High-dose Hydrocortisone Research Articles

Autosomal Recessive Renal Tubular Dysgenesis Caused by a Founder Mutation of Angiotensinogen

IntroductionAutosomal recessive renal tubular dysgenesis (ARRTD) caused by inactivation mutations in AGT, REN, ACE, and AGTR is a very rare but fatal disorder with an unknown prevalence.MethodsWe report 6 Taiwanese individuals with ARRTD from 6 unrelated families diagnosed by renal histology. Clinical features, outcome, and prevalence of carrier heterozygosity were examined.ResultsAll patients exhibited antenatal oligohydramnios, postnatal anuria, pulmonary hypoplasia, and profound hypotension refractory to interventions. Angiotensinogen (AGT) protein levels were diminished in the liver, along with reduced serum AGT, angiotensin I (Ang I) and angiotensin II (Ang II) levels. Neonatal demise occurred in all but 1 case. All individuals carried the same homozygous E3_E4 del:2870bp deletion+9bp insertion in AGT, which led to a truncated protein (1-292 amino acid). The allelic frequency of this heterozygous AGT mutation was approximately 1.2% (6/500), suggesting that ARRTD may not be exceedingly rare in Taiwan. This mutation results in skipping of exons encoding the serpin domain of AGT, which is important for renin interaction and the generation of truncated protein. In silico modeling revealed a diminished interaction between mutant AGT and renin. One patient survived after responding to high-dose hydrocortisone therapy, with resolution of profound hypotension, accompanied by an increase in serum AGT, Ang I, and Ang II levels.ConclusionThis AGT mutation may lead to the diminished interaction with renin and decreased Ang I and Ang II generation. Hydrocortisone may potentially rescue cases of ARRTD caused by this truncated AGT.

SUN-511 Thyroid Storm Caused by Subacute Thyroiditis in a Patient with Methicillin-Resistant Staphylococcus Aureus Septicemia

Introduction:Thyroid storm is a rare disorder with high mortality risk. It is often precipitated by an acute event in a patient with longstanding untreated hyperthyroidism. However, thyroid storm is rarely reported as a result of subacute thyroiditis (SAT). To the best of our knowledge, there are only three documented cases of thyroid storm caused by SAT. Herein we report the first patient with thyroid storm caused by SAT associated with methicillin-resistant Staphylococcus aureus (MRSA) septicemia and intravenous drug abuse (IVDA).Case:A 19-year old Caucasian woman with a history of IVDA presented with right upper extremity abscess. Symptoms included confusion, agitation, fever, chills, generalized pain, malaise, nausea, and vomiting. Heart rate was over 140, and she was found to have fever and leukocytosis. She was admitted with severe sepsis and acute encephalopathy. On exam, she had a diffusely enlarged and exquisitely tender thyroid gland without discrete nodules or bruit. Thyroid tests were consistent with primary thyrotoxicosis (TSH 0.026 IU/mL, free T3 16.90 pg/mL, and free T4 > 6.99 ng/dL). Burch-Wartofsky score was 75, highly suggestive of thyroid storm. In addition to treating her sepsis, the patient was started on a beta blocker, high dose hydrocortisone, and methimazole. Thyroid ultrasound showed a diffusely enlarged heterogeneous thyroid gland with decreased flow on color Doppler. Upon improvement, the patient admitted to symptoms of anterior neck pain, heat intolerance, palpitations, excessive sweating, and anxiety for two days prior to presentation. Blood cultures later grew MRSA. Methimazole was discontinued when the thyrotropin-receptor antibody result came back negative. The patient continued to improve clinically. Her thyroid tenderness improved, and her free T4 and T3 decreased over a 3-week period. Steroids were tapered off.Discussion:SAT usually causes mild to moderate thyrotoxicosis. It is unusual for SAT to cause thyroid storm. Identifying such a diagnosis in a patient with sepsis is complex. In a septic patient, it is crucial to obtain detailed history, perform a comprehensive physical exam (including neck exam), and have a high level of clinical suspicion for thyroid storm in order to reach the diagnosis early and institute appropriate interventions. Establishing the underlying etiology of the thyrotoxicosis would have long term implications regarding prognosis and treatment.

