VITAMIN D RESISTANT HYPOPARATHYROIDISM - IMPAIRED RESPONSE TO 1,25 DIHYDROXYCHOLECALCIFEROL (1,25 DHCC)

Abstract

Resistance to vitamin D is an unusual, frustrating complication of hypoparathyroidism. Magnesium depletion, coincident malabsorption, ↓hepatic or renal hydroxylation, and ↓Ca++ mobilization from bone are postulated mechanisms, but do not explain relative resistance to all vitamin D sterols, including 1,25 DHCC in three patients recently encountered at two institutions.A.G., a 14 year old calciferol-resistant boy with idiopathic hypoparathyroidism, candidiasis and mild malabsorption, maintained for 4 years with oral Dihydrotachysterol (DHT), 4-6 mg/day, suddenly became refractory to DHT in doses up to 15 mg, daily. Oral 1,25 DHCC to 10 μg was ineffective once daily and unaltered by parenteral Mg SO4. A calcemic response to low dose (20-100 U.) PTH was observed. Response to 1,25 DHCC was achieved only with frequent administration (3 μg. q. 6 hours) + 30 Cm elemental Ca++/day. Two other hypoparathyroid patients, one surgical, have been found resistant to calciferol, DHT and ordinary doses of 1,25 DHCC. One responded to 5 μg once daily and has stabilized with 1-2 μg/day, while the other responds to a 5 μg daily dose only with IM parathormone, 20-40 U./day.Plasma 1,25 DHCC (Dr. H. DeLuca) was normal in all 3 patients immediately following ingestion. Preliminary data in A.G. showing a rapid decline in plasma 1,25 DHCC suggest that accelerated sterol metabolism may account for his apparent “resistance”.