Acute biochemical effects of growth hormone treatment compared with conventional treatment in familial hypophosphataemic rickets.
OBJECTIVE
Conventional treatment of familial hypophosphaiaemic rickets with oral phosphate and 1 alpha-hydroxycholecalciferol (1 alpha HCC) does not satisfactorily correct the metabolic or physical defects of the disease and can have adverse effects, such as nephrocalcinosis. Hyperoxaluria from increased oral phosphate intake may contribute to nephrocalcinosis. Growth hormone enhances renal tubular phosphate reabsorption and 1,25-dihydroxy-cholecalciferol production in normal and in GH deficient individuals, and may thus be of benefit to patients with familial hypophosphataemic rickets.


METHODS
We have assessed the acute effects of GH on phosphate and calcium metabolism in 6 children (age 4-14 years) with familial hypophosphataemic rickets.


METHODS
Each patient served as his/her own control and received the following in a sequential non-randomized design: conventional treatment with oral phosphate 1.0-3.4 mmol/kg/day in 3-6 divided doses and 1 alpha HCC 18-31 ng/kg/day-no treatment-GH 0.05 mg/kg daily-GH and 1 alpha HCC-and GH with phosphate and 1 alpha HCC. Each treatment was given for 7 days with 7 day periods of no treatment in between.


RESULTS
Glomerular filtration rate, tubular maximum rate of phosphate reabsorption per litre of glomerular filtrate (TmP/GFR) and serum 1,25-dihydroxycholecalciferol increased with GH. Mean 24-hour plasma phosphate concentrations did not increase with GH but were higher in the treatment phases which included phosphate and 1 alpha HCC (P = 0.002). Serum PTH was higher when GH was given in combination with phosphate and 1 alpha HCC compared to other phases. Urine oxalate excretion did not differ between the treatment phases.


CONCLUSIONS
GH seemed to partially correct the defects in renal tubular phosphate transport and 1 alpha-hydroxylation of 25-hydroxycholecalciferol. We speculate that the net effect of GH treatment was an increase in body phosphate, although this was not reflected in a change in plasma phosphate. Therefore, GH in combination with 1 alpha HCC may act as a phosphate sparing agent, permitting treatment with lower and less frequent doses of oral phosphate and reducing adverse effects such as nephrocalcinosis.
Patel
L
L
Department of Child Health, University of Manchester, UK.
Clayton
P E
PE
Brain
C
C
Pelekouda
E
E
Addison
G M
GM
Price
D A
DA
Mughal
M Z
MZ
D000293:Adolescent; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use; D007015:Hypophosphatemia, Familial / Q000188:drug therapy* / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use
D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D010710:Phosphates; D013006:Growth Hormone; D002117:Calcitriol; D002118:Calcium; C008088:alfacalcidol