© Freund Publishing House Ltd.

, London Journal of Pediatric Endocrinology & Metabolism, 16, 23-25 (2003)

POINT OF VIEW

How Should We Manage Growth Hormone Deficiency in

Adolescence? Transition from Paediatric to Adult Care
Maria Papagianni and Richard Stanhope

Great Ormond Street Hospital for Children and The Middlesex Hospital (UCLH), London, UK

Growth hormone deficiency (GHD) in adult life
is a recognized clinical syndrome that can be
treated with growth hormone (GH) replacement
therapy. Continuing GH replacement therapy in
patients with childhood-onset GHD that persists
into adulthood is an emerging issue. Patients with
multiple pituitary hormone deficiency (MPHD) do
not stop glucocorticoid, thyroxine or sex steroid
replacement treatment in adult life, so why do they
often cease GH treatment at the completion of
linear growth?
It is well established that GH plays an important
role in longitudinal bone growth during childhood
and adolescence. However, 'growth' hormone is a
misnomer, as it has many other important metabolic
functions in addition to growth. As growth comes
to an end, the metabolic effects become more
apparent. GH has an important role in maintaining
normal levels of blood glucose and preventing
hypoglycaemia. Moreover, other common meta-
bolic abnormalities associated with GHD include
insulin resistance and dyslipoproteinemia with high
low density lipoprotein (LDL), high cholesterol,
high triglycerides and low high density lipoprotein
(HDL) serum concentrations' ,2 . Visceral obesity
associated with adult GHD has been implicated as
having an important role in mediating increased
cardiovascular mortality in hypopituitarism3"5. By
contrast, congenital GH/IGF-I deficiency, which
is also associated with obesity, may not affect
lifespan6.
Reprint address:
Dr. Richard Stanhope
Institute o f Child Health
3 0 Guilford Street
London W C 1 N 1EH, U K
e-mail: R.Stanhope@ich.ucl.ac.uk
VOLUME 16, NO. 1,2003
Many studies of adults with GHD have docu-
mented changes in body composition, particularly
increased fat mass, decreased lean mass and
increased body mass index (BMI)7'8. Furthermore,
it has been demonstrated that adolescents and
young adults with GHD lose lean body mass and do
not gain muscle strength; this suggests that GH in
adolescence and young adulthood is of importance
for the maturation of muscle mass and muscle
strength9. The influence of GHD on bone mass is
significant10,11. Bone mineral density (BMD) is
reduced in children and adults with childhood-onset
GHD12'13. Peak bone mass (PBM) is a major
determinant of osteoporotic fracture risk in adult
life and it is considered to be attained by
approximately 20 years of age in both males and
females. Consequently, the accumulation of bone
mass continues after the cessation of linear growth.
Moreover, a high incidence of psychological
problems has been indicated in adults with GHD.
There is evidence that GH replacement therapy has
a beneficial effect on well-being and quality of life
of patients with GHD14.
The traditional cessation of GH replacement
treatment in childhood-onset GHD at completion of
linear growth requires re-evaluation. Consensus
guidelines from the Growth Hormone Research
Society are available15'16. The increasingly recog-
nized importance of GHD in adults underlines the
need for continuing medical follow-up of indivi-
duals with childhood-onset GHD and their
transition from paediatric to adult care. However,
according to several studies, approximately one
quarter of children who have a diagnosis of isolated
GHD and have been treated with GH replacement
KEY WORDS: growth hormone deficiency, adults,
transition, growth hormone treatment
23

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24 Μ. PAPAGIANNI A N D R. STANHOPE
therapy do not have permanent GHD and will pro-
bably not require treatment during adulthood 7 ' 18 ' 19 .
This percentage depends on the population studied
and the·, diagnostic criteria for GHD, and rates as
high as 67% have been reported 20,21 . Reversal of
GHD to normal in these children could be related to
GH assay variability, particularly as different tests
are often used for diagnosis and reassessment,
differences in sex steroid priming provocative tests
and reversibility of GH insufficiency in psycho-
social short stature22. Consequently, there are
questions that occur regarding the patients who may
need to continue GH treatment, the necessity as
well as the timing of retesting them, the time that is
needed to stop GH treatment before re-evaluation,
the time of their transition to adult health care, and
finally the dose of GH for their initial replacement
therapy in early adult life. A recently published
consensus statement by the Growth Hormone
Research Society16 and a critical review article
sponsored by the same society23 have tried to
answer some of these questions.
There is no doubt that the majority of children
with certain aetiologies for GHD (e.g. genetic
hypothalamic-pituitary abnormalities, sella/suprasella
tumours and those treated with high-dose irradi-
ation to the hypothalamic area) will be growth
hormone deficient for life 17 ' 20 . Consequently, re-
testing of children with MPHD may not be required
just to reconfirm their GH status. However, all
adolescents with 'idiopathic' isolated GHD will
need to be retested after the attainment of adult
height. Before retesting, the patients should
undergo a washout period, during which no GH
treatment should be given. Retesting could be
performed with confidence at 3 months and perhaps
as early as 4 weeks after the cessation of treatment.
Two different provocative tests are recommended23'24.
GH replacement treatment should be restarted in
patients with confirmed persistent GHD (peak level
of stimulated GH secretion <5 ng/ml) but at a
smaller dose than that used during childhood. A
step-down dose regimen in young adults, reducing
to an 'adult' dose in their mid-20s, would mimic
normal physiology. Given that the long-term con-
sequences of GHD in adulthood are responsible for
considerable morbidity 7 ' 8 , it is essential that
patients with childhood-onset GHD should be
JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
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followed into adult life. The timing of transition to
adult health care requires careful consideration.
Should this be after the completion of linear
growth, or after attainment of peak bone mass?
Moreover, should it be before or after retesting the
patient's GH secretory status? Given that paediatric
endocrinologists have considerable experience with
auxology, it is logical that children with GHD
should be followed up by them at least until they
have achieved their final adult height, but perhaps
until they have achieved peak bone mass 25 .
A successful transfer from paediatric to adult
care should follow certain steps, but needs to be
modified according to local circumstances. First, all
patients with GHD and their families should be
informed by their paediatric endocrinologist about
the long-term consequences of GHD in adulthood
and the potential need for lifetime GH replacement.
Second, there will be a need for retesting
hypothalamic-pituitary function, assessment of
replacement therapy for other pituitary hormone
deficits, measurement of fasting lipid concentration
and the assessment of skeletal integrity. Third, the
option of attending a joint outpatient clinic with
both the paediatric and adult endocrinologist should
be considered. Optimal arrangements need to be
established depending on local factors, such as
geographical location of the two departments. The
age at transfer, timing of retesting GH secretory
status and interpretation of assessments of skeletal
integrity need to be carefully rehearsed by the close
collaboration of the paediatric and adult endocrino-
logists. Last, but not least, the wishes of the patient
should be respected, provided this is possible.
Because in the past there has been suspicion about
GH treatment and its association with accelerated
tumour growth 26 and the development of diabetes
mellitus, it will be essential to follow up patients
with childhood onset GHD treated with GH
throughout adult life, whether or not they are truly
GH deficient.
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 Gl ID: TRANSITION FROM PAEDIATRIC TO A D U L T C A R E 25

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