Starting Glucocorticoid Therapy Research Articles

Neuropsychiatric presentations of hypocortisolaemia - a literature review

IntroductionPatient populations in psychiatry can have low cortisol for many reasons such as adrenalitis, secondary adrenal insufficiency and poor compliance with glucocorticoid replacement therapies. A literature review in 2005 highlighted the prevalence of neuropsychiatric features in those with low cortisol. Unfortunately, this has received little to no attention in the wider literature and hypocortisolaemia is often overlooked as a cause of neuropsychiatric presentations in clinical practice.ObjectivesReview the literature to understand what psychiatric features hypocortisolaemic patients present with and any themes between cases.MethodsA literature review on neuropsychiatric presentations of hypocortisolaemia was performed using PUBMED and Google Scholar. English language studies from 2005 to October 2022 were included and searched for using the following term: (Hypocortisolaemia* OR “Low-cortisol” OR Addisons OR Adrenal-crisis OR “Adrenal insufficiency”) AND (Psychiatric OR Hallucination OR Neuropsychiatric OR “Neuropsychiatric symptoms” OR Pyschosis*). Citations in relevant papers were also reviewed.Results7 case reports were identified, 5 male (71%) and 2 female (29%) with an average age of 42 (28-63). The cause was identified as Addisons’ disease in 4 patients (57%) and secondary adrenal insufficiency in 3 patients (43%). Hallucination or delusion was the most prevalent symptom with 86% of patients initially presenting with it, followed by depression (43%) and speech abnormality (14%). In all cases, basic blood sets (Full blood count, urea & electrolytes and liver function tests) were done in an initial assessment. 6 patients presented with hyponatraemia, and 4 of these patients had hyponatraemia as their only abnormality within their U&E profile. In one patient this delayed their diagnosis by several years. One patient developed psychosis again when being treated with glucocorticoid therapy. In 4 patients, adrenal pathology was not suspected and cortisol was not tested until initial differentials were investigated and ruled out.ConclusionsFurther case reports highlight psychosis being a key feature of hypocortisolaemia that presents initially with neuropsychiatric symptoms. Cortisol levels should be considered in initial investigations of psychosis if hyponatraemia is discovered even in the absence of hyperkalaemia to help aid an earlier diagnosis. A rebound psychosis may be seen once starting glucocorticoid therapy. Additionally, there should be consideration of neuropsychiatric monitoring in stable psychiatric patients undergoing cortisol treatment.Disclosure of InterestNone Declared

PSAT034 A Case of Adrenal Crisis in Association With a Febrile Response to the bnt162b2 mRNA COVID-19 (Pfizer) Vaccine Heralding a Diagnosis of Primary Adrenal Insufficiency.

Abstract Background In the face of the COVID-19 pandemic, messenger RNA (mRNA) vaccines were approved for the first time for use in the general population. Vaccination can trigger a febrile flu-like response that is self-limited in healthy individuals. Febrile illness is a classic trigger of acute adrenal insufficiency in patients who are cortisol deficient, but recognizing this clinical scenario is challenging in patients with undiagnosed adrenal insufficiency. Case Presentation A 24-year-old male presented to an acute care community hospital with fatigue, fever, and vomiting 12 hours after receiving the second dose of the BNT162b2 mRNA Covid-19 (Pfizer) vaccine. He was 6 feet tall, and his weight was 175 pounds. He had a temperature of 103 F, a blood pressure of 88/42 mmHg, and a heart rate of 100 bmp on admission. Hypotension persisted despite aggressive fluid resuscitation and broad-spectrum antibiotics. CT of the chest and CT angiogram of the abdomen and Pelvis did not identify an etiology for his presentation. Over a period of hours, he became obtunded, disoriented, and required vasopressor support. He received 100 mg of IV hydrocortisone followed by 50 mg every 6 hours for treatment of presumed sepsis and was transferred to an intensive care unit. Within 24 hours of starting glucocorticoid therapy, he was awake and oriented, defervesced, and became normotensive. This rapid improvement led to suspicion of adrenal insufficiency as an underlying diagnosis. Further questioning revealed a 4-month history of recurrent nausea, vomiting, severe fatigue, to the point where he had trouble climbing a flight of stairs, and a 40-pound unintentional weight loss. He visited an emergency department 3 times over this period and had outpatient evaluations by gastroenterology and cardiology without identifying a cause. Inpatient evaluation revealed a morning Cortisol of 1.4 ug/dL (n 4.8-19.5 ug/dL), aldosterone <3 ng/dL (n <16 ng/dL), and ACTH 1071 pg/mL (n 7.2-63.3 pg/mL) leading to the diagnosis of primary adrenal insufficiency. He was started on physiologic doses of adrenal replacement hormones and discharged home in stable condition 4 days after his admission date. Conclusions A severe post-vaccination reaction should elicit physicians to look for an alternative diagnosis. Autoimmune adrenalitis is the most common cause of primary adrenal insufficiency and is uniquely associated with a long lag to diagnosis. The diagnosis is often made in the setting of an intervening illness or physiologic stressor when a patient's condition acutely deteriorates. Patients with known adrenal insufficiency should be reminded to address post-vaccination febrile reactions with an increase in glucocorticoid doses. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Glucocorticoid Effects on Tissue Residing Immune Cells in Giant Cell Arteritis: Importance of GM-CSF.

