What are the main inflammatory and infectious causes of secondary hypophysitis?
- Secondary hypophysitis may be caused by an underlying systemic inflammatory disease, usually multivisceral, or an infectious disease that also involves the pituitary gland and/or stalk. The most common etiologies, and their characteristics, are shown in the below table.
- In addition, some sellar lesions (e.g., Rathke’s cleft cyst, meningioma, and germinomas) can be associated with secondary inflammatory cellular reactions consistent with hypophysitis.
- Potential infectious etiologies (very rare): Bacterial (most commonly gram-positive bacteria), granulomatous diseases (e.g., tuberculosis [TB], syphilis, brucellosis), fungal infections (aspergillosis, coccidioidomycosis), and Whipple’s disease.
- Risk factors for pituitary infections: Immunocompromised patients, hematologic/parasellar infections, cavernous sinus thrombosis, and previous pituitary surgery.
- Clinical presentation: Most commonly presents with mass effects (e.g., headaches, hypopituitarism, vision defects, and diabetes insipidus [DI]), and less commonly (< 30%) with classic features of infection (e.g., fever, leukocytosis, meningismus).
- Radiographic features: Pituitary abscess and TB may present as cystic lesions with gadolinium ring enhancement, although often are radiographically nondiagnostic.
- Diagnosis: Usually made during drainage in transsphenoidal surgery (TSS) and follow-up evaluations for infectious etiologies.
- Treatment: Parental antibiotics are generally recommended for infectious causes, depending on etiology and drug sensitivities.
Secondary Hypophysitis.
SARCOIDOSIS | GRANULOMATOSIS WITH POLYANGIITIS | LANGERHANS CELL HISTIOCYTOSIS (LCH) | ERDHEIM-CHESTER DISEASE | |
Age, gender, incidence | Young adults, African American females, 1:100,000 | 40–60 years of age; M > F = 2:1 | Children (< 1:200,0000) > Adults | Middle age (> 50s) M = F |
Clinical presentation | Multivisceral (lungs, heart, eyes, skin, sinuses), neurosarcoidosis: 5%, hypopituitarism/DI: 30% | Systemic vasculitis (kidneys, lungs, sinuses, otitis media), DI | Children – DI/GHD Adults – DI (25%) and diffuse disease (bone, skin, lungs) | Multivisceral (osteosclerosis: knees + ankles, heart, kidneys, liver, lungs, spleen, thyroid) |
Evaluation (in addition to pituitary hormones) | Serum/CSF ACE, CXR, +/− Chest CT | c-ANCA, PR3-ANCA, CXR, Chest and abdomen CT | CXR, Chest CT, bone scan, FDG-PET, bone marrow aspiration | Bone scan, Chest and Abdomen CT |
Tissue biopsy results | Noncaseating epithelioid cell granulomas | Necrotizing granulomas | Langerhans/dendritic cells | Non–Langerhans cell histiocytosis |
Treatment | Supraphysiologic prednisone: start 1 mg/kg/day × 2 weeks, then taper | Steroids, rituximab, methotrexate | Focal versus systemic chemotherapy and steroids, XRT | Steroids, chemotherapy, surgery, XRT, vemurafenib |
ACE, Angiotensin-converting enzyme; c-ANCA, cytoplasmic anti-neutrophil cytoplasmic antibody; CSF, cerebrospinal fluid; CT, computed tomography; CXR, chest x-ray; DI, diabetes insipidus; FDG-PET, fluorodeoxyglucose positron emission tomography; GHD, growth hormone deficiency; PR3-ANCA, proteinase 3-ANCA; XRT, radiation therapy.