Endocrinology and Metabolism
Peter A. Singer, M.D.
November 26, 2002 11-12 am
PITUITARY TUMORS —Clinical Features, Diagnosis, and Management
Objectives
By the end of this teaching activity, students will be able to:
1. Discuss the differential diagnosis of lesions of the sella turcica.
2. Describe the clinical presentation of pituitary tumors, including both non-functioning
and functioning tumors.
3. Outline a diagnostic approach to pituitary tumors.
4. Describe various treatment options for pituitary tumors, and select appropriate therapies.
Reading - Recommended/Supplemental
1. Harrison's Online; Chapter 28 (excellent source - this is encouraged)
2. Principles and Practice of Endocrinology and Metabolism, Chaps 12,13,16,17,20-24.
www.usc.edu/nml - ovid - books on file
Points of Integration
Case 5
Introduction
Pituitary tumors, as well as other lesions in the area of the sella
turcica, are relatively common. The prevalence of clinically apparent
pituitary lesions is estimated to comprise approximately 10 % of all
intracranial lesions, while incidental pituitary tumors are detected in
approximately 11% of individuals at autopsy. Moreover, CT and MRI
scanning performed for disorders unrelated to pituitary disease uncover
similar numbers of pituitary lesions, most of which are less than 1 cm
in size.
Pituitary tumors (and other sellar masses) result in morbidity by
presenting with neurologic symptoms and signs, by hypopituitarism, or
by hormonal excess. The purpose of this syllabus material is to outline
a clinical approach to the diagnosis and management of such lesions.
Differential diagnosis of sellar lesions
Pituitary tumors are the commonest lesions occurring in the sella
turcica. Table 1 provides a differential diagnosis of lesions of the
sella, including prevalences of lesions from a surgical series in our
clinical practice at USC-University Hospital.
Table: University of Southern California- University Hospital Surgical
Experience for Sellar Lesions from 1991 to 2002 (n=833)
Tumor Type Macroadenoma (>10mm) Microadenoma (<10mm) M:F ratio
Non-Functioning 401 4 1.5 : 2
Functioning
ACTH 16 70 1 : 5
GH 86 10 1.5 : 1
TSH 7 1 : 1
Prl 74 68 1 : 1.3
Other Tumors (Lesions) 91 1 : 1
Abbreviations: ACTH=adrenocorticotropin hormone; GH= growth hormone;
TSH=thyrotropin hormone; Prl=prolactin; M=male; F=female.
Other tumors include: craniopharyngioma (n=33); Rathke's cleft cyst
(n=31); clivus chordoma (n=6); sellar meningioma (n=18); hyperplasia
(n=3); metastatic (0) (breast, prostate, renal); sarcoid - 1 ; fibrosis
- 1; hemangioma - 1
Note that among sellar lesions craniopharyngiomas, Rathke's cleft
cysts, and meningiomas are relatively common. Craniopharyngiomas and
Rathke's cysts are outgrowths from remnants of Rathke's pouch.
Meningiomas are benign lesions arising from the meninges. All of these
lesions may mimic the clinical findings associated with non-functioning
pituitary tumors, namely pressure effects resulting in visual changes,
and impairment of secretion of trophic hormones. The other lesions
listed in the differential diagnosis are very uncommon, accounting for
only a few percent of sellar lesions. Not included in Table 1 (since we
haven't seen cases in our surgical series) are lymphocytic
hypophysitis, pituitary abscess, or arteriovenous fistulas of the
cavernous sinuses.
Pituitary tumors are virtually always benign adenomas. Pituitary
carcinoma has been reported to comprise about 0.5 % of pituitary
tumors, although that has not been our experience, having seen only one
carcinoma in more than 600 tumors.
Tumors are classified according to size, and function. For example, a
tumor less than 1 cm in size is a microadenoma and a lesion 1 cm or
larger is a macroadenoma. Most tumors are non-functioning, meaning that
they are not hormonally active, while functioning tumors may secrete
either prolactin, growth hormone (GH), corticotropin (ACTH), or
thyrotropin (TSH). Each of the functioning tumors results in a specific
clinical syndrome (see below). Strictly speaking, so-called
non-functioning tumors may secrete gonadotropins, but are very
infrequently associated with a syndrome of gonadotropin excess, which
would include elevated target organ sex steroid levels.