Giant cell arteritis (GCA) is a systemic granulomatous vasculitis clinically characterized by a prompt response to glucocorticoid therapy. Dendritic cells (DCs) play a central role in the pathogenesis of the disease and are increased in temporal arteries from GCA patients. The aim of this study was to determine the effects of glucocorticoid therapy on granulomatous infiltrates and on peripheral DCs of GCA patients. Immunohistochemical staining of temporal artery specimens from 41 GCA patients revealed a rapid reduction of the number of DCs after initiation of glucocorticoid treatment. TUNEL staining was performed to quantify apoptotic S100+ DC, CD3+ T cells, and CD68+ macrophages in the granulomatous infiltrates. An increase of apoptotic cells up to 9 ± 2% after 4–5 days of glucocorticoid therapy and up to 27 ± 5% (p < 0.001, compared to earlier timepoints) after 6–10 days was detected. A decrease of CCL19 and CCL21 expression was observed after starting glucocorticoid therapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also significantly decreased under glucocorticoid therapy. No GM-CSF expression was detected in the control specimens. Glucocorticoid therapy leads to a rapid, time-dependent reduction of DCs in temporal arteries from GCA patients and reduction of mediators for cell migration. Our data suggest GM-CSF as a novel therapeutic target of GCA.

Glucocorticoid therapy suppresses Wnt signaling by reducing the ratio of serum Wnt3a to Wnt inhibitors, sFRP-1 and Wif-1.

Our previous study suggested that suppression of Wnt/β-catenin signaling by increasing serum Wnt co-receptor inhibitors, sclerostin and Dickkopf-1, impairs bone formation in the first week after starting glucocorticoid therapy. The objective of this study was to investigate the involvement of the Wnt/β-catenin signaling pathway and its clinical significance in the subsequent suppression of bone formation. A total of 53 patients with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60mg daily) were prospectively enrolled. We measured serum levels of Wnt3a and Wnt inhibitors, secreted Frizzled-related protein 1 (sFRP-1) and Wnt inhibitory factor 1 (Wif-1), before starting glucocorticoid therapy and every week for 4 weeks after its initiation. Serum levels of sFRP-1 and Wif-1 slightly decreased compared with before glucocorticoid therapy from the second week. The serum Wnt3a level decreased from the first week. The ratios of Wnt3a to sFRP-1 and that of Wnt3a to Wif-1 both decreased from the first week onward. The reduction of the ratio of Wnt3a to Wnt inhibitors, sFRP-1 and Wif-1, suppresses Wnt signaling, which may result in impaired bone formation. Taken together with our previous studies, glucocorticoids may suppress Wnt signaling by inhibiting co-receptors of the Wnt/β-catenin signaling pathway in the early phase of glucocorticoid therapy and inhibiting its ligand in the subsequent weeks, which together impair bone formation. Key Points • The decrease in Wnt pathway-related molecules by glucocorticoids impairs bone formation. • Glucocorticoids inhibit co-receptors of Wnt signaling in the early phase of therapy. • Glucocorticoids inhibit ligands of Wnt signaling in the subsequent phase of therapy.

