Effects of Etomidate Combined With Dexmedetomidine on Adrenocortical Function in Elderly Patients: A Double-Blind Randomized Controlled Trial

Introduction Etomidate has been advocated to be used in anesthesia of the elderly and the critically ill patients due to its faint effect on cardiovascular system. But the dose-dependent suppression of etomidate on adrenal cortex function leads to the limitation of its clinical application. Clinical research shows that dexmedetomidine can reduce the dose requirements for intravenous or inhalation anesthetics and opioids, and the hemodynamics is more stable during the operation. The objective is to observe the effect of etomidate combined with dexmedetomidine on adrenocortical function in elderly patients. Methods 180 elder patients scheduled for elective ureteroscopic holmium laser lithotripsy were randomly allocated to PR group anesthetized with propofol- remifentanil, ER group anesthetized with etomidate-remifentanil, and ERD group anesthetized with dexmedetomidine combined with etomidate-remifentanil. Patients in each group whose operation time was less than or equal to 1h were incorporated into short time operation group (PR1 group, ER1 group and ERD1 group), and whose operation time was more than 1h were incorporated into long time operation group (PR2 group, ER2 group and ERD2 group). The values of SBP, DBP, HR and SpO2 were recorded at T0, T1, T2, T3, T4, T5, T6 and T7.The time of operation, the dosage of etomidate and remifentanil administrated during surgery, the time to spontaneous respiration, recovery and extubation, and the duration of stay in the PACU were recorded. The serum cortisol and ACTH concentration was measured at t0, t1, t2, t3, t4 and t5. Results The dosage of etomidate was significantly lower in ERD1 group and ERD2 group compared with ER1 group and ER2 group(P < 0.05), respectively. The SBP in ER2 and ERD2 group were higher at T1 and T3 compared to PR2 group (P < 0.05). The DBP in ER1 and ERD1 group were higher at T1compared to PR1 group (P < 0.05). The Serum cortisol concentration were higher at t1 ~ 2 in ERD1 group compared to ER1 group (P < 0.05). The Serum cortisol concentration were higher at t1 ~ 3 in ERD2 group compared to ER2 group (P < 0.05).The Serum ACTH concentration were lower at t1 ~ 2 in ERD1 group compared to ER1 group (P < 0.05). The Serum ACTH concentration were lower at t1 ~ 3 in ERD2 group compared to ER2 group (P < 0.05). Conclusion The administration of dexmedetomidine combined with etomidate can attenuate the inhibition of etomidate on adrenocortical function in elderly patients and maintain intraoperative hemodynamic stability.

Circadian Rhythms of Oxidant-Antioxidant Agents, HPA Axis and Protein Carbonyl Content in Serum, Brain and Adrenal Gland Tissues

The aim of this experiment is to study the circadian rhythm of oxidant-antioxidant components in the body. A total of 20 adult male rabbits were divided into 2 groups (G1and G2)and kept in 2 different rooms. Serum was isolated after blood collection at 12 A.M or 12 P.M respectively from G1 and G2.The results reveal a significant elevation in serum GSH, MDA and SOD during night hours. The B-endorphin showed a value of 84.36±1.36 in rabbits serum during night compared with 53.23±1.12 during day hours. Serum ACTH and cortisone concentration during night hours expressed a value of 71.03±0.16 and 24.46±0.38 compared to 52.80±0.37 and 11.80±0.57 during day hours respectively. Protein carbonyl contents shows a regular variation between serum and tissues during day and night hours. It was concluded that the oxidant-antioxidant imbalance lead to such variation between day and night hours due to activities and metabolism. Extensive research is needed to minimize and overlap such stress.

Continuous Etomidate for the Management of Cushing’s Syndrome Complicated by Pulmonary Nocardiosis

Severe Cushing’s syndrome is associated with significant complications including opportunistic infections. In the setting of infection, urgent reduction of circulating cortisol is warranted and commonly used oral medications have a slow onset of effect. Here we describe a 29-years old female who presented to an outside hospital with symptoms of untreated Cushing’s syndrome on ketoconazole. Following identification of a pulmonary Nocardia spp infection, she was transferred for a higher level of care. Her initial serum ACTH and cortisol levels after transfer were 106pg/mL and 53.7mCg/dL respectively. Given the severity of her nocardiosis and lack of response to ketoconazole, the patient was placed in the ICU and started on a continuous etomidate infusion. Her serum cortisol rapidly decreased to 5.7mCg/dL. She was transitioned to metyarapone and the etomidate infusion was weaned to off. The etomidate infusion was well tolerated without adverse effects or need for an advanced airway. Following discontinuation of etomidate, she was found to have a pituitary microadenoma that was resected. The patient was discharged from the hospital on antibiotics for the management of her Nocardia spp infection. In patients with severe Cushing’s syndrome, continuous etomidate may be safe and effective for patients who are unresponsive to other therapies.