Clinical presentation and diagnosis of specific tumors
• Non-functioning tumors
o Clinical features—non-functioning adenomas are the commonest of the
tumors, and, because they are for the most part hormonally inactive,
present with pressure symptoms. Bitemporal hemianopsia is the commonest
visual abnormality, and results from compression of the optic chiasm by
suprasellar extension of the tumor. If chiasmal pressure is severe
enough, decreased visual acuity may occur, and if there is extension of
the tumor into the cavernous sinus, oculomotor palsies may be present.
Unfortunately, tumors grow so slowly that gradual visual changes may
not be noticed by the patient, so that vision at times is permanently
affected. Headache is a very inconsistent symptom, and presumably
occurs from increased sellar pressure; interestingly, most patients,
even those with very large tumors, do not complain of headaches—no
doubt if they did the diagnosis would be made much earlier.
Hormonal deficiencies occur because of destruction or pressure on
normal pituitary tissue (see syllabus section on Hypopituitarism).
Hormonal excess may also occur infrequently, since such lesions
occasional secrete FSH and LH, and may result in ovarian
hyperstimulation, with multiple ovarian cysts and elevated estradiol
levels in premenopausal women, or elevated testosterone levels in
males. These scenarios are very, very infrequent.
o Diagnostic evaluation—the diagnosis of nonfunctioning tumors depends
first of all on recognizing the symptoms of such lesions, such as
symptoms of visual impairment and symptoms of pituitary insufficiency,
and then proceeding with appropriate imaging tests and hormonal
measurements. The imaging procedure of choice for pituitary lesions is
magnetic resonance imaging (MRI). MRI has excellent resolution for
tumors, and can demonstrate pressure (where present) on the optic
chiasm, as well as extension into the cavernous or sphenoid sinuses.
If a tumor is demonstrated on MRI the next step is to determine whether
or not the lesion is functioning. Hormonally active lesions causing
either acromegaly or Cushing's disease are often obvious clinically,
and whether or not to do tests for those disorders depends on the
clinical picture. If patients do not appear clinically to have
functioning tumors, hormonal deficiencies should be checked for. Serum
gonadotropins and serum testosterone should be measured in men, and
gonadotropins (and estradiol in premenopausal women) in women. (The
differentiation between primary and secondary hypogonadism is described
in the syllabus material on Hypopituitarism). If gonadotropins and
either testosterone (males) or estradiol (women) are elevated, the
diagnosis would be a functioning gonadotropinoma. In addition, free T4,
TSH; and fasting serum cortisol determinations should be performed.
Dynamic testing for ACTH or GH reserve is not necessary. It is
imperative to measure serum prolactin, and if the prolactin is
elevated, but less than 100 ng/ml in a patient with a macroadenoma, the
prolactin elevation is almost certainly due to stalk effect in the
presence of a non-functioning tumor—i.e., pressure on the pituitary
stalk, with inhibition of dopamine.
• Prolactinomas
General comments--Prolactinomas are the commonest pituitary tumors, and
are the second-commonest tumors for which patients are referred for
pituitary surgery, usually because of side effects from therapy with
dopamine agonists (Tables 1 and 2). They are more common in women than
men, and may be either macro or microadenomas. Microadenomas appear to
be more common in women, and macroadenomas occur more frequently in
men. The biochemical hallmark of prolactinoma is an elevated serum
prolactin; prolactin may be elevated because of multiple other causes,
however, including both physiologic and pathologic, so it is important
to know the differential diagnosis of hyperprolactinemia:
Physiologic Hyperprolactinemia Pathologic Hyperprolactinemia
-Pregnancy -Prolactinomas
-Nipple stimulation -Stalk effect (other tumors)
-Stress -Other functioning tumors
(E.g. GH)
-Inflammatory diseases--
(E.g. hypothalamic sarcoid)
-Stalk section, trauma
-Chest wall injury and irritation
-Chronic renal failure
-Drugs (e.g. haloperidol, metoclopramide, phenothiazines, risperidone, estrogen)
-Idiopathic
-Hypothyroidism
Note that "hypothyroidism" is bolded in the list of pathologic
elevations of prolactin—this is because it is essential that
hypothyroidism be ruled out before embarking on a further work-up for
hyperprolactinemia. Indeed, long-standing and pronounced primary
hypothyroidism may result in pituitary hyperplasia, and enlargement of
the pituitary may lead to an erroneous diagnosis of a pituitary tumor.
