CHAPTER 31

Tumors of the Pituitary Gland
John W. Gittinger, Jr.

ANATOMY OF THE PITUITARY COMPLEX PITUITARY CARCINOMA
PITUITARY ADENOMAS METASTASES TO THE SELLA TURCICA AND PITUITARY
General Considerations GLAND
Types of Pituitary Adenomas MIMICS OF PITUITARY ADENOMAS
Ophthalmic Manifestations of Pituitary Tumors PITUITARY ABSCESS
Treatment of Pituitary Adenomas Hypophysitis
Visual Prognosis in Patients with Pituitary Adenomas

Tumors of the pituitary gland are so important from a histopathologic features of pituitary tumors, the clinical pre-
neuro-ophthalmologic standpoint that they are considered in sentations of patients with pituitary tumors, the various
a separate chapter. In this chapter, we discuss the normal modes of treatment of pituitary tumors, and the prognosis
anatomy of the pituitary endocrine unit, the endocrine and in patients with various types of pituitary tumors.

ANATOMY OF THE PITUITARY COMPLEX
The hypophysis cerebri or pituitary gland lies at the weighs about 0.6 g, and may double in size during pregnancy
base of the brain below the third ventricle nestled in a (1). The larger anterior lobe or glandular portion is the ade-
‘‘Turkish saddle’’ (sella turcica) of bone that is part of nohypophysis; the posterior lobe or neural portion is the
the body of the sphenoid. Lying above the pituitary is a neurohypophysis. The hormones of the neurohypophysis are
sheet of dura, the diaphragma sellae, that connects the oxytocin and vasopressin. Those of the adenohypophysis are
clinoid attachments of the tentorium cerebelli. This is discussed below. The adenohypophysis is derived from an
perforated by a hole that allows the infundibular stem or evagination of stomodeal ectoderm called Rathke’s pouch,
stalk of the neural portion of the gland to connect to the remnants of which are thought to give rise to craniopharyngi-
hypothalamus (Fig. 31.1). omas. Adenohypophyseal cells give rise to pituitary adeno-
The gland itself normally measures 12 ⳯ 9 ⳯ 6 mm, mas and the much rarer pituitary carcinomas.

PITUITARY ADENOMAS
GENERAL CONSIDERATIONS especially the chiasm, and the ocular motor cranial nerves
The characteristic pituitary tumor is the adenoma. Uncom- in the cavernous sinus (Fig. 31.2
mon in children (2), its incidence increases with age and may TYPES OF PITUITARY ADENOMAS
approach 30% in an older population (3). Pituitary adenomas
constitute 6–12% of all symptomatic intracranial tumors Pituitary adenomas are arbitrarily grouped by size into
(4,5). Most are sporadic, but pituitary adenomas are a com- microadenomas (less than 10 mm in greatest diameter) and
ponent of multiple endocrine neoplasia type 1, a familial macroadenomas. They are also classified according to their
endocrine cancer syndrome characterized by primary hyper- secretory function, although a single tumor may secrete more
parathyroidism, endocrine enteropancreatic tumors, and ad- than one hormone. Many tumors that secrete hor-
renocortical and thymic/bronchial neuroendocrine tumors mones—prolactin, growth hormone (somatotrophin), adre-
(6). As a pituitary adenoma grows and extends beyond the nocorticotropic hormone (ACTH or corticotrophin), and thy-
sella turcica, it may then impinge upon the visual pathways, roid-stimulating hormone (TSH)—present clinically as
1531

1. The location of the pituitary gland. Schematic drawing showing the relationship of the pituitary gland to the intracranial optic nerve (ON) and chiasm (C). internal carotid arteries. the lightly stippled portion is the neurohypophysis. vidian nerve. A. The arrows point to the diaphragma sellae. maxillary division of the trigeminal nerve. VII. 3. The open white arrows on the left side of photograph outline the boundaries of cranial nerves. (Courtesy of Dr. 4. (From Renn WH. Coronal section through the pituitary gland. William F.N. V. Microsurgical anatomy of the sellar region.2. 6. J Neurosurg 1975.) Figure 31. VI. The open white arrows on the right side of photograph indicate the boundaries of the cavernous sinus. The heavily stippled portion of the gland is the adenohypophysis. showing its relationship to the optic chiasm. Rhoton AL Jr. Hoyt. A postmortem specimen cut midsagittally through the pituitary gland. sphenoid sinus.. oculomotor nerve. abducens nerve.1532 CLINICAL NEURO-OPHTHALMOLOGY Figure 31.43⬊288–298. and cavernous sinuses. showing its relationships. trochlear nerve. ophthalmic division of the trigeminal nerve. B.) .

