27

The Pituitary Gland and

Associated Pathologic States
S.C. Daly
H.S. U
J.C. Drummond
The pituitary is often referred to as the “master” hormonal gland because of the
innumerable influences it exerts over physiologic homeostasis. It is located in the
sella turcica, a bony cavity at the base of the skull in close proximity to the
undersurface of the brain. Pituita, latin for phlegm, was the source of the name of
the pituitary gland, implying early perceptions of its function. Its true function
became apparent when acromegaly was linked to the gland by Harvey Cushing in his
1912 treatise, “The pituitary gland and its disorders”.1

The anatomy and physiology of the

pituitary gland
Neurodevelopment
The pituitary gland, also known as the hypophysis, is composed of three
substructures at maturity, namely, the anterior, intermediate, and posterior lobes.
The intermediate lobe is morphologically distinct from the anterior and posterior
lobes but its function is uncertain. The anterior and posterior lobes are derived from
two distinct embryological structures, Rathke’s pouch and the infundibular process
respectively. Rathke’s pouch is a cephalad evagination of the stomodeal ectoderm,
which will later become the pharynx. The infundibular process is a caudad
evagination of the floor of the portion of the diencephalon that will eventually form
the hypothalamus. These two structures, Rathke’s pouch and the infundibular
process, begin to come together in approximately the 4th week of gestation. With
maturity, Rathke’s pouch follows the infundibular process into the intracranial
cavity and these two structures merge to give rise to the mature pituitary gland. The
mature pituitary gland is anatomically distinct from the brain and is connected to it
by the infundibular process (the pituitary stalk). The histology of the two lobes of
the mature pituitary gland reflects their embryological origins. The anterior
pituitary (adenohypophysis) consists of glandular tissue while the posterior
pituitary gland (neurohypophysis) is neural in character. The cells in the anterior
pituitary are those that ultimately manufacture and secrete the critical trophic
hormones responsible for growth, development and the maintenance of
homeostasis. They are, therefore, active early in gestation. Biologically active
follicular stimulating hormone (FSH) and luteinizing hormone (LH) has been
detected in fetuses at 14 weeks, and biologically active thyroid stimulating hormone
(TSH) at 17 weeks.2

The Anatomy of the Adult Pituitary Gland

The pituitary gland weighs about 0.5 to 1 g and is approximately 1 cm in horizontal
diameter3 in normal adults. The vertical dimension of the gland varies with age and
physiologic status, but is normally less than 8 mm. The gland tends to be the
greatest in height between the ages of 10 and 29 years in both sexes and in females
there is another increase in height in the fifth decade of life.4 There is normal
physiologic enlargement during the teenage years and pregnancy when it can exceed
10 mm in height.5
The anterior pituitary gland makes up 75% of the gland and is the most common site
of origin of pituitary adenomas. There is a small intermediate lobe, the function of
which is not well established. However, it is often the location of Rathke’s pouch
cysts and craniopharyngiomas. The posterior pituitary, which includes the pituitary
stalk, is an extension of the hypothalamus. Lesions of the posterior pituitary are
rare.
The pituitary gland resides in the sella turcica, a saddle-like structure in the superior
aspect of the sphenoid bone. Its location in the roof of the sphenoid sinus has made
it amenable to surgical approaches through that sinus. Since the sella turcica is a
component of the skull, it is lined and enclosed by the dura. Superiorly, a reflection
of the dura forms the diaphragma sella, effectively forming a dural sac in which the
gland is encased. A small opening in the diaphragma sella accommodates the
pituitary stalk, allowing communication between the hypothalamus and the
posterior pituitary lobe. The sella is bordered laterally by the cavernous sinuses,
which are venous sinuses entirely enclosed by dura. Within these sinuses are the
carotid arteries and cranial nerves III, IV, VI, V1 and V2 (Fig. 27.1). Communications
between the cavernous sinuses are variably found in the dura lining the anterior wall
and floor of the sella. Dural communications across the anterior surface of the
pituitary sometimes complicate transsphenoidal access to the gland. Beyond the
confines of the sella are structures that are essential to the genesis of symptoms
from pituitary tumors. These structures must be taken into consideration in the
surgical treatment of pituitary diseases. Superiorly, the subarachnoid space sits
directly on the diaphragma sella. Within this latter space are the optic nerves and
chiasm, which can be impinged upon should a pituitary tumor extend superiorly
into the intracranial cavity. In the event that the opening in the diaphragma sella is
larger than the diameter of the pituitary stalk, the subarachnoid space will extend to
and make direct contact with the superior surface of the pituitary gland or tumors
arising from it. In this circumstance, vigorous removal of a pituitary adenoma can
lead to tearing of the thin arachnoid membrane and subsequent cerebrospinal fluid
leak into the nasal cavity (CSF rhinorrhea). The sella is bordered posteriorly by the
basilar sinus and the interpeduncular/prepontine cisterns, in which reside the
basilar artery and the brainstem.6 The venous system of the skull base surrounds the
pituitary gland and is important in the surgical approach.

F I G . 2 7 . 1 The pituitary gland and adjacent anatomy in the coronal plane as seen in a tissue dissection. The pituitary
gland is superior to the sphenoid sinus, within the sella turcica. The optic chiasm lies superior to the pituitary gland.
Because of the inferior bony boundary of the sella, an enlarging pituitary lesion will often press upwards toward the
optic chiasm. The carotid artery follows a serpiginous path lateral to the pituitary gland.

