C h a p t e r 3 2
Disorders of Endocrine Control of Growth and Metabolism
773
The same pathology is responsible for dwarfism of the
African pygmies. IGF-1 is now produced by recombi-
nant DNA technology. Since GH produces its effects by
promoting IGF-1 secretion, IGF-1 is an effective replace-
ment therapy for Laron dwarfism, mimicking most of
the effects ascribed to GH.
9
Growth Hormone Deficiency in Adults
There are two categories of GH deficiency in adults:
GH deficiency that was present in childhood, and GH
deficiency that developed during adulthood, mainly as
the result of hypopituitarism resulting from a pituitary
tumor or its treatment.
15
Growth hormone levels also can
decline with aging (described as the
somatopause
), and
there has been interest in the effects of declining GH levels
in the elderly.
16
Growth hormone replacement obviously
is important in the growing child; however, the role in
adults (especially for the somatopause) is being assessed.
The clinical features of adult GH deficiency include
changes in body composition, such as a decrease in lean
body mass and an increase in fat mass, hyperlipidemia,
decreased bone mineral density, and reduced exercise
capacity, and diminished sense of well-being. Growth
hormone deficiency is associated with a cluster of cardio-
vascular risk factors including central adiposity (associ-
ated with increased visceral fat), insulin resistance, and
dyslipidemia.
15
These features also are associated with
the
metabolic syndrome
(see Chapter 33). In addition
to these so-called traditional cardiovascular risk fac-
tors, nontraditional cardiovascular risk factors (e.g.,
C-reactive protein [CRP], which is a marker of the
inflammatory pathway) are also elevated.
17
Several recombinant human GH preparations have
been approved for treatment of adults with diagnosed
GH deficiency. The most common side effects of GH
treatment in adults with hypopituitarism are periph-
eral edema, arthralgias and myalgias, carpal tunnel
syndrome, paresthesias, and decreased glucose tol-
erance.
15
Side effects appear to be more common in
people who are older, have greater weight, and are
overtreated as determined by high serum IGF-1 levels
during therapy.
Tall Stature and Growth Hormone
Excess in Children
Just as there are children who are short for their age and
gender, there also are children who are tall for their age
and gender.
9,18
Normal variants of tall stature include
genetic tall stature and constitutional tall stature.
Children with exceptionally tall parents tend to be taller
than children with shorter parents. The term
constitu-
tional tall stature
is used to describe a child who is taller
than his or her peers and is growing at a velocity that is
within the normal range for bone age. Other causes of
tall stature are genetic or chromosomal disorders such
as Marfan syndrome or XYY syndrome (see Chapter 6).
Endocrine causes of tall stature include sexual precocity
because of early onset of estrogen and androgen secre-
tion and excessive GH.
Exceptionally tall children (i.e., genetic tall stat-
ure and constitutional tall stature) can be treated with
sex hormones—estrogens in girls and testosterone in
boys—to effect early epiphyseal closure. Such treatment
is undertaken only after full consideration of the risks
involved. To be effective, such treatment must be insti-
tuted 3 to 4 years before expected epiphyseal fusion.
9,18
Growth hormone excess occurring before puberty and
the fusion of the epiphyses of the long bones results in
gigantism
19
(Fig. 32-3). It usually develops when exces-
sive secretion of GH by somatotrope adenomas leads to
high levels of IGF-1, the mediator of excessive skeletal
growth. Fortunately, the condition is rare because of
early recognition and treatment of the adenoma.
Growth Hormone Excess in Adults
When GH excess occurs in adulthood or after the epiph-
yses of the long bones have fused, it causes a condition
called
acromegaly
(from the Greek words
acros
, mean-
ing “end portion,” and
megalos
, meaning “large”),
FIGURE 32-3.
Primary gigantism. A 22-year-old man with
gigantism due to excess growth hormone is shown to the left
of his identical twin. (From Gagel RF, McCutcheon IE. Images
in clinical medicine. N Engl J Med. 1999;340:524. Copyright ©
2003. Massachusetts Medical Society.)
