Pituitary Adenomas: Current Methods of Diagnosis and Treatment

Pituitary Adenomas: Current Methods of Diagnosis and Treatment

ABSTRACT: Pituitary adenomas are benign neoplasms that can be effectively managed by a variety of therapeutic options. The clinician's goal in managing patients with these tumors should be to minimize the morbidity of each intervention used in diagnosis and treatment. Standard diagnostic interventions include MRI, hormonal assessment, and tissue diagnosis. Therapies include transsphenoidal surgery, external-beam radiotherapy, newer stereotactic irradiation techniques, and medical management. Appropriate treatment selection requires detailed knowledge of the expected outcomes and side effects of each option. Newer and perhaps less toxic treatment techniques are evolving and require further evaluation. [ONCOLOGY 11(6):791-796, 1997]


Pituitary adenomas comprise 10% to 15% of all intracranial tumors in
adults.[1] In addition, 10% of normal adults have asymptomatic abnormalities
on MRI that are consistent with a pituitary adenoma, and perhaps 20% or
more are found to have an asymptomatic adenoma on autopsy.[1,2] Patients
requiring intervention have a characteristic constellation of signs and
symptoms that are easily recognized by the astute primary care physician.
Furthermore, these signs and symptoms are critical gauges for the specialist
neurosurgeon, endocrinologist, and radiation oncologist in recommending
appropriate management.

Once a pituitary adenoma is suspected, diagnostic evaluation with hormonal
and neuroradiologic studies is indicated. These studies, along with patient
status, preference, and symptoms, guide decisions about medical, surgical,
or radiotherapeutic management. Each of these therapies has distinct and
characteristic profiles of response and toxicity that influence the recommended
treatment plan. In nearly all cases of benign tumors, the possibility of
cure exists. This probability of cure should be maximized at the time of
primary diagnosis and treatment because multiple recurrences of benign
tumors may lead to increased morbidity with further treatment and perhaps,
in some cases, to increased mortality from the disease.[3]

Signs and Symptoms

Patients with pituitary adenomas usually have either neurologic or hormonal
manifestations of their disease. The most commonly reported neurologic
symptoms are headache and visual disturbances. Other cranial nerve palsies
and mental deterioration are reported less often but may occur more frequently
with giant adenomas.

Endocrinopathies may cause a host of patient complaints, ranging from
the polyuria and polydipsia of diabetes insipidus (rare) to menometrorrhagia
attributable to abnormal prolactin, luteinizing hormone, or follicle-stimulating
hormone levels. Decreased libido and general apathy may be related to luteinizing-hormone
deficiency or panhypopituitarism. Skin changes may occur and produce symptoms
indicative of imbalances in pituitary hormones, including thyroid and adrenal
hormones. Finally, the stigmata of Cushing's disease may lead the patient
to complain of a myriad of difficulties, ranging from irritability to a
change in body habitus, diabetes, hypertension, or easy bruising. Patients
with acromegaly also have characteristic stigmata, which family members
may slowly recognize as a change from their former appearance.

Although the development of these symptom complexes is usually insidious
from the patient's perspective, the clinicopathologic features of pituitary
adenomas often make them readily suspected at the time of diagnosis.

Clinicopathologic syndromes can be identified based on the patient's
signs and symptoms and physical findings, as well as the results of biochemical
evaluation. These syndromes may be divided into those of primarily neurologic
vs hormonal character.

Neurologic Syndromes

Pituitary adenomas frequently extend beyond the sella proper. In general,
the path of tumor growth is upward, which pushes the optic chiasm superiorly.
Suprasellar extension may also cause headache and pressure on the pituitary
stalk, which may cause hormonal abnormalities independent of the tumor's
secretory abilities.

Presentations of classic bitemporal hemianopia represent the pure form
of this model of injury. More often, however, the patient may have a partial
hemianopia and blurred vision in the lateral fields.[4] Rigorous pretherapy
ophthalmologic assessment is necessary to accurately gauge the outcome
of intervention and the severity of injury at presentation.