AN UNUSUAL CAUSE OF ENCEPHALOPATHY: STEROID RESPONSIVE ENCEPHALOPATHY ASSOCIATED WITH AUTOIMMUNE THYROIDITIS (SREAT)

SESSION TITLE: Critical Care 4 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: SREAT is an autoimmune disease associated with anti-thyroid antibodies. Its features mimic the fatal Creutzfeldt-Jacob disease (CJD), but SREAT responds to steroids. We present a case of SREAT to increase physician awareness of an important fully reversible disease. CASE PRESENTATION: An 84-year-old woman with hypothyroidism was brought to our hospital due to decreased responsiveness for 1 day. Examination: BP: 75/42 mmHg, heart rate: 38 bpm, temperature: 33.8 ºC, minimal response to sternal rub, no focal neurological abnormalities. Chest X-ray: Small right pleural effusion. CT head: Chronic microvascular changes. ECG: Sinus bradycardia. Laboratory evaluation: WBC: 2.2 K/CUMM, mild hyponatremia and acute kidney injury. After initial resuscitation, we started IV fluids, high dose levothyroxine, antibiotics and hydrocortisone for myxedema coma and pneumonia. TSH and free thyroxine were normal, making myxedema coma unlikely and levothyroxine was discontinued. Encephalopathy did not improve and seizures developed. SREAT was considered due to rapid onset encephalopathy, seizures and prior hypothyroidism. Thyroid peroxidase antibody level was 1,021 IU/mL (normal < 4 IU/mL). EEG: Moderate diffuse slowing and triphasic waves. CSF: Normal protein and cell count. IV methylprednisolone 1 g/day was started, and on day 3, she became alert, oriented and started conversing. Subsequently, she developed uremic encephalopathy requiring hemodialysis due to worsening acute tubular necrosis (ATN), recurrent sepsis, and upper gastrointestinal bleed and expired despite aggressive ICU care. DISCUSSION: SREAT presents with acute/subacute encephalopathy consistently. Myoclonus, seizures, stroke like or psychiatric manifestations are associated features. Due to reversibility of SREAT, antithyroid antibodies should be ordered in acute encephalopathy syndromes associated with neuropsychiatric manifestations. Diagnosis is based on clinical features, high titer antithyroid antibodies and response to steroids. Most patients with SREAT have generalized slowing in EEG, but focal temporal or frontal slowing, triphasic waves and periodic sharp waves may be seen. 60% develop seizures. MRI is normal in 50%, but generalized cerebral atrophy, restricted diffusion, and increased T2 and flair white matter signal may be seen. Patients may be euthyroid, have subclinical or overt hypothyroidism, or rarely hyperthyroidism. CSF shows elevated protein in 85% of cases. 98% of patients with SREAT respond well to high dose steroids. CONCLUSIONS: SREAT is important to consider in unexplained encephalopathy, due to its excellent response to steroids. Though high dose steroids have excellent efficacy in SREAT, steroids are associated with adverse events such as GI bleed and sepsis. ATN in ICU patients has a mortality of > 60%, and high dose steroids increases risk of uremic bleeding. Early institution of hemodialysis may improve ATN outcome. Reference #1: Laurent, Charlotte, et al. “Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis (SREAT): Characteristics, Treatment and Outcome in 251 Cases from the Literature.” Autoimmunity Reviews, vol. 15, no. 12, Dec. 2016, pp. 1129–33. CrossRef, https://doi.org/10.1016/j.autrev.2016.09.008. Reference #2: Lee, Susan W., et al. “Steroid Responsive Encephalopathy Associated with Autoimmune Thyroiditis (SREAT) or Hashimoto’s Encephalopathy: A Case and Review.” Psychosomatics, vol. 52, no. 2, Apr. 2011, pp. 99–108. PubMed, https://doi.org/10.1016/j.psym.2010.12.010. Reference #3: Annals of Long-Term Care: Clinical Care and Aging. 2015;23(9):25-27. DISCLOSURES: No relevant relationships by Camelia Arsene, source=Web Response No relevant relationships by Maxwell Cretcher, source=Web Response no disclosure on file for E.M. Malitha Hettiarachchi; No relevant relationships by Katherine Kelley, source=Web Response No relevant relationships by Aditya Kotecha, source=Web Response No relevant relationships by Parker Latshaw, source=Web Response no disclosure on file for Sidrah Najam; no disclosure on file for Udorji Ogochukwu; no disclosure on file for Christina Rose

Thyrotoxicosis leading to adrenal crises reveals primary bilateral adrenal lymphoma.