EP33 Sjögren’s and lymphoproliferative disorders

Case report - IntroductionSjögren’s syndrome (SS) is a chronic autoimmune inflammatory condition characterised by lymphocytic infiltration of predominantly exocrine glands as well as other organs involving more commonly in skin, lungs, and neurological system. It is associated with increased risk of both benign and malignant lymphoproliferative disorders.Case report - Case descriptionA 29-year-old woman with 5-year history of Primary SS (ANA, Ro/La positive) was reviewed in a routine follow up. She has mild dry eyes, intermittent vasculitic rash around the ankles, occasional pleuritic chest pain but no cough or dyspnoea initially. She used artificial tears but took no regular mediations. Oxygen saturation at rest was 99% and BP 127/70. Heart sounds were normal, and chest was clear.Blood results showed alanine transaminase (ALT) had risen from 50 (normal 5-45) to 145 over 6 months. Viral screen (hepatitis, HIV, CMV, EBV) and liver ANA panel were negative. C4 was low 0.09 (n 0.15-0.55), C3 normal and DsDNA antibodies 1 (n 0-15.1). Ig G was high, fluctuating between 27 - 33 (n 7.67-15.9). ESR had been mildly elevated at 26 (n 0-19). CRP had always been within normal limits. Ultrasound abdomen showed enlarged spleen (15 cm). CT chest abdomen and pelvis showed multifocal groundless opacification affecting mid to upper zones, bilateral cyst formation, solid nodularity, and mild septal thickening with no pleural effusion. There were multiple prominent bilateral axillary and mediastinal lymph nodes measuring upto15 mm. The spleen measured 15.4 cm. Six months later, she developed mild dyspnoea on exertion. Examination revealed fine basal crackles. Oxygen saturation remained 99% at rest. TLco was mildly reduced and Kco in lower limit of normal. Echocardiogram was normal. Ultrasound guided core biopsy of axillary lymph node showed benign reactive features with follicular hyperplasia and plasmacytosis.The diagnosis of lymphocytic interstitial pneumonitis was made. She was started on a reducing dose of Prednisolone 30 mg and Mycophenolate stepwise increment to 1 gm BD. Chest pain resolved shortly after starting glucocorticoid therapy and exercise tolerance improved.Liver enzyme normalised. Case report - DiscussionThe diagnosis of lymphocytic interstitial pneumonia (LIP) in this patient was incidental from the retrospective investigation of the persistently abnormal unexplained liver function test. Splenomegaly is a recognised manifestation of active systemic SS. The main differential diagnoses are lymphoma and other types of interstitial lung diseases (ILD). Her presentation was insidious and there were no constitutional symptoms. Her ANA, Ro, La and Rheumatoid factor were strongly positive. She has hypergammaglobulinemia which is commonly associated with LIP. Histological findings were typical reactive changes with characteristic polymorphic plasmacytosis. In the absence of malignant lymphoid cells and radiological features of ground glass changes and bilateral cysts formation suggested that the most likely diagnosis was LIP secondary to primary SS.The management strategies vary for different types of ILD based on their etiological conditions. There are no specific guidelines for the treatment of LIP. For initial acute stage, glucocorticoid therapy is usually prescribed for symptomatic improvement. For later stages and cysts, immunosuppressants are used and depending on the severity, azathioprine, cyclosporin, rituximab and cyclophosphamide have been used.Median survival for LIP is 11.2 years. Increased risk of secondary infection because of immunosuppressive therapy is common and there are recommendations for atypical chest infection prophylaxis.Case report - Key learning pointsInterstitial lung disease is commonly associated with SS and predicts a higher mortality rate.Glucocorticoid is the main stay of treatment for ILD acute stage with active inflammatory changes.For refractory cases and chronic cystic stages on radiological findings, further immunosuppression therapy may be required.Standardised treatment guidelines are not available.Secondary chest infections may be seen in those with cystic disease and on immunosuppression.Close monitoring and MDT approach is required in the management of LIP.LIP may transform into lymphoma or co-present with lymphoma associated with SS.

