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.

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.

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.

[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.

Insuficiencia suprarrenal iatrogénica por la interacción entre ritonavir y fluticasona inhalada. Revisión de la literatura / Iatrogenic adrenal insufficiency secondary to an interaction between ritonavir and inhaled fluticasone. A review of the literature

INTRODUCCIÓN: El tratamiento antirretroviral de alta eficacia ha incrementado la expectativa de vida en los pacientes con infección por el virus de inmunodeficiencia humana (VIH), lo que ha traído consigo un aumento de comorbilidades propias del envejecimiento de la población, como es el caso de la enfermedad pulmonar obstructiva crónica (EPOC). Todo esto conlleva la necesidad de utilizar un mayor número de medicamentos y un aumento en el riesgo de interacciones farmacológicas con los antirretrovirales, especialmente con los inhibidores de la proteasa. MÉTODOS: Describimos un caso de insuficiencia suprarrenal iatrogénica por interacción entre ritonavir y fluticasona inhalada en un paciente diagnosticado de infección por VIH y EPOC. Posteriormente realizamos una revisión de casos clínicos publicados en adultos en la literatura médica (Medline) hasta diciembre del 2012. RESULTADOS: En el periodo estudiado se identificaron 34 casos, con una media de edad de 48 años. La dosis promedio de ritonavir fue de 187 mg/día, mientras que la de fluticasona fue de 866 μg/día. El promedio de tiempo de la interacción entre el ritonavir y la fluticasona fue de 8 meses. En el 85% de los casos se retiró la fluticasona una vez hecho el diagnóstico de insuficiencia suprarrenal/síndrome de Cushing. El 90% de los pacientes presentó una resolución completa del cuadro clínico con la modificación del tratamiento. CONCLUSIÓN: En los pacientes en tratamiento antirretroviral con un inhibidor de la proteasa potenciado con ritonavir en los que sea preciso el uso de corticoides inhalados, la beclometasona sería la mejor opción terapéutica

INTRODUCTION: Highly effective antiretroviral treatment has improved the life expectancy of human immunodeficiency virus (HIV) infected patients, but has led to an increase in the comorbidities related to aging, such as the chronic obstructive pulmonary disease (COPD). All this implies the need for a greater number of drugs and an increasing risk of drugs interactions with antiretroviral treatment, particularly protease inhibitors. METHODS: We report a case of iatrogenic adrenal insufficiency interaction secondary to ritonavir and inhaled fluticasone in an HIV-infected patient with COPD. A review was made of the cases reported in adults in the medical literature (Medline) up to December 2012. RESULTS: A total of 34 cases were reported. The mean age was 48 years. The mean dose of ritonavir was 187 mg/day, while the fluticasone dose was 866 μg/day. The average time of the interaction between ritonavir and fluticasone was 8 months. In 85% of cases fluticasone was discontinued at the time of diagnosis of adrenal insufficiency/Cushing syndrome. Almost all (90%) patients had a complete resolution of the symptoms after changing the treatment. CONCLUSION: HIV-infected patients on antiretroviral therapy with protease inhibitor boosted with ritonavir which requires the use of inhaled corticosteroids, beclomethasone would be the best treatment option

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.

Extrapontine myelinolysis as presenting manifestation of adrenal failure: a case report.

BACKGROUND: Hyponatremia is a fairly common metabolic disorder. Hyponatremic myelinolysis is a relatively rare, life threatening complication with poorly understood pathophysiology, varied clinical manifestations and uncertain treatment. This case report highlights the range of clinical and imaging phenomena associated with hyponatremic myelinolysis. METHODS: Case report. RESULT: A middle aged lady presented with an acute delirious state, hypotension and severe hyponatremia on a background of skin hyper-pigmentation and weight loss. Her clinical course evolved to an akinetic-rigid state and later to parkinsonism. Extensive investigations for recognizing a primary neurologic disorder, including brain MRI and CSF analysis were normal, though she had disseminated miliary tuberculosis involving multiple organs. Brain MRI changes characteristic of extrapontine myelinolysis appeared two weeks after the onset of symptoms. The patient recovered completely over several weeks. CONCLUSION: This case of hyponatremic extrapontine myelinolysis occurred as the presenting manifestation of adrenal failure secondary to disseminated tuberculosis. Extraponine myelinolysis is difficult to diagnose in the context of delayed brain MRI changes and can have a favorable outcome with modern management.

Identification of Paracoccidioides brasiliensis in adrenal glands biopsies of two patients with paracoccidioidomycosis and adrenal insufficiency.

The authors report two cases of adrenal insufficiency secondary to infiltration of the adrenal glands by Paracoccidioides brasiliensis. The first patient had been treated for a chronic multifocal form of paracoccidiodomycosis 11 years ago. The diagnosis of the mycosis was done simultaneous with that of the adrenal insufficiency in the second patient. In both patients the diagnosis was done by direct visualization of fungus in adrenal biopsies. They were treated with hormonal supplements and itraconazol by 12 and six months, without relapses during the follow-up period.

Identification of Paracoccidioides brasiliensis in adrenal glands biopsies of two patients with paracoccidioidomycosis and adrenal insufficiency / Identificação do Paracoccidioides brasiliensis nas amostras de glândulas adrenais de dois doentes com paracoccidioidomicose e insuficiência adrenal

The authors report two cases of adrenal insufficiency secondary to infiltration of the adrenal glands by Paracoccidioides brasiliensis. The first patient had been treated for a chronic multifocal form of paracoccidiodomycosis 11 years ago. The diagnosis of the mycosis was done simultaneous with that of the adrenal insufficiency in the second patient. In both patients the diagnosis was done by direct visualization of fungus in adrenal biopsies. They were treated with hormonal supplements and itraconazol by 12 and six months, without relapses during the follow-up period.

Os autores apresentam dois casos de insuficiência supra-renal secundária à infiltração das adrenais pelo Paracoccidioides brasiliensis. O primeiro paciente tinha sido tratado de paracoccidioidomicose crônica multifocal 11 anos atrás. No segundo paciente, o diagnóstico da micose foi feito de forma simultânea com o da insuficiência adrenal. Em ambos os pacientes, o diagnóstico foi feito pela visualização direta do fungo nas biopsias adrenais. Eles foram tratados com suplementos hormonais com itraconazol por seis a 12 meses, sem recaídas durante o período de acompanhamento.

Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization.

BACKGROUND: Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia. OBJECTIVES: The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization. DESIGN AND SETTING: An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan. PATIENTS: Thirty-one adult CAP patients who required hospitalization were enrolled. MEASUREMENTS AND RESULTS: Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses. CONCLUSIONS: In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy.