http://www.pituitarysociety.org/vance1.htm
Pituitary Tumors:
Frequently Asked Questions About Pituitary Tumors
by Mary Lee Vance, M.D.
Professor, Medicine and Neurosurgery
University of Virginia Medical Center
Charlottesville, Virginia
I. General Questions About a Pituitary Tumor
1. What causes a pituitary tumor to develop?
Pituitary tumors are common. In autopsy studies of patients who did
not have known pituitary disease, as many as 26% had a small tumor
(adenoma) in the gland. Molecular biology studies have shown that a
change in the DNA of pituitary cells can cause unregulated growth of
a particular cell type resulting in a pituitary tumor. There are no
known environmental causes. An uncommon type of pituitary tumor is
inherited, this is called Multiple Endocrine Neoplasia, Type I. In
this situation, there is usually a family history of endocrine
tumors, most commonly a parathyroid tumor, a pituitary tumor and less
commonly, a tumor of the pancreas. This occurs in less than 4% of
patients with a pituitary tumor.
2. Is a pituitary tumor a brain tumor?
The pituitary gland is NOT in the brain and pituitary tissue is
different from brain tissue. Since the pituitary gland is located at
the base of the brain and is connected to the brain by a thin stalk,
there is often confusion, particularly by insurance companies, about
the classification of a pituitary tumor. A pituitary tumor is NOT a
brain tumor.
3. Is a pituitary tumor cancer?
No, in over 99% of patients, this is NOT a cancer; it is benign.
Although the tumor is benign, it can cause problems because of its
size, because it causes the normal pituitary gland to become
underactive (hypopituitarism) or because of excessive hormone
production by the tumor.
4. What are the symptoms of a pituitary tumor?
This depends on the type of tumor and the size of the tumor. A large
tumor may cause loss of vision, particularly peripheral vision, if it
compresses the optic chiasm (where the optic [eye] nerves converge).
Headache may also occur; the type of headache varies from patient to
patient. Headache may occur with a large or a small tumor. A tumor
may interfere with normal pituitary function causing hypothyroidism
(low thyroid hormone level), adrenal insufficiency (low cortisol
level), hypogonadism (loss of sexual function in men, loss of
menstrual periods or infertility in women). Occasionally a pituitary
tumor causes diabetes insipidus which results in frequent urination
and excessive thirst. Diabetes insipidus is not high blood sugar
levels, it is a problem with the ability of the kidney to retain
fluid because of a deficiency of the pituitary hormone, vasopressin
(also called antidiuretic hormone).
Specific types of tumors cause various symptoms and changes in body
function as a result of excessive hormone secretion from the tumor.
These hormones enter into the blood and act on various tissues to
cause an effect. Although these are normal hormones, when produced
excessively they can cause unwanted effects.
Prolactinoma:This refers to a pituitary tumor secreting excess
prolactin. This type of tumor most commonly causes loss of sexual
function and infertility in men. Men may also have enlargement of the
breasts. In women of reproductive age a prolactin-producing tumor may
cause milk in the breasts, a change in menstrual periods or loss of
menses or infertility. Women who have gone through menopause do not
have a change in menstrual periods to signal the problem; in this
situation, headache and loss of vision may be the first indicator of
a prolactinoma.
Acromegaly: This type of tumor is associated with excessive growth
hormone secretion. Enlargement of the hands, feet and face and
excessive sweating are the most common features of excessive growth
hormone production. Other problems which occur include joint pains
(osteoarthritis), sleep apnea (excessive snoring, stopping breathing
during sleep), hypertension, diabetes mellitus (elevated blood
sugar), colon polyps, change in teeth spacing, oily skin and acne.
Cushing's: The term "Cushing's Disease" refers to the overproduction
of cortisol by the adrenal glands caused by a pituitary tumor
producing an excessive amount of the hormone ACTH. Dr. Harvey
Cushing, a neurosurgeon, first described this condition. Excessive
cortisol production causes weight gain (particularly in the abdomen
and neck), loss of muscle mass (legs, arms) and muscle weakness,
depression, thinning of the skin with easy bruising, hypertension,
diabetes mellitus, loss of calcium from the bones (osteoporosis) with
a risk for bone fractures and weakening of the immune system with a
higher risk of developing infections.
TSH Secreting Tumor: This is the least common type of hormone
producing pituitary tumors. Excessive TSH stimulates the thyroid
gland to produce an excessive amount of thyroid hormone
(hyperthyroidism). Symptoms of hyperthyroidism include weight loss,
nervousness, rapid heart beat, difficulty sleeping, frequent bowel
movements and in women, scant menstrual periods.
