Early hyperbaric oxygen therapy inhibits aquaporin 4 and adrenocorticotropic hormone expression in the pituitary gland of rabbits with blast-induced craniocerebral injury

In the present study, rabbits were treated with hyperbaric oxygen for 1 hour after detonator-blastinduced craniocerebral injury. Immunohistochemistry showed significantly reduced aquaporin 4 expression and adrenocorticotropic hormone expression in the pituitary gland of rabbits with craniocerebral injury. Aquaporin 4 expression was positively correlated with adrenocorticotropic hormone expression. These findings indicate that early hyperbaric oxygen therapy may suppress adrenocorticotropic hormone secretion by inhibiting aquaporin 4 expression.

Adrenocorticotropic hormone-secreting pancreatic neuroendocrine carcinoma with multiple organ infections and widespread thrombosis:A case report

BACKGROUND Ectopic adrenocorticotropic hormone(ACTH)-secreting neuroendocrine tumors are rare diseases.Patients with ACTH-secreting pancreatic neuroendocrine carcinomas have a poor prognosis.Infections and coagulopathies have been reported as the cause of death.However,detailed clinical descriptions of the morbid complications of ACTH-secreting neuroendocrine carcinomas have not been reported.CASE SUMMARY A 78-year-old Japanese woman consulted a medical center due to systemic edema and epigastric discomfort.Laboratory analysis revealed hypercortisolemia with increased ACTH secretion without diurnal variation in serum cortisol level.An enhanced computed tomography(CT)scan revealed a 3-cm tumor in the pancreatic head.The cytological material from endoscopic ultrasound-guided fine-needle aspiration was compatible with ACTHsecreting pancreatic neuroendocrine carcinoma.The Ki-67 index was 40%.She was transferred to Mie University Hospital for surgical treatment.The patient was diagnosed with urinary tract infection,cytomegalovirus hepatitis,esophageal candidiasis,pulmonary infiltrates suspicious for Pneumocystis carinii pneumonia,peripheral deep vein thrombosis,pulmonary embolism,and disseminated intravascular coagulation.The multiple organ infections and thromboses responded well to antimicrobial and anticoagulant therapy.Radioisotope studies disclosed a pancreatic tumor and a metastatic lesion in the liver,whereas somatostatin receptor scintigraphy showed negative findings,suggesting the primary and metastatic tumors were poorly differentiated.A CT scan before admission showed no metastatic liver lesion,suggesting that the pancreatic tumor was rapidly progressing.Instead of surgery,antitumor chemotherapy was indicated.The patient was transferred to another hospital to initiate chemotherapy.However,she died four months later due to the rapidly progressive tumor.CONCLUSION ACTH-secreting pancreatic neuroendocrine neoplasm is a rare disease with a very poor prognosis.The clinical course and acute complications of the tumor remain unreported.Here we report the clinical course of a rapidly progressive case of ACTH-secreting pancreatic neuroendocrine tumor that developed infectious complications due to many types of pathogens in multiple organs,widespread thromboses,pulmonary embolism,and disseminated intravascular coagulation.

Pituicytoma Associated with Serum Adrenocorticotropic Hormone Elevation

Background: Pituicytoma is a rare benign tumor of the neurohypophysis or hypophyseal stalk. Endocrinological abnormalities derived from this tumor are even rarer. Although three cases of pituicytoma with elevated plasma adrenocorticotropic hormone (ACTH) have been reported previously, the etiological mechanisms remain unknown. Case Description: We present a 47-year-old woman who was referred to a hospital complaining of headache. On investigation using magnetic resonance imaging (MRI), a tumor was detected in the sellar region. Elevation of basal ACTH and serum cortisol was identified, suggesting an ACTH-producing pituitary adenoma. However, physical findings and results of other hormonal examination showed no evidence of Cushing disease. The tumor had been detected incidentally eight years earlier when MRI was performed, and showed considerable enlargement on this consultation. Endoscopic endonasal transsphenoidal surgery was performed in order to remove the tumor completely. The histopathological diagnosis was pituicytoma. The patient’s postoperative clinical course was excellent, and both ACTH and cortisol levels returned to normal following surgery. Conclusions: It appears that ACTH was being secreted from the tumor cells. We discuss the possible mechanism of ACTH elevation in cases of pituicytoma.

