Replacement Therapy for Hypopituitarism
- What is hypopituitarism?
- Why does hypopituitarism occur?
- Is all normal pituitary function lost in hypopituitarism?
- What are the pituitary hormones and what do they do?
- Can all of these hormones be replaced?
- What does hormone replacement involve? What must I do?
- How long must I take hormone replacement?
- Should a woman receive estrogen (female hormone) treatment?
- Why should a man receive testosterone (male hormone) treatment?
- Is fertility possible in a patient with loss of pituitary function?
- Is growth hormone important in adults?
1. What is hypopituitarism?
Hypopituitarism is a condition where one or more pituitary hormones are being
produced in inadequate amounts and replacement with hormones is necessary.
2. Why does hypopituitarism occur?
Normal pituitary function may be lost as the result of a pituitary tumor,
which compresses and destroys the normal gland. Other common causes of destruction
of the normal pituitary and its hormone-secreting functions include bleeding
into a tumor and normal gland (called pituitary apoplexy), surgery, and radiation
therapy. Hypopituitarism can also be caused by damage to the hypothalamus (e.g.,
radiation damage). Regardless of the cause, hormone replacement is required.
3. Is all normal pituitary function lost in hypopituitarism?
No. Some patients have only a single hormone deficiency, others have 2 or
3 deficiencies, and in some patients, all pituitary hormones are deficient.
4. What are the pituitary hormones and what do they do?
| Pituitary Hormone |
Target Organ |
Function |
| ACTH |
Adrenal glands |
Cortisol production |
| TSH |
Thyroid gland |
Thyroid hormone production |
| LH, FSH |
Ovaries, testes |
Reproduction, sexual function |
| GH (growth hormone) |
Entire body, including bones, muscle, and fat |
Growth, body composition |
| Prolactin |
Breast |
Milk production |
| ADH (vasopressin) |
Kidney |
Water, salt balance |
| Oxytocin |
Uterus
Breast
|
Contractions during labor and delivery
Stimulates release of milk and prepares breast for nursing |
ACTH deficiency: ACTH stimulates the adrenal glands to produce cortisol.
Cortisol is essential for life. When cortisol is inadequate, patients experience
fatigue, weakness, weight loss, nausea and vomiting, low blood pressure and
may develop shock and die unless treated.
TSH deficiency: TSH stimulates the thyroid gland to produce thyroid hormone.
Low thyroid hormone causes fatigue (loss of energy), weight gain, constipation,
dry skin, and feeling cold.
LH and FSH deficiency: LH and FSH control the reproductive system and
sexual function. Deficiency of these hormones causes loss of menstrual periods,
low estrogen and progesterone levels, and infertility in women and causes
loss of sexual function, a low blood testosterone level and loss of fertility
in men.
Growth hormone (GH) deficiency: GH is necessary for normal growth in children
and also has important effects on metabolism in adults. GH deficiency is the
most common pituitary hormone deficiency and occurs in approximately 85% of
patients with a pituitary tumor. Loss of growth hormone in children causes
lack of normal growth (growth retardation, short stature). In adults, symptoms
of decreased energy and vitality are common. Changes in body composition can
also occur - more fat is accumulated and muscle mass decreases. The risk of
heart disease is increased and abnormalities of cholesterol can occur. Bone
density also decreases and there is an increased risk of bone fractures.
Prolactin deficiency: Prolactin stimulates milk production by the breast
The only problem of prolactin deficiency is the inability to nurse after pregnancy.
There are no known ill effects of prolactin deficiency in men.
ADH (vasopressin) deficiency: ADH (anti-diuretic hormone) is produced by
the posterior (back part pituitary and is responsible for water balance. Deficiency
of this hormone causes excessive and frequent urination and excessive thirst.
If the patient does not drink an adequate amount of water, severe dehydration
can occur and the blood sodium (salt) increases to abnormally high levels...
Most patients can drink enough water to maintain normal hydration, but this
is extremely inconvenient for the patient and often requires drinking large
amounts (often more than a gallon per day) of water and urinating as often
as every hour because of the inability of the kidneys to conserve water. If
normal thirst sensation is lost or the patient is unable to drink, sodium levels
may increase , sometimes to dangerously high levels
5. Can all of these hormones be replaced?
With the exception of prolactin and oxytocin, all can be replaced, although
for some, it is more practical to replace the hormones from the glands normally
stimulated by the pituitary.