Serum prolactin elevations from stalk effect are rarely greater than
100 ng/ml, and elevations from hypothyroidism, drugs are rarely greater
than 100 ng/ml. Similarly, idiopathic elevations also remain under 100
ng/ml; the likelihood is that such patients have microadenomas too
small to detect.
o Clinical manifestations—in premenopausal women the commonest clinical
features are oligo/amenorrhea, galactorrhea, and infertility. Since
most tumors in younger women are microadenomas, neurologic pressure
symptoms and signs do not occur. Such symptoms and signs may occur with
macroprolactinomas, though. Hypopituitary symptoms associated with
microprolactinomas are related to the degree to which prolactin
inhibition of LH secretion lowers serum estradiol levels—the greater
the prolactin increase, the lower the estrogen level; symptoms of
estrogen deficiency, in addition to oligo/amenorrhea, may include hot
flushes and vaginal dryness. In women with macroprolactinomas, pressure
effects on the visual apparatus and deficiencies of other pituitary
hormones may also be present. In postmenopausal women
microprolactinomas rarely cause symptoms, since they are already
amenorrheic, and rarely develop galactorrhea.
In men, symptoms and signs of prolactinoma are from pressure effects,
including visual changes (if there is suprasellar extension), and
hypopituitarism. The commonest endocrine abnormality is related to
testosterone deficiency, and decreases in libido, impotence, and
infertility, are common symptoms. Such symptoms are frequently
overlooked, however, since sexual dysfunction may be ascribed to other
issues and stresses. Thus, it may not be until there is significant
visual impairment that the diagnosis of prolactinoma is made.
Galactorrhea may occur in men, but is uncommon.
o Diagnostic Evaluation—the cornerstone in the evaluation of a woman
with amennorhea/galactorrhea, and a man with impotence is the serum
prolactin. An elevation in serum prolactin, regardless of the level
(and providing that there are no other causes of hyperprolactinemia
(see Table above) warrants an MRI scan. As mentioned, a serum prolactin
above 100 ng/ml is usually due to prolactinoma, and a level above 200
ng/ml is virtual assurance of the diagnosis. The larger the adenoma,
the greater the degree of prolactin elevation, so that some patients
with large, invasive tumors have prolactin concentrations in the
thousands.
If a macroadenoma is discovered on MRI, additional pituitary endocrine
testing should be done (see syllabus material on Hypopituitarism).
Patients with microprolactinomas do not have endocrine deficiency due
to pressure effects, so no additional workup in such patients is
necessary.
• Growth hormone producing tumors
-
General comments—Growth hormone producing pituitary tumors cause the
clinical syndrome of acromegaly, from excess GH secretion. By far the
commonest cause of acromegaly is pituitary tumor; rare causes also
include ectopic production of GH from carcinoid or small cell-lung
cancer, or from rare tumors secreting growth hormone releasing hormone
(GHRH).
GH- producing adenomas account for about
one-third of functioning pituitary tumors. Approximately 75% of tumors
are macroadenomas, and the mean age at the time of diagnosis is in the
mid-40's. If GH tumors develop during childhood or adolescence, before
epiphyseal closure, gigantism results. This is uncommon, though.
Acromegaly results in particularly distressing morbidity for many
patients, because of the disfiguring, non-reversible acral changes that
occur. Patients often are particularly sensitive about their
appearance, and support groups for patients with pituitary tumors
consist primarily of patients with acromegaly, because of the
psychological issues associated with the tumors.
o Clinical features--The clinical manifestations of GH-producing tumors
result primarily from increased serum levels of insulin-like growth
factor-1 (IGF-1), which is synthesized in the liver under the influence
of GH. Excess GH secretion results not only in growth of various
tissues, but in metabolic abnormalities as well. Moreover, since most
GH-producing tumors are macroadenomas, pressure symptoms and signs of
pituitary tumor may also occur.
Acromegaly tends to develop slowly, often over many years, so that many
patients attribute the soft tissue and acral changes to the natural
process of aging. It is in retrospect, though, especially when looking
at photos, that patients and their families can recognize the
slowly-developing changes.
The principle symptoms of acromegaly consist of soft tissue and acral
changes. Patients universally admit to an increase in hand and foot
size, and complain of difficulty with wearing rings, and the need to
purchase ever-larger shoes. (One of my patients went to a local
emergency department to have a ring cut off; it had finally become so
tight that it was painful. In retrospect he had noticed his ring
becoming tighter over the prior 8-10 years). Patients also notice
prominence of the jaw, and a change in the bite, and it is not uncommon
that visits to the dentist are made. Since bony growth is such a
prominent feature of acromegaly, patients commonly develop arthritic
symptoms, especially of large joints and the lumbar spine.
