The Kidney and Hypertension Center, Cincinnati, Ohio.
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
Clin Endocrinol (Oxf). 2019 Jan;90(1):214-221. doi: 10.1111/cen.13886. Epub 2018 Nov 14.
Activating antibodies directed at the extracellular calcium-sensing receptor (CaSR) have been described in autoimmune hypoparathyroidism in the setting of isolated hypoparathyroidism or autoimmune polyglandular syndrome type 1.
A 34-year-old female presented with hypocalcaemia (6.0 mg/dL) and hypomagnesaemia (1.1 mg/dL) accompanied by low serum PTH (2.4 pg/mL) as well as urinary calcium and magnesium wasting. She was diagnosed with hypoparathyroidism, which was refractory to standard therapy. She was started on 60 mg prednisone and 150 mg azathioprine treatment daily on suspicion of an autoimmune aetiology. The patient was tested for CaSR antibodies.
The patient was positive for CaSR antibodies of the IgG1 subtype, which stimulated phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and inositol phosphate (IP) accumulation. Post-treatment with prednisone and azathioprine, her serum calcium and magnesium normalized, as did her CaSR antibody titre and antibody-mediated stimulation of ERK1/2 phosphorylation and IP accumulation.
This is the first demonstration of CaSR antibody-mediated hypoparathyroidism responsive to immunosuppressive therapy, adding to the evidence that autoimmune hypoparathyroidism can be, in some cases, reversible and not the result of autoimmune parathyroid destruction.
在孤立性甲状旁腺功能减退症或自身免疫性多腺体综合征 1 型中，已描述了针对细胞外钙敏感受体 (CaSR) 的激活抗体。
一名 34 岁女性因低钙血症（6.0mg/dL）和低镁血症（1.1mg/dL）伴低血清 PTH（2.4pg/mL）以及尿钙和镁丢失而就诊。她被诊断为甲状旁腺功能减退症，对标准治疗无反应。怀疑自身免疫病因，她开始每天接受 60mg 泼尼松和 150mg 硫唑嘌呤治疗。对 CaSR 抗体进行了检测。
该患者的 IgG1 亚型 CaSR 抗体呈阳性，可刺激细胞外信号调节激酶 1 和 2 (ERK1/2) 的磷酸化和肌醇磷酸盐 (IP) 积累。泼尼松和硫唑嘌呤治疗后，血清钙和镁恢复正常，CaSR 抗体滴度和抗体介导的 ERK1/2 磷酸化和 IP 积累刺激也恢复正常。
这是首次证明 CaSR 抗体介导的甲状旁腺功能减退症对免疫抑制治疗有反应，这增加了证据表明，自身免疫性甲状旁腺功能减退症在某些情况下是可逆的，而不是自身免疫性甲状旁腺破坏的结果。
