cosyntropin and Arthritis--Rheumatoid

To assess the additional benefit of synacthen depot over standard inpatient care for patients hospitalized with active rheumatoid arthritis (RA).. All patients admitted to our unit with active RA without exclusion criteria were invited to participate and randomized to subcutaneous synacthen depot 0.5 mg on alternate days for 2 injections or 2 injections of saline. Patients, staff, and assessors of response were blinded to the intervention. Assessment [OMERACT set, American College of Rheumatology (ACR) global improvement, dose of intraarticular (IA) or intramuscular (IM) methylprednisolone] was performed at admission to hospital, at discharge, and at 3 and 6 months. Oral prednisone use constituted a protocol violation.. Of 137 patients with RA admitted over the period of recruitment, 36 (26%) were enrolled; 31 completed followup. There were no between-group differences in the change from admission of any individual disease activity measure at any time point. However, using a rigorous global response measure (ACR 50%), a difference was detected in favor of synacthen depot at discharge (52.6% of the intervention group improved vs. 17.6% of controls; p = 0.029, number-needed-to-treat 2.86). Patients treated with synacthen depot showed a trend toward more IA or IM corticosteroid between discharge and 3 months (mean dose 56 vs. 31 mg; p = 0.19) and a trend toward more patients requiring a change in slow acting antirheumatic drug after discharge (4 vs. 1; p = 0.27).. There is some additional benefit of synacthen depot in the hospital treatment of RA, but the effect is lost by 3 months, with a suggestion of rebound worsening in these patients. We postulate that oversuppression of corticotrophin releasing hormone by exogenous adrenocorticotrophic hormone in patients who already have a hypothalamic deficit may contribute to the rebound worsening of disease activity seen in these patients.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cosyntropin; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Inpatients; Male; Methylprednisolone; Middle Aged; Patient Selection; Placebos; Treatment Outcome

The effect of synthetic adrenocorticotrophic hormone (Synacthen), in conjunction with hydroxychloroquine, aurothioglucose, or penicillamine, was evaluated retrospectively in 21 patients with rheumatoid arthritis (RA). One mg of depo Synacthen was administered at increasing intervals of 4 to 14 days for a total period of 3 to 7 months. Fourteen patients with RA on either hydroxychloroquine or aurothioglucose and not on Synacthen, served as controls. Patients in the Synacthen group were, on the whole, sicker, as indicated by a lower functional capacity, higher mean erythrocyte sedimentation rate, and systemic and articular indices. Physicians' estimate of the patients condition after 1 - 2 months of therapy showed no improvement or deterioration in 10 out of 13 cases in the control group. Likewise, the erythrocyte sedimentation rate decreased significantly more and seronegativity was achieved in more of the Synacthen-treated cases. Six to 8 months after the beginning of therapy (1 to 4 months after cessation of Synacthen) clinical improvement was comparable in both groups, although seroconversion was more common in patients who had received Synacthen (7 out of 10 as compared to 1 out of 7 respectively). It is suggested that Synacthen may be used safely in the early phase of selected RA patients, until the effect of second-line drugs is achieved.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Arthritis, Rheumatoid; Aurothioglucose; Blood Sedimentation; Clinical Trials as Topic; Cosyntropin; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Injections, Intramuscular; Male; Middle Aged; Penicillamine; Retrospective Studies; Time Factors

