Hypothalamitis: a diagnostic and therapeutic challenge

Abstract

To report an unusual case of biopsy-proven autoimmune hypophysitis with predominant hypothalamic involvement associated with empty sella, panhypopituitarism, visual disturbances and antipituitary antibodies positivity. We present the history, physical findings, hormonal assay results, imaging, surgical findings and pathology at presentation, together with a 2-year follow-up. A literature review on the hypothalamic involvement of autoimmune hypophysitis with empty sella was performed. A 48-year-old woman presented with polyuria, polydipsia, asthenia, diarrhea and vomiting. The magnetic resonance imaging (MRI) revealed a clear suprasellar (hypothalamic) mass, while the pituitary gland appeared atrophic. Hormonal testing showed panhypopituitarism and hyperprolactinemia; visual field examination was normal. Pituitary serum antibodies were positive. Two months later an MRI documented a mild increase of the lesion. The patient underwent biopsy of the lesion via a transsphenoidal approach. Histological diagnosis was lymphocytic "hypothalamitis". Despite 6 months of corticosteroid therapy, the patient developed bitemporal hemianopia and blurred vision, without radiological evidence of chiasm compression, suggesting autoimmune optic neuritis with uveitis. Immunosuppressive treatment with azathioprine was then instituted. Two months later, an MRI documented a striking reduction of the hypothalamic lesion and visual field examination showed a significant improvement. The lesion is stable at the 2-year follow-up. For the first time we demonstrated that "hypothalamitis" might be the possible evolution of an autoimmune hypophysitis, resulting in pituitary atrophy, secondary empty sella and panhypopituitarism. Although steroid treatment is advisable as a first line therapy, immunosuppressive therapy with azathioprine might be necessary to achieve disease control.

Lymphocytic Hypophysitis Successfully Treated with Stereotactic Radiosurgery: Case Report and Review of the Literature

“…In patients with a severe form of primary LH, if the disease is recurrent after surgery or resistant to corticosteroid medications, other therapeutic modalities may be introduced such as immunosuppressive/lympholytic therapy (cyclosporine, methotrexate, azathioprine, or rituximab, a monoclonal antibody against CD20 that selectively induces apoptosis of B lymphocytes) (►Table 2). 13,[22][23][24][25][26][27][28][29][30] In our patient, in the view of the high dose of corticosteroids required to avoid clinical symptoms and the evidence of iatrogenic Cushing's syndrome, the immunosuppressive drug azathioprine was used as an alternative long-term treatment. In the first case describing the use of azathioprine in an aggressive form of LH, after 1 month of azathioprine treatment the suprasellar mass had completely disappeared.…”

“…In patients with refractory disease, various immunosuppressive therapies are used: cyclosporine, methotrexate, azathioprine, or rituximab. 14,[22][23][24][25][26][27][28][29][30] Only a few refractory patients have been treated with stereotactic radiosurgery (SRS). [31][32][33] SRS is a radiation therapy technique that delivers a precise high dose of irradiation (either single-fraction or multi-fraction SRS) to well-defined small to moderate targets.…”

Clinical aspects of autoimmune hypothalamitis, a variant of autoimmune hypophysitis: Experience from one center

“…As the disease progresses or subsides, the lesion enlarges or reduces accordingly, occasionally resulting in an ES. 3,7 Cases of AH with secondary ES have also been reported. 14,15 In our series, we suggested that secondary ES (2/5, 40%) could be the consequence of AHT.…”

Anti–Ma-1 and Anti–Ma-2 Antibodies in Isolated Fatal Hypothalamitis

“…However, the presence of antipituitary antibodies has been documented. Imaging confirms pituitary gland inflammation that overextends and compromises the hypothalamus [ 5 , 13 ]; empty Sella can be seen in late stages of the disease [ 5 ].…”

“…Second-line treatment options include rituximab, cyclophosphamide [ 14 ], and azathioprine [ 3 , 5 , 6 ] as well as dual-therapy rituximab with cyclophosphamide. Rituximab as monotherapy may be considered second line due to its more favorable side effect profile; it should be considered mainly in critically ill patients or if a patient remains significantly impaired after first-line therapy.…”