The Majority of Inpatient Short Synacthen Tests Are Performed Incorrectly, Due to Imprecise Timing, Incorrect Sampling and Failure to Interrupt Steroid Administration

Introduction: The short synacthen test (SST) is commonly used to assess adrenal function. Accurate timing and appropriate holding of exogenous steroids are essential to ensure correct interpretation of results. Aims & Methods: We reviewed all SSTs performed on inpatients in our hospital over a 1-year period, in order to determine accuracy of testing. Results: 42 patients (Male 15, Female 27), with mean age 68 years (range 43–90), underwent SST. The majority (39/42; 93%) of tests were requested by internal medicine physicians. The indications for testing were; suspected adrenal insufficiency (18), HPA axis suppression (9), fatigue (7), hyponatremia (5), suspected pituitary disease (2) and vomiting (1). 7 (44%) of the 16 patients taking steroids did not have medication appropriately held. 31 (74%) patients did not have serum ACTH measured prior to the test. 28 (66%) tests were not started at the correct time. Only 10 (24%) of the 30 minute samples were completed within the 25-35min sample window. The mean time between the 0min and 30min samples was 42mins (median 62mins; range 0-209mins). 12 (29%) tests involved an unnecessary 60min sample. 8 (19%) tests had no interpretation of results documented in the medical notes. 4 (10%) patients underwent repeat testing, necessitated by an incorrect first test. Discussion: The vast majority of inpatient SSTs (33/42;79%) were performed suboptimally, with the most common errors pertaining to incorrect timing of the test, inaccurate sampling and inappropriate pre-test steroid administration. Considering these errors, some results may have been interpreted incorrectly. Repeat tests were recognised as required in 10% of patients, with associated inconvenience, cost and discomfort. Improved training and guidelines for performing SSTs should be available to hospital staff to ensure more accurate application of the test.

A Rare Case of Resistant Pigmentation

Introduction: Familial glucocorticoid deficiency (FGD) is characterised by ACTH resistance & isolated glucocorticoid deficiency, with typical biochemical findings of low serum cortisol & high plasma ACTH. Patients present with hyperpigmentation (due to stimulation of MC1R by POMC products) & hypoglycemia. Clinical presentation includes failure to thrive & susceptibility to infections. Case Report: A 14 year old girl presented to us with generalised hyperpigmentation of the skin and oral mucosa- it started when she was 4 years of age. There was history of recurrent respiratory infections around the same time the hyperpigmentation appeared - the patient required multiple hospitalisations for the same (she was admitted 3 times in 6 months). Her random serum cortisol was measured – it came out to be 8.27nmol/L. Her serum Na+ was 140 mEq/L & K+ was 3.5 mEq/L. She was also diagnosed with subclinical hypothyroidism at that time (TSH- 7.3 mIU/L, anti TPO antibodies positive). There was no history of alacrimia or achalasia. Her 17-OHP was 2.20 nmol/L. A probable diagnosis of autoimmune polyendocrine syndrome was made & oral hydrocortisone (@ 12 mg/m2) & levothyroxine (@25 mcg) was started. The patient was compliant with the treatment, but the mother complained that her hyperpigmentation improved only by 20–30 % despite continued treatment. There was no history of salt wasting crises or hospitalisations after the initiation of treatment. Her serum ACTH values were checked 2 times (2011 & 2015) and were &gt; 2000 pg/ml on both the occasions. The hydrocortisone dose was increased to 20mg/m2 for 1 year in between, without any improvement in hyperpigmentation. Patient presented to us with persistent hyperpigmentation in 2019. She was a product of consanguineous marriage. Non-compliance was ruled out. She had attained menarche at the age of 12 years. There was history of delayed pubarche (started @ age of 13 years) & axillary hair was absent. Again, her serum ACTH was &gt; 2000 pg/ml and electrolytes and BP were normal. In view of normal electrolytes with low cortisol at the time of diagnosis & persistent hyperpigmentation even on supraphysiological doses of hydrocortisone, Familial Glucocorticoid Deficiency was considered. Genetic analysis showed mutation in Thioredoxin Reductase (TXNRD2) Gene. This gene mutation has recently been reported in FGD. (Prasad R et al, JCEM Aug 2014.) Conclusion: In cases of primary adrenal insufficiency with normal electrolytes & resistant hyperpigmentation, familial glucocorticoid deficiency should be thought of. Treatment with standard glucocorticoid therapy should be given. Serum ACTH values should not be chased. The hyperpigmentation may not resolve completely. TXNRD2 deficiency leads to impaired redox homeostasis, highlights the important redox pathway in addition to defective ACTH signaling, giving us new insights in regard to steroidogenesis.

