Case of the Week

Background:

• IgG4-related hypophysitis is a pituitary manifestation of IgG4-related disease, a disease characterized by tumor-like involvement of multiple organs with IgG4-positive plasma cells.

Clinical Presentation:

• The patient typically presents with hypopituitarism (diabetes insipidus and/or anterior pituitary hormone deficiencies).
• The other main presenting symptoms are due to local mass effect, including vision changes and headaches.

Key Diagnostic Features:

• MRI demonstrates loss of the normal posterior pituitary T1 bright spot, a sellar mass, and thickening and enhancement of the infundibulum.
• Imaging is required to assess for systemic manifestations of IgG4-related disease outside the brain; this includes the orbits, paranasal sinuses, salivary glands, thyroid, lungs, pancreas, and kidneys.
• Although serum IgG4 levels are often elevated, more definitive diagnosis requires histopathologic analysis of the pituitary or other affected organ, which demonstrates lymphoplasmacytic infiltration of predominantly IgG4-positive plasma cells (proposed cutoffs include IgG4+/IgG+ plasma ratio of >40%, however, this varies by organ).

Differential Diagnoses:

• Lymphocytic hypophysitis: Seen in the pregnancy/early postpartum period
• Infectious granulomatous hypophysitis, such as tuberculosis: Presence of systemic illness
• Granulomatosis with polyangiitis: Associated findings in the sinuses (erosion of the nasal septum/turbinates) and lungs (nodules or consolidation with or without cavitation).
• Neurosarcoidosis: Seen in the presence of other typical CNS findings (pachymeningeal or leptomeningeal involvement) and chest findings (hilar adenopathy)
• Langerhans cell histiocytosis: Classically associated lytic calvarial lesions with beveled edges
• Germinoma: May be multifocal and involve the pineal region
• Lymphoma: Can be primary or secondary; when the pituitary is involved, there is typically an aggressive appearance with potential involvement of the skull base, cavernous sinus, and cranial nerves
• Metastasis: Typically seen in adults with known primary tumor

Treatment:

• IgG4-related hypophysitis typically demonstrates rapid response to corticosteroid therapy.
• Treatment also entails managing pituitary dysfunction with hormone replacement.