Primary adrenal lymphoma is a rare malignancy. It frequently presents bilaterally and with symptoms of adrenal insufficiency. Amiodarone may induce secondary organ dysfunction, and thyrotoxicosis develops in 15% of cases. The symptomatology of both conditions is nonspecific, especially in the elderly, and a high suspicion index is necessary for appropriate diagnosis. A 78-year-old female presented to the emergency department with confusion, nausea and vomiting. She had recently been to the emergency department with urinary tract infection, vomiting and acute hypochloremic hyponatremia. Upon re-evaluation, the leukocyturia persisted and because of TSH 0.01 µU/mL and free-T4 68 (10–18) pmol/L, she was admitted to the Endocrinology ward. Further evaluation supported amiodarone-induced thyroiditis type 2. Sepsis ensued, in the setting of nosocomial pneumonia. Hemodynamic instability, hyponatremia, hypoglycemia and vomiting raised the suspicion of adrenocortical insufficiency. Fluid resuscitation and hydrocortisone led to clinical improvement, and adrenal insufficiency was admitted. The thoracoabdominal tomography suggested an endobronchic primary lesion with hepatic and adrenal secondary deposits (6.6 and 7 cm), but this was confirmed neither on pleural effusion nor on bronchofibroscopic fluid analyses. The adrenals were not accessible for biopsy. Despite high-dose hydrocortisone maintenance, the patient died before definite diagnosis. The autopsy confirmed primary non-Hodgkin lymphoma.Learning points:Primary adrenal lymphoma is a rare cause of adrenal insufficiency, but progression can be fast and fatal.Hyperpigmentation is frequently absent.The presenting symptoms are nonspecific and might mimic infection. Disproportion of the general state with signs of specific organ symptomatology is a diagnostic clue.Infection may precipitate adrenal crisis and worsen thyroid function with further adrenal insufficiency exacerbation.In the context of thyrotoxicosis, there may be little clinical response to a therapeutic trial with standard dose glucocorticoids.High-dose glucocorticoid substitution may be required to achieve clinical stability in thyrotoxic patients.

FUNCTIONAL CAPACITY OF MEMORY CELLS CD8+ UNDER LYMPHOPENIA INDUCED BY INJECTION OF HYDROCORTISONE

Background. Wide use of glucocorticoids therapy for neoplasms, autoimmune diseases and allergies is associated with suppression of adaptive immunity that requires profound study of their immunoregulatory properties and immunotoxicity. Results. In this work, using our model of selective activation of mouse CD8 + memory cells in the mixed lymphocyte reaction (MLR) in vitro, we show for the first time that intraperitoneal injection of high dose hydrocortisone (2.5 mg per animal) allows to detect memory cells in the thymus of animals immunized with allogeneic tumor cells. Similar to memory cells from other lymphoid organs, hydrocortisone-resistant thymic lymphocytes from immune animals respond on allogeneic stimulators subjected to severe heat shock and are immunologically specific to immunizing alloantigen. Thus, cortisone-resistant thymocytes are partially or completely represented by memory cells. We also show here that memory responses of heterozygotes on TCR a-chain knock-out (genetically incapable to secondary rearrangement of TCR achains) are significantly enhanced as compared with the ones of wild type mice. Conclusion. These findings allows to suggest the hypothesis according to which memory T cell clones proliferating in primary immune response migrate into thymus providing necessary microenvironment for reexpression of recombinases. After editing of genes encoding TCR achains, such T lymphocytes can return to peripheral repertoire maintaining its wideness.