(From Anaesthesia for Patients with Endocrine Disease edited by James (2010) Fig. 2.1, p.16, by
permission of Oxford University Press. http://www.oup.com/.) Cranial nerves III, IV, V1, VI, and
V2 lie within the cavernous sinus, which surrounds the pituitary gland laterally. CN, cranial
nerve.

The blood supply to the anterior and posterior pituitary gland is provided by the
superior hypophyseal arteries, which branch off of the internal carotid arteries
within the cavernous sinus. In addition, a portal circulation system allows for
humoral communication between the hypothalamus and the anterior pituitary (Fig.
27.2). This portal system is essential for the multiple feedback loops between the
hypothalamus and the anterior pituitary. Sensors reside in the hypothalamus to
detect the levels of the end organ hormones (e.g., thyroid hormone, cortisol).
Depending on whether the end organ hormone is above or below physiologic levels,
releasing or inhibitory factors are manufactured and released by specific cells in the
hypothalamus. These factors then enter the portal circulation in the hypothalamus
and are carried to the anterior pituitary. At the anterior pituitary, these releasing or
inhibitory factors in turn act on the respective trophic hormone producing cells to
stimulate or inhibit the release of trophic hormones (e.g., TSH, ACTH). These
trophic hormones then enter the general circulation to influence the function of the
end organs, for example, the thyroid and adrenal glands. The intricate portal
vasculature thereby allows minute amounts of factors secreted by the hypothalamus
to achieve precise control of hormone secretion by the target endocrine glands.
There is a substantial reserve in the function of the pituitary gland. Ten percent of
the gland is normally sufficient for the maintenance of endocrine homeostasis.

FIG.27.2

The release of hormones and mediators for the pituitary gland. A branch of the superior hypophyseal artery arborizes to
form a capillary bed in the lower hypothalamus and infundibulum (also called the pituitary stalk). Releasing factors
produced in the hypothalamus are taken up by these capillaries and transported by the hypothalamic-hypophyseal
portal veins (blue) to the anterior pituitary (identified as “pars distalis”) where they are released from a secondary
capillary plexus. This latter capillary plexus also transports the hormones and stimulating/inhibiting factors subsequently
produced in the anterior pituitary to draining veins and on to the systemic circulation.7 Axons of neurons of the
supraoptic and paraventricular nuclei descend through the infundibulum to release hormones directly into the posterior
lobe of the pituitary gland (identified as “pars nervosa”). A capillary plexus derived from the inferior hypophyseal artery
takes up and carries these hormones, principally ADH and oxytocin, to draining veins and on to the systemic circulation.

(From Anaesthesia for Patients with Endocrine Disease edited by James (2010) Fig. 2.2, p. 17 by
permission of Oxford University Press. http://www.oup.com/.)

Radiologic Examination
The pituitary gland is effectively imaged with magnetic resonance imaging (MRI)
with and without gadolinium.8 The anterior pituitary gland is isointense on T1
weighted imaging and the posterior pituitary is hyperintense. With contrast, the
anterior lobe becomes brightly enhanced probably as a result of the lack of a
“blood–brain barrier”. Evaluation of pituitary adenomas should entail studies with
contrast enhancement. Microadenomas are small tumors residing entirely within
the substance of the gland. These tumors appear as “punched out lesions” on
contrast enhanced MRI scans in which normal gland is brightly enhanced while the
tumor appears markedly “underenhanced”. In intermediate sized tumors, which
often occupy the entire confines of the sella, enhancement of the tumor appears to
increase. The normal gland is often visualized as a crescent at the periphery of the
tumor (Fig. 27.3B). With large tumors extending into the intracranial cavity, tumor
enhancement is increased but is often not homogeneous.

FIG.27.3

Magnetic resonance images demonstrating a large pituitary adenoma and the anatomy adjacent to
the sella turcica. A, Coronal plane. Residual normal pituitary tissue is demonstrated being pushed
laterally and superiorly by the enlarging pituitary mass. Superiorly, the mass is compressing the optic
chiasm, a small portion of which is visible. A thin layer of the bone of the sella turcica can be seen on
the inferior border of the mass, with a portion of the sphenoid sinus visible immediately inferior to it.
Because of the bony inferior border, the tumor has grown superiorly with resultant compression of
the optic chiasm. B, Sagittal plane. The third ventricle is superior to the macroadenoma and the
prepontine/interpeduncular cistern lies posteriorly. This cistern contains portions of the circle of Willis
and its branches. Violation of this cistern can result in significant vascular and neurologic injury. The
route to the mass through the nasal cavity and the sphenoid sinus is demonstrated on this image by
the trajectory of the arrow through the sphenoid sinus.

Diseases of the sellar and parasellar

regions
Pathologic processes within the sella include various pituitary tumors,
craniopharyngiomas, and Rathke’s pouch cysts.

