Adrenocorticotropin Hormone Levels Research Articles

Experience with Congenital Adrenal Hyperplasia in Tripoli Children's Hospital, Libya

AbstractCongenital adrenal hyperplasia (CAH) denotes a group of autosomal recessive disorders. Its clinical spectrum varies from classical CAH (CCAH) to nonclassic CAH. It may be a simple virilizing form or salt-wasting type. The study described the clinical presentation, treatment modalities, and sequelae of CAH, including its effect on patient growth during long-term follow-up. A case series study was conducted on patients with CAH who attended and followed up in the Endocrine Clinic in Tripoli Children's Hospital from January 1, 2000 to December 31, 2018. The presentation and the last visit captured demographic and clinical features at the time of diagnosis, types of CAH (classical vs. nonclassical), investigations, treatment details, and height. All patients underwent biochemical testing and hormonal assay, including adrenocorticotropin hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and plasma renin activity (PRA) levels before and after treatment. Fifty-eight patients were included; 38 (65.5.2%) were female, age at presentation in 94.8% ranged between 1 day and 10 years, with a mean age of 2.3 ± 1.1 years. Ambiguous genitalia was the presenting feature in 55.2 and 84% of total and female patients, respectively. Salt wasting was present in 37.9%. Of 32 female patients with ambiguous genitalia, only 11 (34.4%) out of them and 19% of all patients had a surgical correction. The mean and standard deviation of height at diagnosis was 78.327 + 31.070, and the last visit after treatment was 108.345 + 31.781. The relation between the date of birth and height throughout follow-up for those at last visit with age ranges from 13 to 18 years old, their mean and standard deviation of height was 135.650 + 29.286, and for patients who were less than13 years at last visit, the mean and standard deviation of height was 101.079 + 32.121; p-value = 0.003. The Z-scores were calculated and showed that about eight patients were positively above the average mean of the population. Biochemical disturbances were improved after treatment, including sodium, potassium, and glucose in CCAH type; p-value < 0.001. Hormonal findings included levels of ACTH, 17-OHP, and PRA; all levels were reduced with treatment; p-value < 0.001. In this single-center series, most of our patients with biochemical and hormonal abnormalities were normalized with hormonal replacement and limited surgical correction of females with ambiguous genitalia.

Multi-Omics Analysis Reveals the Systematic Relationship Between Oral Homeostasis and Chronic Sleep Deprivation in Rats.

Sleep disorders were associated with oral health. Inflammation has especially been thought to be a key factor in linking oral diseases and sleep deficiency. However, how chronic sleep deprivation (CSD) affects oral homeostasis, particularly oral inflammation and oral microbiota, is still unknown. This study aimed to uncover the systematic relationship between oral homeostasis and CSD in rats. The metabolomics in serum, proteomics in the tongue tissues, and microbiome analysis in the oral cavity in CSD rats were performed. Multi-omics data integration analysis was performed to uncover the systematic relationship between oral homeostasis and CSD through the weighted correlation network analysis. We found that CSD could lead to oral inflammation in rats. CSD significantly increased systemic inflammation by enhancing the serum levels of IL-1β, IL-6 and inhibiting the serum level of IL-10. Serum levels of adrenocorticotropin hormone, corticosterone, and triiodothyronine were increased in CSD rats, and the steroid hormone biosynthesis pathway was also found to be involved in the perturbation resulting from CSD, together suggesting the activation of the hypothalamic-pituitary-adrenocortical and hypothalamic‐pituitary‐thyroid axis. CSD led to changes of oral microbiota composition, and g_Acinetobacter, Candidatus Chryseobacterium massiliae, and g_Moraxella were significantly correlated with multiple proteins in bacterial invasion of epithelial cells pathway, which may partially responsible for oral inflammation resulting from CSD. The changes of proteomic profiling expression caused by CSD in tongue tissues were mainly enriched in neurodegenerative diseases pathways and immune/inflammation-related pathways. Multi-omics analysis indicated that the inflammatory response-related modules were significantly correlated with the neurodegenerative disease-related module suggesting a possible link between neurodegenerative diseases and oral inflammation. Together, CSD induced oral inflammation and subtle changes on oral microbiota. Our study is helpful to further understand the role that oral homeostasis plays in the process by which CSD affects human health and disease.

Effects of interleukin-1 antagonism on cortisol levels in individuals with obesity: a randomized clinical trial.