Non Secretory Tumor: This refers to a tumor that does not produce an
excessive amount of a pituitary hormone. This type of tumor most
commonly causes sexual dysfunction in men and loss of regular menses
in premenopausal women. This type of tumor is usually detected after
it has become a large tumor causing loss of vision and/or headache
and/or hypothyroidism or adrenal insufficiency.
Craniopharyngioma/Rathke's Cleft Cyst: These tumors are congenital -
a defect in the development of the pituitary gland which is present
at birth but may not cause a problem until adulthood. This is not a
malignant (cancerous) tumor but it may interfere with normal
pituitary function causing hypopituitarism. These tumors may also
cause diabetes insipidus, frequent urination and excessive thirst.
Pituitary Cyst: Any endocrine gland may develop a cyst. This occurs
commonly in the ovaries and thyroid gland; cysts are benign but cause
problems because of enlargement causing headache and interference
with normal pituitary function. Most common symptoms are headache
and, if the cyst is large, loss of vision and loss of normal
pituitary function.
5. What is the best treatment for a pituitary tumor?
The best treatment depends on the type of pituitary tumor. Prolactin
producing tumors are most successfully treated with medical therapy
(pills). In over 90% of patients, medical therapy reduces tumor size
and blood prolactin levels. In approximately 8-10% of patients,
medical treatment in not completely effective and surgery may be
necessary. The best treatment for other types of pituitary tumors is
removal of the tumor by an experienced neurosurgeon who performs
pituitary surgery frequently. Although most neurosurgeons have some
experience with pituitary surgery, only a few have devoted their
career to pituitary surgery and have the "best" records of success.
There is medical treatment for acromegaly (excessive growth hormone
production), but this is usually administered after surgical removal
of the tumor if there is persistent excessive growth hormone
production (discussed in more detail below).
6. If a tumor was successfully removed, why are regular visits, blood
tests and MRI scans necessary?
Complete removal of a tumor is the desired goal. However, a small
minority of patients will have a recurrence of the tumor.
Approximately 10% of patients will have a tumor recurrence within 10
years. Since it is not possible to predict which tumor will recur,
all patients need regular medical follow up. Additionally, a tumor
may recur 20 years or more after the original treatment. If the tumor
was producing a hormone that caused particular symptoms (Cushing's,
acromegaly, prolactin tumor), the patient is usually the first to
recognize this. Measurement of the appropriate hormone level in blood
or urine is the most accurate method of determining if there is a
tumor recurrence. Non secretory tumors do not produce an excessive
hormone that can be measured in the blood or urine and the MRI scan
is the best method of surveillance.
7. Is radiation necessary in all patients? Who should have radiation
to the pituitary?
Radiation to the pituitary is not the first line of treatment for
most pituitary tumors. It does not produce an immediate effect to
lower excessive hormone production or shrink the tumor. Radiation is
used when there is tumor remaining after surgery or when surgery
cannot be performed. Pituitary radiation may take several years to be
effective. For example, in patients with acromegaly (excessive growth
hormone production), growth hormone levels may remain elevated for 10
to 20 years after conventional (fractionated) radiation.
8. Are all types of pituitary radiation the same?
No. There are different methods of delivering radiation to the
pituitary gland. Conventional (fractionated) radiation refers to
delivery of a small amount of radiation daily for 4 to 5 weeks.
Stereotactic radiation refers to delivery of a precisely focused beam
of radiation, usually as one treatment. The decision as to which type
of radiation to administer must be made only after a careful review
of the MRI scan to assess the size and location of the residual
tumor. A large tumor near the optic chiasm (eye nerves) is not
suitable for stereotactic radiation because of the intensity of the
single treatment and risk of damage to vision. In general,
stereotactic radiation is reserved for a small residual tumor which
is not near the optic chiasm.
9. What are the side effects of radiation?
The most common side effect is loss of pituitary function. This may
occur within a year or many years after treatment. One study reported
that 50% of patients treated with conventional radiation developed
deficiency of one or more pituitary hormones within 2 years of
treatment. Although development of a pituitary hormone deficiency is
not desirable, hormone replacement therapy is available. An uncommon
side effect is damage to vision. These risks must be weighed against
the risk of tumor re-growth.
