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Chapter 78

Pituitary Surgery

Brooke Swearingen and Nicholas A. Tritos

Key Points

1 Clinical manifestations of sellar masses may include local mass effect, pituitary hormone excess or

deficiency.

2 Pituitary adenomas account for the vast majority (91% to 92%) of sellar lesions in surgical series,

although the differential diagnosis is broad.

3 Incidental sellar lesions are common findings on cranial imaging performed for unrelated

indications.

4 Despite recent advances in genetics and molecular biology, the pathogenesis of most sellar masses

remains obscure.

5 Thorough clinical, radiologic and endocrine testing can help significantly narrow the differential

diagnosis before pituitary surgery.

6 With the exception of many prolactin-secreting pituitary adenomas, transsphenoidal pituitary

surgery remains first-line therapy for pituitary adenomas associated with mass effect or hormone

excess.

7 There are a number of surgical techniques and approaches in current use with similar outcomes; the

trend is toward increasing use of endoscopy.

8 Medical therapy is generally considered first-line treatment in patients with prolactin-secreting

pituitary adenomas.

9 Medical therapy has an adjuvant role in patients with other secretory adenomas (acromegaly,

Cushing disease) who are not cured after pituitary surgery.

10 Management of pituitary adenomas is best delivered in a multidisciplinary setting, where the

multiple treatment options available can be individualized to a given patient.

INTRODUCTION

1 The pituitary, as the “master gland,” is responsible for the control of much of the body’s endocrine

function. Directly or indirectly, it affects the function of the thyroid, adrenals, and ovaries or testes, and

regulates growth, lactation, and ovulation. Its posterior lobe helps to regulate water homeostasis and

parturition. Surgical disorders of the pituitary can manifest as either an endocrinopathy, with syndromes

of hypo- or hypersecretion of necessary hormones, or as abnormalities caused by mass effect, especially

visual field deficits, related to its anatomic location. This chapter will review the basic anatomy and

endocrine physiology of the gland, as well as the diagnosis, imaging, and pathology of pituitary

disorders and describe the surgical management in the setting of multidisciplinary treatment options.

ANATOMY

The pituitary lies within a bony cavity in the posterior sphenoid bone, the sella turcica, or “Turkish

saddle.” Anatomic boundaries are formed anteriorly and inferiorly by the sphenoid sinus, posteriorly by

the dorsum sella and posterior clinoids, anterosuperiorly by the tuberculum sella, and superiorly by the

diaphragm sella, a thin dural reflection over the superior margin of the gland (Fig. 78-1A,B). The lateral

boundaries are formed by the cavernous sinuses. The gland itself is composed of an anterior,

intermediate, and posterior lobe (the adenohypophysis, pars intermedia, and neurohypophysis or pars

nervosa, respectively). Embryologically, the gland is derived from the apposition of stomodeal

ectoderm (anterior lobe) and neuroectoderm (posterior lobe). The anterior lobe consists of a pars

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distalis, within the sella, and pars tuberalis, along the anterior infundibulum, which penetrates the

diaphragm sella and connects the gland to the hypothalamus. The vascular supply is formed by the

inferior hypophyseal arteries arising bilaterally from the intracavernous carotids, and supplying the

neurohypophysis, and the superior hypophyseal arteries, which supply the median eminence and

infundibulum as well as forming the capillary network of the hypophyseal-portal system. This portal

system carries hypothalamic releasing hormones along the infundibulum to the anterior lobe. Venous

drainage leaves through the cavernous and superior and inferior petrosal sinuses bilaterally and thence

to the transverse sinuses and internal jugular veins. There is often a variably developed dural venous

sinus, the circular sinus, usually at the level of the tuberculum sella, connecting the two cavernous

sinuses, and there may be dural venous plexi of variable size and location beneath and posterior to the

sella.

Important anatomic relationships, both in terms of pathologic effects and surgical approach, include

the laterally placed cavernous sinuses, and superiorly the suprasellar cistern, through which course the

optic nerves and chiasm. The cavernous sinuses are formed by venous drainage from the ophthalmic

veins, middle and inferior cerebral veins, and sphenoparietal sinuses. Traversing structures include the

intracavernous carotid artery, and multiple cranial nerves, including cranial nerve III (oculomotor),

cranial nerve IV (trochlear), the ophthalmic branch of the trigeminal (V1), and the maxillary branch of

the trigeminal (V2). These nerves travel in the dural reflection which forms the lateral wall of the

cavernous sinus, from superior to inferior. The VIth cranial nerve (abducens) runs along the lateral

aspect of the intracavernous carotid. Nerves III, IV, VI, and V1 exit into the superior orbital fissure,

while V2 exits through the foramen rotundum. The optic nerves and chiasm travel above the gland,

within the suprasellar cistern. Superior extension of the sellar contents, for example, from a pituitary

neoplasm, can compress the chiasm from below, leading to visual abnormalities. Axons from the nasal

retinal ganglion cells (which receive input from the ipsilateral temporal visual fields) cross in the

chiasm en route to the opposite occipital cortex. Compression of these crossing fibers at the level of the

chiasm leads to a bitemporal hemianopsia, pathognomonic of a sellar mass.

Figure 78-1. A: Sagittal view. B: Coronal view. ICA, internal carotid artery; CN, cranial nerve.

