Lymphocytic infundibulo neurohypophysitis

Lymphocytic adenohypohysitis and lymphocytic infundibulo neurohypophysitis are rare autoimmune mediated diseases of the anterior and posterior pituitary, respectively.

Lymphocytic infundibulo-neurohypophysitis (LINH) was first reported by Saito et al. and Imura et al. as a cause of idiopathic central diabetes insipidus ¹⁾.

Lymphocytic infundibulo neurohypophysitis is an uncommon inflammatory disease postulated to be autoimmune in origin.

Still unknown ²⁾.

Yasuda et al., reported that rabphilin-3A (RPH3A)an autoantigen and that anti-rabphilin-3A antibodies constitute a possible diagnostic marker for LINH. However, the involvement of rabphilin-3A in the pathogenesis of LINH remains to be elucidated. This study was undertaken to explore the role of rabphilin-3A in lymphocytic neurohypophysitis and to investigate the mechanism. They found that immunization of mice with rabphilin-3A led to neurohypophysitis. Lymphocytic infiltration was observed in the neurohypophysis and supraoptic nucleus 1 month after the first immunization. Mice immunized with rabphilin-3A showed an increase in the volume of urine that was hypotonic as compared with control mice. Administration of a cocktail of monoclonal anti-rabphilin-3A antibodies did not induce neurohypophysitis. However, abatacept, which is a chimeric protein that suppresses T-cell activation, decreased the number of T cells specific for rabphilin-3A in peripheral blood mononuclear cells (PBMCs). It ameliorated lymphocytic infiltration of CD3+ T cells in the neurohypophysis of mice that had been immunized with rabphilin-3A. Additionally, there was a linear association between the number of T cells specific for rabphilin-3A in PBMCs and the number of CD3+ T cells infiltrating the neurohypophysis. In conclusion, we suggest that rabphilin-3A is a pathogenic antigen, and that T cells specific for rabphilin-3A are involved in the pathogenesis of neurohypophysitis in mice ³⁾.

Because of the location of inflammation, it selectively affects the posterior lobe of the pituitary (neurohypophysis) and pituitary stalk (infundibulum). The most common presentation is central diabetes insipidus.

In the majority of patients, Hypophysitis can be reliably identified by characteristic clinical signs and symptoms, obviating histological confirmation. The diagnostic approach should be standardized ⁴⁾.

Although the definitive diagnosis is established histologically by a pituitary biopsy, radiological imaging can be valuable in diagnosing this condition ⁵⁾.

Magnetic resonance (MR) imaging with a contrast medium demonstrates thickening of the pituitary stalk, enlargement of the neurohypophysis, or both with homogeneous enhancement. Histological examination reveals a posterior pituitary that is heavily infiltrated by lymphocytes with occasional plasma cells and other inflammatory cells. In early reports of the disorder, the lesion seemed to be limited to the neurohypophysis, but Abe ⁶⁾, showed cases with a combination of hypopituitarism and diabetes insipidus. Some of them showed partial hypopituitarism. The so-called lymphocytic infundibulo-panhypophysitis (LIPH) is now regarded as a lymphocytic hypophysitis variant. Lymphocytic infundibulo-neurohypophysitis (LINH) and LIPH are essentially self-limited.

In typical cases, conservative care with steroids and hormone replacement is recommended. Surgical intervention should be avoided because the natural course of the disorder may be self-limited ⁷⁾,

Shibue et al. describe a case showing the serial progression of lymphocytic infundibuloneurohypophysitis (LINH) to panhypopituitarism with extrapituitary inflammatory invasion in a short period, and responding favorably to high-dose glucocorticoid treatment. PATIENT CONCERNS: Polyuria, General fatigue and Nausea/Vomiting. DIAGNOSES: Central diabetes insipidus (CDI), Lymphocytic infundibuloneurohypophysitis (LINH). INTERVENTIONS: Desmopressin acetate, High-dose glucocorticoid (GC) treatment. OUTCOMES: He was prescribed desmopressin acetate and subsequently discharged. A month later, he revisited our hospital with general fatigue and nausea/vomiting. A screening test disclosed hypopituitarism with adrenal insufficiency. MRI revealed expanded contrast enhancement to the peripheral extrapituitary lesion. He received high-dose GC treatment and the affected lesion exhibited marked improvement on MRI, along with the recovery of the anterior pituitary function. LESSONS: This case demonstrates the potential for classical LINH to develop into panhypopituitarsim. We consider this is the first documentation of approaching the cause of atypical LINH with progressive clinical course from the pathological viewpoint ⁸⁾.