Disturbed calcium and phosphate homeostasis during treatment with ACTH of infantile spasms

Kidney histology of five infants who died during or immediately after treatment with adrenocorticotrophic hormone (ACTH) showed severe tubular and interstitial calcinosis. We therefore studied serum concentrations of calcium, inorganic phosphate, and parathormone, serum activities of alkaline phosphatase, and urinary excretion of calcium, inorganic phosphate, and cyclic adenosine monophosphate (cAMP) in 16 other children with infantile spasms before, during, and after 6 weeks of treatment with ACTH. During the treatment the following observations were made: hypocalcaemia developed in three infants; the mean daily urinary excretion of calcium in the group increased threefold and seven infants had hypercalciuria; the excretion of phosphate increased but its tubular reabsorption remained stable; and in most infants serum parathormone and urinary cAMP excretion increased, and in four infants they increased to supranormal concentrations. These biochemical changes were reversible in most infants. Radiographs suggested loss of bone mass by 3-4 weeks of treatment, with rapid recovery after treatment. We conclude that infants treated with ACTH for infantile spasms are at risk of suffering disturbance in calcium and phosphate homeostasis, which leads to nephrocalcinosis.