Tetracosactide 250micrograms/1ml solution for injection ampoules

Abstract Objectives Rotator cuff tendinitis (RCT) is a tendon inflammation often following subacromial impingement syndrome. One of the non-surgical management modalities for RCT is subacromial injection of corticosteroids. Some studies have claimed a correlation between ACTH (Adrenocorticotropic Hormone) deficiency and rotator cuff lesions; hence, intramuscular ACTH analogue injection has been recommended as an option. This research aimed to compare the effectiveness of these two treatment methods. Methods We conducted a study with 86 patients suffering from RCT. The patients were randomly divided into two groups of 43; one group received a subacromial injection of 40 mg of triamcinolone acetonide, while the other group received 1 mg of intramuscular tetracosactide injection. We recorded the Constant–Murley (CM) and visual analogue scale (VAS) scores for each patient before and 4 weeks after injections to measure pain acuity and joint functionality. Later, we compared and analysed the two scores in each group. Results Based on the statistical analysis, the mean ages of the participants in the triamcinolone and tetracosactide groups were 53.21 ± 11.37 and 54.56 ± 11.98, respectively. Both groups demonstrated an improvement in VAS for pain and CM scores (P < 0.05). However, the VAS for pain score decreased, and the CM score increased more significantly in the triamcinolone group than in the tetracosactide group (P < 0.05). Conclusion Although both treatment methods exhibit promise for pain relief, subacromial injection of triamcinolone appears more efficacious than intramuscular injection of tetracosactide in patients with RCT, based on a 4-week follow-up. Trial registration Iranian Registry of Clinical Trials, https://irct.behdasht.gov.ir, IRCT20240110060673N1.

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INTRODUCTION: Cortisol is an essential stress hormone and failure of its production, known as adrenal insufficiency (AI), is associated with significant mortality due to adrenal crisis. The Short Synacthen Test (SST) is the current diagnostic test of choice for AI, but it is both invasive and resource intensive. Globally, there is an unmet need for a non-invasive, cost-effective test. A novel formulation, Nasacthin, has been developed, which can be delivered intranasally, with the resultant glucocorticoid levels measured in saliva instead of blood. The Salivary Test of Adrenal Response to Liquid Intranasal Tetracosactide (STARLIT-2) study aims to clinically validate the Nasacthin test in healthy volunteers. METHODS AND ANALYSIS: STARLIT-2 is a randomised, placebo-controlled, double-blinded, four-way crossover trial. 32 healthy adults and children will be randomised to receive each of four study drugs (Synacthen, Nasacthin and their respective placebos) over four study visits (one per visit). Paired blood and saliva samples will be collected from participants at baseline, and then at 30, 60, 90 and 120 min after drug administration. Additional salivary samples will be collected at 180, 240, 360 and 480 min after drug administration. The primary outcome measures are to compare the mean serum cortisol at 30 min after Synacthen or Nasacthin dose, with a view to determine non-inferiority; and to compare the mean change from baseline in serum cortisol at 30 min after active and placebo doses of both Synacthen and Nasacthin, aiming to demonstrate superiority of active over placebo. In addition, the proportion of participants for which Nasacthin produces a rise above a preset serum cortisol threshold at 30 min will be determined, with the negative per cent agreement with the SST calculated using the SST as the reference standard. ETHICS AND DISSEMINATION: The study and its amendments have been reviewed and approved by South Central-Hampshire A Research Ethics Committee. Results will be disseminated in peer-reviewed journals and conference presentations, and feedback to trial participants will be facilitated following consultation with patient and public involvement and engagement groups. TRIAL REGISTRATION NUMBER: ISRCTN62724177.

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INTRODUCTION: Inadequate production of the essential stress hormone, cortisol, results in adrenal insufficiency (AI), which is associated with significant morbidity and mortality. The current standard diagnostic test for AI is the Short Synacthen Test (SST), but this is both invasive and resource-intensive, involving cannulation and blood sampling. A novel formulation, Nasacthin, has been developed in which the same Active Pharmaceutical Ingredient can be delivered intranasally, with the resultant glucocorticoid levels either measured in serum, or in saliva samples to render the test non-invasive, thus creating a potentially more cost-effective test. The Salivary Test of Adrenal Response to Liquid Intranasal Tetracosactide (STARLIT-3) study aims to determine the diagnostic utility of the test in patients with AI. METHODS AND ANALYSIS: STARLIT-3 is a randomised 2-way crossover trial which aims to collect data from 32 AI patients allocated to receive both Synacthen and Nasacthin in a random order across two study visits. Paired blood and saliva samples will be collected from participants at baseline, and then at 30 and 60 min after drug administration. Glucocorticoid levels in study samples will be quantified with the aim to determine whether the Nasacthin test is able to correctly diagnose patients with AI by estimating the positive percent agreement with the standard SST using serum cortisol at 30 and 60 min. Data on any reported harms and on the acceptability, usability and tolerability of the Nasacthin test will also be collected. ETHICS AND DISSEMINATION: The study and subsequent amendments have been reviewed and approved by South Central-Hampshire A Research Ethics Committee. Results will be published in peer-reviewed journals and presented at national and international conferences. Plans for dissemination of results to trial participants will be developed in collaboration with patient and public involvement and engagement groups. TRIAL REGISTRATION NUMBER: ISRCTN26461337.

