Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is increasing evidence supporting the use of corticotropin as an alternative treatment of refractory proteinuric glomerulopathies. The efficacy of short-acting corticotropin, however, remains unknown and was tested here in an adolescent with steroid-dependent nephrotic syndrome caused by minimal change disease. After developing Cushing syndrome and recently being afflicted with severe cellulitis, the patient was weaned off all immunosuppressants, including corticosteroids. This resulted in a relapse of generalized anasarca, associated with massive proteinuria and hypoalbuminemia. Subsequently, mono-therapy with short-acting animal-derived natural corticotropin was initiated and resulted in a rapid response, marked by substantial diuresis, reduction in body weight, and partial remission of proteinuria. Ten days later, the patient developed mild skin rash and subcutaneous nodules at injection sites. A relapse followed despite doubling the dose of corticotropin, consistent with delayed-onset resistance to treatment. Immunoblot-based antibody assay revealed de novo formation of antibodies in the patient's serum that were reactive to the natural corticotropin. In cultured melanoma cells known to express abundant melanocortin receptors, addition of the patient's serum strikingly mitigated dendritogenesis and cell signaling triggered by natural corticotropin, denoting neutralizing properties of the newly formed antibodies. Collectively, short-acting natural corticotropin seems effective in steroid-dependent nephrotic syndrome. De novo formation of neutralizing antibodies is likely responsible for acquired resistance to corticotropin therapy. The proof of concept protocols established in this study to examine the anticorticotropin neutralizing antibodies may aid in determining the cause of resistance to corticotropin therapy in future studies.
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PMID:Acquired Resistance to Corticotropin Therapy in Nephrotic Syndrome: Role of De Novo Neutralizing Antibody. 2864 75

A 74-year old man presented to us with difficulty urinating. The laboratory examinations revealed an elevated prostate-specific antigen (PSA) level. A prostate biopsy revealed prostate adenocarcinoma. The computed tomography scan showed metastasis to lymph nodes in the pelvic cavity and both adrenal glands. Combined androgen blockade therapy was started, and PSA levels began to decrease gradually. However, 2 months later, he was hospitalized for treatment of cellulitis and was found to have hypertension, hyperglycemia, and hypokalemia. Endocrinological studies showed elevated serum adrenocorticotropic hormone (ACTH) and serum and urinary cortisol levels. The plasma cortisol level was not reduced by either the 1 mg or 8 mg dexamethasone suppression test, and the plasma cortisol and ACTHlevels did not respond to the corticotropin-releasing hormone test. Computed tomography indicated increased metastasis, and endocrinological studies and other examinations suggested a diagnosis of ectopic ACTHsyndrome. Combined androgen blockade therapy was continued, and inhibitors of adrenocortical synthesis were also administered. However, 16 weeks later, he died of prostate cancer. On autopsy, the histological examination revealed small cell carcinoma in the prostate and adrenal glands and other sites of metastasis, while immunohistochemistry findings revealed that the tumors in the prostate and adrenal glands were strongly positive for ACTH.
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PMID:[Development of Ectopic Adrenocorticotropic Hormone Syndrome in a Patient with Prostate Cancer during Combined Androgen Blockade Therapy]. 2977 20