P273 The role of multimodality imaging in the evaluation of arteritis

Abstract A 61-year-old man was admitted to the hospital with an atypical pain lumbar with oligoanuria. Other comorbidities were: arterial hypertension, diabetes mellitus and smoking .On examination the patient was comfortable at rest, with a heart rate of 89 b.p.m. and a blood pressure of 147/2 mmHg. Normal S1 and S2 heart sounds were present. There were no signs of heart failure present. Patients complained of pain in hypogastrium on palpation. Creatinine 2.33 mg / dL. PCR 72. The immunological studies were normal (including IgG and IgA serological levels, antinuclear antibodies, extractable nuclear antigens, anti-neutrophil cytoplasmic antibodies. An Body CT was performed, it shows mass that includes the ureters as well as the iliac arteries and parietal thickening in aorta wall. The positron emission tomography–computed tomography (PET CT) scans was performed that evidences pathological hypermetabolism that surrounds both primitive iliac arteries with maximum SUV 12 g / ml. Pathological hypermetabolism in ascending aorta until reaching arch with maximum SUV of 9.1 mg / ml compatible with periaortitis in the ascending aorta. A study was completed with retroperitoneal mass biopsy that showed areas of retroperitoneal fibrosis with predominantly lymphoplasmacytic areas. IgG4 / IgG&amp;gt; 40% , Obliterative involvement of small venules suggestive of IgG4 disease. A transthoracic echocardiogram was performed which showed normal biventricular function, absence of significant valvular disease and thickening of the aortic wall compatible with periaortitis. The patient started glucocorticoid therapy with favorable response. A PET CT control was performed that showed disappearing retroperitoneal masses around iliac vessels and disappearance of activity in lateral wall of aorta and decrease activity about ascendent aorta. DIAGNOSIS : IgG4 -related aortitis Abstract P273 Figure.

Strongyloides stercoralis Hyperinfection Syndrome as a Cause of Fatal Gastrointestinal Hemorrhage.

ABSTRACTStrongyloides stercoralis is a small intestinal nematode that is widespread in regions with poor sanitation. We present a 57-year-old man from Colombia who was undergoing corticosteroid therapy for a meningioma who presented after neurosurgery with abdominal pain and a profound gastrointestinal (GI) bleed. The patient underwent an esophagogastroduodenoscopy (EGD), an attempted embolization, and an exploratory laparotomy to remove the necrosed duodenum. His pathology examination revealed Strongyloides infection of the duodenum, and he died of profound blood loss. This rare diagnosis displays the importance of screening patients at a high risk of Strongyloides infection before starting glucocorticoid therapy.

Use of 18F-fluorodeoxyglucose positron emission tomography in the diagnosis of polymyalgia rheumatica-A prospective study of 99 patients.

Previous studies have shown that the majority of patients with PMR have increased 18F-fluorodeoxyglucose (FDG) uptake around the shoulders, hips and processes of the cervical and lumbar spine on PET. The specificity of these findings for PMR is, however, not known. We prospectively included 99 consecutive patients with a possible clinical diagnosis of PMR. All patients underwent 18F-FDG-PET scanning before treatment with glucocorticoids was started. The clinical suspicion of PMR was quantified by the treating physician on a scale from 1 to 5. FDG uptake was scored visually in 12 articular regions (scores 0-2) and a total skeletal score was calculated reflecting the FDG uptake in these 12 articular regions. Receiver operating characteristics analysis was performed to determine the optimal clinical and total skeletal score for diagnosing PMR. The gold standard for a diagnosis of PMR was the judgement of an experienced clinician after at least 6 months of follow-up. Sixty-seven patients were diagnosed with PMR while 32 patients got another diagnosis. A clinical score of 4 or more had a sensitivity of 67.2%, specificity of 87.5%, positive predictive value (PPV) of 91.8% and a negative predictive value (NPV) of 56.0% for the diagnosis of PMR. A total skeletal score of 16 or more had a sensitivity, specificity, PPV and NPV of, respectively, 85.1, 87.5, 93.4 and 73.7%. 18F-FDG-PET before starting glucocorticoid therapy improves the diagnostic accuracy compared with a clinical scoring system in patients with clinical suspicion of PMR.

