Pituitary adenomas are
biologicallly benign tumors originating from adenohypophyseal cells
capable of producing various pituitary hormones. Although Cushing
pioneered this particular chapter of neurological surgery, research and
treatment of pituitary tumors are still developing.
The peak incidence is in
the third and fourth decade. Recent MR evaluation in the general
population shows that about 10% of the normal adult population has
pituitary abnormalities that are compatible with the diagnosis of
asymptomatic pituitary adenomas.
account for about 10-15% of all surgically and histologically diagnosed
intracranial neoplasms. Incidence is about 1.5-2/100,000 and they are more
common in females.
Most of them are slow growing and benign; however
some grow faster and invade the surrounding structures.
They vary in size, endocrine function,
cellular composition, and morphology.
They are greyish red and soft, usually well demarcated separated from
the adjacent compressed normal gland by
a 'pseudocapsule'. There is no fibrous
Different cell types, and
hence the adenomas
have different preferential sites.
GH adenomas are seen in the lateral
PRL adenomas can occur anywhere, but
mostly in the lateral 'wings'.
ACTH & TSH adenomas occur in the central
The rarer LH & FSH adenomas have no site
proliferation of round cells, arranged in an acinar pattern and in
sheets or trabeculae
Historically, they were
classified on the basis of their tinctorial affinity for acidic or basic
dyes into acidophilic (secrete growth hormone), basophilic (secrete ACTH),
or chromophobic (hormonally inactive) adenomas. This was of no help to an
understanding of the cytogenesis or tumor behavior.
Depending on Endocrine
activity, they are classified into
TSH – and LH/FSH-secreting < 1%
Modern classification (Horvath & Kovacs, 1976) uses the electron
microscopy and immunocytochemical analysis of hormones to distinguish:
Prolactin cell adenomas (
Growth hormone cell adenomas
Plurihormonal adenomas- Mixed prolactin, and growth hormone cell
- Acidphilic stem cell adenomas
- Mammosomatotroph cell adenomas
Null cell adenomas (nononcocytic
classification introduced by Hardy (1969) and complemented by Wilson
(1979) is based on the imaging capabilities of plain skull X-rays and
computerized tomography, and cannot exactly define parasellar
resonance imaging and surgical related classification allows a
comprehensive morphological differentiation of tumor extension, giving
the neurosurgeon more selective criteria for surgical decision making.
microadenomas refer to tumors that are less than 1 cm in size.
represent tumors greater than 1 cm in size, and
they may be
microadenomas (<1cm) without sella expansion.
macroadenomas (>1cm) and may extend above the sella, without sella
macroadenomas (<1cm) with enlargement and invasion of the floor or
Stage 4- is
destruction of the sella.
They may be
on the degree of
Extension to suprasellar cistern only.
Extension to recesses of the 3rd
Extension to involve the whole 3rd ventricle.
Two main theories
dominate current concepts of the pathogenesis of pituitary tumors (Reichlin,
suggests that adenomas arise as a consequence of target gland feed back or
Loss of normal feedback inhibition by target gland as seen
in thyrotrophinomas and gonadotrophinomas, loss of hypothalamic inhibition
in prolcatinomas and
somatotrophinomas, and excessive secretion of
CRF in ACTH-producing adenomas,
GHRH in acromegaly (Ezzat, 1994) and PRFs in prolactinomas support
theory suggests that adenomas arise as a consequence of
activation of oncogenes. A significant proportion of ACTH - producing
tumors are monoclonal. 40% of GH-secreting tumors show two different
mutations of Gsa gene regulatory protein converting it to an oncogene. The
genetic susceptibility to MEN 1 (in PRL-, GH- and ACTH secreting adenomas)
is attributed to deletions mapped to a small region within the chromosome
band 11q13 and signifies a loss of growth–inhibitory allele. Pituitary
tumors develop in transgenic mice carrying the growth inducer SV-40 T
antigen, suggesting that an intrinsic genetic defect leads to clonal
expansion of a transformed pituitary cell.