10. Does a pituitary tumor shorten life?
If properly treated and if the patient receives appropriate hormone
replacement. Having a pituitary tumor should not shorten life. All
medications must be taken as directed. Additionally, there is a need
for regular medical care and monitoring of medical treatments. Most
patients who have had a pituitary tumor engage in normal work and
social activities. If a patient requires steroid (cortisol)
replacement, a "medic alert" bracelet or necklace should be worn at
all times. Another illness such as the flu, pneumonia or an accident
requires an increase in the steroid dose. If the patient is brought
to the hospital and unable to give the medical history, the
physicians will have no way of knowing that additional steroid is
necessary. Thus, with attention to these important details, a patient
with a pituitary tumor should have a full and productive life.
II. Medical Treatment of Pituitary Tumors
Any medical therapy for a pituitary tumor should reduce hormone
overproduction by the tumor, and, ideally, decrease the size of the
pituitary tumor so that if there is a visual abnormality, this is
corrected. Reduction in tumor size should improve or relieve headache
associated with the tumor. Since not all pituitary tumors produce an
excessive amount of a hormone or hormones, the only measure of
successful medical therapy for the non hormone producing tumor is the
effect on tumor size and clinical symptoms (visual problems,
headache).
A. Prolactin producing tumor (Prolactinoma):
1. What are the benefits and limitations of medical treatment?
Medical therapy is usually more effective than surgery for this tumor
type, particularly for large tumors (macroadenoma,
patients with large tumors, surgery results in normal prolactin
levels in < 20% of patients. Surgery is effective in removing the
bulk of the tumor, but prolactin levels remain elevated; surgery does
not produce a "cure". In this situation, medical treatment is
indicated. In patients who have a small tumor (< 10 mm), the chances
of a "cure" with surgery are greater, on the order of 80% to 90%.
However, even with successful surgery, there is a risk of recurrence
of the tumor at a later date (months, years); approximately 13 to 20%
of patients have a recurrence of elevated prolactin within 5 years of
surgery.
2. How do the medications work?
Prolactin is normally inhibited (suppressed) by the hypothalamic
(brain) hormone, dopamine. Drugs known as dopamine agonists act like
dopamine to inhibit prolactin production. Dopamine agonists available
in the U.S. include bromocriptine (Parlodel) and pergolide (Permax).
A very effective drug, Norprolac, is only available in Europe and
Canada. An newer dopamine agonist, cabergoline (Dostinex), is now FDA
approved and available in the U.S. Bromocriptine and pergolide are
usually given 1 to 3 times a day, cabergoline is given once or twice
a week.
All of these drugs act on the tumor in the same way - by inhibiting
or reducing the amount of prolactin made by the tumor and thus
causing the tumor to shrink. Over 90% of patients treated with these
medications have a decrease in prolactin and in tumor size. Some
patients are not able to take these medications because of side
effects (nausea, vomiting, nasal stuffiness, constipation). The newer
medication, cabergoline is associated with fewer side effects than
bromocriptine and pergolide. Some studies indicate that cabergoline
may be more effective than bromocriptine or pergolide in reducing
prolactin and tumor size.
A minority of patients does not have a very good response to these
drugs. Why? These drugs act on dopamine "receptors" which are on the
surface of the tumor. A receptor can be visualized as a keyhole, the
drug is the key - in order for the drug to be effective, the tumor
must have an adequate number of receptors ("keyholes") and the drug
must be able to bind (attach) to the receptor. In patients who do not
have a good response to medication, there are not enough receptors on
the tumor surface and the binding is not adequate. In this situation,
alternative treatments such as surgery and/or radiation therapy may
be necessary.
Is there a way to measure a tumor's "receptors"?
Not in routine medical laboratories. Research studies have been done
which have demonstrated this principle. The only way to judge the
effect of medical treatment is a trial of a dopamine agonist drug
(bromocriptine, pergolide, cabergoline)
3. Why don't these medications always reduce prolactin to normal?
Although these medications are effective in lowering prolactin and
reducing tumor size, the prolactin level may not decrease to normal
(< 20). Why?
In the situation of a large tumor and very high prolactin level ( in
the thousands), the medication may lower prolactin by 90%; if the
level before treatment level is 10,000, a 90% reduction lowers
prolactin to 1,000, certainly not normal, but a substantial
reduction. The tumor size is decreased but it does not disappear.
This may be acceptable if there are no other ill effects of the
tumor. The most frequent hormonal problem resulting from an elevated
prolactin is hypogonadism. Hypogonadism in a pre-menopausal woman
results in loss of menstrual periods and difficulty becoming
pregnant. Hypogonadism in men causes impotence (difficulty obtaining
an erection) and infertility. Hypogonadism is treatable with hormone
replacement, testosterone in men, estrogen and progesterone in women.
Restoration of fertility may require additional treatments with
injections of the pituitary hormones, LH and FSH.
