W. M. Drake,
S. J. Howell,
J. P. Monson and
S. M. Shalet
Departments of Endocrinology, St. Bartholomew’s Hospital, London
EC1A 7BE, United Kingdom; and Christie Hospital, Manchester, United
Kingdom
Correspondence: Address all correspondence and requests for reprints to: Dr. W. M. Drake, Department of Endocrinology, St. Bartholomew’s Hospital, West Smithfield, London EC1A 7BE, United Kingdom. E-mail:
w.m.drake{at}mds.qmw.ac.uk
Until the advent of modern neuroradiological imaging techniquesin
1989, a diagnosis of GH deficiency in adults carried little
significanceother than as a marker of hypothalamo-pituitary disease.
Therelatively recent recognition of a characteristic clinical syndrome
associatedwith failure of spontaneous GH secretion and the potential
reversalof many of its features with recombinant human GH has prompted
acloser examination of the physiological role of GH after linear
growthis complete. The safe clinical practice of GH replacement
demandsa method of judging overall GH status, but there is no
biologicalmarker in adults that is the equivalent of linear growth in
achild by which to judge the efficacy of GH replacement. Assessmentof
optimal GH replacement is made difficult by the apparentdiverse
actions of GH in health, concern about the avoidanceof iatrogenic
acromegaly, and the growing realization that anindividual’s risk of
developing certain cancers may, atleast in part, be influenced by
cumulative exposure to the chiefmediator of GH action, IGF-I. As in
all areas of clinical practice,strategies and protocols vary between
centers, but most physiciansexperienced in the management of pituitary
disease agree thatGH is most appropriately begun at low doses,
building up slowlyto the final maintenance dose. This, in turn, is
best determinedby a combination of clinical response and measurement
of serumIGF-I, avoiding supraphysiological levels of this GH-dependent
peptide.Numerous studies have helped define the optimum management of
GHreplacement during childhood. The recent requirement to measureand
monitor GH status in adult life has called into questionthe
appropriateness of simplistic weight- and surface area-baseddosing
regimens for the management of GH deficiency in childhood,with
reliance on linear growth as the sole marker of GH action.It is clear
that the monitoring of parameters other than lineargrowth to help
refine GH therapy should now be incorporatedinto childhood GH
treatment protocols. Further research willbe required to define the
optimal management of the transitionfrom pediatric to adult GH
replacement; this transition willonly be possible once the benefits of
GH in mature adults aredefined and accepted by pediatric and adult
endocrinologistsalike.
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