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Pituitary Adenomas: Current Methods of Diagnosis and Treatment

Pituitary Adenomas: Current Methods of Diagnosis and Treatment

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 homeostasis.

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.[1] 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 adenomas.

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.[2] 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 hypophysitis.

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.[3] 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 steroids.

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 surgery.

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.

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