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Pituitary Dysfunction in Granulomatosis With Polyangiitis: The Mayo Clinic Experience Ekta Kapoor, Rodrigo Cartin-Ceba, Ulrich Specks, Jacqueline Leavitt, Bradley Erickson, and Dana Erickson Divisions of General Internal Medicine (E.K.), Pulmonary and Critical Care Medicine (R.C.-C., U.S.) Ophthalmology (J.L.), Radiology (B.E.), and Endocrinology (D.E.), Mayo Clinic, Rochester, Minnesota 55905

Context: Pituitary involvement in granulomatosis with polyangiitis (GPA) has been described in case reports. The aim of this study was to describe the clinical presentation and outcomes of pituitary disease in patients with GPA evaluated at a tertiary referral center. Setting: A retrospective review of patients with GPA-related pituitary disease seen at the Mayo Clinic in Rochester, Minnesota. Patients: A total of 637 patients with antineutrophil cytoplasmic antibodies-associated vasculitis were followed at our institution from 1996 through 2011. Eight patients (1.3%) with clinically confirmed pituitary involvement formed the basis of this study. Interventions: None. Measurements: Pituitary function was assessed with hormonal testing, including TSH, free T4, cortisol, ACTH, prolactin, FSH, LH, estradiol, T, IGF-1, and simultaneous serum and urine osmolalities. Results: Secondary hypogonadism and diabetes insipidus were the predominant manifestations of pituitary disease (87.5 and 75% of patients, respectively). All patients had abnormal pituitary imaging. A sellar mass with central cystic change and peripheral enhancement was the commonest imaging finding. Pituitary disease was managed with glucocorticoids in combination with cyclophosphamide or rituximab, achieving disease remission in all but one patient. However, permanent anterior pituitary dysfunction was noted in 63% of the patients. Diabetes insipidus was more often reversible, with resolution in 66.7% of the patients. Conclusions: Pituitary involvement in GPA is rare, but it needs to be recognized to avoid unnecessary biopsies of sellar lesions encountered in the context of GPA, and to minimize the risk of irreversible pituitary function loss by prompt implementation of definitive medical therapy for the vasculitis. (J Clin Endocrinol Metab 99: 3988 –3994, 2014)

G

ranulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, is a systemic disease characterized by pauci-immune, necrotizing, small-vessel vasculitis, and is often associated with positive antineutrophil cytoplasmic antibodies (ANCA) (1–3). Any organ system can potentially be affected, but the disease has a predilection for ear, nose, and throat

(ENT), lungs, and kidneys. Pituitary gland involvement of GPA is rare. The literature describing pituitary involvement in GPA comprises only case reports or small case series of two to three patients, and long-term follow-up of these patients is seldom described. To characterize the clinical presentation, response to therapy, and functional outcomes, we herein review the longitudinal experience

ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2014 by the Endocrine Society Received April 4, 2014. Accepted July 21, 2014. First Published Online July 31, 2014

Abbreviations: ANCA, antineutrophil cytoplasmic antibodies; ENT, ear, nose, and throat; GPA, granulomatosis with polyangiitis; MRI, magnetic resonance imaging.

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with pituitary disease in a large cohort of patients with GPA seen at our medical center.

Table 1. Demographic Features and Other Organ Involvement in Patients with Pituitary Disease Due to GPA

Patients and Methods

Case No.

Age, y

Sex

ENT

Pulmonary

Renal

Other Organ Sites

1 2 3 4 5 6 7 8

67 48 28 55 35 54 68 28

F F F M M M M F

Yes Yes Yes Yes Yes Yes Yes Yes

No Yes Yes Yes No Yes No No

Yes No Yes Yes No Yes No No

None Skin None Skin, joints None Cardiac Joints None

After institutional review board approval, the Mayo Clinic Life Sciences System was utilized to retrospectively identify all patients with pituitary involvement by GPA evaluated at the Mayo Clinic in Rochester, Minnesota, between January 1996 and December 2011. An electronic query tool was used to identify patients with pituitary disease in this cohort by searching the clinical notes for the following terms: pituitary disease, pituitary disorder, pituitary, hypopituitarism, panhypopituitarism, pituitary tumor, pituitary enlargement, pituitary abnormality, or diabetes insipidus. Patients were eligible for our study if they had provided authorization for review of their medical records, were older than 18 years at the time of the search, had a biopsy-proven diagnosis of GPA (at any site), or fulfilled both the American College of Rheumatology criteria for GPA (1) and the Chapel Hill Consensus definition for GPA (4). Medical information was abstracted to characterize pituitary involvement, clinical symptoms, including mode of presentation, organ systems involved, evaluation of anterior and posterior pituitary hormonal function, head imaging results, disease course, and response to therapy. A neuroradiologist on the study team, blinded to the clinical context, individually reviewed the initial and follow-up scans of the patients. Pituitary involvement was based on the presence of characteristic findings on magnetic resonance imaging (MRI), in the presence or absence of pituitary hormonal dysfunction. Secondary hormonal deficiencies were diagnosed based on low levels of the primary hormones with low or inappropriately normal corresponding trophic pituitary hormones. Adrenal insufficiency was diagnosed on the basis of a low morning cortisol (⬍5 ␮g/dL) with low or inappropriately normal ACTH. If the basal cortisol was greater than 10 ␮g/dL, ACTH was not checked. If patients were already on a supraphysiological dose of steroids for the vasculitis at the time of initial evaluation by us, we did not assess their hypothalamic-pituitaryadrenal axis due to its potential suppression by the exogenous steroids. Some patients were already on replacement hormone therapy when referred to us, and their baseline hormonal assessment was not always available. GH deficiency was suspected on the basis of abnormally low IGF-1. None of the patients had dynamic stimulation tests for evaluating GH deficiency. This may have been due to concern regarding risk and lack of reliability associated with such testing in these multisystemically ill patients with an underlying inflammatory disorder. The normal ranges of hormones used for diagnosis of deficiency are mentioned in Supplemental Tables 1 and 2. Diabetes insipidus (DI) was diagnosed based on typical symptoms of polyuria and polydipsia and simultaneous abnormal serum and urine osmolalities (normal, 275–295 and 300 – 800 mOsm/kg, respectively). Water deprivation testing was reviewed when available. Visual field testing results were independently reviewed by a neuro-ophthalmologist on the study team who was blinded to the clinical details.