PATHOLOGY OF SELLAR LESIONS

Pituitary Adenomas

2, 3 Pituitary adenomas are the most common tumors of the sella and most important surgical

pathology, but the differential diagnosis of sellar lesions is broad (Tables 78-1 and 78-2). The true

incidence of adenomas is difficult to determine as it varies depending on whether the series is based

upon clinically significant tumors, autopsy findings, or imaging data. The prevalence of incidental sellar

masses found in imaging studies is about 10% to 22%, while it is about 14% in autopsy series.1 The

original pathologic classification was based upon staining affinity for histologic dyes, that is,

acidophilic, basophilic, or chromophobe. A more recent and clinically useful pathologic classification

from the WHO is based upon immunocytochemistry of various hormone subtypes. These include:

Prolactinomas (Lactotroph Adenomas)

Although less important in surgical series since the advent of dopamine agonist treatment, these are one

of the most common pituitary adenomas with an incidence of 6 to 10 per million per year and a

prevalence of 60 to 100 cases per million.2 Also known as lactotroph adenomas, they arise from the

prolactin-secreting cells of the adenohypophysis. They are commonly microadenomas in women, but

2209

especially in men may become large and invasive.

Table 78-1 Tumors of the Pituitary

Growth Hormone-Secreting Adenomas (Somatotroph Adenomas)

These tumors secrete excess levels of growth hormone, leading to gigantism in children and acromegaly

in adults. The incidence of acromegaly is about 2 to 4 cases per million per year.3 These tumors may

sometimes coexpress prolactin (mammosomatotroph adenomas) and rarely TSH, as these cellular

subtypes appear to arise from a common stem cell origin. They are typically invasive macroadenomas.

ACTH-Secreting Adenomas (Corticotroph Adenomas)

These tumors secrete excess levels of ACTH, leading to excess production of cortisol by the adrenal

glands (Cushing disease). They are uncommon, with an estimated incidence of 1.2 to 1.7 cases per

million per year.4 Pathologic diagnosis can be difficult, given that these tumors are often quite small

and surgical specimens limited. Corticotroph adenomas typically manifest loss of normal glandular

architecture, with positive immunocytochemistry for ACTH.

Table 78-2 Differential Diagnosis of Nonpituitary Sellar Lesions

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TSH-Secreting Adenomas (Thyrotroph Adenomas)

These tumors are uncommon and typically comprise less than 1% of surgical series. Patients will

sometimes present with hyperthyroidism, but TSH staining without clinical hyperthyroidism is a more

common scenario.5

Gonadotroph Adenomas

These tumors are common and comprise most of the “nonfunctioning” adenomas, as they express

primarily hormone subunits, including beta FSH, LH, or alpha subunits. They become symptomatic via

mass effect, with compression of normal gland leading to pituitary hypofunction, or compression of the

chiasm leading to visual field abnormalities. Very rarely, patients with these tumors may present with

symptoms attributed to excess gonadal steroids, such as precocious puberty, irregular menses, or

psychiatric manifestations.

Null Cell Adenomas

These tumors are uncommon; they manifest no clinical or immunocytochemical evidence of hormone

secretion, but this may be a function of the sensitivity of the immunocytochemical technique.

“Atypical” Adenomas and Pituitary Carcinomas

Pituitary carcinoma is extraordinarily rare. It is defined by the presence of distant metastases or CSF

dissemination. While pituitary carcinomas may demonstrate extensive pleomorphism and/or necrosis,

these pathologic findings are also seen in benign adenomas. The factors correlated with aggressive

clinical behavior include an elevated Ki-67 labeling index (MIB-1 fraction, proliferation index) and

extensive p53 reactivity.6 “Atypical” adenomas have been defined as those tumors manifesting an MIB-1

fraction of greater than 3%, excessive p53 immunoreactivity, and increased mitotic activity.7 Atypical

adenomas are usually larger and invasive, but are not uncommon (15% in some surgical series), and the

factors predisposing to malignant degeneration and metastasis are not well defined.8

Nonadenomatous Lesions of the Sella

Although pituitary adenomas are the most common neoplasms of the sella, a variety of other lesions can

occur (Table 78-2).9,10

Neoplasms

Other neoplasms of the sella are uncommon but remain important in the differential diagnosis.

Craniopharyngiomas are benign, solid, or partially cystic masses which presumably arise from remnants

of Rathke pouch.11 They occur in a bimodal distribution with peaks in childhood and in older adults.

The adamantinomatous type is typical in children, and is often cystic and partially calcified. The cysts

contain a “motor oil” appearing fluid, which can produce severe chemical meningitis when in contact

with the CSF. The epithelium produces keratinaceous debris and cholesterol clefts. There is often a

pronounced inflammatory reaction. The papillary type is seen almost exclusively in older adults. It may

be cystic and/or solid, and can be densely adherent to surrounding neural structures, especially the optic

nerves and hypothalamus. Meningiomas can arise anywhere along the intracranial dura, including within

the sella. Meningiomas arising from the diaphragm sella or tuberculum sella can mimic pituitary

adenomas and lead to endocrine dysfunction and chiasm compression. Germ cell tumors are most

common in children and young adults and occur predominantly in males. The sella is the second most

common location after the pineal; the most common subtype is the germinoma followed by teratomas.

Metastases to the sella are fortunately rare, most commonly from breast and lung.12

Cysts

A variety of nonneoplastic cysts can occur within the sella. Although most are incidental findings seen

on routine MRI imaging, large cysts can sometimes lead to endocrine dysfunction or chiasm

compression. The most common cystic structure is Rathke cleft cyst, arising from a remnant of Rathke

pouch within the pars intermedia. Rathke cysts can sometimes enlarge with time and compress

surrounding structures; they may then require drainage and/or resection. Most, however, are incidental

findings, and require no treatment. Epidermoid or dermoid cysts arise from ectopic squamous or dermoid

tissue and can fill with keratinaceous debris. Arachnoid cysts are CSF containing structures which may

also occur within the sella, presumably arising by means of a “one-way valve” mechanism allowing CSF

to enter the cyst cavity but not exit; enlarging cysts may become clinically symptomatic.

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