Any mass in the sella
will compromise the function of neural structures in the vicinity,
including the optic nerve, chiasm, and tracts, the hypothalamus, the
pituitary gland, the cranial nerves related to the cavernous sinus, the
brain itself, and the ventricles.
Symptoms due to mass
effect are more likely to appear due to endocrine inactive tumors and
sometimes in large, late diagnosed hormone secreting adenomas.
Visual compromise is
to be expected only if the suprasellar tumor exceeds 15mm as measured from
the plane of the diaphragma sellae.From
subtle compression of the anterior visual pathways to disabling
diplopia and headache, the symptoms and signs of pituitary tumors require
a thorough ophthalmologic evaluation which can suggest the tumor
extensions in relation to the chiasma.
A chiasma situated directly over the sella is present in about 80% of
patients, a prefixed chiasm
(overlie the tuberculum sella) in about 10%, and a postfixed chiasma (overlie
the dorsum sella) in about 10%. These relationships have a direct bearing
on the configuration of the visual field defects resulting from an
encroaching pituitary tumor. The resultant field defect can thus be
monocular, in postfixed chiasma or in extensive anterior tumor.
Involvement of the
optic nerve accounts for the scotoma and involvement of the crossing
inferior nasal fibers from the opposite optic nerve (von Wilbrand’s knee)
results in quadrantic defect.
Bitemporal hemianopia uniquely localizes a lesion to the optic chiasm.
Due to involvement
of crossing fibers of the optic chiasm, the superior temporal quadrants
are affected initially, followed by the inferior temporal quadrants.
Further damage will affect the non crossing fibers and eventual total
blindness and optic nerve atrophy.
The optic tracts are more likely to be injured with a pituitary tumor
growing posterosuperiorly or with a prefixed optic chiasm with resultant
homonymous visual field defect that are typically incomplete and
On fundoscopy , papilledema
is a rare finding in patients with pituitary adenomas. About 30% of the
patients will show temporal pallor.
Rarely, an extremely large pituitary tumor may compress the upper midbrain
, resulting in see-saw nystagmus.
Distension and distortion
of the dura mater
and diaphragma sellae sometimes result in headache.
may present in many ways:
is the most sensitive hormonal axis. Its dysfunction bears clinical
significance only in children.
secondary hypogonadism. In women it is the gynecologist who should be able
to detect the pituitary origin of the menstrual disturbances. In men
decrease in libido and potency will only occasionally be the presenting
leads to secondary hypothyrodism.
with secondary adrenocortical insufficiency. Adynamia, arterial
orthostatic hypotension, and hypokalaemia suggest a secondary
anterior pituitary insufficiency. If this is associated with an impairment
of the posterior pituitary lobe function (exceptional in pituitary
adenomas) the patient is said to have a panhypopituitarism.
Hypothalamic dysfunction may
result in various
neurological abnormalities due to its role in consciousness, sleep,
emotion, and behavior. Hypothalamus regulates anterior and posterior
pituitary function, water balance, and body temperature; its dysfunction
results in altered physiological body functions, and endocrinopathies.
Diabetes insipidus is clinically characterized by the combination of
polydipsia and polyuria associated with low specific gravity (< 1010).
The pituitary stalk
compression syndrome or ‘stalk phenomenon’.
This is the result of
mechanical impairment of the PIF (prolactin inhibiting factor) regulation
of PRL secretion. The regulatory axis can be interrupted at the secreting
(hypothalamus) or transportation (pituitary stalk) level of PIF. This
results in loss of inhibition of pituitary PRL secretion with consecutive
functional hyperprolactinaemia. Five to ten fold increase in serum PRL
levels a larger pituitary tumor is more likely to be functional, rather
than the result of a prolactin cell adenoma.
invasion of the cavernous sinus results in neurological signs
of involvement of neural and vascular intracavernous structures
palsies: especially of the oculomotor and abducent nerves (adenomas with a
postero-lateral extensionto the tentorium), as well as of the trochlear
onset of ophthalmoplegia associated with clinical signs of a SAH suggests
an acute intratumoral hemorrhage in a pituitary adenoma with parasellar
extension. The presurgical duration of the acute ophthalmoplegia is of no
prognostic significance, and 70%of them can expect complete recovery.
