C h a p t e r 3 2
Disorders of Endocrine Control of Growth and Metabolism
769
deficiency) prior to development of headache, visual
loss, and other neurologic symptoms due to the mass
effect of the expanding tumor.
Assessment of Hypothalamic-Pituitary
Function
The precise assessment of hypothalamic-pituitary func-
tion has been made possible by radioimmunoassay of
the anterior pituitary hormones and their specific target
gland hormones. Magnetic resonance imaging (MRI)
is used for imaging the hypothalamus and pituitary. It
has largely replaced the use of computed tomography
(CT) because it allows better visualization of normal
structures and has better resolution in defining tumors.
2
When further information regarding pituitary function
is required, combined hypothalamic-pituitary function
tests (e.g., rapid ACTH stimulation test or GH suppres-
sion test) may be undertaken.
2
Pituitary Adenomas and
Hyperpituitarism
The most common cause of hyperpituitarism is a pitu-
itary adenoma, or a benign tumor arising from the
anterior pituitary.
2–5
Other, less common causes of
hyperpituitarism are hyperplasia and carcinoma of
the anterior pituitary, secretion of hormones by extra-
pituitary tumors, and certain hypothalamic lesions.
Clinically diagnosed pituitary adenomas are responsi-
ble for about 10% of intracranial neoplasms. They are
discovered incidentally in as many as 25% of routine
autopsies and are increasingly being detected as inci-
dental findings on MRI and CT scans of the head per-
formed for other reasons.
6
The usual pituitary adenoma is a well-circumscribed
lesion that can range in size from small lesions that do
not enlarge the gland (microadenomas, <1 cm) to large,
expansive tumors (macroadenomas, >1 cm) that erode
the sella turcica and impinge on surrounding cranial
structures.
2,5
The adenomas can be divided into non-
functional tumors and functional tumors that secrete
pituitary hormones.
The signs and symptoms of pituitary adenomas
include endocrine abnormalities related specifically
to functional hormone-secreting adenomas and to the
local mass effects of the expanding tumor. Lactotrophic
adenomas are the most frequent type of hyperfunction-
ing pituitary adenoma, accounting for about 30% of all
diagnosed cases.
2,4,5
Lactotrophic adenomas are usually
small, benign tumors composed of prolactin-secreting
cells. Hyperprolactinemia inhibits the pulsatile secre-
tion of LH, which is essential for normal ovulation in
women. Thus, the manifestations of hyperprolactinemia
are most easily recognized in women of reproductive
age and include amenorrhea (lack of menstruation),
galactorrhea (spontaneous milk secretion unrelated to
pregnancy), and infertility. In males, the symptoms of
hyperprolactinemia are vague and may include erectile
dysfunction and loss of libido.
Because of the close proximity of the sella turcica to
the optic nerves and chiasm, expanding pituitary lesions
often compress the decussating fibers of the optic chi-
asm, giving rise to visual field abnormalities.
2,5
Cranial
nerve deficits, which are much less common, can result
in blurred or double vision or, very rarely, paresthesia
(abnormal nonpainful burning or prickling sensation)
on one side of the face. As in the case of any expand-
ing intracranial mass, pituitary adenomas may produce
signs and symptoms of increased intracranial pressure,
including headache, nausea, and vomiting. In some
cases, pituitary adenomas may extend beyond the sella
turcica into the base of the brain, producing seizures and
obstructive hydrocephalus. On occasion, acute hem-
orrhage into an adenoma may occur, producing rapid
enlargement of the pituitary. The condition, termed
pituitary apoplexy
, is accompanied by a combination of
acute nerve palsies, severe headache, and systemic symp-
toms related to ACTH deficiency.
Hypopituitarism
Hypopituitarism is characterized by a decreased secre-
tion of pituitary hormones that causes hypofunc-
tion of the secondary organs that depend on trophic
stimuli from the pituitary.
1
It may selectively involve
one subset of pituitary cells (e.g., somatotropes that
produce growth hormone) or all of the pituitary cells,
in which case it is referred to as
panhypopituitarism
.
Typically, 70% to 90% of the anterior pituitary must
be destroyed before hypopituitarism becomes clini-
cally evident. The cause may be congenital, or result
from a variety of acquired abnormalities that cause
destruction of the anterior pituitary, or from a second-
ary phenomenon resulting from a deficiency of hypo-
thalamic hormones that normally act on the pituitary.
Space-occupying lesions cause hypopituitarism by
destroying the pituitary gland or hypothalamic nuclei
or by disrupting the hypothalamic-hypophysial portal
system.
Anterior pituitary hormone loss is usually gradual,
especially with progressive loss of pituitary reserve
due to tumors or previous pituitary radiation therapy
(which may take 10 to 20 years to produce hypopitu-
itarism). The loss of pituitary function tends to follow
a classic course beginning with the loss of GH, LH, and
FSH secretion followed by deficiencies in TSH, then
ACTH, and finally prolactin. Impairment of GH secre-
tion causes decreased growth in children but may be
clinically unapparent in adults. Hypogonadism, mani-
fested by amenorrhea in women and decreased libido
and erectile function in men, may precede the clinical
appearance of other manifestations. The manifestations
of hypothyroidism caused by TSH deficiency (e.g., cold
intolerance, dry skin, mental dullness) are similar to
those observed in primary thyroid failure but less severe.
Adrenocorticotropic hormone deficiency is the most
serious endocrine deficiency. It causes secondary adre-
nal insufficiency, leading to weakness, nausea, anorexia,
fever, and postural hypotension.