cause. metoclopramide. or more (Fig.g. As a result. above 200 ng/mL and. The majority of persons not taking 10% of clinically diagnosed pituitary adenomas (7). are common. Galactorrhea. enous hypercortisolism. the differential of which remains a agnosed while still microadenomas. refers to excess secretion of ACTH by a headache. of ‘‘TSH toxicosis’’ or with visual loss. Hypercortisolism from any mas tend to be large and invade surrounding structures (25). but ec- ciated with amenorrhea (Forbes-Albright syndrome). they plastic causes of moderately elevated prolactin levels include may not be noticed until far advanced. Because the clinical picture is less spe. of hypercortisolism on corticotropin secretion and tumor formed both with and without gadolinium (10). When women who have not recently been pregnant develop galac. Somatotroph (Growth Hormone-Secreting) Adenomas torrhea. Review of old photo- pregnancy. in some cases. In about 30% of per- Prolactin-Secreting Adenomas sons with Nelson’s syndrome. plasia that mimics an adenoma on imaging studies (19.and They may be obese with gynecomastia but do not usually corticotropin-secreting tumors and nonsecreting adenomas have galactorrhea. are less often detected as microadenomas. is frequently asso. 31. where formal visual ciated with excessive growth hormone than galactorrhea or fields should probably be obtained at least once a trimester. thus tending to present as macroadenomas. and headaches. a large aggressive pituitary tumor is eventually recognized (7). produces Cushing’s of patients (36%) had visual field defects (26). topic acromegaly from growth hormone-secreting carcinoid cause the prolactinomas are usually small. syndromes are sometimes the first clinical manifestations lactinomas are generally associated with prolactin levels (22). there are no visual or pancreatic islet cell tumors also stimulates pituitary hyper- symptoms or signs. affected individuals are not at risk for .000 ng/mL. medications that affect dopamine metabolism graphs may reveal evolution of acromegaly over a decade (e. Proximal myopathy and carpal tunnel pamil). a disorder much more common in have grown large enough to produce visual symptoms or women than men. but the risk of visual loss during pregnancy tors. In contrast to pregnant As it is harder to recognize the dysmorphic changes asso- women with known macroadenomas. aly because of growth hormone’s effects on insulin recep- ing adenoma. Diabetes is observed in persons with acromeg- Pregnancy may result in enlargement of a prolactin-secret. such patients often develop progressive cutaneous melanosis (Nelson’s syndrome) (18).3). especially small cell carcinoma of the lung. but significant minorities have adrenocortical or microadenomas. The corticosteroids with Cushing’s syndrome have Cushing’s widespread use of imaging has led to the discovery of silent disease. Freed from the restraint nomas. TUMORS OF THE PITUITARY GLAND 1533 endocrinopathies. cific than in women. renal failure. suprasellar extension and visual field defects in somatotroph Men with prolactinomas become impotent and infertile. phenothiazines. The prevalence of microadenomas at autopsy When adenomas were difficult to detect prior to modern may be as high as 30%. Pro. these nonfunctional tumors represented about sia and hypercortisolism. and hypertrophic arthropathy—are gradual. many patients underwent bilateral adrenalec- in the detection of parasellar tumors. They usually present with hyperthyroidism as the result Cushing’s syndrome refers to the effects of excessive glu. is high-field magnetic resonance (MR) imaging per. men with prolactinomas tend to have larger tumors at presentation. its is most often caused by a prolactin-secreting ade- noma. somatotroph adenomas women with microadenomas do not require routine field test. Normal serum prolactin levels are below 25 ng/mL in The differential diagnosis is made even more difficult be- women and below 20 ng/mL in men. to Graves’ disease. clinical challenge (16). and primary hypothyroidism (12).20). measuring other tumors. or methylprednisolone. Be. nonneo. growth. tomies for their Cushing’s disease. In contrast syndrome. including pituitary ade. the serum feet (the literal meaning of ‘‘acromegaly’’). Galactorrhea is normal following pregnancy. termed ‘‘incidentalomas’’ (8). Levels increase 10. Thyrotroph adeno- cocorticoids on the body (15). In the NIH series of 25 thyrotroph adenomas. Thyrotroph (TSH-Secreting) Adenomas Corticotroph (ACTH-Secreting) Adenomas Fewer than 3% of pituitary adenomas secrete thyrotropin (24). secreting tumors are often di. risperidone. giantism. hirsutism. and other parasellar processes may compress the pituitary Because the characteristic coarsening of facial features stalk. exceed 10. Adenomas that do not secrete prolactin are features of multiple endocrine neoplasia type 1 (21). in this setting. Most such tumors are pituitary adenomas. (23). not necessarily related to tumor growth. Such tumors account for about 40% of all pituitary Growth hormone-secreting tumors cause acromegaly and tumors (11). der- prolactin level is only moderately elevated. as small as 2–3 mm and present in 10–20% of the general that secrete ACTH (17). including taking corticosteroids such as prednisone. from a microadenoma is low (13). The frequency of ing during pregnancy (14). cause both neuroendocrine tumors and pituitary adenomas fold in pregnancy. decreasing the normal dopaminergic inhibition and and other bodily changes—enlargement of the hands and increasing prolactin secretion. Endocrinologists are more concerned with endog.. adenomas is therefore intermediate between prolactin. In this instance. population (9). mopathy. the stigmata of Cushing’s syndrome. Nonsecreting tumors are usually recognized when they Cushing’s disease. By the pituitary adenoma that results in secondary adrenal hyperpla- mid-1990s. as are hypertension and premature vascular disease. Other. vera. The imaging procedure of choice neuroimaging. about one third dexamethasone.