Clinical and pathological evolution of giant cell arteritis: a prospective study of follow-up temporal artery biopsies in 40 treated patients

Although clinical signs and symptoms of giant cell arteritis improve promptly after starting glucocorticoid therapy, reports have suggested that the vascular inflammation may persist. To assess the duration and quality of histopathologic changes in treated patients, we prospectively obtained second temporal artery biopsies in patients treated for 3 to 12 months after their first diagnostic biopsy. Forty patients (28 women, 12 men, median age 77 years) agreed to have a second temporal artery biopsy randomly assigned to 3, 6, 9, or 12 months subsequent to the first. Clinical and laboratory evaluation of the patient cohort revealed a typical rapid response and continued suppression of clinical manifestations as a result of glucocorticoid treatment. Histopathologic findings, evaluated in a blinded manner by a cardiovascular pathologist, showed unequivocal findings of vasculitis in 7/10 patients with second temporal artery biopsy at 3 months, 9/12 at 6 months, 4/9 at 9 months, and 4/9 at 12 months. Lymphocytes were present in all positive initial biopsies and remained the dominant cell population in chronically treated patients. Granulomatous inflammation decreased in a time-dependent manner from 78 to 100% at initial biopsy to 50% at 9 months and 25% at 12 months. The increased medial fibrosis noted in the second biopsies (60 vs 33% in primary temporal artery biopsies) suggested that the finding may represent a chronic finding in arteritis. In summary, the response to glucocorticoids in giant cell arteritis was frequently discordant. Clinical manifestations were readily suppressed, but vascular changes were gradual and often incomplete.

Glucocorticoid therapy causes contradictory changes of serum Wnt signaling-related molecules in systemic autoimmune diseases.

The objective of this study was to investigate the clinical significance of the Wnt/β-catenin signaling pathway in glucocorticoid-induced osteoporosis. A total of 91 patients with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60mg daily) were prospectively enrolled. We measured serum levels of N-terminal peptide of type I procollagen (P1NP), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), N-telopeptide cross-linked type I collagen (NTX), sclerostin, Dickkopf-1 (Dkk-1), and Wnt3a before starting glucocorticoid therapy and every week for 4weeks after its initiation. The effects of dexamethasone on expression of mRNA and protein of sclerostin and Dkk-1 by cultured normal human osteoblasts (NHOst) were evaluated by RT-PCR and ELISA, respectively. Serum levels of sclerostin and Dkk-1 increased significantly by 1week of glucocorticoid therapy and then decreased from the second week onward. Serum Wnt3a tended to decrease and serum P1NP showed a significant decrease. However, TRACP-5b was significantly elevated from the first week of treatment onwards. In vitro study, dexamethasone increased Dkk-1 mRNA expression in cultured NHOst, but sclerostin mRNA was not detected. Dexamethasone also increased Dkk-1 protein production by osteoblasts, whereas sclerostin protein was not detected. Bone formation might be impaired at least in the first week of the initiation of glucocorticoid therapy by increase of the serum Wnt signaling inhibitors; however, their reductions in the subsequent weeks were contradictory to the maintained suppression of the bone formation markers after glucocorticoid therapy for patients with systemic autoimmune diseases.

Apparent Hypothalamic-Pituitary-Adrenal Axis Suppression via Reduction of Interleukin-6 by Glucocorticoid Therapy in Systemic Autoimmune Diseases.

ContextSuppression of the hypothalamic-pituitary-adrenal (HPA) axis is a serious complication of systemic glucocorticoid therapy.ObjectiveTo clarify the influence of proinflammatory cytokines on the HPA axis after onset of glucocorticoid therapy in patients with systemic autoimmune diseases.Patients and MethodsForty-eight glucocorticoid-naïve patients with systemic autoimmune diseases (28 women) who were starting prednisolone therapy according to our standard regimens were prospectively observed. Patients were classified into high-dose and low-dose groups depending on the dose of prednisolone administered as indicated for their diseases. Plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels were measured by electrochemiluminescence immunoassay. The corticotropin-releasing hormone (CRH) test was performed at baseline and second and forth weeks after starting glucocorticoid therapy. The increased levels of ACTH (ΔACTH) and cortisol (Δcortisol) were investigated. Serum levels of 10 proinflammatory cytokines were measured simultaneously by a multi-spot assay system.ResultsIn the high-dose group, both basal and stimulated levels of ACTH and cortisol were significantly decreased by glucocorticoid therapy. In the low-dose group, basal ACTH and cortisol levels were also significantly decreased by glucocorticoid therapy, but ΔACTH and Δcortisol were unchanged. Among 10 cytokines, only interleukin (IL)-6 was significantly decreased by glucocorticoid therapy in both groups and was more closely correlated with cortisol than ACTH. Basal cortisol level was positively correlated with serum IL-6 level in all patients before glucocorticoid therapy.ConclusionIn patients with systemic autoimmune diseases, apparent suppression of cortisol during glucocorticoid therapy may be partly mediated by reduced production of IL-6.

