Hypoparathyroidism caused by gain-of-function mutations of the
calcium-sensing receptor (CaR) in the transmembrane domain is usually severe and difficult to manage. A patient with severe
hypoparathyroidism, caused by CaR activating mutation F821L, was treated for 3 days (Day 1 to Day 3) with synthetic
human parathyroid hormone 1-34 (
teriparatide, PTH). An Ellsworth-Howard test of the patient revealed normal responses of urine
phosphate and
cyclic AMP excretion, indicating that the patient's renal tubules normally responded to extrinsic PTH. On Day 1 to Day 3, 0.9 microg/kg/day of PTH was administered subcutaneously twice daily at 0800 and 2000. On Day 1, the serum
calcium level that was 1.8 mmol/l before PTH administration increased to 2.1 mmol/l at 1200, and gradually decreased to 1.8 mmol/l at 2000. On Days 2 and 3, the maximum
calcium levels were 2.5 and 2.4 mmol/l, respectively, at 1200. At 2000, they returned to or below basal levels at 0800. On Day 4 without PTH administration, the
calcium levels were maintained at the basal levels at Day 0. The urine
calcium/
creatinine (Ca/Cr) ratio that was high (>0.4) before PTH injection decreased after PTH administration (0.4>). Changes in the ionized
calcium levels were almost parallel with the total
calcium levels. The serum
inorganic phosphate (IP) level decreased to 2.4 mmol/l at 1000, but gradually increased before the second PTH injection to the level at 0800 on Day 1. The minimum IP level on Days 2 and 3 was 2.1 mmol/l and 2.0 mmol/l, respectively. In contrast to the remarkable changes in the serum
calcium level by PTH treatment, the serum
magnesium levels showed few changes. These results indicate that PTH
therapy could be effective in correcting serum and urine
calcium and the
phosphate levels in
hypoparathyroidism caused by activating mutation of CaR.