BackgroundAnti-inflammatory treatment with interleukin-1 (IL-1) antagonism decreases both cortisol and adrenocorticotropin hormone (ACTH) levels in individuals with obesity in short term. However, it remains unknown whether these effects persist upon prolonged treatment.MethodsIn this double-blind, parallel-group trial involving patients with features of the metabolic syndrome, 33 patients were randomly assigned to receive 100 mg of anakinra (recombinant human IL-1 receptor antagonist) subcutaneously twice-daily and 34 patients to receive placebo for 4 weeks. For this analysis, change in cortisol and ACTH levels from baseline to 4 weeks were predefined end points of the trial.ResultsThe mean age was 54 years, baseline cortisol levels were 314 nmol/L (IQR 241–385) and C-reactive protein (CRP) levels were 3.4 mg/L (IQR 1.7–4.8). Treatment with anakinra led to a significant decrease in cortisol levels at day 1 when compared to placebo with an adjusted between-group difference of 28 nmol/L (95% CI, −7 to −43; P = 0.03). After 4 weeks, the cortisol-lowering effect of anakinra was attenuated and overall was statistically not significant (P = 0.72). Injection-site reactions occurred in 21 patients receiving anakinra and were associated with higher CRP and cortisol levels.ConclusionsIL-1 antagonism decreases cortisol levels in male patients with obesity and chronic low-grade inflammation on the short term. After prolonged treatment, this effect is attenuated, probably due to injection-site reactions (ClinicalTrials.gov, NCT02672592).

MON-408 Development of Rapidly Progressive Cushing's Disease Following Pituitary Apoplexy Several Years Prior

Cushing’s disease is characterized by hypersecretion of adrenocorticotropin hormone (ACTH), typically from a pituitary microadenoma, resulting in excess cortisol. It accounts for up to 70% of cases of Cushing’s syndrome and is associated with significant morbidity and increased mortality. We present a case of a patient with a history of pituitary apoplexy of a non-secretory adenoma who developed Cushing’s disease 4 years later. The patient is a 61-year-old woman with a history of hypertension, prediabetes, and renal cell carcinoma status post cryoablation who presented to our multidisciplinary skull-base clinic for management of a right parasagittal meningioma, left anterior clinoid nodule, and pituitary apoplexy that occurred 4 years prior. She had no signs or symptoms of pituitary hormone excess at that time. She also had an incidental 1 cm left adrenal adenoma that was recently seen on CT scan of the abdomen and she had not undergone biochemical evaluation at the time of her presentation to our clinic. As part of her evaluation of the adrenal incidentaloma, she underwent a 1 mg Dexamethasone suppression test with an 8 am cortisol of 71 ug/dL. 24 hour urine cortisol was also significantly elevated at 394 ug/24 hours (reference range <45 ug/24 hours). An ACTH level was measured to determine if the excess cortisol secretion was ACTH-dependent or ACTH-independent. The ACTH level was quite elevated at 166 pg/mL (reference range 0-46 pg/mL). MRI of the pituitary showed multinodular areas of enhancement within the sella and interval growth of tissue within the right cavernous sinus compared to an MRI obtained a year prior. While undergoing evaluation of the cortisol excess, the patient developed progressive proximal muscle weakness, worsening hypertension, easy bruising, mood swings, severe fatigue, and a 14 pound weight loss. The patient’s prediabetes progressed to diabetes with an A1c of 11%. Given the rapid progression of her symptoms, her prior history of carcinoma, her prior history of pituitary apoplexy and no definite pituitary lesion on MRI, the patient underwent inferior petrosal sinus sampling (IPSS) to determine if the source of ACTH was ectopic or from the pituitary. The results from IPSS revealed a pituitary source of excess ACTH secretion. The patient underwent endoscopic transsphenoidal resection of tissue on the right side of the pituitary. Surgical pathology was consistent with a pituitary adenoma with immunostaining positive for ACTH. Following surgical resection, the patient’s hyperglycemia and hypertension significantly improved. This case highlights a very rare presentation of Cushing’s disease following an episode of pituitary apoplexy. To our knowledge there is only one other reported case of a patient who developed Cushing’s disease in the setting of pituitary apoplexy. We will review the key clinical features and approach to diagnosis in patients with this rare presentation.