Symptomatic trigeminal neuralgia, especially of the maxillary division is
another possible mode of presentation.
Retro-orbital pain and occasionally exophthalmos are the result of
vascular congestion and occlusion of intracavernous vascular structures.
Occlusion of the Foramen of Monro
with subsequent obstructive hydrocephalus causing signs and symptoms of
raised intracranial pressure.
such as the frontal or temporal lobes may be compressed, resulting in
personality problems and seizures.
Depending on their
frequency, one may consider four main clinical syndromes of pituitary
Amenorrhoea-galactorrhoea syndrome (hyperprolactinaemia) in women and
impotence and occasional galactorrhoea in men.
excess (gigantism in children and acromegaly in adults)
Hypothalamo-pituitary dependent hypercortisolism (Cushing’s disease)
is an uncommon presentation (1%to 10%) due extensive hemorrhage or
ischemic necrosis (infarction) within a pituitary adenoma that causes a
life threatening acute crisis, mimicking SAH, with signs of meningeal
irritation, disturbed consciousness, and opthalmoplegia.
The exact cause is not known. The blood supply of the normal gland has
special features with an arterial supply to the median eminence and
posterior pituitary and with a portal venous supply to the anterior
pituitary from the median eminence and posterior pituitary. This unique
anatomy predisposes to apoplexy. Bromocreptine therapy and radiotherapy
have been blamed.
to the intimate relationship of neural, endocrine, vascular, meningeal,
and skeletal tissues in the parasellar region, a number of pathological
lesions, though rare, must be kept in mind.
may be neoplastic (Primary pituitary carcinoma, Pituitary metastases (from
the breasts and the lungs), optic nerve and hypothalamic gliomas,
craniopharyngiomas, hamartomas, histocytosis X, ganglioneuromas etc), non-neoplastic
( Empty sella syndrome, Rathke’s cleft cyst, Epidermal cyst,
Mucoceles, Arachnoid cysts), inflammatory disorders (abscesses,
sarcoidosis, etc), aneurysms and other vascular malformations.
addition to recognizing any hypersecretory syndromes associated with
pituitary adenoma, recognition of hypopituitarism prior to surgery is
imperative. A screening should include measurement of thyroid,
corticosteroid, prolactin, and gonadotropic and somatotrophic hormones.
Deficiency of adrenal, thyroid, and gonadal hormones may be mild.
selected patients, pituitary hormones should be measured under conditions
designed to stimulate their release, tailored to the individual
deficiency can be diagnosed by measuring simultaneously basal serum TSH
and thyroid hormone levels. A low serum T4 in the presence of an
inappropriately low TSH level suggests a central cause of hypothyroidism.
To distinguish a hypothalamic from a pituitary defect, the TSH reserve may
be assessed by performing a TRH test. In the intact pituitary, TSH and
prolactin rise in response to TRH stimulation and growth hormone level
falls. TSH over secretion, as in the context of a rare functional tumor,
will result in elevated circulating levels of both TSH and T4.
Dynamic tests are required to diagnose a state of ACTH deficiency as the
morning cortisol is persistently low only when ACTH deficiency is very
severe. The CRH test will distinguish a hypothalamic CRH deficiency from a
pituitary ACTH deficiency. Insulin-induced hypoglycemia and the glucagons
test will stimulate the entire hypothalamic-hypophyseal-adrenal axis. The
ACTH stimulation test evaluates the capacity of the adrenals to secrete
Gondotropin deficiency can be diagnosed by measuring simultaneously basal
serum FSH and LH levels and gonadal steroids, estradiol (in premenopausal
women), and testosterone in men. In the event of primary gonadal failure,
the lack of negative feedback by the gonadal steroids on the hypothalamic
GnRH and pituitary LH and FSH secreting cells leads to an elevation of LH
and FSH. A low level of circulating gonadal steroids associated with an
inappropriately low gonadotropin level suggests a hypothalamic or
pituitary disturbance. Lack of response of LH and FSH to GnRH indicates a
lesion at the pituitary, rather than the hypothalamic level.
