Endocrine Abstracts

Introduction: ADH1, caused by gain of function (GoF) variants in the Calcium Sensing Receptor (CASR), leads to hypoparathyroidism, hypocalcaemia, seizures, hyperphosphatemia, hypomagnesaemia, and severe hypercalciuria. Conventional treatment (alphacalcidol and calcium) can cause nephrocalcinosis, renal impairment and may not reduce seizures. Our previous data on six patients showed that CSPI via insulin pump increases serum calcium and reduces seizures, hospital admissions, and calcium excretion (mean CSPI duration=3.2±0.6 years). This retrospective observational study provides long-term data on CSPI’s safety and efficacy.

Methods: Five ADH1 patients, aged 6-30years, treated with CSPI for 8.22±1.26 years, were included. The sixth patient stopped CSPI after renal and parathyroid transplantation. All had GoF CASR variants and recurrent hypocalcaemic seizures requiring hospital admission before CSPI. Data on serum calcium, calciuria, seizures, growth, bone mineral density (BMD), and hospital admissions were collected semi-annually from January 2018.

Results: Results of CSPI treatment (duration 5.99-9.01 years):

Patient(P)1 (8.77yo*): CSPI:8.67years, corrected calcium(cCa):1.98±0.31(1.55,2.71) mmol/l**, UCa/Cr***:1.12±0.61(0.48,2.50)**.

P2 (9.43yo*): CSPI:8.58years, cCa:1.94±0.36(1.49,2.57) mmol/l**, UCa/Cr***:0.74±0.29(0.27,1.19)**.

P3 (30.86yo*): CSPI:8.86years, cCa:1.90±0.20(1.7,2.35) mmol/l**, UCa/Cr***:0.58±0.23(0.21,0.87)**.

P4 (9.15yo*): CSPI:9.01years, cCa:2.06±0.28(1.41,2.48) mmol/l**, UCa/Cr***:0.49±0.21(0.13,0.74)**.

P5 (6.23yo*): CSPI:5.99years, cCa:2.27±0.22(1.89,2.6) mmol/l**, UCa/Cr***:0.45±0.31(0.14, 1.00)**.

*yo=years old

**Mean±SD(Minimum, Maximum)

***Urine Calcium/Creatinine Ratio

Mean total hospital admission duration was 6.8±8.3(0,21)**days/patient. P2 and P3 had one seizure. Four patients had stable/no nephrocalcinosis, P1 developed mild nephrocalcinosis. Four patients developed other conditions (autoimmune hypothyroidism, frequent vomiting, anxiety/depression, dental issues, central precocious puberty); the relationship between these and CSPI/ADH1 is unclear. Intellectual development, height, weight and BMD remained normal for patients initiating CSPI before age 1 year. P3 has short stature and learning difficulties.

Conclusion: CSPI remains a safe and effective long-term treatment for children and young people with ADH1, maintaining serum calcium and normal calcium excretion. Our patients had a small number of seizures and only a few days of admission despite severe ADH1. CSPI is a viable option for severe ADH1 in the absence of other effective treatment.