Neonatal adrenal insufficiency: Turkish Neonatal and Pediatric Endocrinology and Diabetes Societies consensus report.

It is difficult to make a diagnosis of adrenal insufficiency in the newborn, because the clinical findings are not specific and the normal serum cortisol level is far lower compared to children and adults. However, dehydratation, hyperpigmentation, hypoglycemia, hyponatremia, hyperkalemia and metabolic acidosis should suggest the diagnosis of adrenal insufficiency. Hypotension which does not respond to vasopressors should especially be considered a warning. If the adrenocorticotropin hormone level measured simultaneously with a low serum cortisol level is 2-fold higher than the upper normal limit of the reference range, a diagnosis of primary adrenal insufficiency is definite. Even if the serum cortisol level is normal, a diagnosis of relative adrenal insufficiency can be made with clinical findings, if the patient is under heavy stress. The serum cortisol level should be measured using the method of ‘high pressure liquid chromatography’ or ‘LC mass spectrometry’. Adrenal steroid biosynthesis can be evaluated more specifically and sensitively with ‘steroid profiling’. Rennin and aldosterone levels may be measured in addition to serum electrolytes for the diagnosis of mineralocorticoid insufficiency. Adrenocorticotropic hormone stimulation test may be used to confirm the diagnosis and elucidate the etiology. In suspicious cases, treatment can be initiated without waiting for the adrenocorticotropic hormone stimulation test. In schock which does not respond to vasopressors, intravenous hydrocortisone at a dose of 50-100 mg/m2 or a glucocorticoid drug at an equivalent dose should be initiated. In maintanence treatment, the physiological secretion rate of hydrocortisone is 6 mg/m2/day (15 mg/m2/day in the newborn). The replacement dose should be adjusted with clinical follow-up and by monitoring growth rate, weight gain and blood pressure. Fludrocortisone (0,1 mg tablet) is given for mineralocorticoid treatment (2x0,5-1 tablets). A higher dose may be needed in the neonatal period and in patients with aldosterone resistance. If hyponatremia persists, oral NACl may be added to treatment. In the long-term follow-up, patients should carry an identification card and the glucocorticoid dose should be increased 3-10-fold in cases of stress.

Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals.

Increased cortisol levels in obesity may contribute to the associated metabolic syndrome. In obesity, the activated innate immune system leads to increased interleukin (IL)-1β, which is known to stimulate the release of adrenocorticotropin hormone (ACTH). We hypothesized that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal axis, leading to decreased cortisol levels. In this prospective intervention study, we included 73 patients with obesity (body mass index [BMI] ≥30 kg/m2) and at least one additional feature of the metabolic syndrome. The primary end point was change in morning cortisol from baseline to after the administration of the IL-1 receptor antagonist (anakinra/Kineret®, total dose 3 × 100 mg). Secondary end points were effects on salivary cortisol and ACTH. Median age was 56 years, 50.7% of patients were female, and median BMI was 36.3 kg/m2. Median morning serum cortisol levels (nmol/L) decreased significantly after IL-1 antagonism [from baseline, 452 to 423; absolute difference, -38.7; 95% confidence interval (CI), -64 to -13.4; P = 0.0019]. Similar effects were found for salivary cortisol levels (-2.8; 95% CI, -4.4 to -1.3; P = 0.0007), ACTH levels (-2.2; 95% CI; -4.2 to -0.1; P = 0.038), systolic blood pressure (-5.2, 95% CI, -8.5 to -1.8; P = 0.0006), and heart rate (-2.9; 95% CI, -4.7 to -1.0; P = 0.0029). IL-1 antagonism in obese individuals with features of the metabolic syndrome leads to a decrease in serum cortisol, salivary cortisol, and ACTH levels along with a reduction in systolic blood pressure and heart rate.

Characterizing and predicting the Nelson-Salassa syndrome.