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BACKGROUND: Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction. This was a sensitivity analysis of a drug (tetracosactide; TCS10) targeting melanocortin receptors (MCRs) in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders. METHODS: Sensitivity analysis was based on a randomized, two-arm, multicenter, double-blind, controlled trial. The Naïve Bayes classifier was performed by density-based sensitivity index for principal strata as proportional hazard model of 30-day surgical risk mortality according to European System for Cardiac Operative Risk Evaluation inputs-outputs in 100 consecutive cases (from August to September 2013 from Emilia Romagna region, Italy). Patients included an agent-based TCS10 group (10 mg, single intravenous bolus before surgery; n = 56) and control group (n = 44) and the association with cytokines, lactate, and bleeding-blood transfusion episodes with the prior-risk log-odds for mortality rate in time-to-event was analyzed. RESULTS: Thirty-day mortality was significantly improved in the TCS10 group vs. control group (0 vs. 8 deaths, P < 0.0001). Baseline levels of interleukin (IL)-6, IL-10, and lactate were associated with bleeding episodes, independent of TCS10 treatment [odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.39-2.79; OR = 1.53, 95%CI 1.17-2.12; and OR = 2.92, 95%CI 1.40-6.66, respectively], while baseline level of Fms-like tyrosine kinase 3 ligand (Flt3L) was associated with lower bleeding rates in TCS10-treated patients (OR = 0.31, 95%CI 0.11-0.90, P = 0.03). For every 8 TCS10-treated patients, 1 bleeding case was avoided. Blood transfusion episodes were significantly reduced in the TCS10 group compared to the control group (OR = 0.32, 95%CI 0.14-0.73, P = 0.01). For every 4 TCS10-treated patients, 1 transfusion case was avoided. CONCLUSIONS: Sensitivity index underlines the quality target product profile of TCS10 in the runway of emergency casualty care. To introduce the technology readiness level in real-life critically ill patients, further large-scale studies are required. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT Number: 2007-006445-41 ).

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Hypotension is a common complication during hemodialysis that develops due to high ultrafiltration rate and sometimes requires intravenous fluid replacement. Intradialytic hypotension may reduce the effectiveness of dialysis and contributes to hemodialysis-related morbidity and mortality. Adrenal insufficiency is one of the causes of hypotension in the community. Our case was diagnosed with end-stage renal failure and was undergoing routine hemodialysis with a central venous catheter 3 days a week. Upon the patient's hypotension attacks during the dialysis sessions and hypoglycemia attacks in the follow-ups, the morning cortisol was 6.2 μg/dL. Adrenocorticotropic hormone was 39 pg/mL, and testosterone was 0.0442 ng/mL. Adrenocorticotropic hormone stimulation test was performed on the patient with 250 mcg tetracosactide. The patient did not show adequate cortisol response, was detected to have partial empty sella on pituitary magnetic resonance imaging, and was diagnosed with secondary adrenal insufficiency, and then the hemodialysis hypotension improved with prednisolone treatment. We present a case of adrenal insufficiency, which is a rare cause of hypotension in patients on routine hemodialysis.

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Serum cortisol levels vary according to the daily circadian cycle, with peak levels seen in the morning. There is evidence in ambulatory patients that a morning cortisol level can predict an adequate cortisol response to Synacthen (tetracosactide) stimulation. The aim of this study is to determine the utility of baseline analysis of the serum cortisol levels in the morning “baseline morning cortisol”, determined using a newer immunoassay, in the screening for adrenal insufficiency amongst non-critically ill hospital inpatients. This is a retrospective cross-sectional cohort study. 64 adult inpatients had undergone a short Synacthen test (SST) (measurement of serum cortisol levels 30 and 60 min after administration of tetracosactide) during the study period. 17 patients returned an abnormal SST result. The measured level of cortisol in the morning correlated to both the 30 min and 60 min stimulated cortisol values (r = 0.612, p < 0.001 and r = 0.639, p < 0.001). After inspecting the receiver operating characteristic curve, a cortisol concentration of 200nmmol/L measured in the morning was selected as a threshold for predicting the SST result. Using this cut off, sensitivity for predicting a normal SST was 100 %, specificity 56 %, positive predictive value 45 % and negative predictive value 100 %. A morning cortisol measurement, determined using a newer immunoassay, is sufficient in most cases to screen for adrenal insufficiency amongst non-critically ill hospital inpatients. Use of clinical judgement in conjunction with single morning cortisol measurement is likely to reduce the need for SST testing amongst inpatients.