4. Do these medications "cure" the tumor? Can I stop the
medication later?
Usually not. These medications control the tumor, they do not destroy
the tumor. The medications are only effective as long as they are
taken. If the medication is stopped, the prolactin will usually
increase and the tumor will also increase in size. This is similar to
a person who has high blood pressure - the blood pressure is
controlled only as long as the person takes the medication. Thus,
medication for a prolactin producing tumor must be taken as
prescribed, to control the problem.
In the situation of a very small tumor (< 10 mm), the medication is
often stopped after a year to see if the prolactin stays normal. In a
minority of patients, this is successful and the prolactin remains
normal. The possible reason for this is that the small tumor has
somehow self-destructed (this occurs in a few patients). If the
prolactin is normal after stopping the medication, the level should
be monitored every few months to make sure it remains normal.
5. Is one medication more effective than another?
Usually not, the different drugs act the same way. Usually the
responses to different drugs are similar in reducing prolactin and
tumor size. The benefits of one drug over another are related to:
(a) side effects,
(b) cost,
(c) ease of taking the medication.
Some patients have side effects with one drug and little to no side
effects with another drug. The only way to determine this is a trial
of a different medication. The most important thing about avoiding
side effects is to always take the medication with food. This will
minimize side effects such as nausea or vomiting.
The issue of cost is particularly important for patients who do not
have an insurance plan to cover the costs. There is one potential
limitation of taking the less expensive medication (pergolide) in
women who wish to become pregnant. Pergolide is only approved in the
U.S. for another indication (Parkinson's disease). There is not
enough information about babies born to women taking pergolide to
assure us that it is safe for the developing baby. Therefore, we do
not prescribe this particular drug to women who wish to become
pregnant or who are at risk for becoming pregnant. The FDA approved
medication, bromocriptine, has been given to several thousand women
who wished to become pregnant. A worldwide surveillance has shown
there that there is no increased risk (above the normal risk in the
general population) of birth defects (there is always some risk, even
for a woman taking no medications). Cabergoline (Dostinex) is not
approved for pregnancy; information on several hundred women who
became pregnant while taking cabergoline reveals no increase (above
the normal risk) of birth defects in the baby.
The convenience of taking the medication is important for most
patients who are busy with work and other activities. Bromocriptine
is often given three times a day; some patients can be treated twice
a day. Pergolide is usually given either twice a day or once a day.
Norprolac (not available in the U.S.) is taken once at night.
Cabergoline is a long acting drug which is given once or twice a week.
6. What is the cost of these medications?
Local retail pharmacy charges:
Bromocriptine, 2.5 mg three times a day: $ 181/month; $ 2,172/year
Pergolide, 0.05 mg twice a day: $ 40/month; $ 480/year
Pergolide, 0.1 mg twice a day: $ 80/month; $ 960/year
Cabergoline, 0.5 mg/week: $ 127/month; $ 1,524/year
Cabergoline, 0.5 mg twice a week: $ 254/month; $ 3,048/year
7. If my prolactin level returns to normal, will I be able to get
pregnant?
Yes - if the only reason for infertility is the high prolactin level.
There are many causes of infertility, but if high prolactin is the
only reason, lowering prolactin to normal results in the same chances
for pregnancy as the general age-matched population (fertility
declines with increasing age).
8. I don't want to become pregnant now. Can I take a birth
control pill?
Usually yes - if the prolactin is reduced with medication
(bromocriptine, pergolide, cabergoline), then a birth control pill
can be added. It is very important to use "mechanical contraception"
(condom and foam; diaphragm; IUD) until the response to medication
(bromocriptine, pergolide, cabergoline) is assessed.
B. Growth hormone producing tumor (Acromegaly):
1. What is the role of medical treatment for a growth hormone
producing tumor?
Medical treatment is usually given if there is persistent
overproduction of growth hormone after surgery. Although medications
can lower growth hormone, they are less effective in shrinking the
tumor. Therefore, the usual first treatment is surgical removal of as
much of the tumor as is possible. In the situation of a large tumor,
particularly if it has grown into an area that is not accessible to
the surgeon, the majority of the tumor may be removed, but a small
portion remains - and continues to produce too much growth hormone.
Because of the long-term complications of excessive growth hormone
(joint problems, diabetes, high blood pressure, facial changes,
sweating, risk of colon polyps and colon cancer, and premature heart
disease and death), it is important to reduce growth hormone levels
to normal. In most cases, radiation therapy is given if surgery is
not completely successful. Since it may take months or a few years
before the radiation therapy is effective, medical treatment is used
to control excessive growth hormone production while waiting for the
radiation to become effective. Medications do not cure the problem.
