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Primary Hypophysitis

  • Sonia Nagi
Chapter
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Abstract

Hypophysitis, a chronic inflammation of the pituitary gland, is a rare condition which can be classified as secondary or primary. Secondary hypophysitis includes the cases where an etiological agent is identified, whereas primary hypophysitis refers to those that do not currently have identifiable causes. Primary hypophysitis is the most common form of hypophysitis and comprises five histologic forms: lymphocytic, granulomatous, xanthomatous, necrotizing, and immunoglobulin G4 (IgG4) plasmacytic. The two main types are lymphocytic and granulomatous hypophysitis. IgG4-related hypophysitis is a recently reported new variant. Although lymphocytic hypophysitis is the most common form of primary hypophysitis, it is rare, representing less than 1 % of pituitary masses and estimated to be the cause of hypopituitarism in 0.5 % of cases. Lymphocytic hypophysitis predominantly affects women, particularly during late pregnancy or in the early postpartum period. However, cases in men, menopausal women, and children have been described. Available data strongly suggest an autoimmune pathogenesis: association with autoimmune conditions affecting other organs in 50 % of cases (thyroid, parathyroid, and adrenal glands), histopathological findings comprising fibrosis and lymphocytic infiltration, with antipituitary antibodies described in a few cases. Granulomatous hypophysitis represents less than 1 % of all operated cases of hypophysitis. It is usually diagnosed in middle- to old-age patients without gender predominance. Primary granulomatous hypophysitis is rare and its pathogenesis is still not understood. The secondary form of granulomatous hypophysitis is more common, associated with tuberculosis, sarcoidosis, syphilis, Langerhans cell histiocytosis, or Rathke cleft cyst (RCC) rupture. Pathology demonstrates the formation of granulomas, aggregates of lymphocytes, and epithelioid histiocytes with multinucleated giant cells. It usually involves the anterior lobe but may extend to involve the posterior lobe, the stalk, and even the hypothalamus. Xanthomatous hypophysitis predominantly affects young females. Its cause remains unknown, although autoimmune, infectious, and localized endothelial dysfunction have been suggested. It is pathologically characterized by mixed inflammatory infiltrate of foamy histiocytes called xanthoma cells and mature lymphocytes with cyst-like areas typically confined to the anterior pituitary. The basic structure of anterior pituitary is usually preserved without alteration of the pituitary stalk. Necrotizing hypophysitis is pathologically characterized by a marked mononuclear infiltrate showing significant necrosis. It involves the adenohypophysis, pituitary stalk, infundibuloneurohypophysitis, and hypothalamus. The pathogenesis of this rare hypophysitis variant remains unknown. IgG4-related hypophysitis is part of a multifocal systemic disease of unknown etiology called “IgG4-related autoimmune disease.” This disease, which mainly affects middle-aged to elderly males, is characterized by elevated serum IgG4 concentration and tissue infiltration by IgG4+ plasma cells with fibrosis and sclerosis. Diagnostic criteria include involvement of various organs such as the CNS, salivary glands, lacrimal glands, thyroid gland, lungs, pancreas, bile ducts, kidneys, prostate, lymph nodes, retroperitoneum, mesentery, gastrointestinal tract, skin, breast, and arteries. Adenohypophysitis, infundibuloneurohypophysitis, or panhypophysitis may be distinguished according to the anatomic involvement of the gland. Classical manifestations of adenohypophysitis may be tumoral or endocrine symptoms. Tumoral syndrome consists of headaches and visual impairment. The sudden onset of these signs is related to the rapid pituitary volume increase. Oculomotor disorders caused by cavernous sinus involvement are seldom seen. Endocrine symptoms consist of partial or total anterior hypopituitarism. ACTH secretion is most frequently impaired, followed by TSH and LH/FSH secretion. Hyperprolactinemia caused by pituitary stalk compression can be seen. Hypogonadism is typically encountered in xanthomatous hypophysitis. A few cases of aseptic meningitis with meningeal syndrome have been reported. Infundibuloneurohypophysitis occurs in older patients without gender predilection, and typically presents with diabetes insipidus. Young age at onset (<30 years), vasopressin-cell antibodies, and association with other autoimmune diseases support the autoimmune hypothesis for pathogenesis. Diabetes insipidus is seldom encountered in xanthomatous hypophysitis. The role of MRI in primary hypophysitis is to eliminate a pituitary adenoma. Diffuse and symmetric enlargement of the pituitary gland is seen in adenohypophysitis, with frequent upward tongue-like extension. Optic chiasm compression is inconstant. This tumoral syndrome contrasts with a normal-sized pituitary fossa. Signal intensity is usually hypointense on T1WI and more or less hyperintense on T2WI. Postgadolinium enhancement is usually homogeneous and intense but can be moderate and heterogeneous (Fig. 40.1). The pseudocapsule formed by compressed normal