, improves HPO axis function by increasing E2 levels and decreasing FSH and LH levels, reverses HPA axis hyperactivation by decreasing CORT, ACTH, and CRH levels, and upregulates NE, 5-HT, and 5HIAA levels in model rats. The findings suggested that HSO could improve depression-like behavior in OVX-CUMS rats by regulating HPO/HPA axis function and neurotransmitter disturbance.

Pituitary imaging findings in pediatric patients with idiopathic hypogonadotropic hypogonadism.

Objective. Idiopathic hypogonadotropic hypogonadism in children is a disease leading to a puberty absence. Some hypothalamic and pituitary defects cause hypogonadotropic hypogonadism. Pituitary magnetic resonance imaging is routinely performed in these patients. In our study, we provide an information about pituitary pathologies associated with an idiopathic hypogonado-tropic hypogonadism in childhood. Methods. Twenty-two patients, who were admitted to the pediatric endocrine outpatient clinic of our hospital because of their undeveloped secondary sex characteristics during adolescence, were included in our study. Age, gender, history, physical examination findings, and laboratory tests were recorded in patients. Pituitary magnetic resonance imaging results were examined. The criteria for the diagnosis of hypogonadism were: absence of puberty or delayed puberty, clinical signs or symptoms of hypogonadism, and presence of low or normal gonadotropin levels. Results. In the present study, 22 patients were diagnosed with hypogonadotropic hypogonadism. The mean age of the patients was 15.90±1.09 years. Basal and stimulated luteinizing hormone and follicular stimulating hormone levels of the patients were found to be low. Prolactin, cortisol, adrenocorticotropic hormone, free thyroxine, and thyroid stimulating hormone levels were within normal limits in all patients. The pituitary magnetic resonance imaging revealed six patients with pituitary adenoma, one with empty sella turcica, and five with pituitary hypoplasia. Conclusions. The present data showed that in the presence of hypogonadotropic hypogonadism, the hypothalamic-pituitary abnormalities are more likely to be present in the children compared to the adult population. Thus, it can be strongly emphasized the importance of the pituitary imaging examination, especially in the idiopathic hypogonadotropic hypogonadism cases.

Intermittent Hypoxia and Weight Loss: Insights into the Etiology of the Sleep Apnea Phenotype.

Sleep apnea (SA) is a major respiratory disorder with increased risk for hypertension and obesity; however, our understanding of the origins of this complex disorder remains limited. Because apneas lead to recurrent drops in O2 during sleep, intermittent hypoxia (IH) is the main animal model to explore the pathophysiology of SA. Here, we assessed the impacts of IH on metabolic function and related signals. Adult male rats were exposed to 1week of moderate IH (FiO2=0.10-30s, ten cycles/hour, 8h/day). Using whole-body plethysmography, we measured respiratory variability and apnea index during sleep. Blood pressure and heart rate were measured by the tail-cuff method; blood samples were taken for multiplex assay. At rest, IH augmented arterial blood pressure, respiratory instability, but not apnea index. IH induced weight, fat, and fluid loss. IH also reduced food intake and plasma leptin, adrenocorticotropic hormone (ACTH), and testosterone levels but increased inflammatory cytokines. We conclude that IH does not replicate the metabolic clinical features of SA patient, thus raising our awareness of the limitations of the IH model. The fact that the risk for hypertension occurs before the appearance of apneas provides new insights into the progression of the disease.

Ectopic adrenocorticotrophic hormone syndrome secondary to treatment-related neuroendocrine differentiation of metastatic castrate-resistant prostate cancer.

A 64-year-old man with progressive metastatic castrate-resistant prostate adenocarcinoma presented with recurrent fluid overload, severe hypokalaemia with metabolic alkalosis and loss of glycaemic control. Clinical features were facial plethora, skin bruising and proximal myopathy. Plasma adrenocorticotrophic hormone (ACTH), serum cortisol and 24-h urinary cortisol levels were elevated. Low-dose dexamethasone failed to suppress cortisol. Pituitary MRI was normal and 68Gallium-DOTATATE PET-CT scan showed only features of metastatic prostate cancer. He was diagnosed with ectopic ACTH syndrome secondary to treatment-related neuroendocrine prostate cancer differentiation. Medical management was limited by clinical deterioration, accessibility of medications and cancer progression. Ketoconazole and cabergoline were utilised, but cortisol remained uncontrolled. He succumbed 5 months following diagnosis. Treatment-related neuroendocrine differentiation of prostate adenocarcinoma is a rare cause of ectopic ACTH syndrome. Neuroendocrine differentiation following prostate adenocarcinoma treatment with androgen deprivation has been described. Ectopic adrenocorticotrophic hormone (ACTH) syndrome should be considered where patients with metastatic prostate cancer develop acute electrolyte disturbance or fluid overload. Ketoconazole interferes with adrenal and gonadal steroidogenesis and can be used in ectopic ACTH syndrome, but the impact may be insufficient. Inhibition of gonadal steroidogenesis is favourable in prostate cancer. More data are required to evaluate the use of cabergoline in ectopic ACTH syndrome. Ectopic ACTH syndrome requires prompt management and is challenging in the face of metastatic cancer.

PS-R03-10: CASE REPORT: CUSHING SYNDROME IN A YOUNG MALE

A 27-year-old male without any significant past medical history was advised to visit a hospital for elevated blood pressure, elevated liver enzymes, and dyslipidemia in a workplace health checkup. His body weight had increased by more than 10 kg in the last two years. He presented to our department and underwent laboratory work-up. He had bilateral lower limb pitting edema, hypokalemia, and elevation of low-density lipoprotein. No sign of dysthyroidism, renin-angiotensin-aldosterone system disorder, or increased catecholamine secretion was found. Diet and exercise therapy and calcium channel blocker did not improve his hypertension, and he suffered from lumber vertebral fracture, refractory hypokalemia, and lower leg cellulitis. He was admitted to our department for detailed examination of worsening lower limb edema. On admission, he had striae on his abdomen and legs as well as edema of both lower extremities. The endocrinological data showed high levels of adrenocorticotropic hormone (ACTH) and cortisol. Overnight 1 mg dexamethasone suppression test resulted in a non-suppression response, and his circadian rhythm of cortisol was absent. Urine cortisol level was high. These findings confirmed the diagnosis of ACTH-dependent Cushing syndrome. A contrasted magnetic resonance imaging (MRI) scan demonstrated enlargement of the pituitary gland more than 1 cm in length. Taking into account drug-resistant hypokalemia and vulnerability to infection, he was administered with metyrapone 500 mg per day until he underwent transsphenoidal hypophysectomy. The pathological findings were consistent with that of a pituitary adenoma. Postoperative MRI scan showed remnant lesions which stretch to the bilateral cavernous sinuses and the right middle cranial fossa. Although a decrease in urine cortisol was observed, the absence of a circadian rhythm of cortisol, hypertension, and hypokalemia persisted. He is now treated with somatostatin analog and craniotomy followed by gamma knife surgery is planned. Cushing syndrome should be suspected in cases of early-onset hypertension with symptoms including weight gain, hypokalemia, and bone fracture.