NONTUMOROUS LESIONS OF THE PITUITARY GLAND AND PITUITARY STALK
The nontumorous lesions of the pituitary gland that can affect function include lymphocytic hypophysitis, granulomatous disorders (e.g., sarcoidosis, tuberculosis, Langerhans cell histiocytosis, Wegener granulomatosis), head trauma with skull base fracture, iron overload states (e.g., hemochromatosis, hemosiderosis), intrasellar carotid artery aneurysm, primary empty sella, pituitary cyst infection (e.g., encephalitis, pituitary abscess), mutations in genes encoding pituitary transcription factors, and developmental midline anomalies.
Lymphocytic hypophysitis is an autoimmune disorder characterized by lymphocytic inﬁltration and enlargement of the pituitary gland followed by selective destruction of pituitary cells. The most common clinical setting is in late pregnancy or in the postpartum period. Patients typically present with headaches and signs and symptoms of deﬁciency of one or more pituitary hormones. Frequently, there is a curious preferential destruction of corticotrophs. However, these patients may have panhypopituitarism (including diabetes insipidus [DI]). Magnetic resonance imaging (MRI) usually shows a homogeneous, contrastenhancing sellar mass with pituitary stalk involvement. The pituitary hormone deﬁcits are usually permanent, but recovery of both anterior and posterior pituitary function may occur.
Granulomatous hypophysitis can be caused by sarcoidosis, tuberculosis, Langerhans cell histiocytosis, or Wegener granulomatosis. The granulomatous inﬂammation may involve the hypothalamus, pituitary stalk, and pituitary gland and cause hypopituitarism, including DI.
Head trauma that results in a skull base fracture may cause hypothalamic hormone deﬁciencies, resulting in deﬁcient secretion of anterior and posterior pituitary hormones. Head trauma may lead to direct pituitary damage by a sella turcica fracture, pituitary stalk section, trauma-induced vasospasm, or ischemic infarction after blunt trauma.
Iron overload states of hemochromatosis and hemosiderosis of thalassemia may involve the pituitary, resulting in iron deposition (siderosis) in pituitary cells. Iron overload most commonly results in selective gonadotropin deﬁciency.
The term empty sella refers to an enlarged sella turcica that is not entirely ﬁlled with pituitary tissue. A secondary empty sella occurs when a pituitary adenoma enlarges the sella but is then surgically removed or damaged by radiation or infarction. In a primary empty sella, a defect in the sellar diaphragm allows cerebrospinal ﬂuid to enter and enlarge the sella (50% of patients with a primary empty sella have benign increased intracranial pressure). With a primary empty sella, pituitary function is usually intact. On MRI, demonstrable pituitary tissue is usually compressed against the sellar ﬂoor.
Hypopituitarism is also associated with mutations in genes that encode the transcription factors whose expression is necessary for the differentiation of anterior pituitary cells (e.g., HESX1, LHX3, LHX4, PROP1, POU1F1 [formerly PIT1], TBX19 [also known as TPIT]). Mutations in PROP1 are the most common cause of familial and sporadic congenital hypopituitarism. PROP1 is necessary for the differentiation of a cell type that is a precursor of somatotroph, lactotroph, thyrotroph, and gonadotroph cells. The protein encoded by POU1F1, which acts temporally just after the protein encoded by PROP1, is necessary for the differentiation of a cell type that is a precursor of somatotroph, lactotroph, and to a lesser degree, thyrotroph cells. TBX19 is required for speciﬁc differentiation of the corticotroph cells. Because the proteins encoded by HEXS1, LHX3, and LHX4 act early in pituicyte differentiation, mutations in these genes cause combined pituitary hormone deﬁciency, which refers to deﬁciencies of growth hormone (GH), prolactin, thyrotropin (thyroid-stimulating hormone [TSH]), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) (see Plate 1-13).
Developmental midline anomalies may lead to structural pituitary anomalies (e.g., pituitary aplasia or hypoplasia). Craniofacial developmental anomalies may result in cleft lip and palate, basal encephalocele, hypertelorism, and optic nerve hypoplasia, with varying degrees of pituitary dysplasia and aplasia. Congenital basal encephalocele may cause the pituitary to herniate through the sphenoid sinus roof, resulting in pituitary failure and DI.