PTU-051 Iatrogenic Hypokalaemia in Acute Severe Colitis

Introduction Intravenous corticosteroids have been established as the mainstay treatment of acute severe colitis since 1974.1 BSG and ECCO guidelines advise either IV hydrocortisone 100 mg qds or IV methylprednisolone 30 mg bd in this setting.2,3 The potent mineralocorticoid effect of hydrocortisone however is well known.4 This could predispose to hypokalaemia in this susceptible patient cohort. For this reason, we have recently changed our practice at Glasgow Royal Infirmary (GRI) to treat these patients with methylprednisolone. Methods We performed a retrospective review of electronically held records of patients who presented to GRI with acute severe colitis treated with IV hydrocortisone or methylprednisolone. We collected data on the duration of treatment, potassium level on presentation, nadir potassium level, fall in potassium level and potassium replacement per patient. Results 20 patients were treated with IV hydrocortisone for a median of 6 days, and 16 patients were treated with IV methylprednisolone for a median of 5.5 days (ns). Median serum potassium concentration on admission was 3.8 mol/l (IQR 3.4–4.1 mmol/l) in the cohort receiving hydrocortisone which was not significantly different from 4.1 mmol/l (IQR 3.7–4.1 mol/l) in the cohort receiving methylprednisolone. Following IV steroids, median nadir potassium concentration in the group receiving methylprednisolone was 3.75 mmol/l (IQR 3.5–4.1 mmol/l), not significantly different to pre-treatment values. In those receiving hydrocortisone however, potassium concentration fell by a median of 0.85 mol/l (IQR 0.2–1.1 mol/l) to a nadir of 3.1 mol/l (IQR 2.8–3.3 mol/l), significantly lower than the group receiving methylprednisolone (p Conclusion Hypokalaemia is a common occurrence in patients with acute severe colitis treated with IV hydrocortisone but is rare when methylprednisolone is used. Given that both drugs are considered to be equally effective, methylprednisolone appears to be a safer choice of corticosteroid. References 1 Truelove SC, Jewell DP. Intensive intravenous regimen for severe attacks of ulcerative colitis. Lancet 1974;1:1067–1070. 2 BSG Guidelines for management IBD 2011. 3 ECCO consensus guidelines for UC 2012. 4 Ramsahoye BH, Davies SV, et al. The mineralocorticoid effects of high dose hydrocortisone. BMJ 1995;310:656. Disclosure of Interest None Declared

Glucocorticosteroids for sepsis: systematic review with meta-analysis and trial sequential analysis.

Introduction Glucocorticosteroids (steroids) are widely used for sepsis patients. However, the potential benefits and harms of both high and low dose steroids remain unclear. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis (TSA) might shed light on this clinically important question.MethodsA systematic review was conducted according to a published protocol and The Cochrane Handbook methodology including meta-analyses, TSA of randomised clinical trials, and external validity estimation (GRADE). Randomised clinical trials evaluating steroids were included for sepsis patients (systemic inflammatory response syndrome, sepsis, severe sepsis or septic shock) aged >18 years. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/Medline, Embase, Web of Science and Cinahl were searched until 18 February 2015. No language restrictions were applied. Primary outcomes were mortality at longest follow-up and serious adverse events.ResultsA total of 35 trials randomising 4682 patients were assessed and reviewed in full text. All trials but two had high risk of bias. No statistically significant effect was found for any dose of steroids versus placebo or no intervention on mortality at maximal follow-up [relative risk (RR) 0.89; TSA adjusted confidence interval (CI) 0.74–1.08]. Two trials with low risk of bias also showed no statistically significant difference (random-effects model RR 0.38, 95 % CI 0.06–2.42). Similar results were obtained in subgroups of trials stratified according to high (>500 mg) or low (≤500 mg) dose hydrocortisone (or equivalent) (RR 0.87; TSA-adjusted CI 0.38–1.99; and RR 0.90; TSA-adjusted CI 0.49–1.67, respectively). There were also no statistically significant effects on serious adverse events other than mortality (RR 1.02; TSA-adjusted CI 0.7–1.48). The effects did not vary according to the degree of sepsis. TSA showed that many more randomised patients are needed before definitive conclusions may be drawn.ConclusionEvidence to support or negate the use of steroids in any dose in sepsis patients is lacking. The results of ongoing and future well-designed, large randomised clinical trials are needed.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-015-3899-6) contains supplementary material, which is available to authorized users.