OBJECTIVE Nelson-Salassa syndrome (NSS) is a rare consequence of bilateral adrenalectomy (ADX) for refractory hypercortisolism due to Cushing disease (CD). Although classically defined by rapid growth of a large, invasive, adrenocorticotropin hormone (ACTH)-secreting pituitary tumor after bilateral ADX that causes cutaneous hyperpigmentation, visual disturbance, and high levels of ACTH, clinical experience suggests more variability. METHODS The authors conducted a retrospective chart review of all patients 18 years and older with a history of bilateral ADX for CD, adequate pituitary MRI, and at least 2 years of clinical follow-up. Statistical tests included Student's t-test, chi-square test, Fisher's exact test, multivariate analysis, and derived receiver operating characteristic curves. RESULTS Between 1956 and 2015, 302 patients underwent bilateral ADX for the treatment of hypercortisolism caused by CD; 88 had requisite imaging and follow-up (mean 16 years). Forty-seven patients (53%) had radiographic progression of pituitary disease and were diagnosed with NSS. Compared with patients who did not experience progression, those who developed NSS were significantly younger at the time of CD diagnosis (33 vs 44 years, p = 0.007) and at the time of bilateral ADX (35 vs 49 years, p = 0.007), had larger tumors at the time of CD diagnosis (6 mm vs 1 mm, p = 0.03), and were more likely to have undergone external-beam radiation therapy (EBRT, 43% vs 12%, p = 0.005). Among NSS patients, the mean tumor growth was 7 mm/yr (SE 6 mm/yr); the median tumor growth was 3 mm/yr. Prevalence of pathognomonic symptoms was low; the classic triad occurred in 9%, while hyperpigmentation without visual field deficit was observed in 23%, and 68% remained asymptomatic despite radiographic disease progression. NSS required treatment in 14 patients (30%). CONCLUSIONS NSS is a prevalent sequela of CD after bilateral ADX and affects more than 50% of patients. However, although radiological evidence of NSS is common, it is most often clinically indolent, with only a small minority of patients developing the more aggressive disease phenotype characterized by clinically meaningful symptoms and indications for treatment. Young age at the time of CD diagnosis or treatment with bilateral ADX, large tumor size at CD diagnosis, and EBRT are associated with progression to NSS and may be markers of aggressiveness.

Abstract 2810: Pterostilbene, a natural phytoalexin, weakens the antioxidant defenses of aggressive cancer cells in vivo: a pituitary gland- and Nrf2-dependent mechanism

Abstract Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies lack of correlation to the bioavailable concentrations is a critical issue. We studied the underlying mechanisms using different human melanomas (A2058, MeWo and MelJuso) and pancreatic cancers (AsPC-1 and BxPC-3) (with genetic backgrounds correlating with most tumors in patients), growing in nude mice as xenografts, and pterostilbene (Pter, 3’,5’-dimethoxy-4-stilbenol; abundant in e.g. blueberries and a natural dimethoxylated analog of resveratrol). RESULTS: Intravenous administration of Pter decreased human melanoma and pancreatic cancer growth (an effect associated with lower rates of tumor cell proliferation and increased apoptosis) in vivo. However Pter, at levels measured within the tumors, did not affect cancer growth or viability in vitro. Pter inhibited pituitary production of the adrenocorticotropin hormone (ACTH), decreased plasma levels of corticosterone and, thereby, down regulated the glucocorticoid receptor- and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent antioxidant defense system in growing cancers (i.e. the glutathione and thioredoxin systems, superoxide dismutases, catalase, and NADPH supplying dehydrogenases). Exogenous corticosterone or genetically-induced Nrf2 overexpression in the cancer cells prevented the inhibition of tumor growth and antioxidant defenses in these malignant cells. Glutathione depletion (selected as a potential anti-cancer strategy) facilitated the complete elimination by chemotherapy of cancer cells isolated from mice treated with Pter. CONCLUSIONS: This report shows a novel link between a neuroendocrine system- and stress response-dependent mechanism and the regulation of cancer growth in vivo. Natural polyphenols can interfere with the growth and defense of cancer cells by down-regulating the pituitary gland-dependent ACTH synthesis. Lower levels of plasma ACTH cause a decrease in the suprarenal glands-dependent glucocorticoid production, thus decreasing the glucocorticoid receptor and Nrf2-dependent signaling/transcription and the antioxidant protection of melanoma and pancreatic cancer cells. Hence facilitating identification of molecular targets to sensitize aggressive cancers to oncotherapy. Citation Format: Maria Benlloch, Soraya L. Valles, Maria L. Rodriguez, J. Antoni Sirerol, Javier Alcacer, Jose Pellicer, Rosario Salvador, Concha Cerda, Guillermo T. Saez, Jose M. Estrela. Pterostilbene, a natural phytoalexin, weakens the antioxidant defenses of aggressive cancer cells in vivo: a pituitary gland- and Nrf2-dependent mechanism. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2810.