Basal Growth hormone level is often low. Plasma IGF-I level permits a more
accurate diagnosis. Stimulatory tests to assess somatotropic function
include sleep and exercise studies, insulin-induced hypoglycemia,
administration of arginine, L-dopa, clonidine, propranolol, or GHRH.
diagnosis of vasopressin deficiency may be established by simultaneous
measurements of fasting plasma and urine osmolalities and of vasopressin.
During a water-deprivation test, the diagnosis of diabetes insipidus is
based on the development of abnormally concentrated plasma (osmolality
greater than 300 mosm per kg) and urine, which remains dilute (osmolality
less than 270 mosm per kg). The urine volume is not reduced. Exogenous
vasopressin will correct these abnormalities.
demonstrate the size, shape and morphology of the sella and
the sphenoid sinus.
Due to its multiplanar and its three-dimensional imaging capability, and
due to the vascular imaging possibilities, thin-collimation, high field
MRI is able to delineate the tumor anatomy clearly and provide precise
information about the fine anatomical structure of the cavernous sinus and
the other surrounding anatomical structure, depicting accurately the
characteristics of tumor development. MRI also visualizes the major
vessels and the proximity of these to the tumor.
Large tumors usually have similar signal intensity to brain on T1 images.
The normal pituitary, infundibulum, and cavernous sinuses enhance with
GADO. However, in delayed images, the tumor will enhance and the normal
pituitaries will washout the contrast before the tumor does.
be performed if MRI is not available or as a supplement to MRI. CT offers
relevant information regarding bony landmarks, intratumoral hemorrhage or
objectives of the treatment are a) relief of mass effect, b) correction of
endocrinopathies, c) control of tumor growth.
Null cell microadenomas
may be observed
periodically and does not require any therapy. Macroadenomas,
especially with visual problems, need surgery ideally. Large tumors may
cause the so called stalk section effect (loss of dopaminergic inhibition
to prolactin release) and elevated prolactin levels (<200ng/mL). They must
be treated as null cell adenomas. 10% of these tumors will respond to
bromocreptine. In patients with medical conditions that preclude surgery,
it is worth a trial.
Prolactinomas are the commonest pituitary
tumors. It has been observed that few microprolactinomas progress to
macroadenomas. In contrast, macroadenomas, frequently present in men, may
be aggressive and associated with very high prolactin levels.
Microadenomas may be treated with bromocreptine or surgical excision;
surgery may be a better option if the prolactin level is not significantly
high. Surgery is widely employed in large tumors, although there are
occasional reports of complete cure of macroadenomas with bromocreptine.
Growth hormone secreting adenomas
usually present early as microadenomas and are best dealt with surgery;
post operative radiotherapy and / pharmacotherapy is usually indicated.
Other rarer tumors
(ACTH secreting, TSH secreting, Gonadotroph secreting adenomas) are best
treated with surgery.
requires intensive therapy with due attention to electrolytes and
hormones. Medical management alone may be sufficient in mild cases, but
surgery is advised. In some cases, ‘spontaneous cure’ of an adenoma have
been reported. In patients who have not been operated, the necrotic
material is replaced by an intra and /or suprasellar cyst, empty sella, or
squamous metaplasia; chiasmal arachnoiditis is a possibility.
Sir Victor Horsley
(1889) was the first to perform pituitary surgery. He attempted to remove
a pituitary adenoma via the transcranial approach. Schloffer (1907)
reported on the first successful transsphenoidal operation for a pituitary
tumor, via a lateral rhinotomy. Kocher (1909) modified the superior
nasal procedure, and was the first to use a submucosal approach. Hirsch
(1909-1910) entered the sella through a transseptal approach using a nasal
(1910) ingeniously combined the advantages of previous techniques and
developed the basic oronasal midline rhinoseptal transsphenoidal approach.