Pituitary Tumors
Pituitary tumors are classified functionally into two categories – nonfunctional and
functional tumors. The majority of tumors are nonfunctioning (nonsecretory)
adenomas. Tumors that oversecrete a specific trophic hormone are considered
functional tumors and they lead to distinct hormonal syndromes. Pituitary tumors
are also classified according to size as macroadenomas (> 1 cm) or microadenomas
(< 1 cm). The vast majority of pituitary tumors are benign. Pituitary cancers are
distinctly rare.

Nonfunctional Pituitary Tumors

Nonfunctional pituitary tumors arise from the growth of transformed cells of the
anterior pituitary. These tumors do not secrete any trophic hormones in excessive
amounts. Hence, their manifestations are anatomic. As the tumor increases in size,
surrounding structures are compressed. Within the sella, the normal gland is
compressed and displaced around the tumor mass. This is generally well tolerated
until more than 90% of the gland is rendered nonfunctional. In this event, a
hypopituitary state ensues. In the female, this is manifested early with abnormalities
of menstruation. In the male, a loss of libido occurs.
Growth generally follows the path of lowest structural resistance. Extension
superiorly is common since the aperture in the diaphragma sella is frequently
incompetent (i.e., it is larger than the diameter of the pituitary stalk). As the tumor
extends superiorly above the diaphragma sella, it first occupies the subarachnoid
space that separates the diaphragma from the optic nerves/chiasm. With continued
growth, the optic structures are elevated and compressed leading to visual field
defects. Bitemporal field cuts are the most common since the majority of optic
chiasm resides directly above the sella. Variations of the optic structures do exist.
These may lead to the observation of monocular or homonymous field defects from
compression of the optic nerve and tract respectively.
Lateral extension of a pituitary tumor into the cavernous sinuses is typically well
tolerated and seldom leads to clinical symptoms. Tumor may abut the carotid artery
but actual invasion of that vessel is rare. This is presumed to be due to the slow
growth and typically nonmalignant nature of these tumors. Inferior extension into
the sphenoid sinus also occurs from erosion of the floor of the sella. These are
seldom symptomatic as the tumor fills out the sphenoid sinus and is usually
discovered before it erodes into the pharynx.

Hypersecretory Pituitary Adenomas

While the majority of tumors are nonfunctional, some secrete specific hormones in
excessive amounts leading to specific clinical syndromes. These are classified as
hypersecretory pituitary adenomas.9

Cushing’s Disease
Cushing’s disease is a condition of glucocorticoid excess/hypercortisolism
(Cushing’s syndrome) caused by excessive secretion of adrenocorticotropic hormone
(ACTH) from a tumor in the anterior pituitary gland. This leads to diffuse
hyperplasia of the adrenal glands. Because of high cortisol levels, endogenous ACTH
secretion by nonadenomatous cells is suppressed. ACTH secreting adenomas
comprise about 1–2% of all pituitary adenomas10 and are seen mostly in females (8:1
female to male ratio) with a peak incidence in the third and fourth decades of
life.11 The clinical characteristics include central obesity with moon facies but sparing
of the limbs, dorsocervical and supraclavicular fat pad engorgement, red-purple
striae, thin fragile skin, hirsutism, easy bruising, acne, proximal myopathy,
hypertension, impaired glucose tolerance, insulin resistance, osteopenia,
amenorrhea, decreased libido, sexual dysfunction, psychiatric abnormalities ranging
from depression and lethargy to paranoia and psychosis, and recurrent superficial
fungal skin infections.12 Other findings may include hypokalemic alkalosis (in about
10–15% of patients), hyperlipidemia, and increased intraocular pressure and/or
exophthalmos. The clinical diagnosis is confirmed using one or more of the
following tests: late night salivary cortisol levels, low-dose and high dose
dexamethasone suppression test, urinary free cortisol, serum ACTH levels and if
necessary inferior petrosal sinus sampling to verify the location of ACTH
secretion.13 As the duration of hypercortisolism increases, so does the risk of
mortality for the patient;14aggressive treatment is therefore indicated. Tumor
resection is the first line treatment with success rates ranging from 69% to
98%.15 Although most adenomas that cause Cushing’s disease are noninvasive in
nature, the relatively uncommon Crooke’s cell tumors are more invasive and often
difficult to resect.16
Acromegaly
The incidence of acromegaly is 3–4 cases per million per year.17 This condition
results from the overproduction of growth hormone (GH) from an anterior pituitary
adenoma. The GH in turn stimulates the overproduction of insulin-like growth
factor 1 (ILGF-1) from the liver. This leads to enlargement of acral, that is, the hands
and feet, and other parts of the body. In addition, there is enlargement of the heart
and vasculature. The clinical characteristics include features such as hypertension,
diabetes mellitus, obstructive sleep apnea, mandibular hypertrophy, facial
hyperostosis and skin thickening. The diagnosis of acromegaly is based on clinical
findings as well as laboratory tests including serum GH, glucose tolerance test,
serum ILGF-1, and MRI findings. Laboratory findings indicative of active disease
are: random GH ≥ 1 ng/mL; nadir GH after oral glucose tolerance test ≥ 0.4 ng/mL;
and elevated ILGF-1 for age.18 Since acromegaly is associated with increased
mortality, aggressive treatment is warranted, usually including surgical excision of
the adenoma.