To examine adrenal cortex reserve in patients with rheumatic and musculoskeletal diseases (RMD) who relapse upon tapering of low glucocorticoid dose, despite concomitant treatment with disease-modifying anti-rheumatic drugs (DMARDs).. A morning standard dose of 250 mcg tetracosactide (Synacthen test) was given in 25 consecutive patients (13 rheumatoid arthritis, 2 psoriatic arthritis, 5 systemic lupus erythematosus, 2 dermatomyositis, 1 systemic sclerosis, 2 temporal arteritis) at the time of relapse upon small reductions (1-2 mg daily) of low prednisolone dose (<7.5 mg daily), while being on stable concomitant treatment with methotrexate, leflunomide, hydroxychloroquine, azathioprine, mycophenolate, tofacitinib, belimumab, anti-TNF, anti-IL-6 or anti-IL-1 regimens (n=14; 3; 9; 1; 2; 1; 1; 5; 2; 1, respectively). Sex-matched apparently healthy individuals (n=45) served as controls.. Baseline cortisol levels and time-integrated cortisol response to tetracosactide were lower in patients than controls (12.01±4.47 vs. 15.63±4.16 mcg/dl, p=0.001, and 1050±286 vs. 1284±182, p<0.001, respectively). No significant associations were observed between the cortisol response to tetracosactide and age, duration of disease or glucocorticoid treatment. An abnormal Synacthen test, indicative of adrenal insufficiency, presumably secondary to chronic glucocorticoid administration, was noted in 5/25 patients. The remaining 20 patients (80%) had normal Synacthen test demonstrating, however, lower cortisol response than controls, independently of age (β-coefficient=-0.373, p=0.033).. Patients with RMD in remission under DMARDs who relapse upon concomitant low glucocorticoid dose tapering should be tested for iatrogenic adrenal insufficiency. Whether a marginally normal Synacthen test should discourage further attempts to withdraw glucocorticoid treatment in these patients warrants further investigation.

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Adrenal Insufficiency; Antirheumatic Agents; Arthritis, Rheumatoid; Azathioprine; Chronic Disease; Cosyntropin; Glucocorticoids; Humans; Hydrocortisone; Hydroxychloroquine; Leflunomide; Methotrexate; Prednisolone; Recurrence; Tumor Necrosis Factor Inhibitors

Twenty eight patients who received corticosteroids for rheumatoid arthritis for at least five years were studied. Short synacthen tests were carried out in twenty two of these patients and twelve showed a subnormal response. This response was unrelated to initial or present dose, duration of treatment or activity of disease. Ten patients accepted our offer of steroid reduction. Reduction proved difficult because of patient resistance although the only index of inflammation to worsen was the articular index. We postulate that patient resistance to withdrawal may be due to some factor other than the loss of the anti-inflammatory effect of corticosteroids.

Topics: Adrenal Glands; Adult; Aged; Arthritis, Rheumatoid; Cosyntropin; Female; Humans; Injections, Intravenous; Male; Middle Aged; Prednisolone; Time Factors

Topics: Arthritis, Rheumatoid; Cosyntropin; Drug Evaluation; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Injections, Intra-Articular; Knee Joint; Pituitary-Adrenal System; Triamcinolone Acetonide

An attempt was made to convert 24 patients on corticosteroid treatment from a daily to an alternate daily regimen. Ten patients were successfully converted, 11 failed to convert, and 3 had to be withdrawn for irrelevant reasons. A simple tetracosactrin stimulation test gave some indication of which patients were more likely to convert successfully. Success was not influenced by severity or duration of disease, nor by dose of duration of steroid therapy. Conversion did not influence various clinical and laboratory measures of undesirable steroid side effects, but the follow-up period was probably too short to judge this. The evidence of others suggests that conversion is worth attempting.

Topics: Adrenal Cortex Function Tests; Adult; Aged; Arthritis, Rheumatoid; Cosyntropin; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prednisolone; Time Factors

Thirty-two female patients with rheumatoid arthritis were divided into 3 groups and treated for 6 months with prednisolone, depot tetracosactrin, or indomethacin. Their whole body content of calcium, phosphorus, and nitrogen was measured before and after 3 and 6 months' treatment by in-vivo neutron activation analysis. No significant changes in these body elements were observed as a result of the treatments. The average amounts of calcium, phosphorus, and nitrogen were lower than normal in these patients, a finding consistent with the frequent observation of osteoporosis and muscle wasting in rheumatoid arthritis.