Frazier (1912) used the intracranial transfrontal approach to the
pituitary. This approach was then adopted even by Cushing himself, as the
transsphenoidal operation showed a higher incidence of recurrence. Dott
(1925) believed in Cushing’s transsphenoidal approach and consistently
used it throughout his career. In the sixties Guiot continued
Dott’s tradition and taught Derome and Hardy. Hardy (1962)
reintroduced the procedure in North America, and refined the technique
using the operating microscope and televised radiofluroscopic control.
cortisol, thyroid, and electrolytes levels are mandatory.
Preexisting hypothyroidism may manifest acutely during early postoperative
period. Reestablishment requires approximately one week of treatment prior
to an elective procedure. Concomitant cortisol deficiency must be treated
prior to initiating thyroid therapy to avoid an adrenal crisis.
About 90% of
pituitary tumors are amenable to this approach and is preferred
regardless of the size. Extensive lateral extension of the tumor may
warrant a craniotomy for a radical excision. Many of these will
herniated into the enlarged sella once the sellar component has been
evacuated. Extended procedures may give access to anterior skull base,
clivus, and cavernous
be treated prior to
is occasionally used if transsphenoidal surgery is
contraindicated ( when there is evidence of sinusitis and unacceptable
visual loss) or as a second step in the combined transsphenoidal-
in large (giant) adenomas.
Of late, Endoscopy
is increasingly used in transsphenoidal excision and it facilitates better
clearance of the tumor and is less invasive than a routine transsphenoidal
glucocorticoid is administered to all patients. Dose
regimen is tailored to the individual patient’s needs. The stress of
surgery may provoke an acute crisis in those without sufficient reserve
and should be considered in those with unexplained alteration in mental
status postoperatively. Urine volume and serum electrolytes must be
monitored. Loss of vision may alert the surgeon of an evolving
includes CSF leakage (4.4%), Meningitis (1%), Sinusitis (5%),
Hypopituitarism (4%), SIHADH (3.5%). Incidence of Diabetes insipidus has
been reported to be 1.7% to 18%.
Transient DI is common
following manipulation of the normal posterior pituitary.
DI may be transient or
permanent but only the permanent type is regarded as a complication, and
it is rare, with a reported incidence of 0.5 to 15%.Intraopertive CSF leak
had a high association with postoperative diabetes insipidus.
is thought to be caused by temporary dysfunction of vasopressin-producing
neurons as a result of surgical trauma and occurs in 10 to 60% of reported
cases Usually only 20% of patients require treatment with desmopressin.
Typically, SIADH occurs
5 to 7 days postsurgery. One of the explanations for this phenomenon has
been the release of stored ADH from the damaged posterior pituitary nerve
terminals, and require fluid restriction.
A CSF leak may occur
intra- or postoperatively and entails the risk of meningitis, which is a
potentially fatal complication.
The reported incidence
of CSF fistulas after transsphenoidal surgery is 1 to 4% and the incidence
of meningitis is 0.8 to 2%. A CSF leak that is recognized intraoperatively
can be repaired by packing the sella and the sphenoid sinus with fat or
muscle. Meningitis may also occur without a postoperative CSF leak.
Although a small percentage of these will resolve spontaneously, many will
require operative repair. Prophylactic antibiotic drugs are used by most
surgeons in an attempt to prevent meningitis but the effectiveness of
these prophylactic medications has never been proven.
occurring during transsphenoidal surgery is a rare yet potentially fatal
complication and includes carotid artery (CA) rupture, CA cavernous
fistulas, traumatic aneurysms, subarachnoid hemorrhage, CA vasospasm, and
Postoperative hemorrhage from the cavernous sinus, CA, or tumor bed can
occur, causing visual deterioration or hypothalamic injury. Incidence of
injury varies from 0.4 to 1.4%.
Optic nerve injury
occurred is caused by a misdirected approach and contusion of the optic
nerve. Other possible causes of injury include vasospasm, a postoperative
hematoma, or devascularization of the optic apparatus.
Delayed visual deterioration can also occur with the empty sella syndrome.
