Endocrine Abstracts

CaSR-autoantibodies may cause auto-immune hypercalcemia through either simple blocking or biased properties. The phenotype of this rare disease is most often acquired hypocalciuric hypercalcemia (AAH) (Minanbres JCEM 2020, Makita JCI insight 2022), but sometimes hyperparathyroidism (Pelletier-Morel Intern Med 2008), in elderly. Gender, auto-immune context is variable. Blood calcium may fluctuate, and acute exacerbations may be successfully treated with prednisolone and/or calcimimetics. We present two cases of CaSR-antibodies-associated hypercalcemia with a different phenotype

Case#1: A 80-year-old women (BMI 29) had a history of cured endometrial cancer, auto-immune, thyroiditis and sclerodermic-like syndrome (Sjögren and Raynaud syndrome with severe hypertension, increased level of anti-nuclear centromeric autoantibodies (1/512^th)). In 2002, detectable CaSR-antibodies with normal calcemia (97 mg/l), hypocalciuria (78 mg/24 h), mild 25-OHvitamin D deficiency (21 pg/ml), normal PTH level (36 pg/ml) and moderate CD4 and B lymphopenia was disclosed in a systematic autoimmune screening, after an episode of oral candidosis, without identified pathogenic variant of the AIRE gene. In 2015, she was operated from breast carcinoma. In 2022, blood calcium level was increased (107 mg/l), with normal phosphatemia (37 mg/l), low 25-OH-vitamin D (25 ng/ml) and persistent anti-CASR and anti-nuclear autoantibodies. No parathyroid hypertrophy was identified on US examination.

Case#2: A 70-year-old lady, BMI 30, with a history of cured endometrioid uterine adenocarcinoma was referred for recurrence of hypercalcemia 12 years after a left upper parathyroidectomy with total thyroidectomy for a typical biological hyperparathyroidism profile with hypercalciuria and osteopenia, associated to multinodular goiter without thyroid antibodies. Morphological parathyroid investigations were discordant, but after surgery, blood calcium dropped from 119 to 95 mg/l and remained so until 2019, where a profile of hyperparathyroidism reappeared with the presence of renal lithiasis. There was no excess of 25 or 1-25-OHvitamin D. Calciuria, PTH and CaSR-antibodies levels were increased, without other positive auto-antibodies. The NGS study of the MEN1, HRPT2, CASR, AP2S1, GNA11 and GCM2 genes was negative. Morphological investigations remained discordant.

Conclusion: The presence of CaSR-autoantibodies in these 2 elderly female cases of hypercalcemia: without overt parathyroid adenoma, suggest an auto-immune component to this hypercalcemia. Case#1 had an asymptomatic profile of AAH in an autoimmune context with long-term preexisting CaSR-antibodies. Case#2 had a profile of hyperparathyroidism without autoimmune context except for CaSR-antibodies. Both had a neoplastic history. Measurement of CaSR-autoantibodies in atypical cases of hypercalcemia with discordant morphological investigations could help to orientate diagnosis towards an autoimmune cause and a medical treatment. The functionality of CaSR-antibodies may explain the different phenotypes.