A 20-year-old healthy woman presented to a local hospital with 3 months of headaches and fatigue and 3 weeks of intermittent fevers to 40°C. Physical examination was normal. White blood cell count was 6.1 × 109/L, hemoglobin 10 g/dL, sodium 153 mmol/L, and creatinine 0.80 mg/dL. Magnetic resonance imaging demonstrated a 2.1 × 1.8 × 0.9-cm cystic sellar lesion. Hormone testing revealed panhypopituitarism. Lumbar puncture showed white blood cell count 0.220 × 109/L, 98% mononuclear cells, red blood cell count 3 × 109/L, normal glucose and protein, and sterile cultures. Serum West Nile virus, Coccidioides, Cryptococcus, human immunodeficiency virus, herpes simplex virus, Treponema, and Strongyloides testing was negative, as were urine Histoplasma antigen and sputum acid-fast bacilli smears and cultures. The antineutrophil cytoplasmic antibody indirect immunofluorescence (ANCA IIF) assay was negative.
The patient was transferred to our hospital. Transsphenoidal biopsy showed necrotizing granulomatous hypophysitis, presumed idiopathic when infectious stains and cultures returned negative. She received hydrocortisone, levothyroxine, and desmopressin, with partial symptomatic improvement.
Three months later, she returned with 2 weeks of fatigue, fevers, productive cough with a single episode of hemoptysis, daily epistaxis, and bilateral partial hearing loss. Examination revealed a heart rate of 140 beats per minute, bilateral middle ear effusions, and diminished right-sided breath sounds. C-reactive protein was 196.0 mg/L (normal <6.3), ferritin 939 ug/L, and creatinine 0.72 mg/dL. Urinalysis showed moderate hemoglobin. Spot urine protein-to-creatinine ratio was 0.56. Chest radiography demonstrated 2 bilateral cavitating pulmonary infiltrates (Figure, A). Computed tomography confirmed an 8.4 × 6.2-cm right lower lobe lesion and a 3.9 × 3.4-cm lesion involving the left upper lobe and lingula. Blood and urine cultures were sterile. Bronchoalveolar lavage was nondiagnostic.
Nasal mucosa biopsy demonstrated granulomatous inflammation. The anti-proteinase 3 (anti-PR3) antibody returned at 686.6 CU (normal <20 CU), confirming a diagnosis of granulomatosis with polyangiitis. Corticosteroids and rituximab resulted in symptomatic improvement, decrease in C-reactive protein, and normalization of the urinalysis. Nine months later, chest radiography demonstrated complete resolution of the pulmonary lesions (Figure, B). She continues to require pituitary replacement therapy.
Discussion
Granulomatosis with polyangiitis is a systemic small-vessel vasculitis characterized by sinonasal, pulmonary, and renal disease. Pituitary involvement is uncommon and rarely precedes the diagnosis of granulomatosis with polyangiitis.1 By the time pituitary involvement manifests, other organs are typically already affected.2 Diabetes insipidus and secondary hypogonadism are the most common pituitary manifestations of granulomatosis with polyangiitis.1 While inflammation usually responds to high-dose corticosteroid therapy with or without either rituximab, cyclophosphamide, or methotrexate, pituitary dysfunction usually persists.3
In our patient, the initial ANCA IIF assay was negative, but the anti-PR3 immunoassay was positive. Anti-PR3 immunoassays are more sensitive (75%-81%) than ANCA IIF (65%-77%) for the diagnosis of granulomatosis with polyangiitis.4 Consensus guidelines recommend first-line antigen-specific immunoassays instead of IIF to diagnose ANCA-associated vasculitis.5
Patients with an unexplained sellar mass or unexplained pituitary dysfunction should be evaluated for granulomatosis with polyangiitis. Anti-PR3 and anti-MPO antigen-specific immunoassays should be performed as first-line testing for ANCA-associated vasculitis. Early diagnosis and treatment of ANCA-associated vasculitis can prevent irreversible organ dysfunction.
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-Janet N. Chu, MD, MPH, Sarah Goglin, MD, Sophie Patzek, MD, Sam Brondfield, MD
This article originally appeared in the January issue of The American Journal of Medicine.