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Childhood hypoglycaemia results from impairment or defects in glucose homeostasis and has a blood glucose (BG) operational threshold of 60 mg/dL (&amp;lt;3.3 mmol/L) as below this level, neurological symptoms occur, and if the BG falls below 50 mg/dL (2.8 mmol/L), it is highly likely to cause long-term neurological consequences. A 38-month-old previously healthy boy presented with hypoglycaemic seizures (BG: 30 mg/dL [1.7 mmol/L]) after a brief period of being unwell. The sepsis screen was normal. Hypoglycaemia screen detected a low cortisol level (28 nmol/L [83–555]). This was also associated with a low thyroid-stimulating-hormone (0.768 mIU/mL [0.5–5.5]) and a low-normal T4 (5.57 μg/dL [5–12]). Hydrocortisone and levothyroxine replacement was started. Four weeks from the time of discharge, the short synacthen test (SST; generic name: tetracosactide acetate) for adrenal function revealed a low stimulated cortisol (2/1.51/1.52 nmol/L at 0, 30, and 60 min, respectively, post synacthen [normal range: 83–550; peak &amp;gt;420 μg/dL]) and low basal adrenocorticotropic hormone (4.6 pg/mL [10–60]). A rare diagnosis of isolated secondary adrenocortical insufficiency was made, and the neuroimaging demonstrated a reduced pituitary height (3 mm). Three months later, levothyroxine was tapered and omitted as the child was euthyroid, but the SST showed a similar flat response to the synacthen. The genetic testing demonstrated a pathogenic heterozygous mutation in the nuclear factor kappa B subunit 2 (NFKB2) gene responsive for common variable immunodeficiency (CVID), and this entity has been described as deficient anterior pituitary hormone with CVID syndrome (DAVID syndrome). The immunoglobulin profile showed a decrease in three types of immunoglobulin (IgM, IgG, and IgE), meeting the diagnostic criteria for CVID. Till date, less than 35 cases are reported worldwide, and of which, less than 5 of them presented with adrenal insufficiency prior to immunodeficiency, making this case rare and teaching us a lesson to think beyond the usual causes of hypoglycaemia.

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Introduction: Glucocorticoid-induced adrenal insufficiency (AI) is underestimated and under-reported in children with nephrotic syndrome (NS). This study aimed to estimate the prevalence of AI in children with steroid-sensitive NS, defined by serum cortisol level <18 mcg/dL 30 minutes after low-dose adrenocorticotropin stimulation test (LDST) and/or baseline (8 AM) serum cortisol level <5 mcg/dL, 4-12 weeks after stopping steroid therapy. Methods: In this cross-sectional study, 73 children with steroid-sensitive NS, in remission and off steroids for 4-12 weeks, were enrolled from the Paediatrics Department at a tertiary care hospital. Baseline (8 AM) serum cortisol was measured, and LDST was done using 1 mcg tetracosactide acetate intravenously. The proportion of AI was calculated. Clinical features of AI and steroid toxicity were noted, and the association between the two was analysed. Results: Out of 73 children (45 males), 52 (71.2%, 95% confidence interval: 59.3%-80.9%) had AI as defined by serum cortisol level <18 mcg/dL 30 min after LDST and/or baseline (8 AM) serum cortisol level <5 mcg/dL at 4-12 weeks after completion of steroid therapy. A strong positive correlation was observed between 8 AM baseline serum cortisol levels and post-LDST serum cortisol levels. Children exhibiting features of steroid toxicity, such as cushingoid facies, had 4.96 times higher odds of having AI. Conclusion: There remains a high risk of AI even 4-12 weeks after completion of alternate-day steroid therapy in children with NS. Clinical features of steroid toxicity may serve as useful predictors of AI.

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Abstract West syndrome is an epileptic encephalopathy for which combination therapies with adrenocorticotropic hormone and vigabatrin have emerged as new treatment options. To evaluate the clinical and electroencephalographic remission rates, tolerability, and relapse rates in patients with West syndrome who failed primary treatment and underwent sequential therapy with vigabatrin and adrenocorticotropic hormone. We included 39 patients with West syndrome from 2 specialized centers, aged 2 to 120 months. The patients were treated with intramuscular tetracosactide depot added to vigabatrin and were prospectively followed up for ≥ 1 year. The outcomes were clinical, and electroencephalographic remission rates at 7 and 30 days and 1 year following combined therapy initiation, progression to other epilepsy types, therapy tolerability, and relapse rates were recorded. Of the original sample, 71% of the subjects were boys, and 87% had a known etiology. The clinical and electroencephalographic remission rates were 46.1%, 94.8% (p = 0.001), and 74.1% (p = 0.01) at 7 and 30 days, and 1 year after the initiation of combined therapy, respectively. At the 1-year follow-up, adverse effects were observed in 86.0% and the relapse rate was 21.6%. After a median follow-up of 21 months, 73.6% of the patients developed epilepsy. Combined therapy demonstrated a favorable efficacy profile in achieving clinical and electroencephalographic remission but was associated with significant seizure relapse rates in the medium term. Thus, it represents a feasible option for patients in whom initial treatment has failed.

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