Lithium as an Alternative Option in Graves Thyrotoxicosis.

A 67-year-old woman was admitted with signs and symptoms of Graves thyrotoxicosis. Biochemistry results were as follows: TSH was undetectable; FT4 was >6.99 ng/dL (0.7–1.8); FT3 was 18 pg/mL (3–5); TSI was 658% (0–139). Thyroid uptake and scan showed diffusely increased tracer uptake in the thyroid gland. The patient was started on methimazole 40 mg BID, but her LFTs elevated precipitously with features of fulminant hepatitis. Methimazole was determined to be the cause and was stopped. After weighing pros and cons, lithium was initiated to treat her persistent thyrotoxicosis. Lithium 300 mg was given daily with a goal to maintain between 0.4 and 0.6. High dose Hydrocortisone and propranolol were also administered concomitantly. Free thyroid hormone levels decreased and the patient reached a biochemical and clinical euthyroid state in about 8 days. Though definitive RAI was planned, the patient has been maintained on lithium for more than a month to control her hyperthyroidism. Trial removal of lithium results in reemergence of thyrotoxicosis within 24 hours. Patient was maintained on low dose lithium treatment with lithium level just below therapeutic range which was sufficient to maintain euthyroid state for more than a month. There were no signs of lithium toxicity within this time period. Conclusion. Lithium has a unique physiologic profile and can be used to treat thyrotoxicosis when thionamides cannot be used while awaiting elective radioablation. Lithium levels need to be monitored; however, levels even at subtherapeutic range may be sufficient to treat thyrotoxicosis.

The Quality of General Movements after Treatment with Low-Dose Dexamethasone in Preterm Infants at Risk of Bronchopulmonary Dysplasia

Background: High-dose dexamethasone (DXM) treatment of preterms at risk of bronchopulmonary dysplasia leads to a deterioration in quality of their general movements (GMs). It is unknown whether low-dose DXM affects GM quality similarly. Objectives: To assess the effect of low-dose DXM treatment on the quality of GMs and fidgety GMs (FMs). Methods: A prospective study of preterms admitted to our NICU between 2010 and 2012, and treated with DXM (starting dose 0.25 mg/kg/day). We assessed GM/FM quality and calculated their motor optimality score (MOS) before, during, and after treatment up to 3 months postterm. Neurological follow-up was performed between 12 and 36 months. We related risk factors with infants' GM trajectories and MOSs. At 3 months we compared the MOSs of low-dose DXM infants and a historical cohort of infants treated with high-dose DXM or hydrocortisone. Results: 17 infants were included. GM/FM quality improved in 9 out of 13 initially abnormal infants (p = 0.004). Shorter periods of mechanical ventilation and higher birth weights were associated with better GM trajectories (p = 0.032 and p = 0.042, respectively). Infants starting treatment later had higher MOSs on day 7 (p = 0.047). Low-dose DXM infants had higher MOSs than high-dose DXM infants (β = -0.535; 95% CI -0.594 to -0.132; p = 0.003). Out of 17 infants, 2 died, 14 developed normally, and 1 developed with mild neurodevelopmental impairments. Infants whose GMs/FMs remained normal or improved had better outcomes than infants whose GMs/FMs remained abnormal (p = 0.019). Conclusions: Out of the 17 infants treated with low-dose DXM, 2 died. Of the surviving infants, neurological functioning improved with the majority having normal neurodevelopment at the age of 12-36 months.