It should be noted that while soft tissue and acral changes are the
most obvious changes of acromegaly, patients also have generalized
symptoms of pituitary macroadenoma, including headache, visual change,
and pituitary insufficiency. Indeed, hypogonadism occurs in
approximately 50% of patients.
In addition to the obvious acral and soft tissue changes associated
with acromegaly, visceromegaly also occurs, including the liver,
thyroid, kidneys, and heart. Indeed, cardiovascular disease from both
cardiomegaly and hypertension is a prominent cause of morbidity and
mortality in untreated patients.
Acromegaly is associated with an increase in benign and malignant tumor
development. Women have a much higher prevalence of leiomyomata, and
all patients have a significant risk (up to 30%) for the development of
premalignant colon polyps (and hence, colon cancer).
Metabolic complications of acromegaly are related primarily to the anti-insulin effects of IGF-1;
impaired glucose tolerance is common, and overt diabetes is present in
approximately 25% of patients. Acromegaly is associated with
hyperprolactinemia in about one-third of patients, often due to
secretion of prolactin itself, rather than just from stalk effect.
It should be stressed that in addition to the obvious somatic changes of acromegaly, that untreated, the
disorder is associated with a significant increase in mortality,
principally from cardiovascular disease and cancer. If treated
appropriately, mortality should be no different than normal.
o Diagnostic evaluation—the biochemical diagnosis of acromegaly can be
established by measuring IGF-1, GH, or a combination of both tests.
Since the secretion of GH varies, virtually from minute to minute,
obtaining a random GH measurement may result in either false negative
or false positive results. IGF-1, on the other hand, does not vary over
a 24 hour period of time, and it is therefore the single best test for
the diagnosis of acromegaly, and separates normal individuals from
those with GH excess. A caveat here is that levels of IGF-1 are
age-dependent, with levels gradually decreasing with increasing age.
Growth hormone levels are also elevated in patients with acromegaly,
but because of its pulsatile secretion, "normal" levels may
occasionally be encountered. Moreover, GH secretion changes with
exercise and sleep (increases), and decreases with eating. Thus, in
other than a stable state, GH determinations may lead in an incorrect
diagnosis. On the other hand, in the patient with clinical features of
acromegaly, a GH level of > 30 ng/ml is virtually diagnostic, but
must be confirmed with an IGF-1 determination.
Dynamic testing of GH secretion is employed by some physicians in the
diagnosis of acromegaly; oral glucose administration results in
suppression of GH within 90-120 min after ingestion in normal subjects,
but in those with acromegaly, GH remains unsuppressed, and may even
increase following oral glucose. From a practical point of view there
is little utility in testing GH suppressibility unless the diagnosis of
acromegaly is in doubt.
Measurement of IGFBP-3, the circulating binding protein for IGF-1,
tends to be elevated in states of GH excess, although overlap with
normals limits its usefulness; nevertheless, some physicians employ
this test as well.
Once the diagnosis of acromegaly is established clinically and
biochemically, the next step in the evaluation is to obtain an MRI of
the pituitary gland. Since virtually all acromegaly is due to pituitary
disease, and mostly associated with macroadenomas, the MRI almost
always confirms the presence of pituitary tumor. If the MRI does not
demonstrate a tumor, ectopic sources must be sought, and imaging of the
chest and abdomen are the next steps.
• ACTH producing tumors and TSH producing tumors— these tumors and
their clinical syndromes are discussed in the syllabus sections on
Adrenal disorders and Thyroid disorders, respectively.
Treatment of Pituitary Tumors
The goal of treatment of pituitary tumors is to remove pressure and
relieve neurologic symptoms, and, where abnormal, restore pituitary
function to normal. Therapy nowadays consists of three different forms;
1. Surgery, 2. Radiation therapy; and 3. Medical therapy. Some patients
require all forms of treatment.
• Surgery—surgery, via the transsphenoidal approach, is the primary
form of therapy for patients with non-functioning pituitary tumors, as
well as for patients with Cushing's disease, acromegaly, and TSH
secreting tumors; it is also the choice of therapy among some
physicians for very young (20's) women with prolactinomas. With
experienced neurosurgeons, cure rates approach 90 % for intrasellar
non-functioning tumors, and for patients with functioning
microadenomas, initial cure rates for Cushing's patients and acromegaly
approximates 80%, and for those with microprolactinomas, 90%. If tumors
are larger, or invade adjacent structures, initial cure rates are
significantly lower, and in such patients, adjunctive therapy becomes
necessary. For example, since most patients with acromegaly have
macroadenomas, initial cure rates overall are likely to be lower than
with Cushing's, where microadenomas are more common. For patients with
invasive functioning tumors, surgical cure is the exception, rather
than the rule.