They control the situation. They are effective only as long as they
are taken as prescribed.
2. What medications are available for treatment of Acromegaly?
Currently used drugs include:
Dopamine agonist: bromocriptine (Parlodel), cabergoline (Dostinex),
pergolide (Permax) Somatostatin analogs: octreotide (Sandostatin),
Sandostatin LAR.
3. Which medication is more effective?
The dopamine agonist drugs, bromocriptine and cabergoline, improve
symptoms but are not very effective in lowering growth hormone and
IGF-1 levels to normal (< 10%).
Octreotide (Sandostatin) and Sandostatin LAR are the most effective
medications currently available. Sandostatin and Sandostatin LAR are
identical medications, but the LAR preparation is long acting and is
given less often. Sandostatin is usually self-administered as an
injection under the skin 3 times a day. Sandostatin LAR is
administered at the doctor's office as an injection in the buttock
every 28 days.
Sandostatin and Sandostatin LAR reduce growth hormone and IGF-1
levels in 90% of patients. However it lowers these hormone levels to
normal in approximately 45% to 50% of patients. The reason for this
is the same as the response that occurs with medical treatment of
prolactin producing tumors - the number of "receptors" on which the
medication can act. Octreotide must be given at least every 8 hours
by a subcutaneous (under the skin) injection. A very small needle
(insulin syringe and needle) is used and the discomfort is usually
not a problem for most patients. Some patients have a better response
giving the injection every 6 hours, others use a small pump (worn on
the belt or in a shirt pocket) which delivers the medication
continuously (the needle under the skin is changed every 2 or 3
days). The long acting preparation, Sandostatin LAR is more
convenient to take (once every 28 days) but requires a visit to the
doctor's office.
Some patients have a better response to the combination of
bromocriptine or cabergoline and octreotide. Regardless of which
regimen in used, these medications do not cure the disease, they
control excessive growth hormone production by the tumor. Therefore,
the medication(s) is effective only as long as it is taken regularly.
4. What are the side effects of these medications?
Bromocriptine: nausea, vomiting, nasal stuffiness, constipation. Side
effects are minimized by always taking the medication with food.
Cabergoline: occasional nausea, vomiting, fewer side effects than
bromocriptine.
Octreotide and Sandostatin LAR: when beginning treatment: loose
stools, light-colored stools, occasional diarrhea and abdominal
cramping. This side effect usually lessens or disappears within 1 to
2 weeks. The long term side effect is the risk of developing
gallstones - approximately 18% of people develop gallstones or gall
bladder sludge. The gallstones may not cause a problem, but there is
always a risk of developing problems.
When beginning treatment with Sandostatin LAR, the recommendation is
to first take the short acting preparation as an injection 3 times a
day for 2 weeks in case side effects are too bothersome, in this
case, the long acting preparation, Sandostatin LAR, may not be
suitable.
5. Can medical treatment be used instead of surgery for
acromegaly?
Occasionally. If the patient cannot undergo surgery, medical
treatment, preferably with octreotide, is used. Again, this is not a
cure. Medical treatment controls the problem.
6. Does medical treatment shrink the tumor?
Only in a minority of patients. Approximately 30% of patients have a
reasonable decrease in tumor size (greater than 30% shrinkage). If
there is a large tumor, the likelihood that medical treatment
(octreotide) will substantially shrink the tumor is low. For this
reason, surgery is recommended as the first treatment for most
patients.
7. What is IGF-1 (also called somatomedin C)?
IGF-1 and somatomedin C are the same thing, different names. Growth
hormone acts on the body by causing the liver and other tissues to
produce a hormone known as "insulin-like growth factor-1" (IGF-1) -
it is the IGF-1 which causes the ill effects of too much growth
hormone. Growth hormone is released from the pituitary gland
in "bursts" or "spurts" - the levels vary considerable from minute to
minute, so one measurement does nor reflect overall growth hormone
production. IGF-1 is more constant in the blood and is a better and
more accurate indicator of overall growth hormone production. The IGF-
1 blood test is used to assess the effectiveness of all treatments
(surgery, radiation, medical treatment).
8. What is the cost of medical treatments?
Retail pharmacy charges:
Bromocriptine, 5 mg 3 times a day: $ 362/month; $ 4,344/year
Bromocriptine, 5 mg 4 times a day: $ 482/month; $ 5,749/year
Octreotide (Sandostatin), 100 mcg 3 times a day:
$ 1,111/month; $ 13,332/year
Sandostatin LAR:
10 mg/month: $ 13,740/year
(there may also be a charge for each injection)
20 mg/month: $ 13,740/year
(there may also be a charge for each injection)
30 mg/month: $ 20,340/year
(there may also be a charge for each injection)
9. Since octreotide and Sandostatin LAR are so expensive, is
there any financial help available?