Response to magnesium sulfate and adrenocorticotropic hormone combination therapy for infantile spasms with failed first-line treatments

Importance:Infantile spasm(IS)is a kind of refractory epilepsy.The first-line treatments for IS are adrenocorticotropic hormone(ACTH),oral corticosteroids,and vigabatrin.Objective:This study aimed to evaluate the efficacy of magnesium sulfate and ACTH(MgSO_(4)+ACTH)combination therapy in patients with IS who failed first-line treatments.Methods:In this retrospective study,the clinical data of patients with IS who failed first-line treatments were collected in the Chinese PLA General Hospital.Patients received MgSO_(4)+ACTH combination therapy after first-line treatments failed.The course of treatments was 2 weeks.The therapeutic dose of ACTH and MgSO_(4)was 2.5 U·kg^(-1)·d^(-1)and 0.25 g·kg^(-1)·d^(-1),respectively.Results:A total of 229 patients with IS who failed the first-line treatments were collected.At the end of the MgSO_(4)+ACTH combination treatment,the seizure-free rate was 48.5%(111/229),and the resolution of hypsarrhythmia on electroencephalogram(EEG)was 72.1%(165/229).About 21.4%(49/229)of patients showed side effects,including infectious diseases,hypokalemia,and diarrhea.Interpretation:For patients with IS who failed first-line treatments,in terms of the seizure-free rate and resolution of hypsarrhythmia on EEG,MgSO_(4)+ACTH combination therapy can be considered.

Adrenocorticotropic hormone-producing pheochromocytoma： a case report and review of the literature

Ectopic Cushing＇s syndrome caused by pheochromocytoma is rare. We reported a 15-year-old female patient who was admitted to hospital with typical Cushing＇s syndrome. She had not started menstruation. Her plasma adrenocorticotropic hormone （ACTH） and 24-hour urinary free cortisol levels were extremely high. Gonadal and progestational hormone levels were also abnormal. Abdominal computed tomography scans and enhanced scans revealed multiple irregular tumors in the right adrenal. Pelvic echogram showed an infantile uterus, while the ovaries were at an immature stage of development. Retroperitoneal laparoscopic right adrenalectomy was performed without intraoperative complications. Histology and immunohistochemistry of the tumor were consistent with pheochromocytoma. Retroperitoneal laparoscopic adrenalectomy is a safe procedure with satisfactory outcomes and allows for rapid recovery.

Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism

Background： Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism （IHH） may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone （ACTH） and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal （HPA） axis in patients with and without nonalcoholic fatty liver disease （NAFLD）, and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients. Methods： This was a retrospective case-control study involving 75 Chinese male IHH patients （mean age 21.4 ± 3.8 years, range 17 30 years） and 135 healthy controls after matching tbr gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone. ACTH, and cortisol and biochemical tests. Results： Higher basal serum ACTH levels （8.25 ±3.78 pmol/L vs. 6.97 ±2.81 pmol/L） and lower cortisol levels （366.70 ±142.48 nmol/L vs. 452.82 ± 141.53 nmol/L） were observed ill male IHH patients than healthy subjects （all P 〈 0.05）. IHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD （34.9% vs. 4.4%） than the controls （all P 〈 0.05）. Basal serum ACTH （9.91 ±4.98 pmol/L vs. 7.60 ±2.96 pmol/L） and dehydroepiandrosterone sulfate （2123.7 ±925.8 μg/L vs. 1417.1 ±498.4 μg/L） levels were significantly higher in IHH patients with NAFLD than those without NAFLD （all P 〈 0.05）. We also found that basal serum ACTH levels were positively correlated with NAFLD （r = 0.289, P 〈 0.05） and triglyceride levels （r - 0.268, P 〈 0.05） in male IHH patients. Furthermore, NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis. Conclusions： The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells

Background： Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 （USP8） gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor （EGFR） signaling and promote adrenocorticotropic hormone （ACTH） production. This study was to investigate whether the inhibition of USP8 activity could be a strategy/br the treatment of Cushing＇s disease （CD）. Methods： The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony tbrmation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition. Results： Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 （ERBB2）, and Met leading to a suppression of ArT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis. Conclusions： Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD.

Persistent postoperative hypotension caused by subclinical empty sella syndrome after a simple surgery:A case report