pituitary gland is sometimes not seen after gadolinium administration. A nonspecific perisellar dural enhancement is frequent (Fig. 40.2). This feature, classically described in hypophysitis and meningiomas, can also be encountered in pituitary macroadenomas. A noticeable delay in pituitary enhancement compared with the normal gland (<60 s) has been described on dynamic CE studies. In contrast, we have observed during dynamic MRI an intense and early enhancement of some foci presenting a pronounced hyperintensity on T2WI and probably corresponding to a localized inflammatory process (Fig. 40.3). Enhancement of the diaphragm has been reported in a few cases. A peripheral enhancement pattern seems more common in xanthomatous hypophysitis than in other types of hypophysitis. Restitutio ad integrum is rare (Fig. 40.4). Recurrence can be observed after treatment withdrawal (Fig. 40.5). Anterior pituitary atrophy is frequently the final outcome of adenohypophysitis. Another more specific but later sign has been described by Nakata in lymphocytic hypophysitis, appearing 2–20 months after the initial MR examination. It consists of a dark fibrotic rim encircling the pituitary gland on T2WI (Fig.  41.4). Infundibuloneurohypophysitis is characterized by a thickened pituitary stalk and a loss of the posterior pituitary bright spot as seen on axial noncontrast T1WI. Pituitary stalk thickening usually resolves with time, sometimes very quickly. In the end, atrophy takes place with a threadlike pituitary stalk and a decrease in size of the anterior lobe (Fig. 40.6). However, recurrence of the stalk thickening can be seen. Loss of the posterior lobe bright spot is usually permanent. In cases of panhypophysitis, signs of both entities will be seen. The main differential diagnosis is pituitary adenoma. Other nonadenomatous pituitary masses and secondary hypophysitis can be difficult to distinguish from primary hypophysitis. Approximately 40 % of patients are misdiagnosed as having pituitary macroadenoma and undergo unnecessary surgery. Hence, distinguishing primary hypophysitis from pituitary adenoma is very important. On MR scans, pituitary adenoma can easily be distinguished from normal pituitary parenchyma. The normal pituitary gland is most often located at the upper part of the sella, anteriorly or lateral to the adenoma. It is best seen as a pseudocapsule on coronal T1WI after contrast administration. Another distinctive feature is the absence of thickening of the pituitary stalk. Diabetes insipidus is seldom encountered in adenomas and the posterior bright spot is present, although often ectopic. The other nonadenomatous pituitary masses are germinoma, choristoma, and pituitary metastases. Another differential diagnosis to consider is pituitary hyperplasia secondary to hypothyroidism. In this case, the posterior bright spot is present, the pituitary stalk is normal, and there is no delayed enhancement on dynamic postcontrast scans. Distinguishing primary hypophysitis from secondary hypophysitis is a diagnosis of exclusion (Fig. 40.7). Investigations are required to rule out numerous etiologies; administration of immunomodulatory drugs such as CTLA-4 blocking antibody (ipilimumab) or interferon-α, Wegener granulomatosis, tuberculosis, sarcoidosis, syphilis, tuberculosis, and Langerhans and non-Langerhans cell histiocytosis (see Chap.  41). Other etiologies may induce a secondary hypophysitis such as ruptured RCC, pituitary abscess, and Takayasu disease. The T2 dark fibrotic rim around the pituitary gland and along the dura mater, seen in the chronic stage of lymphocytic and IgG4-related hypophysitis (Figs. 40.8 and 40.9) is not a distinctive sign for secondary hypophysitis and can be observed in granulomatosis, sarcoidosis, or tuberculosis. Primary hypophysitis management remains controversial. Surgery may be indicated when the tumoral syndrome is important. Otherwise, when the diagnosis of primary hypophysitis is the most likely, medical treatment is initiated. Medical treatment consists of corticosteroid therapy and hormonal replacement therapy. This treatment should be carried out under clinical, biological, and neuroradiological supervision. Different outcomes have been reported. The disease may be self-limited, show a relapsing and remitting course, or progress to permanent hypopituitarism. In cases where the tumoral syndrome persists, surgery is indicated to avoid complications.

Keywords

Pituitary Adenoma Pituitary Stalk Lymphocytic Hypophysitis Normal Pituitary Gland Pituitary Abscess 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Further Reading

  1. Khare S, Jaktab VS, Budyal SR et al (2015) Primary (autoimmune) hypophysitis: a single centre experience. Pituitary 18:16–22CrossRefPubMedGoogle Scholar
  2. Nagi S, Megdiche H, Nouira K et al (2002) Hypophysite granulomateuse idiopathique: aspects cliniques et radiologiques. J Neuroradiol 29:43–48PubMedGoogle Scholar
  3. Nakata Y, Sato N, Masumoto T et al (2010) Parasellar T2 dark sign on MR imaging in patients with lymphocytic hypophysitis. Am J Neuroradiol 31:1944–1950CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Sonia Nagi
    • 1
  1. 1.Faculty of Medicine National Institute of NeurologyUniversity of Tunis El ManarTunisTunisia

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