Hypopituitarism refers to decreased secretion of pituitary hormones, which can result from diseases of the hypothalamus or of the pituitary. Hypofunction of the anterior pituitary occurs when approximately 75% of the parenchyma is lost or absent. This may be congenital or the result of a variety of acquired abnormalities that are intrinsic to the pituitary. Most cases of hypofunction arise from destructive processes directly involving the anterior pituitary, such as tumors, ischemic necrosis of the pituitary, and the empty sella syndrome, although other mechanisms have been identified.
Tumors and other mass lesions: Pituitary adenomas, other benign tumors arising within the sella, primary and metastatic malignancies, and cysts can induce hypopituitarism. Any mass lesion in the sellae can cause damage by exerting pressure on adjacent pituitary cells.
Pituitary surgery or radiation: Surgical excision of a pituitary adenoma may inadvertently extend to nonadenomatous pituitary. If sufficient normal tissue is removed, hypopituitarism may ensue. Radiation of the pituitary, used to prevent regrowth of residual tumor after surgery, exposes the nonadenomatous pituitary to the same radiation.
Rathke cleft cyst: These cysts, lined by ciliated cuboidal epithelium with occasional goblet cells and anterior pituitary cells, can accumulate proteinaceous fluid and expand causing symptoms.
Pituitary apoplexy: This is a sudden hemorrhage into the pituitary gland, often occurring into a pituitary adenoma. In its most dramatic presentation, apoplexy causes the sudden onset of excruciating headache, diplopia owing to pressure on the oculomotor nerves, and hypopituitarism.
Ischemic necrosis of the pituitary and Sheehan syndrome: Ischemic necrosis of the anterior pituitary is an important cause of pituitary insufficiency. In general, the anterior pituitary tolerates ischemia reasonably well; loss of as much as half to the anterior parenchyma can occur without clinical consequence. With damage to 75% or more, however, evidence of hypopituitarism develops. Sheehan syndrome, or postpartum necrosis of the anterior pituitary, is the most common form of clinically significant ischemic necrosis of the anterior pituitary. During pregnancy, the anterior pituitary enlarges to almost twice its normal size. This physiologic expansion of the gland is not accompanied by an increase in blood supply from the low-pressure venous system, and hence there is relative anoxia of the pituitary. Thus, sudden infarction of the anterior lobe precipitated by obstetric hemorrhage or shock may occur. Sudden systemic hypotension precipitates vasospasm of the vessels and thus ischemic necrosis of much of the anterior lobe. The posterior pituitary, because it receives its blood directly from arterial branches, is much less susceptible to ischemic injury in this setting and is therefore usually not affected. Pituitary necrosis may also be encountered in other conditions, such as disseminated intravascular coagulation and (more rarely) sickle cell anemia, elevated intracranial pressure, traumatic injury, and shock of any origin. Whatever the pathogenesis, the infarcted adenohypophysis at the outset appears soft, pale, and ischemic or hemorrhagic. Over time, the ischemic area is resorbed and replaced by fibrous tissue. In some long-standing cases, the gland scars down to a fibrous nubbin weighing less than 0.1 gm, attached to the wall of an empty sella.
Empty sella syndrome: Any condition that destroys part or all of the pituitary gland, such as ablation of the pituitary by surgery or radiation, can result in an empty sella. The empty sella syndrome refers to the presence of an enlarged, empty sella turcica that is not filled with pituitary tissue. There are two types: (1) In a primary empty sella, there is a defect in the diaphragma sellae that allows the arachnoidea mater and cerebrospinal fluid to herniate into the sella, resulting in expansion of the sella and compression of the pituitary. Classically the affected patients are obese women with a history of multiple pregnancies. The empty sella syndrome may be associated with visual field defects and occasionally with endocrine anomalies, such as hyperprolactinemia owing to interruption of inhibitory hypothalamic effects. Only rarely is it associated with hypopituitarism because sufficient functioning parenchyma is maintained. (2) In a secondary empty sella, a mass, such as a pituitary adenoma, enlarges the sella but then is removed by surgery or radiation. Hypopituitarism can result from the treatment or spontaneous infarction.
Genetic defects: Rare congenital deficiencies of one or more pituitary hormones have been recognized in children. A defect has been identified in a gene that encodes pit-1, a transcription factor that is important in the expression of pituitary-specific genes, such as GH, prolactin, and TSH. The defective form of the protein can bind to the DNA response element but does not activate the target genes. Consequently, children born with this deficiency cannot synthesize these hormones.
Less frequently, disorders that interfere with the delivery of pituitary hormone-releasing factors from the hypothalamus, such as hypothalamic tumors, may also cause hypofunction of the anterior pituitary. Any disease involving the hypothalamus can alter secretion of one or more of the hypothalamic hormones that influence secretion of the corresponding pituitary hormones. In contrast to diseases that involve the pituitary directly, any of these conditions can also diminish the secretion of ADH, resulting in diabetes insipidus. Such hypothalamic lesions are:
Tumors include benign lesions that arise in the hypothalamus, such as craniopharyngiomas, and malignant tumors that metastasize to that site, such as breast and lung carcinomas. Hypothalamic hormone deficiency can ensue when brain or nasopharyngeal tumors are treated with radiation.
Infiltrative disorders and infections, such as sarcoidosis or tuberculous meningitis, can cause deficiencies of anterior pituitary hormones and diabetes insipidus.
The clinical manifestations of anterior pituitary hypofunction depend on the nature and extent of the causative process as well as the type and degree of hormonal insufficiency. These changes are related to decreased function of the adrenal cortex, thyroid, and gonads. Additional alterations of hypopituitarism include pallor, as a result of loss of melanocyte-stimulating hormone (MSH) atrophy of the genitalia with resultant amenorrhea, impotence, and loss of libido; and loss of pubic and axillary hair.
By Lillian Thompson