ADRENOCORTICOTROPIN HORMONE AND CORTISOL DYNAMIC VARIATION IN CASE OF CHILDREN›S NEUROINFECTIONS

The data presented in the article deal with research of hormone changes in hypophysial-paranephric system in the course of neuroinfections. The given work was carried out with the purpose of detection of dependence of the cortisol and adrenocorticotropin hormone level on aetiology, gender, severity and period (cycle) of the disease.A comprehensive clinical and laboratorial checkup of 109 children with different nosological forms of neuroinfections was carried out: meningitis: viral, enteroviral, purulent and cerebromeningitis. Control board group was composed of 10 healthy children of the identical age. All the patients underwent the Adrenocorticotropin Hormone and Cortisol blood serum level, IFA technique being used, during acuity and reconvalesence. It has been determined that in case of neuroinfections irrrespective of the ethiology, hypophysis trophic funtction undergoes arrest during the whole disease period. While studying adrenal gland functioning during the acuity the increased cortisol secretion is observed, the degree of which is authentically higher in case of purulent meningitis and meningoencephalitis compared to hydromeningitis. On recovery the cortisol values decrease to healthy children’s level. A reliable dependence of the ACTH and cortisol level on the severity degree in case of purulent meningitis and meningoencephalitis was discovered ( brought to light). It is also satisfactorily brought to light that ACTH and cortisol levels depend on the severity degree in case of purulent meningitis and meningoencephalitis. It is proved that adrenal gland system function does not depend on the patients’ gender and age in case of neuroinfections.

Role of the ACTH/MC2R System in the Hair Cycle in Mice

Adrenocorticotropin hormone (ACTH), which is secreted in response to psychological stress, plays an important role in the hair cycle. This study examined the mechanism by which ACTH affects the hair cycle using mice deficient in melanocortin receptor-2(MC2R-/-), which is a main receptor for ACTH. We observed the hair cycle using female MC2R-/- mice at 15 weeks old and five days old to determine whether there were any age-dependent differences. The 15-week-old MC2R-/- mice showed the anagen phase for all mice. On the other hand, all of the MC2R+/+ mice showed the telogen phase at the same age. Moreover, in the five-day-old mice, the hair growth of the MC2R-/- mice occurred earlier than in the MC2R+/+ mice. Both the 15-week-old and five-day-old MC2R-/- mice had higher levels of ACTH and alpha-melanocyte stimulating hormone in the blood than did the MC2R+/+ mice. In addition, in the 15-week-old MC2R-/- mice, the hair cycle shifted to the telogen phase following the administration of a cyclic guanosine monophosphate (cGMP) inhibitor and MC1R/MC5R inhibitor. In the five-day-old MC2R-/- mice, the hair growth was slowed by the administration of corticosterone. These results suggest that the ACTH/MC2R system has an important role in the hair cycle.

Re-examining Nelson's syndrome.

Nelson's syndrome is a rare complication that can occur during the course of management of Cushing's disease. This article summarizes the recent literature on the diagnosis, monitoring and treatment of this potentially life-threatening outcome. Nelson's syndrome, with rising adrenocorticotropin hormone levels and corticotroph tumor progression on diagnostic imaging, can develop following treatment of refractory Cushing's disease with total bilateral adrenalectomy with/without radiotherapy. However, data showing that radiotherapy prevents Nelson's syndrome is inconsistent. In addition to the treatment of Nelson's syndrome with neurosurgery with/without adjuvant radiotherapy, selective somatostatin analogs and dopamine agonists, as well as other novel agents, have been used with increasing frequency in treating cases of Nelson's syndrome with limited benefit. The risk-benefit profile of each of these therapies is still not completely understood. Consensus guidelines on the evaluation and management of Nelson's syndrome are lacking. This article highlights areas in the surveillance of Cushing's disease patients, and diagnostic criteria and treatment regimens for Nelson's syndrome that require further research and review by experts in the field.

Cushing syndrome.

Cushing syndrome.

