Part of “CHAPTER 54 – VITAMIN D“

Because of the wide anatomic distribution of the sites of synthesis, metabolism, and action of vitamin D, clinical deficiency can result from disturbances at many levels (Fig. 54-8). Insufficient intake or production of vitamin D can lead to inadequate substrate concentrations for the conversion to 1,25(OH)₂D. Disturbances in the metabolism of vitamin D at the level of the liver or kidney can cause deficient production of 1,25(OH)₂D. In renal disease, a decline in the functional renal mass combined with increased phosphate retention eventually reduces or entirely eliminates 1,25(OH)₂D production. The loss or failure of parathyroid function in hypoparathyroidism or pseudohypoparathyroidism also is associated with low 1,25(OH)₂D levels. Serum concentrations are low in vitamin D–dependent rickets type I because of an inherited defect in the renal 1 α-hydroxylase enzyme. End-organ resistance in patients with vitamin D–dependent rickets type II also can result from inherited defects in the receptor mechanism for 1,25(OH)₂D. In this disorder, serum 1,25(OH)₂D levels are grossly elevated in response to hypocalcemia. For accurate assessment of vitamin D status, it often is essential to consider both 25(OH)D and 1,25(OH)₂D concentrations. For example, a low 1,25(OH)₂D level need not indicate defective renal production of the metabolite. Instead, it could result from insufficient vitamin D intake (nutritional vitamin D deficiency), indicated by the finding of a low serum 25(OH)D concentration. If, however, 1,25(OH)₂D levels are low in the face of a normal concentration of 25(OH)D, then a disturbance in the renal synthesis of 1,25(OH)₂ D₃ is likely. Further aspects of clinical disturbances in vitamin D metabolism are discussed in Chapter 61, Chapter 63 and Chapter 70.