Pituitary aplasia, the congenital absence of the hypophysis, is a rare abnormality that is often accompanied by other malformations. The agenesis may involve the entire pituitary gland or the adenohypophysis and is caused by defective formation of the Rathke pouch. If the affected new-born survives, severe hypopituitarism develops. Pituitary hypoplasia is the milder form of the same defect.

In anencephaly, the brain, including the hypothalamus, is missing; thus, no neurohumoral regulation is exerted on the pituitary. The posterior lobe is present in some cases and absent in others. The anterior lobe is reduced in size and contains decreased numbers of corticotropes. The other adenohypophysial cell types are well developed and show no major abnormalities.

Remnants of the Rathke pouch persist in 20% to 50% of human pituitaries in the form of squamous cell nests. The nests vary in size and are located at the distal end of the stalk close to the anterior lobe.

Persistence of the cleft of the Rathke pouch is a harmless congenital defect and a common autopsy finding. The cleft fails to close and a distended, colloid-filled space is seen between the anterior and posterior lobes. Although this cleft is generally microscopic in proportion, it rarely may accumulate sufficient colloidal material to become an expansile and clinically significant intrasellar and suprasellar mass. These are known as Rathke cleft cysts, as discussed later (see the section on neoplasms). Although these lesions are most certainly not neoplastic in nature, they are discussed under the heading of neoplasms both for convenience and because they frequently mimic clinically and radiologically true cystic neoplasms of the sellar region.

Pituitary dystopia is a rare condition characterized by a failure of union of the neurohypophysis and adenohypophysis during early development. The pituitary stalk is foreshortened, resulting in an extrasellar location of the neural lobe and a failure of the latter to descend into the sella. Usually, there is no physical attachment between the neurohypophyses and the adenohypophyses, although, occasionally, the two may be tenuously attached by strands of tissue. The anomaly is generally inconsequential, most cases being incidental autopsy findings. Rarely, it may be accompanied by other abnormalities such as hypogonadism, growth retardation, or other congenital anomalies.

Septo-optic dysplasia is a complex developmental disorder characterized by variable and often partial expression of midline structural abnormalities of the brain, hypoplasia of the optic nerves, and hypothalamic dysfunction. The last may manifest as anterior and posterior pituitary failure on a hypothalamic basis. Additional features of hypothalamic dysfunction may also be present, including alterations of temperature regulation, hyperphagia, and precocious puberty. The full syndrome is expressed in only a few cases; most patients come to medical attention during early childhood with pituitary insufficiency and visual dysfunction. Septo-optic dysplasia is a medically treatable condition that is wholly compatible with life.

Anatomic variations in the shape and position of the pituitary and its relationships to neighboring
tissues are common. Although these differences have no major clinical significance, they may be important to radiologists and neurosurgeons.

In virtually all persons, a small ectopic focus of anterior pituitary tissue persists throughout life, and can usually be identified as a minute, oval, midline nodule embedded within the sphenoid bone. Known as the pharyngeal pituitary, this remnant of the Rathke pouch is usually <5 mm in size and is most frequently located deep within the mucosa or periosteum, beneath or near the vomerosphenoidal articulation; less often, it may be found in the nasopharynx or even within the nasal cavity. It is surrounded by a thin connective tissue capsule and consists of small clusters of chromophobic cells mixed with a few acidophilic and basophilic cells. In contrast to the pars distalis, the pharyngeal pituitary is richly innervated but has no portal blood supply; thus, it receives no hypothalamic hormones directly that might otherwise affect its secretory activity. Although immunocytologic techniques have disclosed various adenohypophysial hormones in the pharyngeal pituitary, this structure has no major endocrinologic significance and shows no marked histologic changes in patients with endocrine disorders. It cannot take over the function of the adenohypophysis after hypophysectomy or destructive adenohypophysial disease. The only clinically relevant feature of the pharyngeal pituitary is that it rarely may be the site for pituitary adenoma development.1,2 and 3 Most such tumors have been situated within the sphenoid sinus, and both nonfunctioning and hormonally active tumors have been reported. With respect to the latter, GH-producing tumors have been reported most commonly, followed in frequency by prolactin-producing and ACTH-producing adenomas. In the true “ectopic” pituitary adenoma, the intrasellar pituitary should be normal, although rarely, simultaneous development of an intrasellar and noncontiguous ectopic pituitary tumor has been reported. Another rare site for ectopic pituitary adenomas is the suprasellar region. Such “ectopic” tumors presumably arise from adenohypophysial cells of the pars tuberalis situated on the supradiaphragmatic portion of the pituitary stalk.

The term empty sella refers to the anatomic state resulting from the intrasellar herniation of the subarachnoid space through a defective and enlarged diaphragmatic aperture. The result is compression and posterior displacement of the pituitary gland, enlargement of the sella, and a seemingly “empty” appearance of the sella on both gross and radiologic examination. It is of clinical and pathophysiologic importance to distinguish those cases of empty sella occurring without identifiable cause (i.e., primary empty sella) from those resulting from a loss of intrasellar volume, such as would occur after an infarction, surgery, or the radionecrosis of an intrasellar neoplasm (i.e., secondary empty sella).

