Causes of secondary hypophysitis

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.

Age, gender, incidenceYoung adults, African American females, 1:100,00040–60 years of age; M > F = 2:1Children (< 1:200,0000) > AdultsMiddle age (> 50s)
M = F
Clinical presentationMultivisceral (lungs, heart, eyes, skin, sinuses), neurosarcoidosis: 5%, hypopituitarism/DI: 30%Systemic vasculitis (kidneys, lungs, sinuses, otitis media), DIChildren – 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 CTc-ANCA, PR3-ANCA, CXR, Chest and abdomen CTCXR, Chest CT, bone scan, FDG-PET, bone marrow aspirationBone scan, Chest and Abdomen CT
Tissue biopsy resultsNoncaseating epithelioid cell granulomasNecrotizing granulomasLangerhans/dendritic cellsNon–Langerhans cell histiocytosis
TreatmentSupraphysiologic prednisone: start 1 mg/kg/day × 2 weeks, then taperSteroids, rituximab, methotrexateFocal versus systemic chemotherapy and steroids, XRTSteroids, 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.


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