|side view showing
tumor compressing optic nerves
|front view showing
compression of the
optic nerves and chiasm
Pituitary tumors arise from the pituitary gland within the base of the skull. These tumors are almost always benign. Symptoms arise when these tumors secrete hormones or become large enough to compress adjacent structures. Rarely, these tumors may spontaneously hemorrhage.
As these tumors enlarge, the normal pituitary function is destroyed. This destruction produces various hormonal deficiencies since the pituitary controls the action of other endocrine glands within the body. Pressure on nearby structures can produce double vision and facial numbness. The nerves of vision, the optic nerves, are directly above the pituitary gland and upward growth of pituitary tumors frequently causes progressive visual loss. This visual loss typically begins from each side of the field of vision leading to tunnel vision and then blindness.
The pituitary gland is the "master gland" of the body. The pituitary lies embedded within the skull base in a small cavity called the sellar tursica. The gland is connected to the overlying brain by the pituitary stalk. The brain controls the synthesis, or storage and release, of many hormones from the pituitary gland by secreting hormones through the pituitary stalk to the pituitary gland. These hormones stimulate (or inhibit) the production of trophic hormones by the pituitary. Trophic hormones travel through the blood to the other glands in the body, controlling their functions. For example, corticotrophin releasing hormone (CRH) is produced in the brain and travels from the hypothalamus to the pituitary through the pituitary stalk. CRH causes the pituitary to produce and release thyroid stimulating hormone (TSH). TSH travels through the blood to the thyroid gland in the neck. Here TSH stimulates the production of thyroid hormone which effects the metabolic rate of all tissues of the body. Growth hormone is also released by the anterior pituitary gland and affects growth and maintenance of various tissues directly, without an intermediary gland. And, in a final example, vasopressin is stored but not produced by the posterior pituitary. Its release by the posterior portion of the gland promotes the reabsorption of water by the kidneys.
Types of Tumors
Pituitary tumors make themselves known by the overproduction of certain hormones either by destroying normal pituitary function and causing a lack of hormones, or by enlarging and compressing adjacent structures causing neurological problems. Generally, these tumors can be subdivided in to non-hormone producing tumors of the pituitary gland, hormone producing tumors of the pituitary gland, other intra-sellar tumors, and para-sellar tumors. Para-sellar tumors which occur in the vicinity of the sellar tursica can mimic the symptoms of pituitary tumors.
Nonhormone-producing Tumors: Tumors arising from the pituitary which secrete no hormones are deemed null cell tumors. These tumors are quite common. In fact, null cell tumors measuring a few millimeters in size may be found in up to one-quarter of autopsied pituitary glands. They may grow slowly, destroying normal pituitary function (hypopituitarism) or may compress nearby structures causing neurological problems.
loss of peripheral vision leading to blindness
facial pain or numbness
lack of energy
weight loss, nausea, vomiting, constipation
amenorrhea and infertility
dry skin, increased pigmentation of the skin
mental status changes: sleepiness, psychosis, collapse
Hormone-producing Tumors: Tumors which secrete hormones are usually small and do not cause neurological symptoms or hypopituitarism (although they may). The symptoms of functioning tumors relate to the specific hormone produced by the tumor. Prolactinomas are the most common pituitary tumor.
Prolactin (HPL) secreting tumors or prolactinomas
Growth Hormone (HGH) secreting tumors (acromegaly)
Enlargement of facial features, hands and feet,
Heart disease, hypertension arthritis,
Carpel tunnel syndrome Amenorrhea, impotence, lactation
Adrenal gland stimulating hormone (ACTH) (Cushing's Disease)
Widened face with acne and flushing
Fatty deposits over back of neck, stretch marks, easy bruising, hair growth,
Muscle loss and fatigue,
Depression and psychosis
Nelson's Syndrome (ACTH)
Following adrenalectomy for treatment of Cushing's disease
Increased melanin pigmentation of the skin
Thyroid gland stimulating hormone (TSH)
Some tumors may secrete more than one hormone, such as growth hormone and prolactin. There are very rare tumors which secrete leutinizing hormone (LH) and follicle stimulating hormone (FSH).
There are many other tumors which occur within the sell tursica or in the adjacent cavernous sinus which may mimic pituitary tumors.
The clinical diagnosis depends upon the combination of symptoms and signs resulting from the size of the tumor and/or the type of hormone produced.
Pituitary adenomas may be imaged with CT or MR scans. MR imaging is the most sensitive technique, allowing identification of tumors a fraction of an inch in size.
Evaluation of pituitary function is possible by measuring hormone levels in the blood and urine. Sometimes, provocative tests are necessary to judge pituitary function. Examples include measuring the level of growth hormone hours after ingesting glucose by mouth or measuring serum ACTH and cortisol levels after taking a steroid medication by mouth.