Comparison on model establishment methods and index in common of Yang deficiency mice induced by hydrocortisone

Objective To compare and analyze the index variation of Yang deficiency mice induced by hydrocortisone in different way of administration and dose. Methods The mice model of Yang deficiency were induced by low dose and high dose hydrocortisone（12.5 mg/kg, 25 mg/kg） in two ways of intramuscular and intraperitoneal injection. The symptoms, body weight, the average intake, the index of stress and the coefficient of sex organs and immune organs of animals were observed. Results In the way of intraperitoneal injection, the weight（24.52±3.29）g, body temperature（35.24±0.32）℃ of high dose of model group were significantly lower than that of control group（31.10±6.11）g,（37.02±0.64）℃. The average intake of low dose group（4.30 ± 0.29）g/（per？d） was lower than control group（7.38±0.53）g/（per？d）, and the coefficient of preputial glands（0.10±0.02）, penis（0.15±0.03）, thymus（0.12±0.03）were lower than that of control group. In the way of intramuscular injection, the average intake of high dose group（5.92±2.01）g/（per？d） was lower than control group（8.60±1.33）g/（per？d）. The body temperature（34.90±0.22）℃ and the time of swimming in low temperature （34.00±22.41）s of low dose model group were lower than that of control group（36.43±0.91）℃, （67.17±21.93）s, and the coefficient of thymus of two model groups（0.10±0.02）,（0.11±0.06）were lower than that of control group. Conclusion Various dose and model establishment methods of Yang deficiency mice have different the time of symptom appearing, the degree of symptom and sensitive index. Key words: Hydrocortisone; Mice; Yang deficiency; Model; Index

FRI0267 The influence of anti-malarial drugs (hydroxychloroquine and quinacrine) on the initiation of interferon-alfa production through tlr-9 pathway

BackgroundToll-like receptor 9 (TLR-9) can recognize nucleic acids especially DNA segments, plays an important role in innate immunity. Recently, it has been found that TLR-9 also involves in the recognition...

Hydrocortisone infusion exerts dose- and sex-dependent effects on attention to emotional stimuli

Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to negative words. Healthy volunteers received placebo and either low-dose (0.15mg/kg) or high-dose (0.45mg/kg) hydrocortisone intravenously during two separate visits in a double-blind, randomized design. Seventy-five minutes post-infusion, the subjects performed tests of attention (Rapid Visual Information Processing [RVIP]), spatial working memory (Spatial Span) and emotional processing (Affective Go/No-go task [AGNG]). On the attention task, performance was impaired under both hydrocortisone doses relative to placebo, though the effect on error rate was not significant after controlling for age; Spatial Span performance was unaffected by hydrocortisone administration. On the AGNG task, relative to the placebo condition the low-dose hydrocortisone infusion decreased response time to emotional words while high-dose hydrocortisone increased response time. In the females specifically, both high and low dose hydrocortisone administration attenuated the normal attentional bias toward positively valenced words. These data suggest that, in healthy women, the modulation of attention by the emotional salience of stimuli is influenced by glucocorticoid hormone concentrations.

Initial high dose hydrocortisone (HDC) treatment for 21-hydroxylase deficiency (21-OHD) does not affect linear growth during the first three years of life

An initial high-dose treatment of glucocorticoid has been proposed to prevent chronic androgen excess, improving the final height prognosis of 21-hydroxylase deficiency (21-OHD) patients. In Japan, it is recommended to use an extremely high-dose of hydrocortisone (HDC) (100-200 mg/m(2)/day) for initial treatment by the Japanese Society for Pediatric Endocrinology. However, a precise evaluation of the treatment has not been carried out. In this study, we retrospectively analysed the effects of initial high-dose HDC therapy on the linear growth of classical 21-OHD patients discovered by newborn screening. Thirty patients (14 females) were eligible for this study, all of whom were initiated with high dose HDC therapy. The height standard deviation score (Ht-SDS) was 0.76 ± 0.65 at birth, and decreased to -1SD or less until the age of 12 months, subsequently catching up by 3 years of age (-0.56 ± 0.76). The growth pattern and the height at the age of two years were very similar to those previously observed in patients without initial high dose HDC therapy. We did not find any significant difference in growth retrospectively between the high- or low-dose HDC group (initial treatments of ≥150 mg/m(2)/day and 100 mg/m(2)/day, respectively). Bone ages did not exceed chronological ages at the ages of three and six years. Our data suggest that an initial high-dose HDC treatment does not profoundly affect linear growth during first three years of life and that the treatment could be a valuable option for 21-OHD patients without having an obvious adverse effect on linear growth.

Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

In the pulmonary vasculature, cGMP levels are regulated by soluble guanylate cyclase (sGC) and phosphodiesterase 5 (PDE5). We previously reported that lambs with persistent pulmonary hypertension of the newborn (PPHN) demonstrate increased reactive oxygen species (ROS) and altered sGC and PDE5 activity, with resultant decreased cGMP. The objective of this study was to evaluate the effects of hydrocortisone on pulmonary vascular function, ROS, and cGMP in the ovine ductal ligation model of PPHN. PPHN lambs were ventilated with 100% O(2) for 24 h. Six lambs received 5 mg/kg hydrocortisone every 8 h times three doses (PPHN-hiHC), five lambs received 3 mg/kg hydrocortisone followed by 1 mg·kg(-1)·dose(-1) times two doses (PPHN-loHC), and six lambs were ventilated with O(2) alone (PPHN). All groups were compared with healthy 1-day spontaneously breathing lambs (1DSB). O(2) ventilation of PPHN lambs decreased sGC activity, increased PDE5 activity, and increased ROS vs. 1DSB lambs. Both hydrocortisone doses significantly improved arterial-to-alveolar ratios relative to PPHN lambs, decreased PDE5 activity, and increased cGMP relative to PPHN lambs. High-dose hydrocortisone also increased sGC activity, decreased PDE5 expression, decreased ROS, and increased total vascular SOD activity vs. PPHN lambs. These data suggest that hydrocortisone treatment in clinically relevant doses improves oxygenation and decreases hyperoxia-induced changes in sGC and PDE5 activity, increasing cGMP levels. Hydrocortisone reduces ROS levels in part by increasing SOD activity in PPHN lambs ventilated with 100% O(2.) We speculate that hydrocortisone increases cGMP by direct effects on sGC and PDE5 expression and by attenuating abnormalities induced by oxidant stress.

High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: Interplay between clinical and animal studies

High-dose corticosteroids have been reported to reduce symptoms of acute stress and post-traumatic stress in polytrauma patients and in animal studies. The underlying mechanism of action remains largely unclear. These issues were addressed in parallel in the clinical and preclinical studies below. In this preliminary study, 25 patients with acute stress symptoms were administered a single intravenous bolus of high-dose hydrocortisone (100–140 mg) or placebo within 6 h of a traumatic event in a prospective, randomized, double-blind, placebo-controlled pilot study. Early single high-dose hydrocortisone intervention attenuated the core symptoms of both the acute stress and of subsequent PTSD in patients. High-dose hydrocortisone treatment given in the first few hours after a traumatic experience was associated with significant favorable changes in the trajectory of exposure to trauma, as expressed by the reduced risk of the development of PTSD post-trauma. In parallel, a comparative study of morphological arborization in dentate gyrus and its modulating molecules was performed in stress-exposed animals treated with high-dose hydrocortisone. Steroid-treated stressed animals displayed significantly increased dendritic growth and spine density, with increased levels of brain-derived neurotrophic factor (BDNF) and obtunded postsynaptic density-95 (PSD-95) levels. The animal study provided insights into the potential mechanism of this intervention, as it identified relevant morphological and biochemical associations to the clinical observations. Thus, evidence from clinical and animal studies suggests that there is a “window of opportunity” in the early aftermath of trauma to help those who are vulnerable to the development of chronic PTSD.

In the treatment of flares of inflammatory bowel disease, intravenous hydrocortisone causes greater falls in blood potassium and more severe episodes of hypokalaemia than methylprednisolone

IntroductionCorticosteroids are important treatments for acute exacerbations of inflammatory bowel disease (IBD). In severe flares, or when oral steroid has proven unsuccessful, high dose intravenous steroid can be given in...

Dose-dependent effects of hydrocortisone infusion on autobiographical memory recall.

