C h a p t e r 3 2
Disorders of Endocrine Control of Growth and Metabolism
771
In addition to its effects on growth, GH increases the
rate of protein synthesis by all of the cells of the body,
enhances fatty acid mobilization and increases the use
of fatty acids for fuel, and maintains or increases blood
glucose levels by decreasing the use of glucose for fuel.
Growth hormone has an initial effect of increasing insu-
lin levels. However, the predominant effect of prolonged
GH excess is to increase blood glucose levels despite an
insulin increase. This is because GH induces a resistance
to insulin in the peripheral tissues, inhibiting the uptake
of glucose by muscle and adipose tissues.
2
Many of the effects of GH are mediated by
insulin-like
growth factors
(IGFs), which are produced mainly by the
liver.
9
Growth hormone cannot directly produce bone
growth; instead, it acts indirectly by causing the liver to
produce IGFs. These peptides act on cartilage and bone to
promote their growth. Several IGFs have been identified;
of these, IGF-1 (previously known as somatomedin C)
appears to be the more important in terms of growth, and
it is the one that usually is measured in laboratory tests.
The IGFs have been sequenced and found to have struc-
tures that are similar to those of proinsulin. This undoubt-
edly explains the insulin-like activity of the IGFs and the
weak action of insulin on growth. Insulin-like growth fac-
tor levels are themselves influenced by a family of at least
six binding factors called
IGF-binding proteins
(IGFBPs).
Growth hormone is carried unbound in the plasma
and has a half-life of approximately 20 to 50 minutes.
The secretion of GH is regulated by two hypothalamic
hormones: GH-releasing hormone (GHRH), which
increases GH release, and somatostatin, which inhib-
its GH release. A third hormone, the recently identified
ghrelin,
also may be important (see Chapter 28). The
hypothalamic influences of GHRH and somatostatin are
tightly regulated by neural and metabolic influences. The
secretion of GH fluctuates over a 24-hour period, with
peak levels occurring 1 to 4 hours after onset of sleep.
The nocturnal sleep bursts, which account for 70% of
daily GH secretion, are greater in children than in adults.
Growth hormone secretion is stimulated by hypo-
glycemia, fasting, starvation, increased blood levels of
amino acids (particularly arginine), and stress conditions
such as excitement, emotional stress, heavy exercise, and
trauma. Growth hormone is inhibited by increased glu-
cose levels, free fatty acid release, cortisol, and obesity.
Short Stature in Children
Short stature is a condition in which the attained height
is well below the third percentile or linear growth is
below normal for age and gender. Short stature, or
growth retardation, has a variety of causes, includ-
ing chromosomal abnormalities such as Turner syn-
drome (see Chapter 6), GH deficiency, hypothyroidism,
and panhypopituitarism.
9
Other conditions known to
cause short stature include protein-calorie malnutri-
tion, chronic diseases such as chronic kidney disease
and poorly controlled diabetes mellitus, malabsorption
syndromes such as celiac disease, and certain thera-
pies such as excessive glucocorticoid administration.
Emotional disturbances can lead to functional endocrine
disorders, causing psychosocial dwarfism. The causes of
short stature are summarized in Chart 32-1.
Accurate measurement of height is an extremely
important part of the physical examination of children.
Completion of the developmental history and growth
charts is essential.
10,11
Growth curves and growth velocity
studies also are needed. The Centers for Disease Control
and Prevention (CDC) growth charts are available at
. Diagnosis of short
stature is not made on a single measurement, but is
based on sequential height measurements and on veloc-
ity of growth and parental height.
9
The diagnostic procedures for short stature include
tests to exclude nonendocrine causes. If the cause is
hormonal, extensive hormonal testing procedures are
initiated. Usually, GH and IGF-1 levels are determined
(IGFBP-3 levels also are useful). Tests can be performed
using insulin (to inducehypoglycemia),GHRH, levodopa,
and arginine, all of which stimulate GH secretion so
that GH reserve can be evaluated.
9
Because administra-
tion of pharmacologic agents can result in false-negative
responses, two or more tests usually are performed. If a
prompt rise in GH is realized, the child is considered nor-
mal. Physiologic tests of GH reserve (e.g., GH response
to exercise) also can be performed. Levels of IGF-1 usu-
ally reflect those of GH and may be used to indicate GH
deficiency. Radiologic films are used to assess bone age,
which most often is delayed. Magnetic resonance imaging
of the hypothalamic-pituitary area is recommended if a
CHART 32-1
Causes of Short Stature
Variants of normal
Genetic or “familial” short stature
Constitutional growth delay
Low birth weight (e.g., intrauterine growth retardation)
Functional endocrine disorders (psychosocial
dwarfism)
Growth hormone (GH) deficiency
Primary GH deficiency (idiopathic GH deficiency,
pituitary agenesis)
Secondary GH deficiency (panhypopituitarism)
Biologically inactive GH production
Deficient IGF-1 production in response to normal or
elevated GH (Laron-type dwarfism)
Hypothyroidism
Glucocorticoid excess
Endogenous (Cushing syndrome)
Exogenous (glucocorticoid drug treatment)
Abnormal mineral metabolism (e.g.,
pseudohypoparathyroidism)
Diabetes mellitus in poor control
Chronic illness and malnutrition (e.g., asthma,
especially when treated with glucocorticoids; heart
or renal disease)
Malabsorption syndrome (e.g., celiac sprue)
Chromosomal disorders (e.g.,Turner syndrome)
Skeletal abnormalities (e.g., achondroplasia)