Occasionally, the measurement of ACTH levels in the venous blood draining the pituitary (in the petrosal sinus) gives the surgeon a clue as which side of the gland very small ACTH secreting tumors reside.
Formal evaluation of the visual fields are useful in outlining peripheral visual loss before and after surgery .
Medical therapy is useful in treating some hormone secreting adenomas:
Prolactinomas: Dopamine agonists which effect the D2 receptors for dopamine effectively treat prolactin tumors. About 80% to 90% of patients will normalize their serum prolactin levels. Nearly 80% of tumor will become smaller. Parlodel (bromocriptine) has been used for many years. A new drug, Dostinex (carbergoline), may be more effective with fewer side effects. It can be given by mouth twice a week.
Cushing's disease: Medical treatment for tumors which cause the over secretion of corticosteroids by the adrenal glands is unsatisfactory because of their side effects and response rates. Two classes of medication are used: those which interfere with the production of steroids in the adrenal glands and those which act within the brain. Removal of the adrenal glands is an option when pituitary surgery and medical measures fail to control Cushing's disease. Removal of the adrenal glands may lead to rapid growth of the pituitary tumor and massive blood levels of ACTH. ACTH stimulates melanin production in the skin, darkening the skin color. This darkening is termed Nelson's syndrome
Acromegaly: There are three types of medications which effect the production or utilization of growth hormone. Most patients treated with dopamine agonists, such as Parlodil (bromocriptine), achieve reduction in HGH levels, but few reach normal levels. Somatostatin analogs are a second class of medications useful in the treatment of acromegaly. Somatostatin analogs which are administered by injection every few weeks are available. Most patients develop low levels of growth hormone, but very few develop levels which are considered a cure of the disease. A third class of drugs has just become available. This drug, Somavert-pegvisomant, blocks peripheral HGH receptor and can normalized HGH levels in more than 90% of patients.
The history of pituitary surgery goes back about 100 years. Harvey Cushing was one of the pioneers and his monograph, The Pituitary Body and Its Disorders, was a significant contribution to our field. Cushing helped develop both the transphenoidal approach and transcranial operations for pituitary tumors.
Today, pituitary surgeons utilize the transsphenoidal approach for most pituitary tumors. This approach avoids many of the complications of transcranial surgery. It is safe, effective, and requires a short stay in the hospital. Surgery has the advantage of rapidly lowering hormone levels. The surgeon exposes the sellar tursica through an incision inside the nose or under the upper lip.
The tumor is identified, separated from the pituitary gland, and removed. For small tumors (less than 10 mm in diameter), the cure rate is greater than 50% . Pre-operative pituitary function is preserved in many or most patients. Abnormally high hormone levels are lowered or normalized. Some tumors, especially tumors larger than 1 cm., can recur and may require additional treatment. Infection, cerebrospinal leak, vascular injury, double vision, visual loss, and pituitary deficiency are rare sequels of this commonly-performed procedure.
Fractionated radiotherapy is effective in controlling the growth of nonsecretiong pituitary adenomas. Generally, doses of 45 Gy are given in 1.8 Gy fractions with the expectation that the treatment will control the growth of 70% to 90% of tumors with a 1% chance of optic neuropathy and visual loss. Additionally about one-half of patients treated will developed hypopituitarism and require hormonal treatment. It seems that individuals who have surgery in addition to radiation therapy have a greater chance of control of disease progression after radiation therapy.
Although XRT controls the growth of most secreting tumors, it is less effective in normalizing hormone levels. Less than one-half of patients with secreting tumors will achieve normal levels after many years.
Gamma Knife radiosurgery has become increasingly more important in the control of pituitary adenomas. This technique allows for focused, high-dose treatment of pituitary adenomas and results in greater rate of control of tumor growth and better rates of normalization of increased hormone secretion. It has been used as the primary treatment of small pituitary tumors in individuals who do not require decompression of the optic nerves. There should be a few millimeters of separation of the tumor surface from the optic nerves to allow effective tumor doses and safe doses delivered to the optic nerves.
The image to the left shows Gamma Knife treatment plan for a residual tumor after surgery. The optic nerves are turquoise, the pituitary stalk and gland blue, the tumor is outlines in pink, and the 50% isodose is outlined in yellow. An effective dose is prescribed to the yellow line which covers the entire tumor on successive MR sections. A 85% to 95% control rate is expected.
Approximately 90% of patients treated with Gamma Knife radiosurgery will achieve control of tumor growth and more than one-half of patients will normalize hormone levels over months to years.
Patients are seen within a few days of surgery to remove nasal packing. Post-operative evaluation of pituitary function is carried out weeks to months after surgery. Pituitary dysfunction may occur years after radiation or radiosurgery, so long-term evaluation of pituitary hormones is necessary. Interval measurement of visual fields, and imaging of the pituitary may be carried out as well.
The Pituitary Network Association: http://www.pituitary.org/