Adrenal reserve function after unilateral adrenalectomy in patients with primary aldosteronism

After unilateral adrenalectomy (uADX) in patients with a unilateral aldosterone-producing adenoma (APA), the remaining contralateral adrenal gland is generally considered sufficient to support life. However, few studies have compared adrenal reserve function before and after uADX. Therefore, we closely evaluated adrenal cortisol secretory function before and after uADX in patients with unilateral APA. Patients who were diagnosed with APA and underwent uADX for unilateral APA were initially included in this study. Patients with subclinical Cushing's syndrome (SCS) or Cushing's syndrome were excluded on suspicion of autonomous cortisol secretion. Fourteen patients were finally evaluated. Morning basal serum cortisol and plasma adrenocorticotropin hormone (ACTH) levels were measured, and ACTH stimulation tests under 1-mg dexamethasone suppression (dex-ACTH test) were performed before and after uADX. No patient developed clinical adrenal insufficiency. Basal cortisol levels were not significantly different before and after uADX. However, basal ACTH levels were significantly elevated after uADX. In addition, peak cortisol levels on the dex-ACTH test decreased in all patients after uADX. The peak cortisol level after uADX was 86.6 (81.4-92.4)% of the level before uADX. The adrenal cortisol secretory response to ACTH stimulation is mildly reduced after uADX in patients with unilateral APA without SCS or Cushing's syndrome, although their basal cortisol level is sustained by elevated ACTH. These data will be important as a point of discussion when patients with unilateral APA consider either uADX or specific pharmacotherapy as treatment options.

Abstract 2427: The stress response controls the interorgan glutathione/interleukin-6 cycling activity: A systemic signaling mechanism promoting metastases growth.

Abstract B16 melanoma F10 (B16-F10) cells with high glutathione (GSH) content show very high metastatic activity in vivo. An intertissue flow of GSH, where the liver is the main reservoir, increases GSH content in metastatic cells and promote their growth. We studied possible tumor-derived molecular signals that could activate GSH release from hepatocytes. GSH efflux increases in hepatocytes isolated from mice bearing liver or lung metastases, thus suggesting a systemic mechanism. Fractionation of serum-free conditioned medium from cultured B16-F10 cells and monoclonal antibody-induced neutralization techniques facilitated identification of interleukin (IL)-6 as a tumor-derived molecule promoting GSH efflux in hepatocytes. IL-6 activates GSH release through a methionine-sensitive/organic anion transporter polypeptide 1- and multidrug resistance protein 1-independent channel located on the sinusoidal site of hepatocytes. Specific siRNAs were used to knock down key factors in the main signaling pathways activated by IL-6, which revealed a STAT3-dependent mechanism. Our results show that IL-6 (mainly of tumor origin) facilitates GSH release from hepatocytes and its interorgan transport to metastatic growing foci. Metastatic tumor activated the hypothalamic-pituitary-adrenal axis, thus increasing expression of hypothalamic corticotropin releasing factor and plasma levels of adrenocorticotropin hormone, corticosterone, and cathecolamines. Corticosterone and norepinephrine increased IL-6 expression and synthesis in metastatic cells, thus promoting the interorgan GSH/IL-6 cycling activity. Our results suggest possible mechanisms of cross-talk between metastases and the central nervous system of the host. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2427. doi:1538-7445.AM2012-2427

Examining the safety of prednisolone acetate 1% nasal spray for treatment of nasal polyposis

Topical intranasal corticosteroid sprays are a mainstay of treatment for nasal polyposis. Newer treatment strategies for refractory polypoid disease include "off label" topical steroids such as prednisolone acetate. This study investigates the safety of intranasal prednisolone acetate; evaluating its effect on serum cortisol and adrenocorticotropin hormone (ACTH) levels. This retrospective study included adult patients with refractory nasal polyposis, who had not taken oral steroids for 3 months prior to entry into the study. Patients applied 2 sprays of 1% prednisolone acetate delivered via a 15-mL standardized spray bottle twice daily. Morning serum cortisol and ACTH levels were collected prior to treatment and 6 to 8 weeks posttreatment. Pretreatment and posttreatment values were compared. Nine patients were included in this study. The average serum cortisol and ACTH levels prior to treatment was 12.09 μg/dL (95% confidence interval [CI], 6.94-17.24) and 12.33 ng/L (95% CI, 8.97-15.70), respectively. After 6 to 8 weeks of treatment, the average serum cortisol and ACTH levels were 11.76 μg/dL (95% CI, 9.51-14.00) and 13.22 ng/L (95% CI, 10.68-15.77), respectively. There was no statistically significant difference between pretreatment and posttreatment values for cortisol (p = 0.89) or ACTH (p = 0.63). Intranasal delivery of prednisolone acetate, at the specified dose, does not result in suppression of the adrenal axis. It can be considered as a safe alternative for management of aggressive nasal polyposis refractory to traditional treatment strategies.