Yes. The manufacturer of the drug (Novartis) has an assistance
program for patients who do not have an insurance plan that pays for
medications and cannot afford the drug. The Novartis patient
assistance telephone number is: 1-877-LAR-INFO.
10. I have had surgery, why do I still have a problem and have to
take radiation treatment and take medication?
Some patients are not cured with surgery. The reasons for this are
most commonly related to the size of the tumor: the larger the tumor,
the less likely it can be removed completely. Additionally, the tumor
may have spread to nearby structures such as bone, the cavernous
sinus (location of carotid artery and nerves controlling eye
movements) and the membrane surrounding the gland. In this situation,
the surgeon removes all that can be safely removed, but if the tumor
has invaded surrounding structures such as bone or the cavernous
sinus or the membrane covering the pituitary, excessive growth
hormone production may persist. Surgery is still the first step,
since the medical treatments are not optimally effective in shrinking
the tumor and if present, relieving pressure on the optic nerve.
C. ACTH producing tumor (Cushing's Disease):
1. Are there any medical treatments for ACTH producing tumors?
Yes and no. There are medications which can reduce cortisol
production by the adrenal glands, but these medications do not have
any effect of the pituitary overproduction of the hormone ACTH (the
pituitary hormone that stimulates the adrenal glands to make too much
cortisol). Thus, medications are used to control adrenal gland
cortisol overproduction, but do not treat the source of the problem -
the pituitary gland. Some of the medications used include
ketoconazole (Nizoral) and metyrapone (Metopirone). These medications
are often used for patients who have persistent Cushing's after
surgery and radiation, while waiting for the radiation to become
effective. If a drug to lower cortisol is prescribed, careful
monitoring is necessary to determine if the dose is effective
(measure 24 hour urine cortisol level) and to make sure it does not
reduce cortisol to below normal (measure morning blood cortisol
level).
2. What are the side effects of these medications?
Ketoconazole (Nizoral): the most common side effect is nausea and
abnormalities in liver function. Before this medication is taken, a
blood test should be measured to make sure there are no liver
abnormalities. If the patient develops fatigue or jaundice, liver
tests should be measured again and the medication stopped. Other side
effects include vomiting, abdominal pain and itching.
Metyrapone (Metopirone): nausea, vomiting, diarrhea.
If these block adrenal gland cortisol production completely, adrenal
insufficiency occurs. Dexamethasone (a synthetic cortisol drug) is
often given (in a small dose) to protect against developing adrenal
insufficiency or the dose can be reduced. A morning blood cortisol
level is helpful to determine if the dose is too high. A 24 hour
urine cortisol measurement is the best test to determine the
effectiveness of medical treatment. If the urine cortisol level
remains elevated, the dose of medication may need to be increased.
3. I had surgery for Cushing's, why do I have to take steroid
(cortisol) replacement (hydrocortisone, prednisone, dexamethasone)?
This is the best outcome after pituitary surgery. It means that the
tumor has been removed completely and that the rest of the gland is
still suppressed (relatively "asleep"). It may take several months
for the normal ACTH producing cells to regain function. In the mean
time, steroid replacement is necessary to protect against adrenal
insufficiency (steroid is necessary for normal life). At a later
date, the need for continued steroid replacement is determined by
blood tests.
If a person has to take steroid replacement (hydrocortisone,
prednisone, dexamethasone) he/she should wear a Medic Alert bracelet
or necklace which identifies the need for steroid treatment.
4. I have been cured of my Cushing's - why don't I feel normal, 6
months after my surgery?
This is a common question. Cushing's affects every system of the
body, it causes problems gradually, particularly its effect on
muscles and body fat. With Cushing's, muscles become thin and weak.
It takes a long time for the body to "repair" itself, usually 9 to 12
months. It is quite common for patients to still feel weak several
months after successful surgery. Also, the excess weight does
not "magically" disappear - it takes time and a weight reduction diet
to return to normal body weight. The important word here is: patience.
D. Non functioning pituitary tumor:
1. Is there any medical treatment for this type of tumor?
In general, no. There are no specific medical treatments for this
type of tumor. The best treatment is surgery to remove the tumor.