6. What does hormone replacement involve? What must I do?
The medication(s) must be taken as prescribed in order to have a beneficial
effect; if not there will be no benefit and harmful medical consequences may
occur.
Medications: Hormone replacement is administered with pills, injections,
skin patches, a skin gel, a buccal (under the lip) tablet, and/or a nasal spray,
depending on the type of hormone. Medications are listed by individual endocrine
glands:
- Adrenal Insufficiency: most typically hydrocortisone or prednisone (pills)
- Thyroid Insufficiency: thyroxine (thyroid hormone) (pill)
- Gonadal insufficiency:
- Sex Hormones:
- Estrogen (female hormone) (pill or patch); progesterone (female
hormone) (pill), or combinations
- Testosterone (male hormone): pills
may cause liver damage and should not be
used. Preferable treatment is a skin gel or patch or buccal patch
(under the lip). An injection is also available but does not provide
even blood levels
- Diabetes
insipidus: dDAVP (synthetic vasopressin) as a pill, nasal spray,
or injection.
- Growth hormone deficiency: GH injections
It is most important that all hormone replacement medication(s) be taken
as prescribed and the beneficial effects and possible side effects need to
be monitored regularly by an endocrinologist. If medications are not taken
as directed, serious medical problems can occur. A very important principle
is that not every patient requires the same dose. All hormone replacement may
require dose adjustment based on blood tests, assessment of how the patient
responds clinically, and any side effects. The need for dose adjustment (increase
or decrease) is quite common when beginning any hormone replacement in order
to achieve the goal of an optimal dose for each patient.
If a patient requires steroid (hydrocortisone) replacement, this medication
must be increased if another illness occurs, such as flu, kidney infection,
pneumonia. The hydrocortisone dose should be increased according to the doctor’s
instructions for the duration of the illness so that it mimics the body's normal
response to illness. Patients who require steroid replacement should also wear
a bracelet or necklace (obtained at a local pharmacy or on the internet), 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 in which the patient
cannot communicate the information to the doctors, so that adequate steroid
treatment can be given).
Thyroid hormone is necessary for life. Thyroid hormone deficient patients
have symptoms including, weight gain, lack of energy, tiredness, cold intolerance,
constipation, and dry skin. The diagnosis of hypothyroidism in a patient with
pituitary disease cannot be made by measuring a TSH level; it requires measurement
of thyroid hormone itself. Similarly, the correct dose of thyroid hormone cannot
be established by monitoring TSH levels. Levels of thyroid hormone replacement
need to be judged by the clinical response and blood thyroid hormone level.
7. How long must I take hormone replacement?
In most patients, the pituitary gland does not recover normal function and
hormone replacement is usually life long. However, occasionally, depending
on the type of tumor, the treatment and its effects, there may be a return
of normal pituitary function and replacement hormone(s) can be stopped. This
should only be done with appropriate blood testing to confirm that normal pituitary
function has been resumed. Medication should not be stopped without supervision
from an endocrinologist.
8. Should a woman receive estrogen (female hormone) treatment?
Estrogen relieves symptoms of menopause (hot flashes). However, recent results
of the Women’s Health Initiative study showed a small but increased risk
of developing breast cancer and heart disease in postmenopausal women who took
estrogen and progesterone replacement. However, estrogen replacement in premenopausal
women is indicated as it serves to restore estrogen levels that are normally
present at that stage of life. Symptoms of estrogen deficiency, which may respond
to estrogen replacement include: vaginal dryness, painful intercourse, decreased
libido, breast shrinkage, dry skin, and hot flashes. Estrogen protects the
bones to reduce the risk of developing osteoporosis (thinning of the bones)
and is best taken with calcium and vitamin D for maximum effect. However, there
are other very effective medications to treat osteoporosis. Estrogen treatment
is not given to a woman who has had breast cancer or who has a strong family
history of breast cancer. In all women receiving estrogen, regular mammograms,
pelvic exams and pap smears are necessary. Currently, estrogen replacement
is given as short term treatment to control menopausal symptoms (usually for
one or two, but not more than 5 years).
