Pituitary involvement in granulomatosis with polyangiitis.

G ranulomatosis with polyangiitis (GPA), formerly Wegener granulomatosis, is an antiYneutrophil cytoplasmic antibody (ANCA)Yassociated systemic necrotizing granulomatous small-vessel vasculitis. It typically affects the upper respiratory tract, lungs, and kidneys but can involve virtually any organ including the pituitary. Pituitary involvement in GPA is rare. In this issue, Al-Fakhouri and colleagues have reported 2 cases, and a total of 35 cases have been reported in the English medical literature between 1966 and August 2013. There were only 23 cases when the last major review of pituitary involvement in GPA was published in 2008. Although GPA affects males and females equally, the majority of patients with pituitary involvement are female. The increasing number of reported cases highlights that clinicians need to be aware of GPA as a cause of pituitary insufficiency, and pituitary function needs to be assessed in GPA patients with clinical features. The pathophysiology of the hypothalamus-pituitary involvement in GPA includes granulomatous lesions by contiguous invasion from nasal or paranasal granuloma, in situ granuloma formation, vasculitis of anterior and/or posterior pituitary blood vessels, or a combination of these mechanisms. However, the reason for the pituitary to be involved in a small number of patients with GPA and yet others are spared is unknown. Pituitary involvement in GPA usually occurs in the course of the disease with other organ involvement. There is only 1 reported case with isolated pituitary involvement at the time of presentation. Granulomatosis with polyangiitis can affect partial or global pituitary endocrine function to varying degrees. Central diabetes insipidus has been more commonly observed with or without concurrent anterior pituitary insufficiency due to a preponderance of posterior pituitary involvement. The diagnosis of GPA remains challenging with pituitary involvement because initial clinical symptoms can be nonspecific, often resulting in delayed recognition. The presence of symptoms of pituitary insufficiency in conjunction with epistaxis and/or sinusitis should heighten the clinician’s suspicion of GPA as a potential etiology. In the case series of GPA with pituitary involvement, the majority of patients except for 1 case have all been ANCA positive with antiYproteinase 3 specificity observed in many of these cases. AntiYneutrophil cytoplasmic antibody levels do not typically correlate with severity of disease. With the current limitations of noninvasive tests, tissue biopsy is still necessary for diagnostic confirmation because of the potentially toxic nature of treatment of GPA. In cases of GPAwith pituitary involvement, most patients have other organ involvement, which allow tissue biopsies to be performed, whereas biopsy of the pituitary is only rarely required. Magnetic resonance imaging (MRI) of the pituitary is useful in diagnosis. The classic MRI findings in GPA are pituitary enlargement, diffuse or focal infundibular thickening, and the absence of the normal high-intensity signal in the posterior pituitary lobe, seen on T1-weighted images. However, patients may have a predominantly small vessel vasculitis, and only minimal changes would be visible on MRI. These MRI abnormalities may vary with disease activity. The treatment of GPA with pituitary involvement involves 2 components. First, it involves treatment of relevant endocrine insufficiency, which includes corticosteroid, thyroid hormone, testosterone, vasopressin replacement, or combinations of these therapies as clinically indicated, and second, treatment of the underlying GPA. Treatment for the underlying GPA has been diverse. In the past, some patients have undergone surgical treatment of the pituitary lesion, which would usually lead to varying degrees of permanent pituitary insufficiency. Although this practice has largely been avoided, a case report was recently published about a patient with difficult-to-manage GPA involving the pituitary who underwent surgical intervention for local disease control. Conventional therapy for GPA with pituitary involvement uses the combination of high-dose corticosteroid and cyclophosphamide (oral or intravenous) for induction therapy. In case series, this combination therapy induced remission in all patients, but EDITORIAL