The effects of palm vitamin E on stress hormone levels and gastric lesions in stress-induced rats

IntroductionThis study examines the effects of palm vitamin E (PVE) or α-tocopherol (α-TF) supplementation on adrenocorticotropin hormone (ACTH), corticosterone and gastric lesions in rats exposed to water-immersion restraint stress (WIRS).Material and methodsSixty male Sprague-Dawley rats (200-250 g) were divided into three groups. Group I: 20 rats as a control group were given a normal diet. Group II: 20 rats received oral supplementation of PVE at 60 mg/kg body weight. Group III: 20 rats received oral supplementation of α-TF at 60 mg/kg body weight. After the treatment period of 28 days, each group was further subdivided into two groups: 10 rats not exposed to stress, and the other 10 rats subjected to WIRS for 3.5 h. Blood samples were taken to measure the ACTH and corticosterone levels. The rats were then sacrificed and the stomach excised and opened along the greater curvature and examined for lesions.ResultsRats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementation of PVE or α-TF was able to reduce gastric lesions significantly in comparison to the stressed controls. The WIRS increased plasma ACTH and corticosterone significantly. Palm vitamin E and α-TF treatments reduced these parameters significantly compared to the stressed controls.ConclusionsSupplementation with either PVE or α-TF reduces the formation of gastric lesions, probably by inhibiting the elevation of ACTH and corticosterone levels induced by stress.

Effect of Acupuncture on Hypothalamic–Pituitary–Adrenal System in Maternal Separation Rats

The maternal separation (MS) animal model has been widely used to study early life stress and several psychiatric conditions such as depression and anxiety. In this study, we investigated the effect of acupuncture on anxiety-related behaviors and hypothalamic-pituitary-adrenal (HPA) system in MS-induced early life stress of Sprague-Dawley rat pups (14-21 postnatal days). For determining anxiety-related behaviors, the elevated plus-maze test was performed. The effects of acupuncture on the activation of stress were measured by assessing plasma levels of corticosterone (CORT) and adrenocorticotropin hormone (ACTH). The hypothalamic immunoreactivity (IR) of arginine vasopressin (AVP) was also examined. Acupuncture was conducted at acupoint HT7, which is used to treat mental disorders in Oriental medicine, for seven consecutive days. Acupuncture significantly decreased the frequencies of open arm entries and the amount of time spent in the open arms in MS rats. In addition, acupuncture reduced CORT and ACTH levels in plasma of MS rats, and AVP-IR in the hypothalamic paraventricular nucleus of MS rats. In conclusion, acupuncture reduced anxiety-related behaviors and modulated the HPA system. These findings suggest that acupuncture at HT7 may be useful as a therapeutic treatment in MS-induced early life stress.

Increased morning adrenocorticotrophin hormone (ACTH) levels in women with postpartum thoughts of harming the infant

Some postpartum women experience intrusive thoughts of harming the infant. The hypothalamic-pituitary-adrenal (HPA) axis, which has been linked to postpartum depression, may play a role in the aetiology of postpartum thoughts of harming the infant. We aimed to study whether HPA axis hormones measured early postpartum are related to postpartum intrusive thoughts. 132 women who delivered a child at a university hospital participated in a follow-up study with visits at 2-3 days postpartum and 8th week postpartum. Participants were assessed for trait anxiety, social support, peripartum or postpartum anxiety or depression, stressful life events and obstetric variables including perinatal complications and lactation. Postpartum thoughts of harming the infant were assessed with a semi-structured interview. Serum cortisol, and plasma CRH and ACTH levels were measured within 48 h postpartum at 8-9 AM. A logistic regression was performed to explore the relationship between clinical variables, hormonal measures and postpartum intrusive thoughts. Patients with postpartum thoughts of harming the infant had, when compared to those women without intrusive thoughts, higher ACTH levels (7.59 pmol/L vs 5.09 pmol/L, p<0.05) without significant differences in CRH or cortisol levels. In the logistic regression analysis, adjusted for breast-feeding and psychopathological status, only ln ACTH was associated with the presence of postpartum thoughts of harming the infant (OR=5.2, CI 95% 1.2-22.6, p=0.029). No other clinical variables were associated with postpartum intrusive thoughts. Our study suggests that a dysregulation of the hypothalamic-pituitary-adrenal axis may play a role in the aetiology of postpartum thoughts of harming the infant.