Prolactinomas
Prolactin is produced by the mammotrophs in the anterior pituitary and prolactin
release is normally downregulated by dopamine secreted by the hypothalamus.
Prolactinoma incidence varies from 10 to 50 per 100,000 and prolactinomas
constitute 40% of all pituitary tumors.19,20 They result in prolactin levels above the
normal levels of 3–20 ng/mL in women and 5–15 ng/mL in men.21 Because women
will present with galactorrhea, amenorrhea and infertility, it is usually diagnosed
earlier in women than men. Premature osteoporosis may also occur in women. The
condition is frequently treated first with dopamine agonists, for example,
bromocriptine, carbegoline, terguride, ropinirole, parmipexole, and quinagolide.
When medication is ineffective, when intolerance develops, or when significant
mass effect occurs, surgical excision of the tumor is undertaken. In making the
choice to undertake medical treatment, it must be made clear that the medications
are not tumoricidal. Cessation of treatment will, therefore, permit resumption of
tumor growth. In addition, medical treatment will to lead to scar formation within
the tumor, rendering subsequent surgical treatment complicated and thereby
reducing the surgical success rate. The choice of therapy must take these factors into
consideration and the patient must be fully educated as to the pros and cons of each
therapeutic choice.

Thyrotropin Secreting Hormone Adenomas

Pituitary tumors that release thyrotropin secreting hormone (TSH) are a rare cause
of hyperthyroidism. They comprise less than 2% of pituitary tumors. These tumors
can co-secrete growth hormone and/or prolactin in addition to TSH. The majority
tend to be macroadenomas at the time of diagnosis. In addition, they tend to be
locally invasive and difficult to resect. The cure rate is 30–40% with surgery alone
and there is a high incidence of hypopituitarism after surgery.22 These patients will
have elevated TSH levels and elevated free thyroid hormone levels with the typical
features of hyperthyroidism, which can include a diffuse goiter. Treatment is
surgical excision of the adenoma.

Other Conditions Associated with Pituitary Tumors

Pituitary Apoplexy
This condition is one in which a sudden onset of symptoms occurs as a result of
either hemorrhage or infarction within the pituitary or a pituitary tumor. It
frequently entails the sudden onset of severe headaches that may be associated with
compromise of vision, ocular paresis, and vomiting. This presentation is very similar
to that of a subarachnoid hemorrhage, which must be ruled out by radiographic
studies. Upon identification of an expanding pituitary mass, emergent surgical
decompression of the optic apparatus may be necessary. These patients may also
present with acute adrenal insufficiency from destruction of the normal gland. This
requires high dose intravenous steroid treatment to prevent cardiovascular
collapse.23 Many patients will report a preceding history consistent with either hypo-
or hypersecretion of hormones, representing the antecedent presence of a pituitary
tumor.

Stalk Effect
The “stalk effect” is the phenomenon of hyperprolactinemia occurring in association
with suppression of function of the pituitary stalk. This has traditionally been
attributed to mass effect on, or destruction of, the pituitary stalk, somehow resulting
in decreased dopamine-mediated inhibition of prolactin secretion from the anterior
pituitary. This phenomenon may be more complex than that, with some
investigations suggesting that not all cases of hyperprolactinemia entail lack of
dopamine suppression but rather the secretion of other factors either from the
tumor or the anterior lobe of the pituitary.24,25The clinical significance is that
hyperprolactinemia does not necessarily represent the presence of a prolactin
secreting tumor.

Other Sellar and Parasellar Lesions

Craniopharyngiomas
Craniopharyngiomas are tumors derived from embryonal tissues that occur in
parasellar and sellar locations. They are usually identified in pediatric or adolescent
patients. The incidence is approximately 0.5–2.0 cases per million persons per
year.26 The tumors are often large at the time of diagnosis and many patients will
present with hormone deficiencies and visual field deficits, the latter because these
tumors commonly have suprasellar extension.27 Increased intracranial pressure can
also occur as a result of obstructive hydrocephalus. These lesions are often
associated with the pituitary stalk and may also present with diabetes insipidus.
Treatment is surgical resection by a transsphenoidal, a frontotemporal, or a
combined approach.

Rathke’s Cleft Cysts

Rathke’s cleft cysts are benign lesions in the sellar or supra-sellar areas that occur
when the Rathke’s cleft does not regress fully. These cysts contain mucinous or a
gelatinous material and can exert mass effects, causing headaches or endocrine
disturbances.28They are seldom large enough to cause visual symptoms. For most
cases, a transsphenoidal approach is used for resection. These cysts commonly recur
and may require multiple interventions.

