The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model

Background/aim: In the last years, incidence of carbapenem resistant Acinetobacter baumannii sepsis is increasing with high mortality. However, it is not clear whether this is due to inadequate antimicrobial choice or a more severe clinical course. We aimed to evaluate the inflammation and adrenal involvement in the carbapenem resistant A. baumannii by using experimental mouse model sepsis. Materials and methods: Balb/c female mice were randomly put into control and three sepsis groups ( A. baumannii susceptible to carbapenem-CSAB-, A. baumannii resistant to carbapenem-CRAB-, Escherichia coli). A total of sixty mice were included in this study with each group having 15 mice. Mice were sacrificed 72 h after bacterial inoculation, and blood was taken from each mouse for the assessment of cytokines and corticosterone. Both adrenal glands were dissected; one was used for culture and the other was used for histopathological examination. Bacterial loads of organs were calculated as CFU/g. The histopathological changes, bacterial levels in adrenal and cytokine and corticosterone levels were assessed and compared among the groups. Results: The bacterial level was higher in E. coli (108, 45 ±30, 55 log10 CFU/g) (mean±SD) than other sepsis groups. The lowest level of corticosterone was observed in the E. coli group (p < 0.001). TNF alpha level was highest in the CRAB and E. coli group and this difference was statistically significant than control group (p < 0.05). The IL-6 level in CRAB was significantly higher than the control group (10, 20 pg/mL). The adrenal gland congestion was significantly severe in all the sepsis groups compared to the control. In the group comparison, congestion was significantly more severe in the E. coli group than in CSAB and CRAB groups. Conclusion: Adrenal involvement and inflammatory reactions are seen in E. coli sepsis and in CRAB sepsis. These findings will be focused on in future clinical trials.

Tuberculous Adrenal Abscess Presenting as Adrenal Insufficiency in a 4-Year-Old Boy.

We describe the case of a 4.8-year-old boy who presented with adrenal crisis. The advent of symptoms of adrenal insufficiency in the patient was at around 2 years of age. Congenital causes of adrenal insufficiency were considered over acquired etiologies owing to early onset of symptoms. However, on evaluation, he was found to have left adrenal abscess of tuberculous etiology. The aspirate culture grew multidrug-resistant Mycobacterium tuberculosis complex. He was initiated on glucocorticoid and mineralocorticoid replacement, along with second-line antitubercular therapy. Unique features of our case were early presentation, primary adrenal TB causing adrenal insufficiency, unilateral involvement with adrenal abscess localization, no identifiable extra-adrenal site of tubercular dissemination and resistance to first-line TB drugs.

Mycobacterium Fortuitum infection associated with achalasia.

The association between achalasia and no tuberculosis mycobacterial   lung infection is well described in the literature. MycobactériumFortuitum is often responsible, and the clinical's presentation   is an aspiration pneumonia resistant to usual antibiotic therapy. We report the case of a 15 year-old patient with the history of Allgrove syndrome. The chest imaging showed right lung congestion; the diagnosis was bacteriological and MycobactériumFortuitum resistant to rifampicin, isoniazid, pyrazinamide and ethambutol was isolated. The patient was treated by the association cotrimoxazole, ciprofloxacin and clarithromycin for 12 months and the clinical, radiological and bacteriological outcomes were favorable. To prevent the recurrence the patient benefited from a cardiomyotomy.

Association between gut microbiota and adrenal disease: a two-sample Mendelian randomized study.