Note that I use the term "initial" cure when mentioning functioning
tumors. This is because relapses and recurrences occur, especially with
Cushing's disease, even though there has been an evident cure to begin
with. Relapse/recurrence is less common in patients with acromegaly or
with those who have prolactinomas. Patients who have undergone surgery
for pituitary tumor require careful follow-up.
There are biochemical tests which may be obtained the morning after
surgery in order to assess the likelihood of surgical cure in patients
with functioning adenomas: A serum GH of <2 ng/ml by
radioimmunoassay or < 1 ng/ml by immunoradiometric or
chemiluminescent assay, a cortisol of < 1 mcg/dl, or a serum
prolactin of < 2 ng/ml for patients with acromegaly, Cushing's, or
prolactinomas respectively, is suggestive of cure. Values higher are
worrisome, and further testing is necessary. For patients with
acromegaly the goal is a serum IGF-1 level in the normal range, but
since IGF-1 may remain elevated for 10 days or longer following
surgery, early assessment of cure relies on the immediate postoperative
GH level.
Some patients with giant, invasive pituitary tumors, and who harbor
other lesions in the area of the sella or hypothalamus, such as large
invasive craniopharyngiomas, cannot undergo successful surgery via the
transsphenoidal route; in such circumstances open craniotomy is
performed. Such cases are uncommon, however, and in our experience only
approximately 2% of patients have undergone craniotomy.
Complications of transsphenoidal surgery are fortunately uncommon,
occurring in less than 5 % of patients, and include cerebrospinal fluid
leak, meningitis, intrasellar hemorrhage, injury to the visual
apparatus, or injury to he pituitary gland itself, with the development
of hypopituitarism. Diabetes insipidus is relatively common, and is
nearly always transient, generally lasting only a day or so. In our
experience it occurs in approximately 20 % of patients undergoing
transsphenoidal surgery. Permanent DI is more likely to occur in
patients with craniopharyngiomas, or Rathke's cleft cysts.
• Radiation therapy—radiation therapy had previously been employed as
primary therapy for some patients, but it's use nowadays is reserved as
adjunctive therapy, either following surgery, or in some patients with
functioning tumors in whom medical therapy does not control the
disease. Radiation is administered either by conventional external
beam, fractionated therapy, or in some patients, with stereotactic
radiosurgery (gamma knife). Radiation therapy for nonfunctioning tumors
is reserved for those individuals with residual tumor, or for those in
whom early tumor recurrence is detected. Similarly, radiation is
employed for patients with functioning tumors in whom medical therapy
is ineffective, or incomplete.
In recent years stereotactic radiotherapy has become increasingly
popular, since hypopituitarism occurs much less frequently than with
conventional external beam radiation. Patients receiving conventional
therapy have an approximately 50% likelihood of developing pituitary
insufficiency within 5 years following completion of therapy., Gamma
knife radiotherapy also has the advantage of being administered in a
single dose, whereas conventional treatment requires daily doses over
4-6 weeks. Pitfalls of both types of therapy is that reduction in
hormone levels of functioning tumors may take a few years; moreover,
gamma knife has not been used long enough to assess long-term
effectiveness.
• Medical therapy—drug therapy is available for patients with
functioning adenomas, and is employed as the primary form of treatment
for most patients with prolactinomas:
o Prolactinomas—dopamine agonists have been available for the treatment of prolactinomas
in the United States since the late 1970's. They are an extremely
effective form of therapy, since they bind to dopamine receptors, and
inhibit prolactin secretion, as well as cause a decrease in tumor size,
by binding to dopamine receptors on lactrotrophs. Indeed, patients with
visual abnormalities from macroprolactinomas note an improvement in
vision within days to weeks after initiating oral therapy, and MRI
scans document decreases in tumor size within a few weeks after
commencing treatment.
