Prospective Study of Clinically Nonfunctioning Pituitary Adenomas

PROTOCOL I: Prospective Study of the outcome of conservative non-surgical management of
patients with asymptomatic, clinically non-functioning (CNF) pituitary lesions. This protocol
will evaluate prospectively the outcome of non-surgical management of clinically
non-functioning pituitary lesions that do not appear to need surgery as their initial
therapy. The overall design consists of an initial baseline evaluation and then serial
prospective follow up studies over time for up to 5 years of follow up. The study will
evaluate laboratory testing, clinical examinations, quality of life and neurocognitive
function in these patients. Data will be collected on visual fields and MRI studies of the
pituitary tumor that are done prospectively as part of clinical care to evaluate these
patients.

PROTOCOL II : Prospective study of the outcome of patients with symptomatic, clinically
non-functioning pituitary tumors who are treated with transsphenoidal surgery and in some
cases also radiotherapy. This protocol will evaluate prospectively the outcome of surgical
management of asymptomatic clinically nonfunctioning pituitary lesions. The overall design
consists of an initial baseline evaluation and then serial prospective follow up studies over
time with up to 5 years of follow up. The study will evaluate laboratory testing, clinical
examinations, quality of life and neurocognitive function in these patients. Data will also
be collected on visual fields and MRI studies of the pituitary tumor that are done
prospectively as part of clinical care to evaluate these patients. Data will be analyzed to
determine the safety of observation alone following surgery for patients who do not have a
clinically significant tumor remnant, if the silent corticotroph tumor type is characterized
by elevated plasma levels of ACTH or its precursor, POMC, and if it is associated with an
increased tumor recurrence rate. A group of patients who are planning RT will also be studied
by these same procedures before and after RT in order to determine if the outcomes of
patients who receive RT for treatment of tumor re-growth to that of those who do not receive
RT with respect to further tumor growth, endocrine or neurological dysfunction. Quality of
life and neurocognitive function in patients with clinically non-functioning pituitary
lesions treated with surgery alone or those who also receive radiotherapy will be
prospectively assessed.

GROUP I

Inclusion Criteria:

- adult patients with pituitary lesions that do not require surgical intervention.

- pituitary lesion that has been demonstrated on a magnetic resonance imaging (MRI) to
be consistent with an adenoma (not a cystic lesion such as a Rathke's cleft cyst).

- patients with macroadenomas (> 1 cm) or large microadenomas 6-9 mm.

- a prolactin level < 40 ng/ml.

Exclusion Criteria:

- presence of visual or neurological deficits due to the tumor, tumor impingement on the
optic chiasm and physical or laboratory abnormalities consistent with a biologically
active hormone secreting tumor.

GROUP II

Inclusion Criteria:

- adult patients with pituitary lesions that require surgical intervention and are
planning on surgery or who had surgery in the past and are now undergoing pituitary
radiotherapy.

- pre-surgery patients will have a pituitary lesion that has been demonstrated on a MRI
to be consistent with an adenoma (not a cystic lesion such as a Rathke's cleft cyst)
and that is a macroadenoma (> 1 cm).

- presence of visual or neurological deficits due to the tumor or impingement of the
tumor on the optic chiasm is permitted.

- a prolactin level < 100 ng/ml if lesion is > or = 10 mm in size or a prolactin level <
40 ng/ml if lesion is < 10 mm in size.

- patients with mild/moderate hyperprolactinemia and recommended for dopamine agonist
therapy (on the chance that the lesion is truly a prolactinoma) may re-enter the study
should they be a dopamine agonist failure and require surgery.

- patients with hypopituitarism and no other surgical indication that choose to undergo
surgery is permitted.