Topics: Adult; Aged; Arthritis, Rheumatoid; Body Composition; Calcium; Cosyntropin; Female; Humans; Indomethacin; Middle Aged; Neutron Activation Analysis; Nitrogen; Phosphorus; Prednisolone; Time Factors; Whole-Body Counting

Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Arthritis, Rheumatoid; Cosyntropin; Humans

Topics: Adrenocorticotropic Hormone; Arthritis, Rheumatoid; Cosyntropin; Drug Eruptions; Humans; Urticaria

Topics: Adrenal Cortex Function Tests; Adrenocorticotropic Hormone; Arthritis, Rheumatoid; Cosyntropin; Drug Therapy, Combination; Glucocorticoids; Humans

The addition of phenobarbitone in therapeutic dosage to the drug regimen of prednisolone-treated subjects with rheumatoid arthritis produced measurable deterioration in the clinical status of the patients associated with a more rapid clearance of prednisolone from plasma. It is considered that phenobarbitone induced the hepatic metabolism of prednisolone, effectively reducing the steady state plasma level and resulting in clinical relapse. A slight but significant improvement in the adrenocortical response to tetracosactrin (Synacthen) was noted after phenobarbitone therapy.

Topics: 11-Hydroxycorticosteroids; Adult; Aged; Arthritis, Rheumatoid; Cosyntropin; Drug Interactions; Enzyme Induction; Half-Life; Humans; Microsomes, Liver; Middle Aged; Phenobarbital; Prednisolone

Topics: Adrenocorticotropic Hormone; Adult; Aged; Arthritis, Rheumatoid; Cosyntropin; Drug Evaluation; Female; Gout; Humans; Injections; Male; Middle Aged

44 patients with acute irritations of degenerative articular diseases and 66 patients with soft tissue rheumatism were treated with Synacthen Depot (tetracosactide hexacetate 1 mg/ml). During the first three days of treatment the patients received an average of 2 ampoulbs Synacthen Depot, then treatment was continued at 3-4 day intervals. In the degenerative joint disease group 86.4% and 89.4% in the group with soft tissue rheumatism became free of complaints or improved with the ACTH treatment. Most of the patients with degenerative joint diseases needed a 4 week treatment; 1/3 of the patients with soft tissue rheumatism were already free of complai

Topics: Acute Disease; Adrenocorticotropic Hormone; Adult; Aged; Arthritis, Rheumatoid; Cosyntropin; Delayed-Action Preparations; Drug Evaluation; Female; Fibromyalgia; Hip Joint; Humans; Joint Diseases; Knee Joint; Male; Middle Aged; Rheumatic Diseases; Spondylitis

Lymphocyte transformation to 1-24ACTH, as assessed by the incorporation of tritiated thymidine, has been demonstrated to be associated with severe adverse reactions occurring in patients receiving a Zn-linked 1-24ACTH preparation (Tetra cosactrin depot, 'Synacthen'). Antibodies measured with an isotope-binding assay occurred commonly in all patients receiving therapy and did not correlate with adverse reactions. Lymphocyte transformation with the 1-24ACTH polypeptide, a part of the naturally occurring ACTH molecule, has not been previously recorded. The significance of antibodies and cell-mediated immunity to this polypeptide hormone is discussed.

Topics: Adrenocorticotropic Hormone; Adult; Antibodies; Arthritis, Rheumatoid; Asthma; Child; Cosyntropin; Drug Hypersensitivity; Female; Humans; Immunity, Cellular; Lymphocyte Activation; Male; Middle Aged; Zinc

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cosyntropin; Gastrins; Glycyrrhiza; Humans; Indomethacin; Male; Phytotherapy; Plants, Medicinal; Radioimmunoassay; Rats; Secretin; Succinates; Terpenes; Time Factors

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Arthritis, Rheumatoid; Circadian Rhythm; Cosyntropin; Female; Humans; Hydrocortisone; Hypoglycemia; Hypothalamo-Hypophyseal System; Insulin; Lysine; Male; Metyrapone; Middle Aged; Vasopressins

Topics: Adrenocorticotropic Hormone; Arthritis; Arthritis, Rheumatoid; Biomedical Research; Cosyntropin; Dermatitis Herpetiformis; Drug Eruptions; Drug Hypersensitivity; Drug Therapy; Genetic Diseases, X-Linked; Immune Sera; Immunodiffusion; Leukemia, Hairy Cell; Lymphatic Diseases; Precipitin Tests; Severe Combined Immunodeficiency; Skin Tests; Toxicology