Effects of Propofol versus Sevoflurane on Postoperative Pain and Neuroendocrine Stress Response in Oocyte Pickup Patients

Background. Pain aggravates the autonomic response to stress and raises neuroendocrine stress hormone levels. We compared the effects of propofol and sevoflurane on postoperative pain and neuroendocrine stress hormones. A prospective, randomized, and controlled trial was conducted with 60 patients. Methods. We randomly allocated patients to groups P (remifentanil/propofol, n = 30) and S (remifentanil/sevoflurane, n = 30). Preoperative blood samples were taken to measure serum adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), glucagon, cortisol, aldosterone, and prostaglandin E2 (PGE2) levels. Intraoperatively and postoperatively, clinical parameters were monitored at different time points. The hormone levels were again measured in the follicular fluid and blood postoperatively. Result. Demographic data were similar. The preoperative serum aldosterone levels were significantly higher in group P ( p = 0.001 ). Preoperative and postoperative serum ACTH, glucagon, cortisol, and PGE2 levels were significantly different in group P ( p = 0.009 , p = 0.004 , p = 0.029 , and p = 0.002 ); serum ACTH, glucagon, and PGE2 levels increased while serum cortisol levels decreased postoperatively. In group S, serum CRH and aldosterone levels, both increased in the postoperative period compared to the preoperative ( p = 0.001 , p = 0.006 ). Postoperatively, glucagon and PGE2 levels were both higher in group P than group S ( p = 0.019 , p = 0.015 ). In postoperative follicular fluid, glucagon and PGE2 levels were higher in group P, while cortisol levels were higher in group S ( p = 0.001 , p = 0.007 , and p = 0.001 ). Conclusion. The effects of anesthetic agents were different. In group P, in the preoperative and postoperative evaluation, ACTH, glucagon, and PGE2 increased postoperatively, while cortisol decreased. In group S, aldosterone and CRH increased postoperatively. Glucagon and PG E2 were higher in group P than S, postoperatively.

Recurrence of a neuroendocrine tumor of adrenal origin: a case report with more than a decade follow-up

Background Neuroendocrine tumor (NET) with adrenocorticotropic hormone (ACTH) secretion are very rare. To our knowledge, no follow-up study is published for ACTH-secreting NET, regardless of the primary site, to show second occurrence of tumor after a long follow-up, following resection of primary tumor. Case presentation Here, we describe a 49-year-old-man with cushingoid feature, drowsiness and quadriparesis came to emergency department at December 2005. Laboratory tests revealed hyperglycemia, metabolic alkalosis, severe hypokalemia, and chemical evidence of an ACTH-dependent hypercortisolism as morning serum cortisol of 57 μg /dL without suppression after 8 mg dexamethasone suppression test, serum ACTH level of 256 pg/mL, and urine free cortisol of > 1000 μg /24 h. Imaging showed only bilateral adrenal hyperplasia, without evidence of pituitary adenoma or ectopic ACTH producing tumors. Importantly, other diagnostic tests for differentiating Cushing disease (CD) from ectopic ACTH producing tumor, such as inferior petrosal sinus sampling (IPSS), corticotropin releasing hormone (CRH) stimulation test, octreotide scan or fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan were not available in our country at that time. Therefore, bilateral adrenalectomy was performed that led to clinical and biochemical remission of hypercortisolism and decreased ACTH level to < 50 pg/mL, findings suggestive of a primary focus of NET in adrenal glands. After 11 years uncomplicated follow up, the ACTH level elevated up to 341 pg/mL and re-evaluation showed a 2 cm nodule in the middle lobe of the right lung. Surgical excision of the pulmonary nodule yielded a carcinoid tumor with positive immunostaining for ACTH; leading to decrease in serum ACTH level to 98 pg/mL. Subsequently after 7 months, serum ACHT levels rose again. More investigation showed multiple lung nodules with metastatic bone lesions accompanied by high serum chromogranin level (2062 ng/mL), and the patient managed as a metastatic NET, with bisphosphonate and somatostatin receptor analogues. Conclusion This case of surgically-treated NET showing a secondary focus of carcinoid tumor after one decade of disease-free follow-up emphasizes on the importance of long-term follow-up of ACTH-secreting adrenal NET.