Hemorrhages of the pituitary are rare. They may develop in patients with head trauma, various hematologic abnormalities, or increased intracranial tension. In rapidly growing pituitary adenomas, intrahypophysial pressure may increase, leading to compression of intrahypophysial or extrahypophysial portal vessels and the arrest of portal circulation. Vessels may undergo a subtle, hypoxic injury noticeable on electron microscopic examination. If the damage is severe, the vascular walls cannot withstand the elevations in blood pressure and they rupture, resulting in hemorrhage. Pituitary apoplexy is the extreme variant of this process (see later in this chapter).

Pituitary infarction is a noninflammatory, coagulative necrosis caused by ischemia secondary to interruption of the blood supply. Small adenohypophysial infarcts are common, being found in ˜1% to 6% of autopsies of unselected adult subjects. The lesions remain unrecognized clinically and can be detected only by histologic examination. A loss of 75% of adenohypophysial tissue produces no clinical symptoms of hypopituitarism and no biochemical abnormalities.

Pituitary necrosis can be associated with several diseases. Postpartum pituitary necrosis (Sheehan syndrome) occurs in women who experienced severe blood loss and were in hypovolemic shock about the time of delivery. During shock, the. pituitary circulation may be interrupted and the anterior lobe undergoes ischemic infarction. Adenohypophysial necrosis also may occur in nonobstetric shock, but less frequently than in women with severe circulatory failure secondary to obstetric hemorrhage. This suggests that pregnancy predisposes women to pituitary necrosis, but neither the site of sensitization nor the mechanism leading to necrosis is known (see Chap. 17).

Necrotic foci of varying sizes can be found in the pituitaries of patients with diabetes mellitus, head trauma, cerebrovascular accidents, increased intracranial pressure, and epidemic hemorrhagic fever. Pituitary infarction develops after disruption of the pituitary stalk, which causes an arrest of the adenohypophysial circulation. Adenohypophysial infarcts often can be seen in patients who were maintained on mechanical respirators before they died. The lesions represent coagulative infarcts and often are accompanied by severe hypoxic lesions of the brain.

The pathogenesis of pituitary infarction is unclear, and the mechanism of arrest of the adenohypophysial circulation is not known. Proposed causes include embolism, thrombosis, disseminated intravascular coagulation, vascular compression, vasospasm, and primary capillary damage.

In postpartum pituitary necrosis, Sheehan postulated that severe spasm develops in those arterioles from which portal vessels arise.2 Vasospasm is followed by hypophysial ischemia and secondary thrombosis, resulting in coagulative infarcts that usually spare the posterior lobe and hypophysial stalk because these areas have a rich arterial blood supply.

In cases of postpartum pituitary necrosis, infarcted areas may be large, involving more than 90% of the anterior lobe. Adenohypophysial cells are not capable of sufficient regeneration. Thus, when there is extensive infarction, permanent hypopituitarism develops. Because modern obstetric care usually prevents blood loss and obstetric shock in pregnant women, Sheehan syndrome has become rarer.

Fibrous atrophy is the final phase of ischemic necrosis of the anterior lobe. The necrotic areas are replaced by fibrous tissue. The sequence of events is identical to that occurring in infarcts of other organs.

Necrotic foci may occur in the posterior lobe and hypophysial stalk in association with head injuries, increased intracranial pressure, and obstetric and nonobstetric shock. These patients may develop diabetes insipidus.

Classically defined, pituitary apoplexy9,10 refers to the abrupt and occasionally catastrophic occurrence of acute hemorrhagic infarction of a pituitary adenoma. The clinical syndrome is easily recognized, consisting of acute headache, meningismus, visual impairment, ophthalmoplegia, and alterations in consciousness. Without timely intervention, patients may die of subarachnoid hemorrhage or acute, life-threatening hypopituitarism. As defined herein, pituitary apoplexy is a complication in 1% to 2% of all pituitary adenomas. “Silent,” or subclinical, hemorrhage into a pituitary adenoma is considerably more common, as evidenced by the finding of hemorrhage, necrosis, or cystic change in up to 10% of all surgical specimens. There is little consensus as to which tumor types, if any, are most susceptible to apoplectic hemorrhage. Some have suggested that hormonally active tumors associated with acromegaly and Cushing disease are especially prone to apoplexy, whereas others have found large nonfunctioning tumors to bear the greatest risk. In the experience of the authors, large nonfunctioning pituitary tumors, particularly silent corticotrope adenomas, appear to have the highest inherent tendency to undergo apoplectic hemorrhage.

The pathophysiologic basis of pituitary apoplexy remains speculative. Ischemic necrosis of a rapidly growing tumor, intrinsic vascular abnormalities peculiar to pituitary tumors, and compression of the superior hypophysial artery against the sellar diaphragm have all been suggested as mechanisms contributing to apoplectic hemorrhage.11 Predisposing factors loosely associated with apoplexy include bromocriptine therapy, anticoagulation, diabetic ketoacidosis, head trauma, estrogen therapy, and pituitary irradiation. Most cases, however, occur in the absence of any known predisposing condition.