Autoimmune Hypocalciuric Hypercalcemia Unresponsive to Glucocorticoid Therapy in a Patient with Blocking Autoantibodies against the Calcium-Sensing Receptor

Autor: Anthony P. Weetman, David M. Slovik, Edward M. Brown, J. Carl Pallais, Clemens Bergwitz, E. Helen Kemp, Lakshmi Kantham
Rok vydání: 2011
Předmět:
musculoskeletal diseases
medicine.medical_specialty
endocrine system diseases
Inositol Phosphates
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Drug Resistance
Parathyroid hormone
medicine.disease_cause
Biochemistry
Hypocalciuria
Autoimmune Diseases
Autoimmunity
Endocrinology
Prednisone
Internal medicine
medicine
Humans
Immunoprecipitation
Phosphorylation
Antibodies
Blocking
Extracellular Signal-Regulated MAP Kinases
Receptor
Glucocorticoids
Aged
Autoantibodies
Endocrine Care
business.industry
Biochemistry (medical)
Autoantibody
nutritional and metabolic diseases
Immunoglobulin E
Stimulation
Chemical
Parathyroid Hormone
Antibodies
Antinuclear
Type C Phospholipases
Immunology
Hypercalcemia
Calcium
Female
medicine.symptom
Calcium-sensing receptor
business
Receptors
Calcium-Sensing
hormones
hormone substitutes
and hormone antagonists
Glucocorticoid
medicine.drug
Zdroj: The Journal of Clinical Endocrinology & Metabolism. 96:672-680
ISSN: 1945-7197
0021-972X
DOI: 10.1210/jc.2010-1739
Popis: Autoantibodies directed against the calcium-sensing receptor (CaSR) have been reported in several individuals with various autoimmune disorders and PTH-mediated hypercalcemia. Previously, glucocorticoid treatment has been shown to decrease the CaSR autoantibody titers and normalize the hypercalcemia in a patient with autoimmune hypocalciuric hypercalcemia (AHH).The objective of the study was to evaluate a patient with AHH for the presence of blocking autoantibodies against the CaSR and to monitor her biochemical and serological responses to a trial of glucocorticoid therapy.Glucocorticoid treatment had no effect on serum total or ionized calcium concentration or serum PTH levels, all of which remained at higher than normal levels. In contrast, on prednisone, urinary calcium excretion increased from overtly hypocalciuric levels to normal values. Anti-CaSR autoantibodies were detected at similar levels in the patient's serum before, during, and after glucocorticoid treatment. Functional testing of these antibodies showed that they inhibited the stimulatory effect of extracellular Ca(2+) on ERK1/2 but did not suppress the calcium-induced accumulation of inositol-1-phosphate.We report a patient with AHH with frankly elevated PTH levels who was found to have autoantibodies against the CaSR. The hypercalcemia and CaSR autoantibody titers failed to respond to glucocorticoid therapy, unlike a previously reported patient with similar clinical and biochemical features. The anti-CaSR antibody-mediated inhibition of CaSR-stimulated ERK1/2 activity, but not of inositol-1-phosphate accumulation, suggests that ERK1/2 may mediate, at least in part, the regulation of PTH secretion and urinary calcium excretion by the CaSR.
Databáze: OpenAIRE
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