THU0465 SERUM LEVEL OF ADRENOCORTICOTROPHIC HORMONE IS A CONTRIBUTING HORMONE OF METABOLIC SYNDROME IN NEWLY DIAGNOSED FIBROMYALGIA

Background:Evidence of components of metabolic syndrome including. Obesity dyslipidemia, abnormal glucose tolerance rate and hypertension are associated with fibromyalgia. Adrenocorticotrophic hormone (ACTH) is reported to be significantly higher in fibromyalgia patients, and it causes obesity, high blood pressure.Objectives:This study aimed to assess the serum level of ACTH as a contributing as well as a discriminator hormone in newly diagnosed fibromyalgia women presented with variable components of metabolic syndrome.Methods:This cross-sectional study comprised 100 women with newly diagnosis fibromyalgia and 30 apparent healthy women served as control from Kurdistan region-Iraq. Clinical data including the score of fibromyalgia impact questionnaire-revised (FIQR), tender point, body mass index, waist circumference, blood pressure and fasting serum levels of glucose and lipid profile, and ACTH level. The score of metabolic syndrome was calculated using the formula:Results:Compared to the controls, the Fibromyalgia women displayed significantly higher values of waist circumference (88.9 ± 5.7cm versus 87.1 ± 2.7cm, p=0.019), systolic blood pressure (136.1 ±13.5mmHg versus 131.4 ± 7.1, p=0.014), metabolic syndrome score (3.10 ±0.25 versus 3.03±0.19, p=0.039), and serum ACTH levels (16.66 ± 3.23pg/ml versus 14.42 ± 2.18pg/ml. p<0.001). Serum ACTH levels significantly and inversely correlated with the total score of the FIQR (r = - 0.320. p=0.001) and number of tender points (r= - 0.374, p<0.001). Metabolic syndrome score is significantly and inversely correlated with the total FIQR score (r = - 0.296, p=0.003). Multivariable regression analysis using showed that serum level of ACTH is a significant (p= predictor of 19.7% of fibromyalgia patients (Figure 1), and it is a significant (p=0.007) discriminator of tender points as the area under the curve is 0.325(95%C.I.: 0.212-0.438) (Figure 2).Figure 1.Multivariable regression analysis withposthocANOVA test showed significant correlations between serum level adrenocorticotrophic hormone as a dependent variable with the score s of fibromyalgia impact questionnaire and metabolic syndrome, and the number of tender points. R=0.443, F=7.777, P<0.001, prediction 19.7%),Figure 2.serum level of ACTH (cutoff level ≥14.5pg/ml, sensitivity=72%, specificity=50%) as a discriminator of the tender points (AUC95% C.I: 0.325[0.212-0.438], p=0.007), score of fibromyalgia symptoms (AUC95% C.I: 0.474[0.313-0.581], p=0.409), and metabolic syndrome score (AUC95% C.I: 0.546[0.423-0.668], p=0.480)Conclusion:Fibromyalgia women responded to the stress of pain by increasing the serum level of ACTH which effectively improves the clinical feature of fibromyalgia symptoms, but at the same time elevates the score of metabolic syndrome. Therefore, assessment of serum level of ACTH can serve as a predictor and discriminator of fibromyalgia comorbidity.References:[1]Acosta-Manzano P, Segura-Jiménez V, Estévez-López F, Álvarez-Gallardo IC, Soriano-Maldonado A, Borges-Cosic M, Gavilán-Carrera B, Delgado-Fernández M, Aparicio VA. Do women with fibromyalgia present higher cardiovascular disease risk profile than healthy women? The al-Ándalus project. Clin Exp Rheumatol. 2017; 35 Suppl 105(3):61-67.[2]Marwan S.M. Al-Nimer, Talar A.M. Mohammad, Avin M.A. Maroof. Dysfunction of anterior pituitary gland in women patients with recent fibromyalgia: A cross-sectional observational study. Electron J Gen Med 2018;15(4):em58[3]Soldatovic I, Vukovic R, Culafic D, Gajic M, Dimitrijevic-Sreckovic V. siMS score: simple method for quantifying metabolic syndrome. PLoS One. 2016; 11(1):e0146143Disclosure of Interests: :None declared

Digital analysis of hormonal immunostaining in pituitary adenomas classified according to WHO 2017 criteria and correlation with preoperative laboratory findings