There are currently two dopamine agonists in common use; bromocriptine (Parlodel), and
cabergoline (Dostinex). Bromocriptine is an ergot derivative, and
cabergoline is a non-ergot derivative. Cabergoline has gained more
favor during the past few years, because it may be administered once or
twice a week, while bromocriptine is taken daily, Also, also has less
pronounced side effects—both agents may produce nausea, fatigue,
postural hypotension. If one drug results in untoward side effects, the
other may be tried. If side effects are significant the medication may
be given vaginally rather than orally, although side effects persist in
most patients.
Dopamine agonists are so effective that they are considered to be the first line of therapy for
most patients with microadenomas, and virtually all patients with
invasive macroadenomas. My own method is to offer oral therapy to all
patients, but I often recommend transsphenoidal surgery to very young
women with microadenomas, since the cure rate is >90%, and the
surgery is very low risk, in experienced hands. Since surgery will not
cure patients with invasive tumors, drug therapy is the treatment of
choice. Surgery is indicated, however, in patients who have significant
side effects with drug therapy.
It should be pointed out that drug therapy must be continued indefinitely for patients with
macroadenomas, and for women with microadenomas treatment may be
stopped at the time of menopause; while prolactin levels increase again
after stopping medication, long-term follow-up of patients with
untreated microadenomas shows that the tumors tend to be stable.
The goal of therapy with dopamine agonists is to lower serum prolactin levels to the lower limit
of detectability. Once this has been achieved, and there is MRI
evidence of a decrease in tumor size, then patients may be followed
with serum prolactin levels alone. An increase in serum prolactin while
taking medication may indicate development of resistance to drug
therapy, and in such circumstances repeat MR imaging is necessary. In
patients with very large, invasive tumors, persistent tumor on imaging
is the rule, despite adequate suppression of serum prolactin. In such
patients tumors infrequently shrink more than 50%.
Importantly, reductions in serum prolactin often result in reciprocal increases in serum estradiol
in women, and testosterone in men, due to removal of prolactin's
LH-inhibitory effects. Thus, hormonal replacement may not be necessary
in patients who had hypogonadism prior to medical therapy of their
tumors.
o Growth hormone secreting tumors—medical therapy of patients with acromegaly becomes
necessary all-to-frequently, unfortunately, since most patients have
macroadenomas, which are often invasive. As mentioned above, surgical
cure rates of such patients are disappointing, so that adjunctive
therapy is required. For some patients additional therapy with
radiation may suffice, but because of the long duration between
undergoing radiation and its peak therapeutic effects, the symptoms and
signs of GH excess may persist for several years; fortunately, medical
therapy has been available in recent years to decrease GH secretion,
and very recently, a peripheral inhibitor of GH (IGF-1) action has
become available:
Octreotide and lanreotide (Sandostatin LAR) are analogs of somatostatin
(GH-inhibitory hormone), and are effective inhibitors of GH secretion.
Octreotide became available during the late 1980's, while lanreotide
first became available for clinical use in the mid 1990's. Both agents
result not only in a decrease in GH, but also in tumor shrinkage.
Because of these properties, somatostatin analogues have been advocated
as primary therapy in patients with nonresectable tumors. Predictably,
patients with smaller tumors fare better than those with larger,
invasive tumors, and the response rate in patients with very large
tumors in terms of normalizing serum IGF-1 levels, is only about 50%.
Both octreotide, which is short acting, and lanreotide, the long-acting
preparation, are given by injection, octreotide several times a day
subcutaneously, and lanreotide intramuscularly, once a month. Patients
are generally started on the short-acting form for a few weeks in order
to see whether or not there are significant untoward side effects, and
if not, then lanreotide is substituted. Common side effects include
nausea, bloating, and gastrointestinal cramping (usually resolves
within a week or so after initiating therapy), and the development of
biliary sludge or gallstones. In general, though, therapy is well
tolerated. If therapy is stopped, GH and IGF-1 levels increase again,
and tumors grow.
Pegvisomant is an analog of GH that was recently developed, and it
blocks binding of GH to its receptors, and therefore, inhibits GH
action. This agent has shown early promise, and at this time (2002) has
yet to be approved for general clinical use. A combination of this
agent, along with a somatostatin analog, may prove to be more effective
than either agent alone.
Bromocriptine has been used in the treatment of acromegaly, since it
inhibits GH release. To be clinically useful, however, very large doses
are required, which usually causes significant side effects. I do not
use bromocriptine for my patients, either as sole therapy, or in
combination with other medical therapies.
o ACTH producing and TSH producing tumors—management of these tumors is
discussed in the respective syllabus sections on Adrenal Disorders and
Thyroid Disorders.
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