Background: Some observational studies and clinical experiments suggest a close association between gut microbiota and metabolic diseases. However, the causal effects of gut microbiota on adrenal diseases, including Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism, remain unclear. Methods: This study conducted a two-sample Mendelian randomization analysis using summary statistics data of gut microbiota from a large-scale genome-wide association study conducted by the MiBioGen Consortium. Summary statistics data for the three adrenal diseases were obtained from the FinnGen study. The study employed Inverse variance weighting, MR-Egger, and MR-PRESSO methods to assess the causal relationship between gut microbiota and these three adrenal diseases. Additionally, a reverse Mendelian randomization analysis was performed for bacteria found to have a causal relationship with these three adrenal diseases in the forward Mendelian randomization analysis. Cochran's Q statistic was used to test for heterogeneity of instrumental variables. Results: The IVW test results demonstrate that class Deltaproteobacteria, Family Desulfovibrionaceae, and Order Desulfovibrionales exhibit protective effects against adrenocortical insufficiency. Conversely, Family Porphyromonadaceae, Genus Lachnoclostridium, and Order MollicutesRF9 are associated with an increased risk of adrenocortical insufficiency. Additionally, Family Acidaminococcaceae confers a certain level of protection against Cushing syndrome. In contrast, Class Methanobacteria, Family Lactobacillaceae, Family Methanobacteriaceae, Genus. Lactobacillus and Order Methanobacteriales are protective against Hyperaldosteronism. Conversely, Genus Parasutterella, Genus Peptococcus, and Genus Veillonella are identified as risk factors for Hyperaldosteronism. Conclusions: This two-sample Mendelian randomization analysis revealed a causal relationship between microbial taxa such as Deltaproteobacteria and Desulfovibrionaceae and Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism. These findings offer new avenues for comprehending the development of adrenal diseases mediated by gut microbiota.

Role of toll-like receptors and inflammation in adrenal gland insufficiency.

Adrenal gland insufficiency - the clinical manifestation of deficient production or action of adrenal steroids - is a life-threatening disorder. Among many factors which can predispose to primary adrenal failure, an autoimmune adrenalitis and infectious agents play a major role. The initial host defense against bacterial infections is executed primarily by the pattern recognition receptors, e.g. Toll-like receptors (TLRs), expressed in cells from the innate immune system. Upon activation, TLRs have been found to regulate various levels of innate and adaptive immunity as well as control tissue inflammation. TLRs are implicated in adrenal cell turnover and steroidogenesis during inflammation. Therefore, TLRs play a crucial role in the activation of adrenal inflammation mediating adrenal gland dysfunction during septicemia.

Bilateral adrenal histoplasmosis presenting as adrenal insufficiency in an immunocompetent host in the Philippines.

Disseminated histoplasmosis, with the adrenal glands as being the only site of demonstrable disease in an immunocompetent adult, is a rare infection leading to adrenal insufficiency. This disease carries high mortality when unrecognised. We describe the first reported case of adrenal histoplasmosis in the Philippines in a 72-year-old immunocompetent, Filipino man who presented with a 3-month history of intermittent flank pain, weight loss and generalised weakness. His imaging demonstrated bilateral adrenal masses on ultrasonography and contrast-enhanced CT scan. The initial impression was adrenal cancer, however, fine-needle aspiration cytology revealed the presence of yeast cells and blood culture grew Histoplasma capsulatum The diagnosis of the case represents a diagnostic challenge in immunocompetent individuals because they manifest with non-specific symptoms. A heightened suspicion is therefore needed to prevent significant morbidity and mortality.

[Bilateral adrenal tuberculosis: about a case]. / Tuberculose surrénalienne bilatérale: à propos d'un cas.

Isolated adrenal tuberculosis accounts for less than 2% of adrenal incidentalomas. This is the most frequent infectious cause of adrenal insufficiencies. We report the case of a 53-year old patient with no previous medical history presenting with adrenal insufficiency with slow progression over six months. Physical examination didn't show any mass or hepatosplenomegaly. Blood pressure was 120/60 mmHg. Laboratory tests didn't show inflammatory syndrome. LDH level was normal. CT scan showed bilateral hypertrophy of the adrenal glands characterized by calcifications. Intradermo tuberculin reaction was positive at 25mm. The analyses to detect Koch's bacillus in the sputum and in the urine were negative. Quantiferon® test was positive. Trial antibacillar treatment was started with clinical improvement and 5kg weight gain in 12 months. Hormonal assays were low.

Synchronous presentation of two rare forms of extrapulmonary tuberculosis.

Tuberculosis (TB) remains one of the leading infectious causes of death throughout the world. Extrapulmonary forms, namely adrenalitis and prostatitis, are rare presentations of TB and pose a difficult diagnostic challenge, given their non-specific manifestations. The authors present a case of a 42-year-old man with long-standing symptoms of fatigue, anorexia, weight loss, nightly fever and sudoresis. He also suffered from sporadic vomiting and episodic hypotension, and had skin hyperpigmentation, as well as frequent urination, perineal discomfort and pain at ejaculation. Laboratory investigation confirmed primary adrenal failure. On CT scan there were two hypodense right adrenal nodules and bilateral lung condensations with a tree-in-bud pattern. Another hypodense nodule was seen in the prostate. TB was diagnosed by isolatingMycobacterium tuberculosisfollowing cultures of bronchoalveolar lavage, bronchial secretions, urine and ejaculate. Antibacillary treatment resolved the infectious lesions but the patient remained on corticosteroid replacement therapy for ongoing adrenal failure.

Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality.

CONTEXT: Adequate adrenal function is pivotal to survive meningococcal sepsis. OBJECTIVES: The objective of the study was to evaluate adrenocortical function in meningococcal disease. DESIGN: This was an observational cohort study. SETTING: The study was conducted at a university-affiliated pediatric intensive care unit. PATIENTS: Sixty children with meningococcal sepsis or septic shock participated in the study. MAIN OUTCOME MEASURES: The differences in adrenal function between nonsurvivors (n = 8), shock survivors (n = 43), and sepsis survivors (n = 9) on pediatric intensive care unit admission were measured. RESULTS: Nonsurvivors had significantly lower median cortisol to ACTH ratio than shock survivors and sepsis survivors. Because cortisol binding globulin and albumin levels did not significantly differ among the groups, bioavailable cortisol levels were also significantly lower in nonsurvivors than sepsis survivors. Nonsurvivors had significantly lower cortisol to 11-deoxycortisol ratios but not lower 11-deoxycortisol to 17-hydroxyprogesterone ratios than survivors. Using multiple regression analysis, decreased cortisol to ACTH ratio was significantly related to higher IL-6 levels and intubation with etomidate (one single bolus), whereas decreased cortisol to 11-deoxycortisol ratio was significantly related only to intubation with etomidate. Aldosterone levels tended to be higher in nonsurvivors than shock survivors, whereas plasma renin activity did not significantly differ. CONCLUSIONS: Our study shows that the most severely ill children with septic shock had signs of adrenal insufficiency. Bioavailable cortisol levels were not more informative on adrenal function than total cortisol levels. Besides disease severity, one single bolus of etomidate during intubation was related to decreased adrenal function and 11beta-hydroxylase activity. Decreased adrenal function was not related to decreased 21-hydroxylase activity. Based on our results, it seems of vital importance to take considerable caution using etomidate and consider combining its administration with glucocorticoids during intubation of children with septic shock.

Adrenal insufficiency occurring during septic shock: incidence, outcome, and relationship to peripheral cytokine levels.

PURPOSE: In patients with septic shock, to (1) determine the incidence of adrenal insufficiency (AI), (2) observe the effects of glucocorticoid therapy on outcome in those with impaired adrenal function, and (3) investigate a possible correlation between adrenal function and peripheral cytokine levels. PATIENTS AND METHODS: Twenty-one patients admitted to the medical and surgical intensive care unit with septic shock and 11 healthy volunteers were studied. Cortisol, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels were measured before and after infusion of low (1 microgram) and standard doses (250 micrograms) of adrenocorticotropic hormone (ACTH) within 24 hours of the diagnosis of septic shock. Patients with subnormal adrenal responses to ACTH were treated with stress doses of steroids. Hormone, cytokine, and survival data in patients with normal response were compared to those with subnormal adrenal function. RESULTS: Five patients (23.8%) exhibited AI by ACTH stimulation testing. Three of them received steroid supplementation with rapid improvement in hemodynamic parameters. Autopsies of 2 patients with AI revealed intact adrenal cortices. Sixteen patients had adequate adrenal responses (AAR) to the standard-dose ACTH infusion. TNF-alpha levels were inversely correlated with mean arterial pressure (MAP) (r = -.52, P = 0.038) in AAR but not AI. There was no difference in mean peripheral TNF-alpha levels between AAR and AI. There was no correlation between TNF-alpha levels and mortality or adrenal function in those with septic shock. A trend toward lower IL-6 levels in AI suggests a link between reduced IL-6 levels and understimulation of the pituitary-adrenal axis in this group. Mortality in patients with AI was 80% at 4 weeks as compared with 43.8% in the group with normal adrenal response. CONCLUSIONS: Adrenal hyporesponsiveness is a feature of septic shock in some patients. Its etiology is probably complex. Steroid supplementation appeared to improve short-term survival when AI occurred, although these patients' overall mortality was worse than that of patients with septic shock and AAR. The standard-dose (250 micrograms) rapid ACTH infusion test was adequate for detecting AI. Adrenal insufficiency should be suspected in patients with septic shock who do not respond to conventional treatment. Performing the ACTH infusion test and initiating a trial of stress doses of glucocorticoids pending the results is a reasonable strategy in this situation.