The function of hypothalamus–pituitary–adrenal axis in children with ADHD

Objective:To explore the relationship between hypothalamus–pituitary–adrenal (HPA) axis and Attention Deficit Hyperactivity Disorder (ADHD) in non-stress states. Method: 128 male children with ADHD aged between 6 and 14 years old were recruited, while 30 healthy male children were chosen as a control group. The diagnostic material was based on DSM-IV. The included ADHD children were further classified into the three sub-groups: ADHD-predominantly inattention type (ADHD-I) ( n = 44), ADHD-predominantly hyperactive impulsive type (ADHD-HI) ( n = 32), and ADHD-combined type (ADHD-C) ( n = 52). The levels of cortisol and adrenocorticotropin hormone (ACTH) were evaluated by the automatic particle enzyme immunoassay and electrochemiluminescence respectively per morning (8:00 am). Intelligence test was assessed by the Raven's Standard Progressive Matrices. Results: The children with ADHD had significantly lower intelligence quotient (IQ) (84.5 ± 11.3) in contrast to the control group (98.6 ± 12.4, P < 0.01), although the lower level of IQ in ADHD-C group (79.2 ± 10.7) was also found when compared with other two sub-groups [ADHD-I (85.6 ± 10.4) and ADHD-HI (91.3 ± 12.6)]. In addition, no significant difference between the ADHD-HI group and the control group regarding the level of IQ were revealed. The level of cortisol in the ADHD group (226.47 ± 129.12 nmol/L) was significantly lower than that of the control group (384.53 ± 141.43 nmol/L, P < 0.001). The level of cortisol of the ADHD-HI group (154.36 ± 71.62 nmol/L) was significantly lower than that of other two groups [ADHD-I group (219.42 ± 117.66 nmol/L) ( P < 0.01) and ADHD-C group (258.30 ± 136.39 nmol/L) ( P < 0.01)]. There were no significant differences in the ACTH level either between the ADHD and the control group ( P > 0.05), or between sub-groups in ADHD ( P > 0.05). Conclusion: In the non-stress states, the existence of dysfunction of the HPA axis (lower plasma cortisol) in children with ADHD might be due to the under-reactivity of the HPA axis ; the low plasma cortisol level might contribute less to the outcomes of cognitive behavior of ADHD children and instead more closely relate to the core domains of attention deficit, hyperactivity and impulsive behavior of ADHD patients.

Role of Somatostatin Receptors in Normal and Tumoral Pituitary Corticotropic Cells

Normal and tumoral pituitary corticotropic cells express sst₂ and sst₅, of which sst₅ is the predominantly expressed receptor subtype. Somatostatin (SS) inhibits pituitary adrenocorticotropin hormone (ACTH) secretion in vitro, but the sensitivity to SS is strongly regulated by glucocorticoids. In pathological conditions of a low endogenous cortisol level, i.e. in patients with adrenal insufficiency and in patients with Nelson’s syndrome, SS and sst₂-preferring SS analogs (SSA), such as octreotide, are able to lower circulating ACTH and cortisol levels. On the other hand, sst₂-preferring SSA seem not effective in lowering ACTH and cortisol levels in patients with untreated Cushing’s disease (CD), in which circulating cortisol levels are high. This is likely due to the downregulation of sst₂ receptors by glucocorticoids. sst₅ receptor expression is more resistant to the inhibitory effect of glucocorticoids. In recent years, novel sst subtype-selective and universal SSA have been developed. In particular, SSA with a high sst₅-binding affinity are potent inhibitors of ACTH secretion by pituitary corticotropic adenoma cells. This knowledge has initiated clinical trials evaluating the efficacy of these novel SSA in patients with CD, with the aim to lower circulating ACTH and cortisol levels by targeting multiple ssts on the corticotropic adenoma cells. In this minireview, the effects of SS in the regulation of normal and tumoral ACTH secretion, the role of sst subtypes involved herein, as well as the potentials of novel SSA in the treatment of patients with recurrent or persisting CD are discussed.