BACKGROUND Empty sella is an anatomical and radiological finding of the herniation of the subarachnoid space into the pituitary fossa leading to a flattened pituitary gland.Patients with empty sella may present with various symptoms,including headache due to intracranial hypertension and endocrine symptoms related to the specific pituitary hormones affected.Here,we report a female patient who developed persistent postoperative hypotension caused by subclinical empty sella syndrome after a simple surgery.CASE SUMMARY A 47-year-old woman underwent vocal cord polypectomy under general anesthesia with endotracheal intubation.She denied any medical history,and her vital signs were normal before the surgery.Anesthesia and surgery were uneventful.However,she developed dizziness,headache and persistent hypotension in the ward.Thus,intravenous dopamine was started to maintain normal blood pressure,which improved her symptoms.However,she remained dependent on dopamine for over 24 h without any obvious anesthesia-and surgery-related complications.An endocrine etiology was then suspected,and further examination showed a high prolactin level,a low normal adrenocorticotropic hormone level and a low cortisol level.Magnetic resonance imaging of the brain revealed an empty sella.Therefore,she was diagnosed with empty sella syndrome and secondary adrenal insufficiency.Her symptoms disappeared one week later after daily glucocorticoid supplement.CONCLUSION Endocrine etiologies such as pituitary and adrenal-related dysfunction should be considered in patients showing persistent postoperative hypotension when anesthesia-and surgery-related factors are excluded.

Moxibustion upregulates hippocampal progranulin expression

In China,moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome,but its mechanisms are largely unknown.More recently,the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome,and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis.In the present study,we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms.Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome.The acupoints Guanyuan（CV4） and Zusanli（ST36,bilateral） were simultaneously administered moxibustion.Untreated chronic fatigue syndrome rats and normal rats were used as controls.Results from the forced swimming test,open field test,tail suspension test,real-time PCR,enzyme-linked immunosorbent assay,and western blot assay showed that moxibustion treatment decreased m RNA expression of corticotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone and corticosterone levels in plasma,and markedly increased progranulin m RNA and protein expression in the hippocampus.These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome,at least in part,by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.

Effects of Repeated Electroacupuncture on β-Endorphin and Adrencorticotropic Hormone Levels in the Hypothalamus and Pituitary in Rats with Chronic Pain and Ovariectomy

Objective： To explore the mechanism of electroacupuncture （EA）-induced cumulative analgesic effects on chronic pain in rats with or without ovariectomy （OVX）. Methods： A total of 110 female Wistar rats were randomized into normal control （n=10）, chronic constrictive injury （CCI, n=10）, CCI＋EA （n=30）, OVX＋CCI （n=30）, and OVX＋CCI＋EA （n=30） groups. Each of the latter 3 groups was further divided into 2 days （2 d）, 2 weeks （2 W） and 3 weeks （3 W） subgroups, respectively （n=10 in each subgroup）. The CCI pain model was established by ligature of the right sciatic nerve, and the memory impairment model duplicated by OVX. The paw withdrawal latency （PWL, pain threshold） of the bilateral footplates was detected by radiant heat irradiation, and the bilateral difference in PWL （PWLD） was used to evaluate changes in the pain reaction. Morris water maze test was conducted for evaluating the rats＇ learning-memory ability. EA was applied to bilateral Zusanli （ST36） and Yanglingquan （GB34） for 2 d, 2 W and 3 W, respectively. Pituitary and hypothalamic 13-endorphin （EP） and adrenocorticotrophic hormone （ACTH） contents were detected by immunoradioassay. Results： Compared with the CCI group, PWLD of the CCI＋EA-3 W group decreased significantly （P〈0.05）. Compared with the OVX＋CCI group, PWLD of the OVX＋CCI＋EA-3 W group was lowered considerably （P〈0.05）, but the value was markedly higher than its basal value and those of the normal control and CCI＋EA groups （P〈0.05）. In comparison with the sham-OVX group, the escape latency, swimming distance （SD） in the target quadrant and total SD were increased remarkably in the OVX group （P〈0.05）, while the number of target platform crossings was decreased significantly （P〈0.05）, suggesting an impairment of the OVX rats＇ learning-memory ability. In simple CCI rats, both β-EP and ACTH contents of the pituitary increased markedly （P〈0.05）, and those of the hypothalamus decreased obviously compared to the normal control group （P〈0.05）. After EA, pituitary and hypothalamic ACTH levels were significantly lowered at 2 d and hypothalamic ACTH and β -EP contents increased obviously at 3 W in comparison with the CCI group （P〈0.05）. In OVX＋CCI rats, following EA, pituitary β -EP contents at 2 d, 2 W and 3 W, and hypothalamic β-EP and ACTH contents at 2 W and hypothalamic ACTH levels at 3 W increased significantly （P〈O.05）, but hypothalamic β-EP level at 3W decreased markedly （P〈0.05）. The effects of repeated EA in lowering pituitary ACTH and raising hypothalamic β-EP and ACTH levels disappeared after OVX＋CCI. Conclusions： Repeated EA has a cumulative analgesic effect, which is closely associated with its effects in regulating pituitary and hypothalamic β-EP and ACTH levels. OVX may weaken the analgesic effect of EA by affecting hypothalamic-pituitary axis activity.