Acute adrenal crisis together with unilateral adrenal mass caused by isolated tuberculosis of adrenal gland.

OBJECTIVE: To describe a patient admitted with acute adrenocortical failure and a right adrenal mass without evidence of tuberculosis, who was ultimately diagnosed with isolated adrenal tuberculosis after postoperative histopathologic evaluation. METHODS: A case report is presented, with clinical, laboratory, and imaging findings. We also discuss potential factors that may complicate the diagnosis of tuberculosis. RESULTS: A 61-year-old man was admitted with symptoms and signs of acute adrenal crisis. The patient had an erythrocyte sedimentation rate of 30 mm in 1 hour, a negative tuberculin skin test, a 6-cm right adrenal mass, and left adrenal nodularity in conjunction with normal findings on a computed tomographic scan of the chest. He recovered dramatically after intravenous corticosteroid treatment. Investigation, including acid-fast staining and cultures for tuberculosis of all available specimens, gastroduodenoscopy and rectosigmoidoscopy, intestinal x-ray imaging, and autoantibody studies, did not disclose the diagnosis. Subsequently, bilateral adrenalectomy revealed isolated tuberculosis of the adrenal glands on histopathologic evaluation. Quadruple antituberculous therapy was initiated, and continued follow-up of the patient is scheduled. CONCLUSION: Our case indicates that acute or chronic adrenocortical failure can occur as a result of tuberculosis of the adrenal gland, despite the absence of clinical and laboratory evidence of tuberculosis.

Addisonian crisis and tuberculous epididymo-orchitis.

OBJECTIVE: To describe a case of acute primary adrenal insufficiency in which tuberculosis was subsequently detected as the etiologic factor when the patient presented with tuberculous epididymo-orchitis. METHODS: A case of acute primary adrenal insufficiency associated with bilaterally enlarged adrenal glands is reported, along with the subsequent finding of a scrotal mass diagnosed as tuberculous epididymo-orchitis. Diagnosis, adrenal function, and results of imaging studies after institution of antituberculous treatment are discussed. RESULTS: A 41-year-old Egyptian man, who had immigrated to the United States 5 years previously, had acute psychosis and addisonian crisis. A substantially increased early morning level of plasma adrenocorticotropic hormone and a low level of serum cortisol confirmed the diagnosis of primary adrenal insufficiency. Both adrenal glands were enlarged but without calcification on computed tomography. A previous bacille Calmette-Guérin vaccination complicated the interpretation of a positive tuberculin skin test result. Both lungs were clear on chest radiography and computed tomography. Seven months later, the patient had a left scrotal mass and underwent radical orchiectomy. Examination of the pathology specimen showed caseous granulomatous inflammation and necrosis, and acid-fast bacilli were identified. Culture was positive for Mycobacterium tuberculosis. CONCLUSION: In a patient from a country where tuberculosis is endemic, tuberculosis should be considered in the differential diagnosis when primary adrenal insufficiency is detected, especially in association with enlarged or calcified adrenal glands. Extra-adrenal tuberculous involvement should be actively sought because it may provide indirect microbiologic or histologic clues. Other than the lungs, special attention should be paid to the genitourinary system.

[The significance of corticosteroid insufficiency in the mechanisms of toxicosis in experimental listeriosis]. / Znachenie kortikosteroidnoi nedostatochnosti v mekhanizmakh toksikoza pri éksperimental'nom listerioze.

The infection of mice with Listeria led, in case of the development of an acute generalized form of the disease, to the sharp decrease of the content of ascorbic acid and to the nearly complete delipidization of the glomerular zone of the adrenal cortex, which was indicative of the development of relative adrenal insufficiency. The most pronounced histomorphological and histochemical changes occurred simultaneously with the maximum accumulation of Listeria in the adrenal glands. The administration of hydrocortisone at the period of the development of acute infection produced a temporary decrease in the manifestations of toxicosis. The maximum protective effect was achieved by combined glucocorticoid and antibiotic therapy.