Headaches are a common neurologic complaint. These may be due to a direct
pressure effect of the tumor, an obstructive hydrocephalus effect (rare),
direct hormonal perturbation, or induction of secondary hypertension.[4]

Other cranial nerve palsies may result from direct invasion of the cavernous
sinus or, less often, from erosion of the skull base and anterior clivus.
Deficits of the oculomotor, abducens, or trigeminal nerves occur most frequently.

More serious deficits than those described above are rare because these
tumors generally progress slowly and symptoms of cranial nerve deficits
related to vision usually attract medical attention in all but the most
stoic of patients. Thus, the majority of patients have one or more of the
neurologic clinicopathologic syndromes described above or have hormonal
difficulties that lead to diagnosis before gross neurologic dysfunction

Hormonal Syndromes

Adrenocorticotrophic hormone (ACTH) overproduction leads to stigmata
of Cushing's disease. These may include diabetes, hypertension, infertility,
menstrual irregularity, proximal muscle weakness and atrophy, and skin
changes, including easy bruisability, striae, and hirsutism. Changes in
body habitus caused by excessive adrenal cortisol include characteristic
moon facies, truncal obesity, and humpback appearance, along with wasting
and weakness of the proximal extremities. However, the specific manifestations
seen in a given patient vary greatly and may sometimes be subtle. Furthermore,
the absence of radiographic findings of these macroadenomas often contributes
to difficulty in making a diagnosis. Therefore, the clinician must be vigilant
for these many signs of disease so as to order appropriate laboratory screening
tests. These tests will help locate the origin of hypercortisol production
so that appropriate therapy is delivered.

Approximately 5% to 10% of pituitary tumors cause elevated cortisol
levels, and an additional 5% are positive for ACTH on immunocytochemistry

Growth Hormone--Pituitary adenoma is the most common cause of
acromegaly. Overproduction of growth hormone is the third most common anomaly
seen in pituitary adenomas, with nonfunctioning adenomas and prolactinomas
occurring more frequently.

Excess production of growth hormone by a pituitary adenoma leads to
acromegaly in an adult or gigantism in a child. Stigmata of acromegaly
include coarsening of facial features, excess growth and thickening of
the distal phalanges, soft-tissue swelling, cardiac hypertrophy, hypertension,
diabetes, hirsutism, excessive skin tags, hypertrophic arthropathy, peripheral
neuropathy, hyperparathyroidism, hyperprolactinemia, and hypothyroidism.
While these stigmata often make the diagnosis obvious to the clinician,
their insidious onset often leads to significant delays in diagnosis.

Prolactin--Hypersecretion of prolactin may occur in 60% to 80%
of patients with pituitary tumors, although hyperprolactinemia may not
be the primary endocrinologic defect in many of these cases.[1,5] Elevation
of prolactin secondary to pituitary stalk compression may occur with any
mass within or extending out of the sella; however, a prolactin level above
200 ng/ml is usually accepted as evidence of a prolactin-secreting adenoma.[5]
Elevated prolactin levels result in diminished levels of estrogen and testosterone.
Female patients generally develop menstrual irregularity or frank amenorrhea
or galactorrhea. Decreased libido occurs in both men and women.

Depression and mood alterations are associated with prolactin hypersecretion.
In general, men are less symptomatic from prolactin-secreting tumors, and
therefore, are more likely than women to have neurologic signs and symptoms
of disease and a macroadenoma.

Gonadotropins--Aberrant secretion of follicle-stimulating hormone
and luteinizing hormone is rare and is most often discovered after pituitary
adenomas produce neurologic symptoms. Occasionally, hypogonadism is a presenting

Thyrotropin--Thyroid-stimulating hormone excess occurs in less
than 1% of pituitary adenomas. The resultant hyperthyroidism is often presumed
to be of alternative etiology and is treated with thyroid-suppressing therapy.
Such treatment may be successful until neurologic symptoms occur. Therefore,
these tumors often grow to a large size and extend into adjacent structures,
making treatment difficult. Discovery of a microadenoma-secreting, thyroid-stimulating
hormone is rare, and this condition may be cured by addressing the pituitary


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