774
U N I T 9
Endocrine System
which represents an exaggerated growth of the ends of
the extremities (fingers, hands, and toes). The annual
incidence of acromegaly is 3 to 4 cases per 1 million
people, with a mean age at the time of diagnosis of 40
to 45 years.
2,20,21
The most common cause of acromegaly is GH-secreting adenomas, most of which are benign.
21
The
disorder usually has an insidious onset, and symptoms
often are present for a considerable period before a
diagnosis is made. When the production of excessive
GH occurs after the epiphyses of the long bones have
closed, as in the adult, the person cannot grow taller,
but the soft tissues continue to grow. Enlargement of
the small bones of the hands and feet and of the mem-
branous bones of the face and skull results in a pro-
nounced enlargement of the hands and feet, a broad
and bulbus nose, a protruding jaw, and a slanting
forehead (Fig. 32-4). The teeth become splayed, caus-
ing a disturbed bite and difficulty in chewing. The car-
tilaginous structures in the larynx and respiratory tract
also become enlarged, resulting in a deepening of the
voice and tendency to develop bronchitis. Vertebral
changes often lead to kyphosis, or hunchback. Bone
overgrowth often leads to arthralgias and degenerative
arthritis of the spine, hips, and knees. Virtually every
organ of the body is increased in size. Enlargement of
the heart and accelerated atherosclerosis may lead to
an early death.
The metabolic effects of excess levels of GH include
disorders of fat and carbohydrate metabolism. Growth
hormone causes increased release of free fatty acids
from adipose tissue, leading to increased concentration
of free fatty acids in body fluids. In addition, GH exerts
multiple effects on carbohydrate metabolism, includ-
ing decreased glucose uptake by tissues such as skeletal
muscle and adipose tissue, increased glucose production
by the liver, and increased insulin secretion. Each of
these changes results in GH-induced insulin resistance
(see Chapter 33). Impaired glucose tolerance occurs in
as many as 50% to 70% of persons with acromegaly;
overt diabetes mellitus subsequently can result.
Other manifestations of acromegaly include exces-
sive sweating with an unpleasant odor, oily skin, heat
intolerance, moderate weight gain, muscle weakness
and fatigue, menstrual irregularities, and decreased
libido. Hypertension is relatively common. Sleep apnea
syndrome is present in up to 90% of patients. The
pathogenesis of the sleep apnea syndrome is obstructive
in the majority of patients, due to increased pharyn-
geal soft tissue accumulation. Paresthesias may develop
because of nerve entrapment and compression caused
by excess soft tissue and accumulation of subcutaneous
fluid (especially carpal tunnel syndrome). Headaches
are frequent. Temporal hemianopia (loss of vision for
one half of the visual field) may occur as a result of the
optic chiasm being impinged by a suprasellar growth
of the tumor.
The treatment goals for acromegaly focus on the
correction of metabolic abnormalities and include nor-
malization of the GH response to an oral glucose load;
normalization of IGF-1 levels to age- and sex-matched
control levels; removal or reduction of the tumor mass;
relieving the central mass effects; and improvement
of adverse clinical features.
2
Pituitary tumors can be
removed surgically using the transsphenoidal approach
or, if that is not possible, a transfrontal craniotomy.
Radiation therapy may be used, but remission (reduc-
tion in GH levels) may not occur for several years after
therapy.
Somatostatin analogs (especially long-acting formu-
lations of octreotide or lanreotide) produce feedback
inhibition of GH and are effective in the medical man-
agement of acromegaly. Dopamine agonists also reduce
GH levels and have been used with some success.
2
Growth hormone analogs (e.g., pegvisomant) antago-
nize the actions of GH by binding to GH receptors on
the cell surfaces. These analogs produce symptom relief
and normalize serum IGF-1 levels in most individuals
with acromegaly.
2
Thickened skin
(hypertrophy of
sebaceous and
sweat glands)
Peripheral
neuropathy
Degenerative
arthritis
Increased size
(hands, feet)
Male sexual
dysfunction
(or menstrual
disorders
in women)
Barrel chest
Abnormal glucose
tolerance secondary
to insulin resistance
Hyperostosis
(thoracic
vertebrae)
Cardiomegaly
(hypertension)
Goiter
Acromegalic
facies
Somatotropic
adenoma
of pituitary
FIGURE 32-4.
Clinical manifestations of acromegaly.
