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Pituitary antibodies and lymphocytic hypophysitis

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Lymphocytic hypophysitis (LYH) is a pituitary disease which can cause headache, changes in visual field and pituitary dysfunction. The clinical, histopathological and morphological findings and its association with other autoimmune disorders allow LYH to be included among the autoimmune diseases. Pituitary trans-sphenoidal biopsy is thought to be the diagnostic gold standard for LYH, even if some morphological findings on hypothalamic–pituitary magnetic resonance imaging (MRI) can suggest the occurrence of this disease. Despite the fact that organ-specific antibodies are good markers of many autoimmune endocrine diseases, the pathogenetic and diagnostic roles of anti-pituitary antibodies (APAs) in LYH are still under discussion. In fact, several methods have been used to detect APAs, but the conflicting results from different methods have impaired the clinical relevance of these antibodies. Recently, APAs have been detected by an immunofluorescence method in patients with selective idiopathic hypopituitarism (particularly in those with growth-hormone deficiency) and in adults with autoimmune endocrine diseases. The results suggest that only when they are present at high titres may they be considered a good marker of pituitary involvement, and in particular of growth-hormone-producing cells.

Section snippets

Criteria for organ-specific autoimmunity in lymphocytic hypophysitis

For a long time, on the basis of the criteria for defining a disease as autoimmune, some endocrine diseases previously considered as idiopathic have been recognized as autoimmune.10, 11, 12, 13, 14, 15, 16, 17 LYH fulfils most of the criteria required to define a disease as organ-specific autoimmune (Table 1).

Anti-pituitary antibodies

Organ-specific antibodies are good markers of many autoimmune endocrine diseases. Until now, APAs have not been considered good markers of LYH because of various difficulties in methodology and clinical interpretation. In fact, conflicting results in detecting APAs using different methods has impaired the clinical relevance of these antibodies. Moreover, a longitudinal study demonstrated that these antibodies can disappear over time43; for this reason the time of detection could influence their

Pathogenesis

Autoimmune mechanisms characterizing other organ-specific autoimmune diseases are well known because of the ability to study animal models and the availability of target organ tissues from patients in the subclinical stage or at the clinical onset of the disease. At present, the mechanisms triggering the development and progression of LYH are not known, although the presence of animal models of LYH may open the way to understanding these events.26, 27, 28 The role of CD8 T cells in autoimmune

Different expressions of LYH during the natural history of the disease

Some patients may present with symptoms and signs related to pituitary enlargement with possible extrasellar extension but without pituitary dysfunction, while others with normal characteristics on MRI may present with varying degrees of pituitary failure.25, 65, 71 Moreover, many patients with LYH can show high levels of PRL, while others may have normal or even low levels of PRL (women with failure to lactate in the postpartum period).1, 6 The natural history of LYH is very variable, often

Diagnosis of LYH: role of anti-pituitary antibodies

LYH has to be suspected in patients presenting with hyperprolactinaemia, headache, and impairment of visual field—especially if they are pregnant women or women with recent delivery and have symptoms of hypopituitarism of unclear aetiology. In these patients a trans-sphenoidal pituitary biopsy is thought to be the diagnostic gold standard for LYH.9 However, this procedure is invasive and not always feasible. Moreover, despite the recent development of sophisticated techniques of imaging, the

Therapeutic strategies

Before the start of therapeutic strategies of LYH, two important considerations may be made: first, the different expressions of this autoimmune disease require different therapeutic strategies; and second, since a possible spontaneous remission during the natural history of LYH can be observed, the improvement occurring after surgical or medical treatment could be related to spontaneous resolution rather than to the treatment itself. For this reason a careful follow-up is advisable in patients

Summary

LYH fulfils most of the criteria required to define a condition as an organ-specific autoimmune disease. It has a special place among the spectrum of autoimmune diseases, particularly because of the different forms it takes during its natural history. The presence of clear morphological pituitary characteristics of LYH on MRI, followed by trans-sphenoidal pituitary biopsy, is the diagnostic gold standard for LYH in patients with hypopituitarism and symptoms and signs of an expanding pituitary

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      However, conflicting results in detecting APAs by different methods have impaired the clinical relevance of those antibodies. In addition, those antibodies can disappear over time, as shown by longitudinal research.4 Caturegli et al.1 reported that an immunoblotting method is more sensitive (64% vs. 57%) and specific (86% vs. 76%) than an immunofluorescence method.

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      However, because the criterion standard for the diagnosis of LYH remains trans-sphenoidal pituitary biopsy, more feasible tools are needed to identify this disease at early time points.5 Remarkably, positivity for APAs is emerging as a reliable marker for autoimmune hypophysitis.6 In our case, in fact, early testing could have prevented the bilateral occlusion of the ICAs, stroke, and subsequent disability.

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