In a well-written and focused article, Drs. Buatti and Marcus review
the diagnosis and treatment of pituitary adenomas.
In the review, much emphasis is placed on the importance of tissue diagnosis.
From a neurosurgical perspective, tissue diagnosis for most pituitary tumors
is of secondary importance, as most specific types of pituitary tumors
can be diagnosed preoperatively. The rationale for resection of pituitary
adenomas is twofold: decompression of mass effect and restoration of endocrine
Expanding or Large Pituitary Adenomas
Patients with expanding pituitary adenomas may present with symptoms
of mass effect, including headaches and visual disturbances. The suprasellar
extension of the tumor often exerts pressure on the optic nerve and/or
optic chiasm. Under these circumstances, surgical resection is the most
expeditious way to decompress the neural structures. Moreover, the earlier
the decompression is carried out, the more favorable are the chances of
restoring neural function.
A less urgent, but nonetheless important additional rationale for resection
is the fact that large adenomas and those with a more rapid rate of growth
may develop acute hemorrhagic necrosis (pituitary apoplexy). This, in turn,
may result in rapid tumor expansion with optic chiasm compression and increased
intracranial pressure that may culminate in a coma.
Hypersecretory Endocrine Syndromes
For hypersecretory endocrine syndromes, surgical resection is the treatment
of choice for growth-hormone secreting tumors, Cushing's disease, and thyroid-stimulating
hormone-secreting adenomas, with endocrine remissions achieved in 80% to
90% of patients. These endocrinopathies cannot be viewed as benign, particularly
Cushing's disease with its serious systemic ramifications.
In contrast, prolactin-secreting tumors, with their symptoms of amenorrhea
and galactorrhea, are best treated by observation or medication. Observation
is appropriate if the adenoma is less than 5 mm and the patient does not
mind the amenorrhea and the possibility of osteoporosis that may result
from a chronically elevated prolactin level. Medical management for prolactin-secreting
adenomas is highly effective and generally well-tolerated.
Bromocriptine (Parlodel), a dopa-mine agonist, is the most widely used
medication for the treatment of prolactin-secreting tumors; it normalizes
prolactin levels and fertility in 80% to 90% of patients with microadenomas
and in 60% to 80% of patients with macroadenomas. Newer dopamine agonists,
such as carbergoline, lisuride, pergolide (Permax), and a depot preparation
of bromocriptine, are now available. These new agents seem to be as effective
as bromocriptine and are often better tolerated. Unfortunately, except
in a minority of patients, hyperprolactinemia recurs as soon as dopamine
agonist treatment is discontinued.
Surgery for prolactin-secreting tumors provides an alternative for patients
who poorly tolerate medical therapy, and is the treatment of choice if
pregnancy is desired or if the optic apparatus is compressed.
Pituitary Metastasis and Hypophysitis
Biopsy for tissue diagnosis is also redundant in two other processes
involving the pituitary: pituitary metastasis and hypophysitis. Pituitary
metastases have a fairly characteristic, consistent clinical presentation
characterized by new-onset diabetes insipidus (70%), headaches (50%), and
the ra- diographic finding of an enhancing mass in the sella. In a patient
with known cancer, such findings should raise the clinician's suspicion
for a metastasis. Diabetes insipidus is a rare, late manifestation of pituitary
The cancers that most commonly metastasize to the pituitary are lung,
breast, and gastrointestinal tract primaries. The MRI findings are also
highly suggestive, as are the lesions at presentation, which have an intrasellar
and suprasellar component with a dumbbell shape formed by the indentation
at the level of the diaphragm--a rare finding with adenomas.
In my experience, pituitary metastases tend to be diffuse, adherent,
invasive, and often vascular. The prognosis for patients with a pituitary
metastasis is similar to that of patients with a single brain metastasis;
median survival is approximately 7 months. The cause of death in the vast
majority of cases is systemic disease progression. Based on the clinical
presentation and MRI findings, one can readily forego biopsy and commence
treatment with radiotherapy.
One other pituitary process that can be highly suspected on clinical
grounds alone without surgery or tissue diagnosis is hypophysitis. Two
varieties have been described: lymphocytic hypophysitis and granulomatous
Lymphocytic hypophysitis is rare, with approximately 60 reported cases,
but is probably greatly underdiagnosed because of the number of cases that
resolve spontaneously. Lymphocytic hypophysitis predominantly affects females
and usually presents during late pregnancy or the first year postpartum.
The presentation often includes headaches, weight loss, weakness, anemia,
visual changes, and a low glucose level. In up to 40% of patients, prolactin
levels are elevated, probably as a result of stalk compression. Considered
to be an autoimmune process, lymphocytic hypophysitis often responds to
Pituitary masses in patients with granulomatous diseases, such as sarcoidosis,
Langerhans cell histiocytosis, and Wegener's granulomatosis, should raise
the suspicion of granulomatous hypophysitis. Granulomatous hypophysitis
is more common in females, and clinical manifestations include hypopituitarism
and diabetes insipidus because of the predilection of this disease for
the posterior pituitary gland and hypothalamus.
In over 95% of cases, the diagnosis of pituitary tumors can be based
on the clinical presentation, hormonal assays (which are available for
virtually all the hormones produced by the pituitary), and imaging studies
with high sensitivity and specificity (MRI). In patients with suspected
Cushing's disease, sampling of the venous blood of the cavernous sinus
for adrenocorticotrophic hormone through retrograde petrosal sinus catheterization
may, on occasion, be useful, mainly for localizing the microadenoma before
The goal of surgery is usually curative. A less frequent objective is
reversal of optic nerve or chiasmal compression. Rarely is surgery indicated
for tissue diagnosis or confirmation of the diagnosis.
1. Webster J, Piscitelli G, Polli A: A comparison of carbergoline and
bromocriptine in the treatment of hyperprolactinemic amenorrhea: Carbergoline
Comparative Study Group. N Engl J Med 331:904-909, 1994.
2. Sioutos P, Yen V, Arbit E: Pituitary gland metastases. Ann Surg Oncol,
1997 (in press).
3. Cosman F, Post KD, Holub DA, et al: Lymphocytic hypophysitis: Report
of 3 new cases and review of the literature. Medicine 68:240-256, 1989.