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- .mm, mas and the much rarer pituitary carcinomas 6 ן 9 ן The gland itself normally measures 12 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 1532 CLINICAL NEURO-OPHTHALMOLOGY Figure 31.1. The location of the pituitary gland. A, Schematic drawing showing the relationship of the pituitary gland to the intracranial optic nerve (ON) and chiasm (C). The heavily stippled portion of the gland is the adenohypophysis; the lightly stippled portion is the neurohypophysis. The arrows point to the diaphragma sellae. B, A postmortem specimen cut midsagittally through the pituitary gland, showing its relationships. (From Renn WH, Rhoton AL Jr. Microsurgical anatomy of the sellar region. J Neurosurg 1975;43Ϻ288–298.) Figure 31.2. Coronal section through the pituitary gland, showing its relationship to the optic chiasm, internal carotid arteries, sphenoid sinus, and cavernous sinuses. The open white arrows on the right side of photograph indicate the boundaries of the cavernous sinus. The open white arrows on the left side of photograph outline the boundaries of cranial nerves. 3, oculomotor nerve; 4, trochlear nerve; VI, ophthalmic division of the trigeminal nerve; VII, maxillary division of the trigeminal nerve; 6, abducens nerve; V.N., vidian nerve. (Courtesy of Dr. William F. Hoyt.) TUMORS OF THE PITUITARY GLAND 1533 endocrinopathies. As a result, secreting tumors are often di- enous hypercortisolism, the differential of which remains a agnosed while still microadenomas. clinical challenge (16). Nonsecreting tumors are usually recognized when they Cushing’s disease, a disorder much more common in have grown large enough to produce visual symptoms or women than men, refers to excess secretion of ACTH by a headache, thus tending to present as macroadenomas. By the pituitary adenoma that results in secondary adrenal hyperpla- mid-1990s, these nonfunctional tumors represented about sia and hypercortisolism. The majority of persons not taking 10% of clinically diagnosed pituitary adenomas (7). The corticosteroids with Cushing’s syndrome have Cushing’s widespread use of imaging has led to the discovery of silent disease, but significant minorities have adrenocortical or microadenomas, termed ‘‘incidentalomas’’ (8), measuring other tumors, especially small cell carcinoma of the lung, as small as 2–3 mm and present in 10–20% of the general that secrete ACTH (17). population (9). The prevalence of microadenomas at autopsy When adenomas were difficult to detect prior to modern may be as high as 30%. The imaging procedure of choice neuroimaging, many patients underwent bilateral adrenalec- in the detection of parasellar tumors, including pituitary ade- tomies for their Cushing’s disease. Freed from the restraint nomas, is high-field magnetic resonance (MR) imaging per- of hypercortisolism on corticotropin secretion and tumor formed both with and without gadolinium (10). growth, such patients often develop progressive cutaneous melanosis (Nelson’s syndrome) (18). In about 30% of per- Prolactin-Secreting Adenomas sons with Nelson’s syndrome, a large aggressive pituitary tumor is eventually recognized (7). Galactorrhea is normal following pregnancy. When women who have not recently been pregnant develop galac- Somatotroph (Growth Hormone-Secreting) Adenomas torrhea, its is most often caused by a prolactin-secreting ade- noma. Such tumors account for about 40% of all pituitary Growth hormone-secreting tumors cause acromegaly and tumors (11). Galactorrhea, in this setting, is frequently asso- giantism. Most such tumors are pituitary adenomas, but ec- ciated with amenorrhea (Forbes-Albright syndrome). Be- topic acromegaly from growth hormone-secreting carcinoid cause the prolactinomas are usually small, there are no visual or pancreatic islet cell tumors also stimulates pituitary hyper- symptoms or signs. plasia that mimics an adenoma on imaging studies (19,20). 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. Levels increase 10- cause both neuroendocrine tumors and pituitary adenomas fold in pregnancy. Adenomas that do not secrete prolactin are features of multiple endocrine neoplasia type 1 (21). and other parasellar processes may compress the pituitary Because the characteristic coarsening of facial features stalk, decreasing the normal dopaminergic inhibition and and other bodily changes—enlargement of the hands and increasing prolactin secretion. In this instance, the serum feet (the literal meaning of ‘‘acromegaly’’), hirsutism, der- prolactin level is only moderately elevated. Other, nonneo- mopathy, and hypertrophic arthropathy—are gradual, they plastic causes of moderately elevated prolactin levels include may not be noticed until far advanced. Review of old photo- pregnancy, medications that affect dopamine metabolism graphs may reveal evolution of acromegaly over a decade (e.g., phenothiazines, metoclopramide, risperidone, vera- or more (Fig. 31.3). Proximal myopathy and carpal tunnel pamil), renal failure, and primary hypothyroidism (12). Pro- syndromes are sometimes the first clinical manifestations lactinomas are generally associated with prolactin levels (22), and headaches, not necessarily related to tumor growth, above 200 ng/mL and, in some cases, exceed 10,000 ng/mL. are common. Diabetes is observed in persons with acromeg- Pregnancy may result in enlargement of a prolactin-secret- aly because of growth hormone’s effects on insulin recep- ing adenoma, but the risk of visual loss during pregnancy tors, as are hypertension and premature vascular disease. from a microadenoma is low (13). In contrast to pregnant As it is harder to recognize the dysmorphic changes asso- women with known macroadenomas, where formal visual ciated with excessive growth hormone than galactorrhea or fields should probably be obtained at least once a trimester, the stigmata of Cushing’s syndrome, somatotroph adenomas women with microadenomas do not require routine field test- are less often detected as microadenomas. The frequency of ing during pregnancy (14). suprasellar extension and visual field defects in somatotroph Men with prolactinomas become impotent and infertile. adenomas is therefore intermediate between prolactin- and They may be obese with gynecomastia but do not usually corticotropin-secreting tumors and nonsecreting adenomas have galactorrhea. Because the