9. Why should a man receive testosterone (male hormone) treatment?
Testosterone is not only necessary for sexual function, it is important for
bone strength and protects against osteoporosis (loss of bone mass and increased
risk for bone fractures), to preserve normal muscle mass and strength and normal
red blood cell production by the bone marrow. The effects of long-term testosterone
deficiency include a higher risk of bone fracture, loss of muscle mass and
muscle strength, increased fat, and low red blood cell count (anemia) as well
as loss of interest in sex (libido) and loss of sexual function (erectile dysfunction).
Every man receiving testosterone replacement should have a regular prostate
exam and a yearly blood PSA test (screening test for prostate cancer). Testosterone
does not cause prostate cancer, but if a man has prostate cancer, testosterone
treatment may promote growth of the cancer, which emphasizes the need for such
examinations.
10. Is fertility possible in a patient with loss of pituitary function?
Yes,
but medical treatment is necessary.
Women: If the pituitary hormones (LH and FSH) that regulate the ovaries are
not produced normally, 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, although it may require several months of therapy
before ovulation occurs and pregnancy is achieved. Although it requires more “work” (and
cost, as most insurance companies do not pay for fertility treatments), pregnancy
is often possible in a woman with pituitary hormone deficiency.
Men: Men who do not produce testosterone and who have a low sperm count can
be treated with pituitary hormones (LH and FSH) to stimulate the testes to
produce testosterone and sperm. Sperm production takes a long time. – the
normal sperm cycle is nearly 3 months. It may require a year of more of treatment
in order to increase testosterone and sperm production to levels that will
restore fertility.
11. Is growth hormone important in adults?
Yes. Growth hormone (GH) does more than stimulate growth in children. In
adults, GH affects all aspects of metabolism (body energy) and body composition
(fat mass, muscle mass, bone density). Growth hormone deficient adults may
have increased body fat and decreased body muscle. Bone density may also be
lower in adults who are GH 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 recent;
it has been used in Europe for approximately 17 years and in the U.S. since
1996. Studies of GH replacement have shown that muscle mass increases, fat
mass decreases, and after 18 months, bone mass increases; weight does not change
(GH is not a weight loss hormone). Growth hormone caused a greater reduction
in fat within the abdomen (visceral fat) as compared to other areas and this
is believed important because increased visceral fat is associated with a higher
risk of developing heart disease. Some patients have improvement in exercise
ability and muscle strength. Questionnaires to assess GH effects on psychological
measures have shown that GH-treated patients had improvement in energy levels
and an overall sense of well being.
The diagnosis of GH deficiency is usually made with a GH stimulation test
because a single blood GH level and IGF-1 level are not adequate for the diagnosis
(IGF-1 may actually be normal in patients with GH deficiency). In patients
who have 3 or 4 pituitary hormone deficiencies, GH deficiency is highly likely
(over 90%), and if the blood IGF-1 level is below normal, a stimulation test
may not be necessary. Since GH treatment is expensive, most insurance companies
require the result of a stimulation test before agreeing to provide financial
reimbursement or coverage. Stimulation tests to diagnose GH deficiency in adults
include administration of insulin to lower the blood sugar level, and arginine
and GH-releasing hormone. These tests require measurement of several GH levels,
before and after administration of the stimulating drug.
Growth hormone is administered by an injection under the skin (subcutaneous)
once a day. The needle used is very small (GH deficient children give themselves
this injection every day). Growth hormone replacement must be monitored by
evaluating the clinical response (how the patient feels), any side effects
(most commonly swelling, edema, muscle aches, tingling in the fingers) and
by measuring the blood IGF-1 level to determine if the dose is correct for
a patient (again, not all patients require the same dose of GH for replacement
therapy).
Growth hormone replacement is FDA approved for patients who have pituitary
disease and who have an abnormal GH stimulation test. Growth hormone is expensive.
Therefore, most insurance companies require documentation of the need for this
medication and the results of a stimulation test before agreeing to reimbursement.