The glucocorticoid hormone cortisol has been shown to impair episodic memory performance. The present study examined the effect of two doses of hydrocortisone (synthetic cortisol) administration on autobiographical memory retrieval. Healthy volunteers (n = 66) were studied on two separate visits, during which they received placebo and either moderate-dose (0.15 mg/kg IV; n = 33) or high-dose (0.45 mg/kg IV; n = 33) hydrocortisone infusion. From 75 to 150 min post-infusion subjects performed an Autobiographical Memory Test and the California Verbal Learning Test (CVLT). The high-dose hydrocortisone administration reduced the percent of specific memories recalled (p = .04), increased the percent of categorical (nonspecific) memories recalled (p < .001), and slowed response times for categorical memories (p < .001), compared with placebo performance. Under moderate-dose hydrocortisone the autobiographical memory performance did not change significantly with respect to percent of specific or categorical memories recalled or reaction times. Performance on the CVLT was not affected by hydrocortisone. These findings suggest that cortisol affects accessibility of autobiographical memories in a dose-dependent manner. Specifically, administration of hydrocortisone at doses analogous to those achieved under severe psychosocial stress impaired the specificity and speed of retrieval of autobiographical memories.

Update in Pituitary 2010

This manuscript is based on an invited lecture entitled "The Year in Pituitary," presented at the 91st Annual Meeting of The Endocrine Society in San Diego, California, on June 21, 2010. The purpose of the lecture was to highlight new or evolving issues in the management of pituitary disease. Papers selected were published in major journals between January 2009 and June 2010. Issues addressed include the safety of cabergoline in pregnancy, recurrence of hyperprolactinemia after dopamine agonist withdrawal, pegvisomant and hepatic dysfunction, and high-dose hydrocortisone as a predictor of mortality in patients with acromegaly.

Influence of High-Dose Cortisol on the Biomechanics of Incubated Porcine Corneal Strips

To investigate the change in biomechanical properties of the cornea induced by high-dose hydrocortisone. The influence of hydrocortisone was investigated in 12 fresh porcine corneas incubated in culture medium of 2.5 muM of hydrocortisone for 7 days. Twelve additional porcine corneas incubated in culture medium without hydrocortisone for the same time served as the control group. Strips of cornea were cut and the stress-strain relationship was measured in a biomaterial tester. Young's modulus was calculated. After incubation, the thickness of the cornea was 1120+/-130 mum in the control group and 1320+/-90 mum in the hydrocortisone group. The hydrocortisone-treated corneas were 18% thicker compared to the control corneas. However, the difference in the biomechanical stress value at 10% strain was significantly larger. In the control group, the stress value measured 122+/-40 kPa, and in the hydrocortisone group, it measured 77+/-19 kPa (P=.003), representing a reduction of the corneal stiffness by 37% due to hydrocortisone treatment. Young's modulus was reduced by 42.8% from 2.90+/-1.10 MPa in the control group to 1.66+/-0.49 in the hydrocortisone group. Hydrocortisone is a modulating factor of the biomechanical properties of the cornea. The significance of the cortisol status of the patient and its influence on the biomechanical stability of the cornea should be considered in the development of keratectasia in keratoconus or after refractive surgery.

Enhanced Interaction between Warfarin and High-Dose Ketoconazole: A Case Report

This case describes the increased anticoagulation effect associated with the use of high-dose ketoconazole. A 59-year-old man treated with warfarin for aortic valve replacement was prescribed high-dose ketoconazole and hydrocortisone for the treatment of prostate cancer. Despite lowering the warfarin dosage by 35% during the start of high dose ketoconazole, an additional dose reduction was required subsequently when the INR rose from 2.62 to 3.82 within nine days. After a total dose reduction of 43%, the INR returned to therapeutic range within two weeks. The Naranjo probability scale revealed a probable adverse reaction of increased anticoagulant effect associated with high dose ketoconazole. Due to the inhibition of warfarin metabolism by ketoconazole, patients taking high dose ketoconazole concomitantly with warfarin may need their warfarin dosage reduced by more than is currently recommended, as well as receive more frequent INR monitoring to avoid over anticoagulation.