Bromocriptine has been used in a few patients who could not have
surgery. In this situation, a small minority of patients has had some
improvement in vision because of slight reduction in tumor size and
relief of pressure on the optic chiasm (eye nerves responsible for
vision). However, this medicine does not cause dramatic tumor
shrinkage - the best treatment is to remove as much of the tumor as
possible with surgery.
If surgery has to be delayed for a short time, dexamethasone may be
given to reduce swelling and hopefully relieve the pressure on the
optic chiasm (this is not effective in everyone). The most important
and most effective treatment is to remove the tumor surgically.
2. Should I try medication before surgery?
No. Unless there is a reason surgery cannot be performed, the best
treatment is removal of as much of the tumor as possible. Additional
treatment such as pituitary radiation may be necessary to treat any
remaining tumor and to prevent re-growth.
E. Craniopharyngioma:
1. Is a craniopharyngioma a pituitary tumor?
Technically, no. A craniopharyngioma arises from abnormal development
of the pituitary gland during fetal development. It may be located
within the pituitary gland or above the pituitary gland. This is a
tumor that one is born with and may enlarge at any time. It is not a
cancer. A craniopharyngioma may be discovered in childhood or at any
age in adulthood. This type of tumor does not produce hormones but
frequently interferes with normal pituitary gland function and also
cause diabetes insipidus (a disorder of water balance with frequent
urination and excessive thirst).
2. Is there medical treatment for a craniopharyngioma?
No, there are no medicines to treat this type of tumor. Most patients
do have to take hormone replacement because of damage to the normal
pituitary gland. Surgery is the first choice. Some patients also
require radiation treatment.
III. Replacement Therapy for Hypopituitarism
1. What is hypopituitarism?
Hypopituitarism means that one or more of the pituitary hormones is
not being produced normally and hormone replacement is necessary.
2. Why does hypopituitarism happen?
A pituitary tumor may cause the loss of normal pituitary function;
usually this occurs because of pressure (compression) by the tumor on
the normal gland. Other causes of loss of normal pituitary function,
destruction of the normal gland, include bleeding into the tumor and
normal gland, surgery and radiation therapy. Regardless of the cause,
hormone replacement is required.
3. Is hypopituitarism loss of all normal pituitary function?
No. Some patients have only 1 hormone deficiency, others have 2 or 3,
others have complete pituitary hormone deficiencies.
4. What are the pituitary hormones and what do they do?
Pituitary Hormone Target Organ Regulates
ACTH Adrenal glands Adrenal cortisol production
TSH Thyroid gland Thyroid hormone production
LH, FSH Ovaries, testes Reproduction, sexual function
GH (growth hormone) Whole body, bones Growth, body composition
Prolactin Breast Milk production
ADH (vasopressin) Kidney Water balance
ACTH deficiency: this hormone stimulates the adrenal glands to
produce cortisol. Cortisol is necessary for life. Lack of adequate
cortisol causes fatigue, weight loss, nausea, vomiting, low blood
pressure and ultimately shock and death.
TSH deficiency: this hormone stimulates the thyroid gland to produce
thyroid hormone. Low thyroid hormone causes fatigue (loss of energy),
weight gain, constipation and memory problems. Thyroid hormone is one
of the 2 pituitary controlled hormones that are necessary for life.
LH and FSH deficiency: these hormones control the reproductive system
and sexual function. Deficiency of these hormones causes loss of
menstrual periods and infertility in women and causes loss of sexual
function and loss of fertility in men.
Growth hormone deficiency: this is the most common deficiency and
occurs in approximately 85% of patients who have a pituitary tumor.
Loss of growth hormone in children causes poor growth. In adults,
symptoms of decreased energy and vitality are common. Changes in body
composition can also occur - more fat is accumulated and a decrease
in muscle mass occurs.
Prolactin deficiency: inability to nurse; no known ill effects in men.
ADH (vasopressin) deficiency: this hormone is produced by the
posterior or back portion of the pituitary gland and is responsible
for water and sodium (salt) balance. Deficiency of this hormone
causes excessive and frequent urination and excessive thirst. If the
patient does not drink an adequate amount of water, the blood sodium
can increase abnormally and cause dehydration. Many patients can
drink enough water to maintain a normal blood sodium level, but this
is extremely inconvenient for the patient - having to drink large
amounts of water (day and night) to make up for the large losses from
the kidneys.
5. Can all of these hormones be replaced?
Yes, all except prolactin.
6. What does hormone replacement involve? What do I have to do?
Hormone replacement is administered with pills, injections, skin
patches and a nasal spray, depending on the type of hormone.
