Table 3.

Factors hindering adequate control of secondary hyperparathyroidism during calcitriol treatments

↓ Ionized calcium

Calcium with its associated transcription factor must bind to its DNA binding site in the PTG cell nucleus in order to fully allow the silencing effect of calcitriol to decrease transcription of the PTH mRNA and thus the synthesis of PTH.

↑ Phosphorus.

↑ Stabilization of mRNA in PTG nucleus favors PTH synthesis.

↓ Ionized calcium in those with very high phosphorus.

↑ TGF-α & EGFR to stimulate PTG hyperplasia

Severe parathyroid gland hyperplasia

↓ VDR expression and decreased CaR expression→ Altered “set point” dynamics

Uncontrolled metabolic acidosis

↓ Synthesis of endogenous calcitriol from 25(OH)-vitamin D

↓ Circulating 25(OH)-vitamin D – from ↑ loss into urine (↓ megalin)

Less substrate for synthesis of calcitriol