Injuries to the cranial
nerves (excluding the second cranial nerve) usually occur as a result of
exploration of the cavernous sinus for tumor, and the nerve most commonly
injured is the sixth cranial nerve. The reported incidence is 0.4 to 1.9%
and the injury may be temporary or permanent.
Problems related to the
nasal aspects of the operation are rarely fatal but may produce
significant discomfort and distress, and include sinusitis (1--15%),
septal perforations (0.3--0%), and epistaxis (0.4--4.3%). Nasal septal
perforation can lead to chronic infection and may require secondary
surgical repair. Nasal tip deformities or a saddle nose may occur when the
nasal spine or cartilage is too aggressively removed. Postoperative
sinusitis may require additional medical or surgical treatment.
Epistaxis is rare and can be treated with
nasal packing, cautery, or ligation/embolization of the internal maxillary
artery. Delayed massive epistaxis is a rare but significant complication
of transsphenoidal surgery. Injury to branches of the external carotid
artery, along with injury to the internal carotid artery, should be
suspected in patients who present with delayed epistaxis after
transsphenoidal surgery. Angiography performed in patients with refractory
bleeding should include selective external carotid injections. Epistaxis
that is refractory to anterior and posterior nasal packing may be
effectively treated with endovascular embolization.
Anosmia and hyponosmia is a frequent and
under recognized minor complication. Fibrosis of neuroepithelium, poor
aeration of olfactory receptors, and sinusitis likely contribute.
Prior to discharge, A.M cortisol will determine the need for long term
cortisol replacement. Thyroid levels may be done after a month since
autonomous thyroid function may persist for sometime. Post operative
imaging is best done after 3 months to decide on further therapy.
Immediate improvement in vision may occur, with significant improvement
usually within 2 weeks. The improvement may continue for up to 12 months.
The goal of post operative radiotherapy is to delay the recurrence,
especially in large and invasive lesions. Several studies suggest improved
tumor control with the combination of surgery and radiotherapy.
The combination of surgical decompression followed by radiotherapy in the
dosage range of 4500-5000 cGy over 25 fractions yields tumor control rates
(>90%) in giant pituitary adenomas similar to those of smaller pituitary
general, all large tumors, especially with cavernous sinus involvement,
and those who have failed surgical or medical therapy are considered for
post operative radiotherapy. With functioning tumors, evaluation of post
operative endocrine status may indicate the effectiveness of surgical
is occasionally employed in the elderly and high risk patients. Primary
radiotherapy alone offers a 50% recurrence rate with a 75% local control
rate following salvage.
Adverse effects of radiotherapy range from mild to severe. There is a
significant risk of worsening preexisting hypopituitarism (25% to 100%
among various series). Visual impairment may result as a result of empty
sella syndrome, treatment failure, or direct damage to optic pathways(
especially when the daily dose is >220cGy).
Backlund and Rahn
stereotactic pituitary irradiation using radiosurgery with the Leksell
Gamma Unit. This offers an alternative to those who do not require
decompression of optic pathways or more rapid hormone correction, and in
those where surgery has failed. Ideally, the tumor must be more than 2mm
from the optic pathways. From the available studies, the optimum dose has
not been established; the tumor control is excellent (>90%), and the
endocrinopathy control is suboptimal. Long term studies are awaited.
Quadri and Besser
(1972) reported described his experimental and clinical
report on the effects of bromocriptine in prolactnomas. Liuzzi
(1974) reported on GH suppression in acromegaly by oral bromocriptine.
Tolis (1986) described the therapeutic efficacy of a somatostatin
analogue in acromegaly.
respond best to pharmacotherapy.
a dopamine agonist that suppresses prolactin production and release by the
stimulation of dopamine receptors, has been proven safe and effective.
Most patients respond to 2.5 mg three times daily; some large tumors may
require up to 15 to 20mg daily. However, in certain cases, the dose may be
decreased after achievement of adequate suppression. Surgery may be
considered if adequate response is not achieved in three months. Following
surgery, the hyperprolactinemia is often more responsive, requiring lower
doses. Withdrawal of the drug results in recurrence in most patients. Some
microadenomas do not recur.
