Pituitary Tumors

Approximately 95% of pituitary tumors are benign. The tumors may be primary or
secondary and functional or nonfunctional. Functional tumors secrete pituitary
hormones, whereas non functional do not. The location and effects of these tumors on
hormone production by target organs can have life-threatening effects. Three principal
types of pituitary tumors represent an overgrowth of 1. Eosinophilic cells, 2. Basophilic
cells or 3. Chromophobic cells.

Risk Factors

Family history. Most people who develop pituitary tumors dont have a family
history of the disease. But rarely, pituitary tumors can run in families. Sometimes
when pituitary tumors run in families, they are found along with other types of
tumors as part of an inherited genetic syndrome
Genetic syndromes. Pituitary tumors can be a part of a syndrome that includes
an increased risk of other types of tumors. These syndromes are caused by
abnormal changes (mutations) in a persons genes. They include:
Multiple endocrine neoplasia, type I (MEN1): This is a hereditary
condition in which people have a very high risk of developing tumors of 3
glands: the pituitary, parathyroid, and pancreas. It is caused by changes in
the gene MEN1, and is passed on to about half of the children of an
affected parent.
Multiple endocrine neoplasia, type IV (MEN4): This rare syndrome
includes increased risks of pituitary tumors and certain other tumors.
MEN4 is caused by inherited changes in a gene called CDKN1B.
McCune-Albright syndrome: This syndrome is caused by changes in a
gene called GNAS1 that arent inherited but occur before birth. People
with this syndrome have brown patches on their skin (called caf-au-lait
spots) and develop many bone problems. They can also have hormone
problems and pituitary tumors.
Carney complex: This is a rare syndrome in which people can have
heart, skin, and adrenal problems. They also have a high risk of a number
of different types of tumors, including pituitary tumors. Many cases are
caused by inherited changes in the gene PRKAR1A, but some are caused
by changes in other genes that have not yet been identified.

Pathophysiology
Up until the last decade, there were two prevailing theories for the origin of
pituitary tumors. The most commonly accepted theory was that these tumors represent
intrinsic abnormalities within the gland itself. The other theory favored a hypothalamic
cause for most, if not all, pituitary tumors that is, according to the latter hypothesis,
pituitary tumors originate as a result of continued stimulation by a hypothalamic

hormone or factor. Most authorities favored the former hypothesis, advocating that
pituitary tumors are primary or arise as a result of intrinsic abnormalities within the
gland. The recent advances in molecular biology have facilitated more definitive studies
on these tumors. Using X-allele inactivation methods, studies have demonstrated that
pituitary tumors are monoclonal in origin (Alexander et al. 1990). Thus tumors arise from
a single cell mutation followed by clonal expansion. Pituitary neoplasia is a multi-step
process that involves dysregulation of cell growth or proliferation, differentiation, and
hormone production. It may be initiated as a result of activation of oncogene function or
after inactivation of a tumor suppressor gene, or both. The former process (activation of
oncogene function) is a dominant event and therefore a single allele alteration will lead
to a change in cellular function. An example of such an oncogene is present in about
40% of pituitary somatotropinomas. In such tumors, a point mutation in the Gs- gene
leads to a defective G-protein subunit and GTPase activity. This will lead to persistent
cAMP concentrations and consequently excessive growth hormone (GH) secretion that
bypasses GH releasing hormone (GHRH) (Farfel et al. 1999, Adams et al. 2000). A
similar mechanism is postulated for the development of acromegaly in patients with
McCune-Albright syndrome (Lacroix et al. 1992, Farfel et al. 1999). In contrast, tumor
suppressor inactivation is recessive in nature and therefore both alleles of the gene
must be affected to influence cellular events or function. The heterogeneity of genetic
defects found in pituitary adenomas is consistent with the multi-step neoplastic process.
For example, inactivation of a tumor suppressor gene (either through DNA methylation
or through the loss of heterozygosity by point mutation or deletion) is found in different
loci in various tumors. In multiple endocrine neoplasia type 1, the gene has been
localized to chromosome 11, whereas in sporadic tumors different areas of
chromosomes 11, 9, or 13 have been isolated. The role of hypothalamic and other
growth factors in modulating these events is under investigation (Farrell et al. 1999,
Melmed 1999).

Clinical Manifestations
Eosinophilic tumors that develop early in life result in gigantism. The affected
person may be more than 7 feet tall and large in all proportions, yet so weak and
lethargic than he or she can hardly stand. If the disorder begins during adult life, the
excessive skeletal growth occurs only in the feet, the hands, and superciliary ridge, the
molar eminence, the nose and the chin, giving rise to the clinical picture called
acromegaly. However, enlargement involves all the tissues and organs of the body.
Many of these patients may suffer severe headaches and visual disturbances because
the tumors exert pressure on the optic nerves. Decalcification of the skeleton, muscle
weakness, and endocrine disturbances, similar to those occurring in patients with
hyperthyroidism, also associated with this type of tumor.

Basophilic tumors give rise to Cushing syndrome with features largely attributed
to hyperadrenalism, including masculinization and amenorrhea in females, truncal
obesity, hypertension, osteoporosis and polycythemia.
Chromophobic tumors represent 90% of pituitary tumors. These tumors usually
produce no hormones but destroy the rest of the pituitary gland, causing
hypopituitarism. People with these disease are often obese and somnolent and exhibit
fine, scant hair; dry, soft skin; a past complexion; and small bones. They also
experience headaches, loss of libido and visual defects progressing to blindness. Other
signs and symptoms include polyuria, polyphagia, a lowering basal metabolic rate and
subnormal body temperature.

Assessment and Diagnostic findings

Diagnostic evaluation requires a careful history and physical examination,
including assessment of visual acuity and visual fields. CT and MRI scans are used to
diagnose the presence of tumors. Serum levels of pituitary hormones may be obtained
along with measurements of hormones of target organs to assist in diagnosis.

Medical Management

Hypophysectomy surgical removal of the pituitary gland through a

transsphenoidal approach is the usual treatment.
Stereotactic radiation therapy requires the use of a neurosurgery type
stereotactic frame, may be used to deliver external-beam radiation therapy
precisely to the pituitary tumor with minimal effect on normal tissues.

Pharmacological Treatments

Bromocriptine dopamine antagonist

Octreotide - synthetic analog of GH
These medications inhibits the production and release of GH and and
may bring about marked improvement of symptoms.
Ocrtreotide and Lanreotide - a somatostatin analogue, may also be used
preoperatively to improve the patients clinical condition and to shrink the tumor.

Surgical Management

Hypophysectomy - treatment of choice in patients with Cushing syndrome

resulting from excessive production of ACTH by a pituitary tumor. It may also be
performed on occasion as a palliative measure to relieve bone pain secondary to
metastasis of malignant lesions of the breast and prostate.

Several approaches are used to remove or destroy the pituitary gland, including
surgical removal by transfrontal, subcranial, or oronasal-transsphenoidal
approaches; irradiation and cryosurgery.