pituitary adenomas until they extend well above the pituitary tive tumors include null cell tumors. that serial fields should be more precisely comparable. sella turcica thus indicates a tumor other than a pituitary tional light microscopy were designated chromophobe ade. adenoma. Also note large hands. ticotropin-secreting tumors (27). tumors with agranular cytoplasm on conven. Frise´n found superotemporal defects to a single. but the strategy should incorporate compar- ison of the nasal and temporal hemifields within 20–30 de- grees from fixation (32). small Goldmann isopter that were not detected by the static perimetry then available (33). The variations in examiner skill levels in the performance of Goldmann perimetry and the availability of increasingly accurate and less time-consuming testing protocols. how- ever. Early in the last cen- nomas to distinguish them from chromophiles. at age 32 (B). visual loss and ophthalmoplegia remain important manifestations of pi- tuitary adenomas and other sellar and parasellar tumors. The advent of more sophisticated diagnostic tech- niques has made this classification of historic interest only. and at age 45 (C). glycopeptide-secreting.1534 CLINICAL NEURO-OPHTHALMOLOGY Acidophilic adenomas were likely to secrete growth hor- mone. The gradual development of acromegaly in a woman with placing Goldmann perimetry as the standard (35–37). When Endocrine-Inactive Adenomas viewed from above or below. and thickening of neck. and silent cor. although some secreting tumors do not produce ‘‘a symmetrically deformed letter H. optic atrophy. The optic chiasm or chiasm is a plate of neural tissue formed by the semidecussation of the optic nerves. The Chiasm thyroid-related ophthalmopathy as they do not have the un- derlying immunologic abnormalities.41) recognized that a ‘‘chiasmal syn- had cells with cytoplasmic granules that stained brightly with drome’’ of bitemporal hemianopia. and nor- acid fuchsin (acidophilic) or with aniline blue (basophilic). Threshold static testing appears well suited to this task but may not be more sensitive than Goldmann kinetic perimetry in experienced hands (33. Endocrine-inac. OPHTHALMIC MANIFESTATIONS OF PITUITARY TUMORS While improved endocrine and neuroimaging techniques have reduced the proportion of pituitary adenoma patients with primarily neuro-ophthalmic presentations. Frise´n (38) preferred to describe the chiasm as a minority. The latter tury Cushing (40. the chiasm is usually thought to resemble an X (the Greek letter chi. mal sella on plain skull films was typical of meningiomas . broadening of nasal bones and mandible. mean that automated threshold static perimetry is re- Figure 31. Adding additional isopters did not improve sensitivity. Bitemporal field loss in the presence of a normal-sized Classically. while basophilic adenomas were likely to secrete ACTH.3. Visual Field Testing Strategies Just testing the visual field may be more important than the method used. with a few exceptions (39). Auto- a somatotroph adenoma at age 19 (A). by which time they are macroadenomas of considera- nadotropin-secreting. from which it derives Pituitary adenomas that do not secrete any hormones are its name).’’ The chiasm lies about recognizable endocrinologic manifestations and thus behave 1 cm above the sella turcica and thus is not affected by clinically as though they were nonsecreting. mated threshold static perimetry has the further advantage Note increasing coarseness of facial features. and go.34). oncocytomas. al- lowing better assessment of progression or improvement. but the term ‘‘chromophobe’’ still appears occasionally in the literature to denote a nonfunctioning adenoma. Instances of delay in the diagnosis of pituitary and other chiasmal tumors when this rule is violated abound (28–31). fossa. The classic dictum that an unexplained decrease in acuity should prompt testing of the visual field to look for a bitemporal pattern of field loss remains valid. In a personal series collected before 1985. ble size that have almost always eroded bone.