Following adequate therapy, prolactin levels are usually lowered by over
80%; larger tumors may take longer. Menstruation begins within 6 months
and in men, elevations in testosterone levels precede the normalization of
semen analysis by several months. In most, a progressive in tumor over
several years is observed; in some it may be dramatic and takes only
days/weeks. Bromocreptine therapy induces cell shrinkage, and
degenerative, necrotic, and fibrotic changes in the tumor. These changes
are reversed after bromocreptine withdrawal.
Pregnant women with microprolactinomas rarely develop tumor expansion.
However, in pregnant women with macroprolactinomas, the risk is about 15%,
during all trimesters. Although surgery is recommended prior to
conception, bromocreptine is an effective alternative, with no increased
risk of congenital anomalies, spontaneous abortion, or multiple births.
Significant side effects include malaise, nausea, vomiting, and postural
hypotension. Less commonly, headache, abdominal cramps, constipation,
nasal congestion, and depression have been described. Rarely, CSF
rihnorrhea can occur. The tumor may become fibrous and cause difficulty
in surgery, if required.
is another equally effective dopaminergic agent and may be used in those
who do not tolerate bromocreptine. Long acting, cabergoline, an
ergoline derivative can be given biweekly. CV 205-502 (quinagolide),
a nonergot dopamine agonist, is another long acting, effective agent.
GH secreting adenomas
exhibit a moderate growth and often present as macroadenomas. Most of them
have mixed GH and prolactin hypersecretion. GH secretion is variable, and
depends on activity. GH over-secretion results in elevated IGF-I levels
that are fairly stable and better indicator.
Surgery is the best option, even in microadenomas.
Persistent elevation of GH or IGF-I levels requires pharmacotherapy or
suppresses GH release from the pituitary and GHRH release from the
hypothalamus. Octreotide, a short acting analogue, contains the
active sequence of somatostatin. It is administered 50 to 100mg
subcutaneously every 8 hours. The dose is gradually increased until
adequate suppression. The majority will need 300 to 600mg
per day. The maximum recommended dose is 1500mg
per day. About 80% of patients experience clinical improvement. Normally,
IGF-I levels fall within a week. Plasma prolactin levels in mixed tumors
are suppressed in about 50% of cases. The tumor is softened and
Several side effects have been reported. A transient decrease in
gastrointestinal motility and slowed absorption occur in most patients.
Steatorrheam, presumably due to a reduction in pancreatic enzymes is less
frequent. Cholelithiasis due to suppression of cholecystokinin resulting
in decrease bile flow is a concern. Gallstone formation occurs in about
50% pf patients on long term octreotide.
is a slow-release formutation somatostatin analogue.
such as bromocreptine, stimulate GH secretion in normal individuals. In
contrast, in acromegalic patients, they suppress GH secretion in at least
50% through a PRL-dependent D-receptor mechanism. They are primarily
effective in GH-secreting tumors that also secrete prolactin. Up to 20 to
30mg may be needed. Tumor reduction does not occur.
Few patients who do not respond to either octreotide or bromocreptine
alone, respond to a combination of the two.
ACTH-secreting pituitary adenomas
are usually small and amenable for surgery alone. Macroadenomas are
frequently invasive, requiring post surgical radiotherapy. Preoperatively
and during the months required for radiotherapy to become effective,
hypercortisolism needs to be controlled by medical therapy. Adrenolytic
agent, mitotane is initiated at a dose of 0.5gms/day and increased
to 4gm/day. Dexamethasone replacement therapy should be started to avoid
adrenal insufficiency. Mineralocorticoids is usually not required. 20% of
the patients may not respond and require an adrenal enzyme inhibitor, such
as, aminoglutethimide, metyrapone, and ketoconazole,that
usually controls the disease.
are rare and invasive macroadenomas. Octreotide and lanreotide
has been a useful adjunctive therapy while awaiting radiotherapy
effect. Preliminary reports of recent studies on pharmocotherapy of the
GnRH antagonist Nal-Glu GnRH in gonadotroph-secreting adenomas have
shown encouraging results.