Anesthetic management of surgery for

pituitary tumors
Anesthetic Considerations for Pituitary
Surgery
Preoperative Evaluation
The history and physical examination should be reviewed. Neurologic findings, in
particular visual field deficits and abnormalities of extraocular movements, should
be verified and documented. Signs and symptoms of increased intracranial pressure
may be present if there is hydrocephalus from ventricular obstruction, although this
is rarely seen. Any increase in intracranial pressure should be addressed in
conjunction with the neurosurgical team. The imaging should be reviewed and
evaluated for size and location of the tumor and evidence of impingement on the
optic chiasm, extension into the cavernous sinuses, or the presence of
hydrocephalus.
The endocrine work-up should be reviewed. From among the endocrine
abnormalities that can occur, a principal point of emphasis for anesthesiologists is
that patients should be euthyroid prior to an elective procedure. In most instances,
patients who are clinically hypothyroid or hyperthyroid should be deferred. Serum
electrolytes should be reviewed. Severe hyponatremia may occur, usually in
association with sellar arachnoid cysts, Rathke’s cleft cysts, and pituitary
apoplexy.29 Hyponatremia may represent severe, acute life-threatening adrenal
insufficiency warranting immediate steroid therapy. In patients with hypertension,
cardiac and renal end-organ effects should be sought. The perioperative
administration of steroids should be discussed with the surgical team for all
patients. Steroid administration is far from routine. Most patients with pituitary
tumors will have sufficient residual normal pituitary tissue to maintain sufficient
ACTH release to maintain adequate cortisol levels. These patients will, therefore,
not require steroids.
The perioperative management of patients with Cushing’s disease is not
straightforward. The hypercortisolism is the result of supraphysiologic ACTH
secretion from the pituitary tumor. Secretion of ACTH from the normal gland is
suppressed. These patients must, therefore, be observed closely after surgery as they
are at risk for severe adrenal insufficiency, and the associated cardiovascular
compromise, because of the removal of the excessive ACTH source, that is, the
tumor. In spite of the residual presence of normal anterior pituitary tissue, the
chronically suppressed normal gland will not immediately be able to produce
sufficient amounts of ACTH to maintain homeostasis. Therefore, in anticipation of
removal of the tumor, the patient may be placed on steroid supplementation intra-
and postoperatively. If perioperative steroids are administered, at some stage
postoperatively they must be tapered to assess the need for recovery of glandular
function. In spite of the possibility of hypocortisolism, some teams may specifically
withhold steroids to avoid interference with the postoperative testing that will be
performed to verify that pathological ACTH secretion has been eliminated.
Observation for adrenal insufficiency must be even more careful in these patients.
In patients with acromegaly, because of the difficult airways and obstructive sleep
apnea that can occur in patients with advanced disease (now rare), the airway
management plan should be adjusted accordingly.

Intraoperative Considerations
Lesions of the sellar and parasellar regions are approached via both craniotomies
and transsphenoidal routes. It is, in particular, for lesions with substantial
suprasellar extension that craniotomy may be selected. However, beyond the
endocrine considerations, these approaches entail largely the same considerations
that apply to other tumor-related frontal and frontotemporal craniotomies. The
following discussion will therefore emphasize considerations specific to the
transsphenoidal approaches.

