Effect of Parathyroid Hormone Administration in a Patient with Severe Hypoparathyroidism Caused by Gain-of-function Mutation of Calcium-sensing Receptor

Abstract

Abstract. 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 µg/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.

Clinical Vignette: PTH(1–34) Replacement Therapy in a Child With Hypoparathyroidism Caused by a Sporadic Calcium Receptor Mutation

“…Whereas a prior study comparing PTH to calcium and calcitriol found no difference in serum Ca 2+ between treatment groups, (3) previous work has also shown that patients with CaR mutations require higher doses of PTH to achieve a similar calcemic response compared with patients with postsurgical and/or idiopathic hypoparathyroidism. (13) This argues that the disease pathophysiology is not merely PTH deficiency, as has been suggested, (16) but that the mutated receptor itself also plays a role.…”

Activating calcium‐sensing receptor gene variants in children: a case study of infant hypocalcaemia and literature review

“…Thiazide diuretics that reduce urinary calcium excretion and raise calcium levels are also an option, but they may be associated with electrolyte abnormalities including hyponatremia and hypokalemia . Recently, twice a day, delivery of recombinant PTH 1‐34 has proven beneficial in some children with an otherwise inadequate response to oral calcium treatment , and most recently, Winer et al. found pump delivery of PTH superior to twice daily delivery with regard to a lesser degree of calciuria and magnesiuria and greater stability of serum calcium .…”

Successful treatment of vitamin D unresponsive hypoparathyroidism with multipulse subcutaneous infusion of teriparatide

“…Alternatively, hypercalciuria may also be due to a specially exquisite dependence of PTH in this patient. Also, no calcium sensor gene mutations were found (14), and although no other potential tubular defects were explored, such as concomitant magnesium, losing disorders or CLDN16 gene mutations (9,15), these possibilities were considered unlikely.…”