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.