Surgical Approach
Broadly, there are two techniques for achieving access to the pituitary gland via the
sphenoid sinus; the sublabial, and the transnasal. The choice is determined largely
by operator experience and preference. The sublabial approach enters the nasal
antrum through an incision below the upper lip and above the teeth. The head is
positioned on a “do-nut” foam head rest. Visualization is achieved via an operating
microscope, which allows for significant magnification and illumination. C-arm
fluoroscopy guidance is sometimes used. Transnasal approaches are accomplished
via entry through one nostril. This typically entails some form of neuronavigation
guidance, usually with the head secured in pin fixation.
For both approaches, we employ a RAE-type oral endotracheal tube placed in the
corner of the mouth opposite the surgeon’s dominant hand. A right-handed surgeon
will typically stand at the patient’s right side. Ergo, the endotracheal tube is placed
in the left corner of the patient’s mouth.
We believe that preventing coughing and emesis is an important component of
anesthetic management. Both have the potential to raise venous and arterial
pressure and thereby threaten recent hemostasis. Their prevention is even more
important in the event that the arachnoid has been violated and repaired because we
think that they have the potential to contribute to the development of a CSF leak. As
part of our prevention regiment, we place a pharyngeal pack (a vaginal pack
moistened with water) to assure that blood will neither enter the stomach nor collect
in the glottis above the cuff of the endotracheal tube. We doubt that omitting the
pack and aspirating the blood from the stomach at the end of the procedure nullifies
the emetogenic effect of gastric blood. A generous tail is left protruding from the
mouth in company with the endotracheal tube. We are aware of the possible adverse
effects of pharyngeal packing: sore throat, pharyngeal plexus injury, postoperative
stomatitis, tongue swelling, and pack migration.30–33 These events have not been
observed during our long experience, but should be borne in mind.
Prior to placing the pharyngeal pack, we insert an orogastric tube. We withdraw
slowly it at the end of the procedure using it to suction the pharynx in the belief that
it is less likely to provoke coughing/gagging than the customary Yankauer-type
suction. Our practice is to cover all of the anesthesia paraphernalia (endotracheal
tube, temperature probe, G-tube) with an adhesive edged plastic drape. The
adhesive edge of the drape is placed just under the lower lip for sublabial
approaches and just above the upper lip for transnasal procedures. This practice
allows the anesthesiologist access to the endotracheal tube without intrusion into
the sterile field.
All surgical approaches entail the use of a combination of local anesthetics and
vasoconstrictors, usually epinephrine (adrenaline), to decrease mucosal blood loss
and to blunt the hemodynamic response to dissection. Substantial increases in
blood pressure can occur34,35 and the anesthesiologist should be in continuous
communication with the surgeon. Pauses may be necessary to accomplish the
infiltration safely and the anesthesiologist should be prepared with short-acting
antihypertensive agents to deal with excessive responses that nonetheless occur. The
necessity for prompt recognition of evolving blood pressure responses is one of the
reasons that we believe that intra-arterial pressure monitoring is appropriate for
these procedures.
Guidance using bitemporal fluoroscopy has been mentioned above. Some surgeons,
as a matter of individual preference or training use neuronavigational systems, for
example, Brainlab (Brainlab AG, Germany).
Any anesthetic regimen that is consistent with good hemodynamic control and a
smooth and timely emergence will be appropriate. At the authors’ institution, a
balanced anesthetic is used most often with opioids, a volatile agent, and
occasionally an infusion of intravenous anesthetics such as propofol or
dexmedetomidine.
During the procedure, complete neuromuscular blockade is advisable to ensure
absolute immobility of the surgical field. Movement entails a risk of injuries
including arterial perforation/hemorrhage, visual damage and cranial nerve injury.
The cavernous sinuses, through which the carotid arteries and several cranial nerves
pass (see Fig. 27.1), lie lateral to the sella and the distance separating the carotid
arteries from the pituitary gland is between 0 and 9 mm.36 Once within the sphenoid
sinus, there is very little or no bone separating surgical instruments from the carotid
arteries passing laterally.37
There have been reports of asystole or bradycardia, occurring during dissection of
the tumor, especially during cavernous sinus exploration. These have been
attributed to the trigeminal cardiac reflex. The incidence of this phenomenon, which
we have rarely encountered, is reported in retrospective analyses to vary from
0.003% to 10%.38–41 The events are usually self-limited with cessation of surgical
manipulation.
Cerebrospinal fluid (CSF) leakage intraoperatively may occur if the arachnoid is
violated during dissection of the lesion. The surgeon typically takes measures to seal
the leak in order to prevent a postoperative “CSF leak” and the inherent
communication between the nasal cavity and the CSF space. Tissue sealants and
packing of the sphenoid sinus (with fascia lata and muscle from the thigh, nasal
turbinate mucoperiosteum, or abdominal fat) may be employed. Postoperative CSF
diversion by means of a lumbar drain, placed at the end of the procedure, before
emergence may also be used as an adjunct to preventing the development of a CSF
leak. Anesthesiologists may be called upon to assist with placement.
We facilitate the smooth emergence mentioned above by the introduction of nitrous
oxide in the last 15–20 minutes of the procedure (to allow elimination of the volatile
agent and intravenous anesthetics) and by administration of lidocaine when the
inhaled anesthetic agents are discontinued. Intravenous acetaminophen
administered during the last half hour of the procedure combined with residual
narcotic is usually sufficient to provide analgesia in the PACU.
It is inevitable that some patients who undergo pituitary surgery will suffer from
obstructive sleep apnea and in these patients continuous positive airway pressure
(CPAP) devices will appear desirable. However, CPAP has been reported anecdotally
to have led to the occurrence pneumocephalus, and, therefore, the opening of a
pathway between the nasal cavity and the intracranial space with the inherent
meningitis risk. CPAP should generally be avoided.42 In patients who have a history
of obstructive sleep apnea, a nasal trumpet can be placed by the surgeon into one of
the nares, in lieu of the standard packing, to help to assure a patent airway in these
patients.

Anesthetic Considerations for Specific Disease States

Cushing’s Disease
The stigmata and comorbidities associated with Cushing’s disease have been
described above. In addition, the considerations that argue for and against the
administration of steroids have also been mentioned. The decision to give
preoperative steroids is one that should be made in conjunction with the surgical
team. If steroids are to be withheld, note that because of the half-life of cortisol (~
50–75 minutes) and the hypercortisolemic preoperative state of the patient, serum
cortisol will not reach levels that are potentially critically low until about 20 hours
post-procedure. Observation of the patient for evidence of severe hypoadrenalism
should be careful and continuous in the postoperative period.
TABLE 27.1 Physiologic Changes in Cushing’s Disease and Acromegaly
and Anesthetic Considerations66
Anesthetic Anesthetic
Cushing’s Consideratio Consideratio
Disease ns Acromegaly ns

Visual field or
CN deficits, Document
psychiatric preexisting
disturbance, deficits.
anxiety, Modify
depression, technique to
psychosis Document Visual field or CN avoid further
Increased ICP preexisting deficits. ICP increase
Neurologic (rarely) deficits Increased ICP (rarely) (rarely)

Use smaller
endotracheal
tubes. Prepare
OSA43, greater incidence for difficult
of difficult airway.
Aggressive Rule out intubation44,45(macroglos Attention to
infections, concurrent sia, hypertrophy of OSA in
Pulmonary/airw cervical fat pulmonary epiglottis, tonsils, postoperative
ay pad infection larynx, prognathic jaw) period
 Anesthetic Anesthetic
Cushing’s Consideratio Consideratio
Disease ns Acromegaly ns

Evaluate for
end stage
Hypertension, Evaluate for Hypertension, effects of
myocardial end stage cardiomyopathy46, hypertension
hypertrophy, effects of valvular disease47, and ischemic
Cardiovascular CHF, CAD hypertension arrhythmias, CAD48 symptoms

DVT
Increased prevention
thrombotic (SCDs, early
Hematologic risk ambulation)