Serum Resistin Level and Progression of Atherosclerosis during Glucocorticoid Therapy for Systemic Autoimmune Diseases.

Adipokines are important regulators of several processes, including inflammation and atherosclerosis. In patients with systemic autoimmune diseases, atherosclerosis is accelerated with higher cardiovascular morbidity and mortality. We prospectively investigated the association of adipokines and glucocorticoid therapy with progression of premature atherosclerosis in 38 patients starting glucocorticoid therapy for systemic autoimmune diseases. To detect premature atherosclerosis, carotid ultrasonography was performed at initiation of glucocorticoid therapy and after a mean three-year follow-up period. The ankle-brachial pressure index and cardio-ankle vascular index (CAVI) were measured. Serum adipokine levels were determined with enzyme-linked immunosorbent assay kits. Twenty-three patients (60.5%) had carotid artery plaque at baseline. The carotid artery intima-media thickness (IMT) increased significantly during follow-up. Glucocorticoids reduced the serum resistin level, while increasing serum leptin and high molecular weight-adiponectin. There was slower progression of atherosclerosis (carotid IMT and CAVI) at follow-up in patients with greater reduction of serum resistin and with higher cumulative prednisolone dose. In conclusion, progression of premature atherosclerosis occurred at an early stage of systemic autoimmune diseases before initiation of glucocorticoid therapy. Since resistin, an inflammation and atherosclerosis related adipokine, is reduced by glucocorticoids, glucocortidoid therapy may not accelerate atherosclerosis in patients with systemic autoimmune diseases.

Osteoporosis prevention among chronic glucocorticoid users: results from a public health insurance database

IntroductionLong-term glucocorticoid therapy is the leading cause of secondary osteoporosis. The management of glucocorticoid-induced osteoporosis (GIOP) seems to be inadequate in many European countries.ObjectiveTo evaluate the rate of screening and...

Resistin is associated with the inflammation process in patients with systemic autoimmune diseases undergoing glucocorticoid therapy: comparison with leptin and adiponectin

Objectives: We investigated the role of adipokines in patients with systemic autoimmune diseases who received glucocorticoid therapy.Methods: Fifty-two patients with systemic autoimmune diseases who had started glucocorticoid therapy were prospectively enrolled. One hundred forty healthy persons were also studied as controls. Serum levels of 3 adipokines [resistin, leptin, and high molecular weight (HMW)-adiponectin] were measured with enzyme-linked immunosorbent assay kits before and at weekly intervals for 4 weeks during glucocorticoid therapy. The effects of lipopolysaccharide and dexamethasone on adipokine expression in human peripheral blood mononuclear cells (PBMCs) were also examined.Results: The serum resistin level was significantly higher in patients than in controls before glucocorticoid therapy, and it decreased after glucocorticoid therapy. Consistent with these results, dexamethasone inhibited lipopolysaccharide-induced upregulation of resistin expression in PBMCs in vitro. Serum leptin and HMW-adiponectin levels were lower in the patients than in the controls at baseline, and both adipokine levels were increased after glucocorticoid therapy. There was a significant correlation between serum resistin and high-sensitivity C-reactive protein. However, there was no association between serum adipokines and intima-media thickness.Conclusion: Resistin may be associated with the inflammatory process but not atherosclerosis in patients with systemic autoimmune diseases.

Changes of Serum Soluble Receptor Activator for Nuclear Factor-κB Ligand after Glucocorticoid Therapy Reflect Regulation of Its Expression by Osteoblasts

