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      Systemic effects of intratympanic dexamethasone therapy

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          Abstract

          Objective

          The study aimed to assess the possible systemic effects of intratympanic dexamethasone (IT-Dex) on the hypothalamic–pituitary–adrenal (HPA) axis, inflammation, and bone metabolism.

          Design

          A prospective cohort study including 30 adult patients of a tertiary referral ENT clinic treated with 9.6 mg IT-Dex over a period of 10 days was carried out.

          Methods

          Effects on plasma and salivary cortisol concentrations (basal and after low-dose (1 μg) ACTH stimulation), peripheral white blood cell count, and biomarkers for bone turnover were measured before (day 0) and after IT-Dex (day 16). Additional measurements for bone turnover were performed 5 months after therapy. Clinical information and medication with possible dexamethasone interaction were recorded.

          Results

          IT-Dex was well tolerated, and no effect was detected on the HPA axis (stimulated plasma and salivary cortisol concentration on day 0: 758±184 and 44.5±22.0 nmol/l; day 16: 718±154 and 39.8±12.4 nmol/l; P=0.58 and 0.24 respectively). Concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP) did not differ after dexamethasone (OC on days 0 and 16 respectively: 24.1±10.5 and 23.6±8.8 μg/l; BSAP on day 0, 16, and after 5 months respectively: 11.5±4.2, 10.3±3.4, and 12.6±5.06 μg/l); similarly, there was no difference in the peripheral white blood cell count (5.7×10 12/l and 6.1×10 12/l on days 0 and 16 respectively).

          Conclusions

          IT-Dex therapy did not interfere with endogenous cortisol secretion or bone metabolism.

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          Most cited references21

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          Glucocorticoid-induced osteonecrosis.

          Awareness of the need for prevention of glucocorticoid-induced fractures is growing, but glucocorticoid administration is often overlooked as the most common cause of nontraumatic osteonecrosis. Glucocorticoid-induced osteonecrosis develops in 9-40% of patients receiving long-term therapy although it may also occur with short-term exposure to high doses, after intra-articular injection, and without glucocorticoid-induced osteoporosis. The name, osteonecrosis, is misleading because the primary histopathological lesion is osteocyte apoptosis. Apoptotic osteocytes persist because they are anatomically unavailable for phagocytosis and, with glucocorticoid excess, decreased bone remodeling retards their replacement. Glucocorticoid-induced osteocyte apoptosis, a cumulative and unrepairable defect, uniquely disrupts the mechanosensory function of the osteocyte-lacunar-canalicular system and thus starts the inexorable sequence of events leading to collapse of the femoral head. Current evidence indicates that bisphosphonates may rapidly reduce pain, increase ambulation, and delay joint collapse in patients with osteonecrosis.
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            Oral vs intratympanic corticosteroid therapy for idiopathic sudden sensorineural hearing loss: a randomized trial.

            Idiopathic sudden sensorineural hearing loss has been treated with oral corticosteroids for more than 30 years. Recently, many patients' symptoms have been managed with intratympanic steroid therapy. No satisfactory comparative effectiveness study to support this practice exists. To compare the effectiveness of oral vs intratympanic steroid to treat sudden sensorineural hearing loss. Prospective, randomized, noninferiority trial involving 250 patients with unilateral sensorineural hearing loss presenting within 14 days of onset of 50 dB or higher of pure tone average (PTA) hearing threshold. The study was conducted from December 2004 through October 2009 at 16 academic community-based otology practices. Participants were followed up for 6 months. One hundred twenty-one patients received either 60 mg/d of oral prednisone for 14 days with a 5-day taper and 129 patients received 4 doses over 14 days of 40 mg/mL of methylprednisolone injected into the middle ear. Primary end point was change in hearing at 2 months after treatment. Noninferiority was defined as less than a 10-dB difference in hearing outcome between treatments. In the oral prednisone group, PTA improved by 30.7 dB compared with a 28.7-dB improvement in the intratympanic treatment group. Mean pure tone average at 2 months was 56.0 for the oral steroid treatment group and 57.6 dB for the intratympanic treatment group. Recovery of hearing on oral treatment at 2 months by intention-to-treat analysis was 2.0 dB greater than intratympanic treatment (95.21% upper confidence interval, 6.6 dB). Per-protocol analysis confirmed the intention-to-treat result. Thus, the hypothesis of inferiority of intratympanic methylprednisolone to oral prednisone for primary treatment of sudden sensorineural hearing loss was rejected. Among patients with idiopathic sudden sensorineural hearing loss, hearing level 2 months after treatment showed that intratympanic treatment was not inferior to oral prednisone treatment. clinicaltrials.gov Identifier: NCT00097448.
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              Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment.

              Suppression of the adrenal response is an unpredictable consequence of glucocorticoid treatment. To investigate the kinetics of the adrenal response after short-term, high-dose glucocorticoid treatment, we measured the adrenal response to the low-dose (1 microg) corticotropin stimulation test. We studied 75 patients who received the equivalent of at least 25 mg prednisone daily for between 5 days and 30 days. After discontinuation of glucocorticoid treatment, 1 microg corticotropin was administered intravenously, and stimulated plasma cortisol concentrations were measured 30 min later. In patients with a suppressed response to 1 microg corticotropin, the test was repeated until stimulated plasma cortisol concentrations reached the normal range. The adrenal response to 1 microg corticotropin was suppressed in 34 patients and normal in 41. Subsequent low-dose corticotropin tests showed a steady recovery of the adrenal response within 14 days. In two patients, the adrenal response remained suppressed for several months. There was no correlation between plasma cortisol concentrations and the duration or dose of glucocorticoid treatment. Suppression of the adrenal response is common after short-term, high-dose glucocorticoid treatment. The low-dose corticotropin test is a sensitive and simple test to assess the adrenal response after such treatment.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                14 August 2014
                01 September 2014
                : 3
                : 3
                : 127-131
                Affiliations
                [1 ]Department of Otorhinolaryngology Head and Neck Surgery
                [2 ]Clinic of Endocrinology Diabetology and Clinical Nutrition, Department of Internal Medicine, Kantonsspital Luzern, CH-6000 Luzern 16Switzerland
                Author notes
                Correspondence should be addressed to E Novoa Email: eva.novoa@ 123456gmail.com
                Article
                EC140076
                10.1530/EC-14-0076
                4134486
                25055818
                64963a41-ecb6-4e9d-85cd-f9e566232170
                © 2014 The authors

                This work is licensed under a Creative Commons Attribution 3.0 Unported License

                History
                : 15 July 2014
                : 21 July 2014
                Categories
                Research

                intratympanic,dexamethasone,acute hearing loss,ménière's disease,cortisol,osteocalcin

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