Glycemic
control, verify
Perioperative Consider thyroid
adrenal perioperative function,
insufficiency, steroid Hyperglycemia, consider
hyperglycemi replacement*; lipolysis, dyslipidemia; perioperative
a, hirsutism, glycemic possible steroid
Endocrine amenorrhea control panhypopituitarism replacement

Careful
Protein positioning to
wasting, avoid
centripetal fat peripheral
accumulation, At risk of nerve injury;
spontaneous pathologic Soft tissue, bony document
tendon fractures and overgrowth,49, vertebral preexisting
rupture, injury with fractures, joint bone or nerve
osteoporosis positioning arthropathy pathology

Difficult IV
Atrophy of placement,
epidermis, risk of skin Difficult IV
Dermatologic easy bruising injury Thick skin cannulation

Decreased
immunity; Increased
mucocutaneo attention to
Immunologic us infections sterility

Assess/correct Assess urine

electrolyte output and
Renal stones, status prior to electrolytes
High urine output after
electrolyte procedure; postoperativel
Renal tumor resection
abnormalities evaluate for y; distinguish
 Anesthetic Anesthetic
Cushing’s Consideratio Consideratio
Disease ns Acromegaly ns

(hypokalemia existing renal DI vs.

, alkalosis) injury iatrogenic
diuresis

Growth
Pediatric retardation or Gigantism due to GH
considerations arrest excess

Prolactinomas

The pathophysiology of prolactinomas does not require anesthetic considerations

beyond those related to the mass effects that these tumors may have on adjacent
structures and consideration of the possible adverse effects of their pharmacologic
treatment. The ergot-derived dopamine agonists can cause cardiac valvular
pathology from fibrosis. However, whether or not the low doses of cabergoline used
for hyperprolactinemia actually have such side effects is unclear.50,51 A patient with
known hyperprolactinemia and on an ergot-derived dopamine agonist who is found
to have a murmur may warrant echocardiographic examination.
Dopamine agonists can also cause decreased blood pressure by central and
peripheral mechanisms with decreased sympathetic tone and decreased
norepinephrine (noradrenaline) release. In addition, dopamine agonists may cause
arrhythmias, including atrial fibrillation. Heart failure has been observed in patients
with Parkinson’s disease. Again, it is unclear whether the relatively low doses of
these medications used for hyperprolactinemia actually have these effects.52

Thyrotropin Secreting Hormone Adenomas

The pathophysiology of TSH secreting adenomas may occasionally require medical
management of the hyperthyroid state to prepare the patient for surgery.
Somatostatin analogs can be used in conjunction with a combination of
methimazole, propylthiouracil, and propranolol to return the patient to a euthyroid
state prior to pituitary surgery. Somatostatin analogs, for example, octreotide, have
been shown to decrease the size of goiters and pituitary tumors themselves in about
40% of patients.53 Airway management may occasionally be difficult because of their
goiter. The systemic effects of hyperthyroidism, including cardiac failure and atrial
fibrillation, should be considered, although these are less common than in patients
with other forms of hyperthyroidism and the signs and symptoms of
hyperthyroidism tend to be mild and may even be overshadowed by other hormones
that are cosecreted, for example, growth hormone.54There should be attention to the
possibility of hypopituitarism and perioperative steroid administration should be
considered in the light of the preoperative endocrine evaluation.

Postoperative Management
Pain and nausea and vomiting are the most common complaints in these patients.
We administer 1 g of acetaminophen in the last 30 minutes of the procedure. Nausea
and vomiting may be detrimental in these patients because of its risks for increasing
CSF leakage.55,56 These complaints are usually not severe and are readily managed
with standard pharmacologic therapies.
Surgical complication and mortality rates are low in these cases overall.57 The
mortality rate is approximately 0.5%. Major surgical complications occur in 8-10%
of patients. They include CSF leak (~ 4.7%), meningitis (2%), stroke (1%), vascular
injuries (including carotid-cavernous fistula) (0.4%), vision loss (1.8%) and
permanent panhypopituitarism.58 Vision loss and cranial neuropathy that are
apparent in the immediate postoperative period warrant immediate imaging to seek
evidence of hemorrhage or mass effects, for example, from fat graft packing, that
may justify early re-exploration.
Cerebral spinal fluid leakage is suspected in patients with persistent nasal discharge
that is salty in taste or is worsened by leaning forward. Patients who have combined
approaches and in whom the arachnoid has been violated intraoperatively are at
greater risk.59 CSF leakage is confirmed if the fluid is positive for β2 transferrin.
Treatment for CSF leakage varies with institution, with some choosing early re-
exploration and repair and some first employing lumbar drainage and bed rest.

Abnormalities of Salt and Water Homeostasis

Disorders of water and electrolyte homeostasis are sometimes encountered after
pituitary surgery. Rates of up to 25% of some form of water imbalance have been
reported. However, some surveys have reported incidences of up to 75%.60,61 This
vastly exceeds our experience. There are three types of imbalances that can occur as
a result of disturbances in antidiuretic hormone (ADH) secretion: diabetes insipidus
(DI); a syndrome of inappropriate ADH secretion (SIADH); and combination of DI-
SIADH.

Diabetes Insipidus
The most commonly encountered is DI, usually with onset early in the postoperative
period. DI is the result of a lack of sufficient ADH. DI occurs more commonly in
association with surgery for macroadenomas, craniopharyngiomas, and Rathke’s
cleft cysts.62 The patient will have a large output of dilute urine coupled with
polydipsia with a preference for cold water. In the event of insufficient fluid intake,
the patient will become hypovolemic, hypernatremic and will have an elevated
serum osmolarity. The diagnostic hallmarks are a rising serum sodium (≥ 145
mmol/L) and osmolarity (> 300 mOsm/kg) with a simultaneously dilute (hypo-
osmolar) urine (< 300 mOsm/kg or urine specific gravity ≤ 1.005). The large
majority of cases of DI are transient. The onset of the DI is usually in the first 24–48
hours and in the majority of patients, it will have resolved by the time of discharge.
There are some patients who develop DI in a triphasic fashion with early onset DI in
the first postoperative day followed by antidiuresis about 1 week after surgery with
subsequent and permanent DI.63 It is always important to distinguish between a
physiologic diuresis, perhaps of an iatrogenic fluid load, and DI. The danger lies in
treating a physiologic diuresis with matching fluid replacement. This puts the
clinician and the patient in a “chasing your tail” situation that can lead to critical
fluid overload. Acromegalic patients deserve special consideration with respect to
polyuria because these patients will often exhibit a brisk diuresis of third space fluid
after successful tumor resection and diagnostic care will be required to distinguish
this physiologic diuresis from DI.64
The management of patients with DI must be tailored to the individual. They should
remain in a closely monitored setting with daily weights recorded, strict intake and
outtake monitoring, and frequent analysis of serum sodium, serum osmolarity,
urine osmolarity and subjective thirst rating. With an intact thirst mechanism and
fluids available for oral repletion, the majority of these patients will be able to self-
regulate In cases in which the patient is unable to keep up with the diuresis and
serum sodium exceeds 145 mmol/L, desmopressin (1-deamino-8D-arginine
vasopressin; DDAVP) administration should be considered. DDAVP may be given
1 μg subcutaneously or 0.1 mg orally per day. This puts the patient at risk for
overcorrection, with attendant hypervolemia and hyponatremia and the patient
should continue to be monitored closely.
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) with the
attendant hyponatremia is occasionally encountered after pituitary surgery. The
differential diagnosis should include other potential causes of hyponatremia,
including adrenal insufficiency, hypothyroidism, hyperglycemia, and cerebral salt
wasting (CSW). The clinical hallmark of SIADH is hyponatremia with serum sodium
≤ 135 mmol/L in a euvolemic to hypervolemic state. By undefined mechanisms,
some loss of the normal control of ADH release occurs resulting in SIADH. This
usually occurs later in the postoperative period than DI, with the lowest serum
sodium levels occurring 7–9 days postoperatively. The patient may or may not have
any symptoms, based on the severity of the hyponatremia. The patient may
complain of headache, anorexia, nausea/vomiting, seizures or lethargy. The
patient’s serum will be hypo-osmolar, the urine will be relatively hyperosmolar, and
the patient will be euvolemic or slightly hypervolemic with normal serum blood urea
nitrogen (BUN) and creatinine. This is usually treated with fluid restriction with
liquids limited to 1000 mL or 700 mL per day, salty foods, and in severe cases with
intravenous sodium repletion.65 If intravenous sodium repletion is necessary,
therapy should be aimed at correcting the hyponatremia not more rapidly than 1
mmol/L/h, and if the hyponatremia is deemed to be chronic, no faster than 0.5
 mmol/L/h. This slow correction is necessary to avoid central pontine myelinolysis, a
rare and catastrophic complication. The patient’s serum electrolytes should be
closely monitored during this period with severe cases requiring inpatient
admission and multiple blood analysis daily and mild cases being treated at home
with daily serum analysis. This phenomenon is usually self-limiting and most
patients recover by postoperative day 28. If there has been a considerable amount of
hemorrhage during the operative course or the recognized presence of subarachnoid
blood, cerebral salt wasting, as occurs relatively commonly after subarachnoid
hemorrhage associated with aneurysmal rupture, should also be considered as a
cause of hyponatremia. Cerebral salt wasting is associated with a hypovolemic state
with increased BUN, creatinine, and increased hematocrit indicating a volume
contracted state.

Summary
The disorders of the pituitary gland result in a myriad pathologic conditions. In
order to care properly for these patients, the anesthesiologist should have an
understanding of the potential consequences of both the endocrinopathies and the
mass effects caused by these lesions. The preoperative assessment should include:
(1) evaluation of the patient’s endocrine status and of the physiologic consequences
of any abnormalities; (2) review of imaging studies to identify mass effects and
adjacent structures at risk; and (3) careful definition of the preoperative neurologic
status. A discussion should invariably be held with the surgical team regarding the
hypothalamic–pituitary axis and whether perioperative steroid supplementation is
warranted. The overall rates of morbidity and mortality for these procedures are
low. However, when complications occur, they can be life threatening. Accordingly,
because of the potential for endocrine derangements, the anatomical complexity of
the sella turcica and its close proximity to vascular and neural structures, the
anesthesiologist should be in close and continuous collaboration with the surgeon in
the management of this patient population.

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