Pills: hydrocortisone (or prednisone or dexamethasone), thyroid
hormone, estrogen (female hormone), progesterone (female hormone) and
dDAVP (water balance hormone)
Injections: testosterone (male hormone), growth hormone
Skin patches: estrogen and testosterone
Nasal spray: dDAVP
The most important thing about hormone replacement is that the
medication(s) must be taken as prescribed. If the medications are not
taken as directed, serious medical problems can occur.
If hormone replacement requires steroid (cortisol) replacement - this
medication must be increased if another illness occurs, such as flu,
kidney infection, pneumonia. The hydrocortisone (or prednisone or
dexamethasone) dose should be doubled for the duration of he illness -
this mimics the body's normal response to illness. Patients who
require steroid replacement should also wear a bracelet or necklace
which identifies the need for steroid treatment (the doctors in an
emergency room need to know this in the case of an accident or
illness so that adequate steroid treatment can be given).
7. How long do I have to take hormone replacement?
Usually forever. Depending on the tumor type, the treatment and the
effects of treatment, some patients have return of normal pituitary
function and replacement hormone(s) can be stopped. This should only
be done with the appropriate blood testing to make sure the pituitary
gland has "recovered".
8. Why should a woman take estrogen (female hormone) treatment?
To protect the bones and prevent osteoporosis (thinning of the bones)
and to protect the woman against developing early heart disease.
Estrogen treatment is usually not given to a woman who has had breast
cancer or who has a strong family history of breast cancer. In either
situation, regular mammograms, pelvic exams and pap smears are
necessary.
9. Why should a man take testosterone (male hormone) treatment?
Testosterone is not only necessary for normal sexual function, it is
important to protect the bones against osteoporosis and to preserve
normal muscle mass and blood production by the bone marrow. Men
should have a regular prostate exam and a blood PSA test (screening
test for prostate cancer).
10. If a woman has hypopituitarism can she become pregnant?
If the pituitary hormones (LH and FSH) which regulate the ovaries are
not functioning properly, it is extremely unlikely for a woman to
become pregnant without additional medical treatment. It is possible
to stimulate the ovaries with LH and FSH injections, this may take
several months of injections before ovulation occurs and pregnancy is
achieved. Although it requires more "work", pregnancy is possible in
a woman who had pituitary hormone deficiency. Men can also be treated
with these pituitary hormones to stimulate the testes to produce
testosterone and sperm.
11. Is growth hormone important in adults?
Yes. Growth hormone (GH) does more than stimulate growth in children.
In adults, growth hormone affects all aspects of metabolism and
affects body composition. Adults who are growth hormone deficient may
have an increased amount of body fat and decreased amount of muscle.
Bone density may also be lower in adults who are growth hormone
deficient. In addition to physical features of GH deficiency in
adults, some patients experience symptoms of fatigue, loss of energy
and social isolation. Growth hormone replacement is relatively new,
it has been used in Europe for approximately 11 years and in the U.S.
since 1996. Studies of GH replacement demonstrate that muscle mass
increases, fat mass decreases, and after 18 months, bone mass
increases; weight does not change (it is not a weight loss hormone).
Growth hormone causes a preferential reduction in fat within the
abdomen (visceral fat). Some patients had improvement in exercise
ability and muscle strength. Questionnaires designed to assess the
effect of GH on psychological measures revealed that patients treated
with this hormone had improvement in energy level and an overall
sense of well-being.
Growth hormone deficiency must be diagnosed with a stimulation test
(blood test after receiving a stimulating medication). The most
common stimulation tests include: insulin to lower the blood sugar, L-
dopa, arginine and growth hormone releasing hormone. The maximum GH
level after the stimulating medication is used to determine if a
patient is growth hormone deficient.
Growth hormone must be administered by an injection under the skin
once a day. The needle used is a very tiny insulin needle (GH
deficient children give themselves this injection daily). Growth
hormone replacement must be monitored by assessing the clinical
response, assessment of side effects and by measuring the blood IGF-1
level to determine if the dose is correct for a patient (one dose
doesn't fit all when it comes to hormone replacement therapy).
Growth hormone replacement is FDA approved for patients who have
pituitary disease and who have an abnormal stimulation test. It is
expensive, usually more than $ 10,000/year. Thus, most insurance
companies require documentation of the need for this medication and
the results of the stimulation test before agreeing to reimbursement.
Summary
The patient with a pituitary tumor is a challenge for the medical
community, the family and the patient. Working together, the
challenge is to achieve the correct diagnosis, appropriate treatment
and ongoing medical monitoring. This challenge can be met resulting
in the best possible outcome for the patient and his or her family.