title: Rate of change (modulation) of serum growth hormone concentrations is a more important factor in determining growth rate than duration of exposure.
abstract: OBJECTIVE
  To determine whether duration of exposure to GH and/or rate of change of serum GH concentration are important factors in determining the growth rate of short children.
  
  
  METHODS
  An analysis of parameters of occupancy percentage and rate of change of serum GH concentration was performed as part of a prospective study investigating the relationship between growth and GH in childhood.
  
  
  METHODS
  Sixty-four short prepubertal children (48 male, 16 female) aged between 4.7 and 11.9 years were studied. Thirty-one children were growing with a height velocity standard deviation score between 0 and -0.8 and were defined as short normal. Thirty-three children were growing with a height velocity standard deviation score less than -0.8 and were defined as short slowly growing.
  
  
  METHODS
  Twenty-four hour serum GH concentration profiles were constructed by withdrawing samples at 20-minute intervals. Analysis of occupancy percentage was performed on each data array by determining cumulative distributions and plotting these as linear probits against log serum GH concentration. Estimates of peak (OC95), intermediate (OC50) and trough (OC5) occupancies were calculated. A first-order derivative of the concentration-time data array was determined for each profile as a measure of rate changes.
  
  
  RESULTS
  First-order derivative values were significantly greater in the short normal group than in the short slowly growing children (short normal median 1.41 mU/l/min; short slowly growing median 0.72 mU/l/min; P less than 0.001). OC95 values were significantly higher in the short normal group (median 19.31 mU/l) than the short slowly growing group (median 7.69 mU/l) (P less than 0.001). There was no difference in OC50 values. OC5 values were lower in short normal children (median 0.20 mU/l) than in the short slowly growing children (0.55 mU/l) (P less than 0.003). The most important factor in determining growth rate was the rate of change in serum GH concentration (FOD). Occupancy percentage played no part in the relationship. The regression equation was Height velocity SDS = 1.16 (In FOD) - 1.03; r = 0.75; P less than 0.001
  
  
  CONCLUSIONS
  These data suggest that the pattern of presentation of GH in the circulation is an important factor in determining target organ response. Although occupancy percentages at differing serum GH concentrations differ between short slowly growing and short normal children, it is the rate of change of the hormone in the circulation which appears to be the more important 'signal' in terms of modulating growth.
authors.affiliation: Endocrine Unit, Middlesex Hospital, London, UK.
authors.forename: P C
authors.initials: PC
authors.lastname: Hindmarsh
authors.forename: D R
authors.initials: DR
authors.lastname: Matthews
authors.forename: I
authors.initials: I
authors.lastname: Stratton
authors.forename: P J
authors.initials: PJ
authors.lastname: Pringle
authors.forename: C G
authors.initials: CG
authors.lastname: Brook
mesh_terms: D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D006130:Growth Disorders / Q000097:blood* / Q000188:drug therapy; D013006:Growth Hormone / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D013006:Growth Hormone