OBJECTIVEThe authors sought to evaluate clinical and laboratory data from pituitary adenoma (PA) patients with functioning PA (associated with acromegaly [n = 10] or Cushing disease [n = 10]) or nonfunctioning PA (NFPA; n = 10) that were classified according to 2017 WHO criteria (based on the expression of the transcription factors pituitary-specific positive transcription factor 1 [Pit-1], a transcription factor member of the T-box family [Tpit], and steroidogenic factor 1 [SF-1]) and to assess the immunostaining results for growth hormone (GH) and adrenocorticotropic hormone (ACTH) in the corresponding tumors.METHODSClinical and laboratory data were collected retrospectively. The percentage of tumoral cells positive for Pit-1, Tpit, or SF-1 was assessed and ImageJ software was used to evaluate immunopositivity in PAs with 2 different antibodies against GH (primary antibody 1 [AbGH-1] and primary antibody 2 [AbGH-2]) and 2 different antibodies against ACTH (primary antibody 1 [AbACTH-1] and primary antibody 2 [AbACTH-2]).RESULTSCells with positive Pit-1 staining were more frequently observed in lesions from patients with acromegaly (acromegaly group) than in lesions from patients with Cushing disease (Cushing group; p < 0.001) and those from patients with NFPA (NFPA group; p < 0.001). The percentage of Tpit-positive cells was higher in the Cushing group than in the acromegaly (p < 0.001) and NFPA (p < 0.001) groups. No difference was detected regarding SF-1 frequency among all groups (p = 0.855). In acromegalic individuals, GH immunostaining levels varied depending on the antibody employed, and only one of the antibodies (AbGH-2) yielded higher values in comparison with the values for NFPA patients (p < 0.001). For all of the antibodies employed, no significant correlations were detected between GH tissue expression and the laboratory data (serum GH vs AbGH-1, p = 0.933; serum GH vs AbGH-2, p = 0.853; serum insulin-like growth factor–1 [IGF-1] vs AbGH-1, p = 0.407; serum IGF-1 vs AbGH-2, p = 0.881). In the Cushing group data, both antibodies showed similar ACTH tissue expression, which was higher than that obtained in the NFPA group (p < 0.001). There were no significant associations between ACTH immunohistochemical findings and ACTH serum levels (serum ACTH vs AbACTH-1, p = 0.651; serum ACTH vs AbACTH-2, p = 0.987). However, ACTH immunostaining evaluated with AbACTH-1 showed a significant correlation with 24-hour urinary cortisol (24-hour cortisol vs AbACTH-1, p = 0.047; 24-hour cortisol vs AbACTH-2, p = 0.071).CONCLUSIONSImmunostaining for Pit-1 and Tpit accurately identified lesions associated with acromegaly and Cushing disease, respectively. Conversely, SF-1 did not differentiate NFPA from lesions of the other two groups. Regarding hormonal tissue detection, results of the current investigation indicate that different antibodies may lead not only to divergent immunohistochemical results but also to lack of correlation with laboratory findings. Finally, PA classification based on transcription factor expression (Pit-1, Tpit, and SF-1), as proposed by the 2017 WHO classification of pituitary tumors, may avoid the limitations of PA classification based solely on digital immunohistochemical detection of hormones.

Adrenal Insufficiency Secondary to Peritoneal Dialysis-Related Peritonitis: A Case Report

Peritoneal dialysis (PD)-related peritonitis is one of the most important factors affecting the long-term success of PD. Adrenal insufficiency is a clinical manifestation of inadequate production of glucocorticoids with accompanying deficiency of mineralocorticoids and adrenal androgens. We present a 58-year-old PD patient who admitted to hospital with fever, abdominal pain, vomiting, and confusion. The patient was treated with cephazolin and ceftazidime after the confirmation of peritonitis. Despite the resolution of peritonitis after 2 weeks with appropriate antibiotic treatment, the patient continued to suffer from vomiting, hypotension, and confusion. After the evaluation of basal serum cortisol and 250 µg ACTH stimulation test, the patient had been diagnosed as adrenal insufficiency and treated with fludrocortisone 0.1 mg/day. Patients remaining vomiting, hypotension, and confusion symptoms were corrected after the fludrocortisone therapy. Following 2 months of successful treatment of adrenal insufficiency, the patient had adherence problem with fludrocortisone for 3–4 weeks. On an outpatient visit, serum ACTH and cortisol levels were normal despite the discontinuation of fludrocortisone and so the patient had been evaluated as partial adrenal insufficiency secondary to PD-related peritonitis. In conclusion, adrenal insufficiency should be kept in mind in PD patients suffering from hypotension and peritonitis.