Osteoporosis is a serious complication of systemic glucocorticoid therapy. The role of serum soluble receptor activator for nuclear factor-κB ligand (RANKL) in glucocorticoid-induced osteoporosis remains unclear. The objective of the study was to clarify the influence of serum soluble RANKL on the osteoprotegerin (OPG)/RANKL/receptor activator for nuclear factor-κB system in patients with systemic autoimmune diseases receiving glucocorticoid therapy. Sixty patients (40 women) with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60 mg/d) plus bisphosphonate therapy were prospectively enrolled. Serum soluble RANKL and OPG levels were measured at 0, 1, 2, 3, and 4 wk after starting glucocorticoid therapy. The effects of dexamethasone on production of RANKL and OPG mRNA and protein by cultured normal human osteoblasts were evaluated by RT-PCR and ELISA, respectively. The mean serum soluble RANKL level of the patients was unchanged by glucocorticoid therapy. Because the distribution of serum soluble RANKL was bimodal, the patients were stratified into two groups. Serum soluble RANKL decreased significantly in the higher soluble RANKL group (≥0.16 pmol/liter), whereas it increased significantly in the lower soluble RANKL group. The mean serum OPG level of the patients decreased significantly. Bone mineral density increased in the higher soluble RANKL group after starting glucocorticoid therapy, whereas it decreased in the lower soluble RANKL group. In cultures of unstimulated human osteoblasts, RANKL mRNA expression was increased and OPG mRNA was decreased by dexamethasone. Up-regulation of RANKL and OPG mRNA by IL-6 was suppressed by dexamethasone. Serum soluble RANKL might be a useful marker of bone remodeling in patients with systemic autoimmune diseases receiving glucocorticoid therapy.

Resistin is associated with the inflammation process in patients with systemic autoimmune diseases undergoing glucocorticoid therapy: comparison with leptin and adiponectin

We investigated the role of adipokines in patients with systemic autoimmune diseases who received glucocorticoid therapy. Fifty-two patients with systemic autoimmune diseases who had started glucocorticoid therapy were prospectively enrolled. One hundred forty healthy persons were also studied as controls. Serum levels of 3 adipokines [resistin, leptin, and high molecular weight (HMW)-adiponectin] were measured with enzyme-linked immunosorbent assay kits before and at weekly intervals for 4weeks during glucocorticoid therapy. The effects of lipopolysaccharide and dexamethasone on adipokine expression in human peripheral blood mononuclear cells (PBMCs) were also examined. The serum resistin level was significantly higher in patients than in controls before glucocorticoid therapy, and it decreased after glucocorticoid therapy. Consistent with these results, dexamethasone inhibited lipopolysaccharide-induced upregulation of resistin expression in PBMCs in vitro. Serum leptin and HMW-adiponectin levels were lower in the patients than in the controls at baseline, and both adipokine levels were increased after glucocorticoid therapy. There was a significant correlation between serum resistin and high-sensitivity C-reactive protein. However, there was no association between serum adipokines and intima-media thickness. Resistin may be associated with the inflammatory process but not atherosclerosis in patients with systemic autoimmune diseases.

A Preliminary Study on the Effect of "Low-dose" Glucocorticoid Therapy for Patients with Persistent Acute Respiratory Distress Syndrome

Background: The role of glucocorticoids for treating persistent acute respiratory distress syndrome (ARDS) is matter of debate. In the previous studies, the side effects of moderate doses of glucocorticoids might have negated positive effects of glucocorticoids. This study aimed at determining the feasibility of administering “low-dose” glucocorticoid to treat the patients who suffer with persistent ARDS. Methods: We retrospectively reviewed the medical records of twelve patients with ARDS of at least seven days’ duration and who were treated with “low-dose” glucocorticoid (starting dose of 1 mg/kg) between June 2007 to December 2008. The patients were divided by whether or not they were successfully weaned from the ventilator after glucocorticoid therapy. The baseline characteristics and physiologic parameters were recorded for up to 7 days after starting glucocorticoid therapy. Results: Five patients (42%) were included in the weaned group. There was no significant difference in the clinical characteristics and the physiologic parameters between the two groups on the day of ARDS. Yet the weaned group had a significantly lower Sequential Organ Failure Assess ment (SOFA) score, as compared to that of the failed group [3 (3−6) vs 8 (5− 12), p = 0.009)] at start of glucocorticoid treatment. After 3 days of glucocorticoid therapy, there was significant improvement in the PEEP, the PaO2/FIO2 ratio, the PCO2 , the SOFA score and the Murray Lung Injury Score of the weaned group, as compared to th at of the failed group. There were no major neuromuscular side effects from the therapy. Conclusions: This study suggests that the “low-dose” glucocorticoid therapy is feasible and that the SOFA score and the physiologic parameters may assist in determining whether or not to initiate and to continue glucocorticoid therapy for the patients who are suffering with persistent ARDS.