Abbreviations: F, female; M, male.

Statistical methods Results were primarily descriptive, precluding statistical analysis. Whenever applicable, results were expressed as medians and ranges.

Results Patient characteristics and clinical presentation During the study period, 637 patients with ANCA-associated vasculitides were being followed at our institution. Twenty-five of these patients were initially identified by the search algorithm. However, detailed review of the medical records of these 25 patients revealed that eight patients (1.3%) could be confirmed as having pituitary gland involvement based on characteristic imaging findings and the presence of pituitary dysfunction. Sixteen patients were excluded because they had no identifiable pituitary pathology. Another patient was excluded because the etiology of the pituitary mass could not be determined. The mean age of the patients with confirmed pituitary gland involvement was 48 years (range, 28 – 68 y), with a 1:1 male to female ratio. All patients had histological confirmation of GPA, and all but one tested positive for ANCA reacting with proteinase 3 (normal, ⬍0.4 U). The demographic features of the patients and detailed organ involvement with vasculitis are noted in Table 1. ENT involvement was present in all of the patients, and all of them had headache as one of the presenting features. Most patients had involvement of multiple sites, but two patients (25%) had ENT and pituitary involvement only. Diagnosis of pituitary involvement Pituitary MRIs with follow-up imaging were available for all eight patients. The findings are summarized in Table 2. Six of the eight patients (75%) had the initial head MRI to evaluate DI, whereas the other two (25%) had it for headache and/or sinusitis. The most common imaging

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Table 2. Head MRI Findings in Patients with Pituitary Involvement Due to GPA as Reviewed by a Neuroradiologist Case No. 1 2

3

4

5

6 7

8

Head MRI Findings 11-mm peripherally enhancing cystic sellar mass compressing the stalk Multiple nonenhancing cystic areas in the pituitary, convexity of superior margin of pituitary gland 15-mm sellar mass with large zone of central nonenhancement and peripheral enhancement Stalk preserved on initial imaging, but later displaced posteriorly 10-mm sellar mass with suprasellar extension (outside report; details not available) 15-mm necrotic sellar mass with peripheral enhancement and suprasellar extension Thickening and abnormal enhancement of the stalk Enlarged pituitary measuring 12 mm, with abnormal heterogeneous enhancement Slight diffuse thickening of the stalk 16-mm homogeneously enhancing sellar mass, extending into the cavernous sinus bilaterally Stalk preserved 13-mm sellar mass extending into the suprasellar cistern, with low T2 signal in the periphery and a bright center Peripheral enhancement with central cystic change Thickening of pituitary stalk

finding was a sellar mass with peripheral enhancement and central cystic changes. Stalk compression was noted in five patients (62.5%). Pituitary biopsy was necessary in only one patient. Pituitary MRI findings from two patients are shown in Figure 1, A and B. Hormonal evaluation Pituitary hormonal assessment was done in all the patients. The details of hormonal evaluation for all the pa-

Figure 1. A, Pituitary MRI (coronal view) showing a sellar mass with increased T2 signal changes. B, Pituitary MRI (sagittal view) T1 image showing a sellar mass with central cystic changes.

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tients are available in Supplemental Tables 1 and 2. The most common endocrinopathy in our group was secondary hypogonadism, noted in the first seven of the eight patients (87.5%). Of the three premenopausal women in the series, one was post hysterectomy, and one had irregular menses that ceased completely after cyclophosphamide. Patient 8, the only one without secondary hypogonadism, continued to have normal menstrual cycles. This patient, in fact, went on to have a normal pregnancy subsequently. All four men in the series had laboratory evidence of secondary hypogonadism. One of them had florid symptoms of hypogonadism including decreased libido, loss of muscle mass, fatigue, erectile dysfunction, and decreased testicular size. One had essentially preserved sexual function, and the remaining two did not volunteer any symptoms of hypogonadism. Six patients (75%) had DI; four presented with DI as the initial manifestation of GPA, and another two developed it within 5 and 9 months of diagnosis of GPA. Three of these patients were already on DDAVP at the time of evaluation in our facility, and therefore diagnostic testing for DI was not done. One underwent water deprivation that showed nadir urine osmolality of 92 mOsm/kg, maximum serum osmolality of 304 mOsm/kg, and a projected urine volume of 16 L/d. The remaining two patients were diagnosed on the basis of polydipsia, polyuria, elevated serum osmolality, and depressed urine osmolality. Water deprivation testing was recommended but was not completed by these patients. The presence of DI was accompanied by pituitary stalk thickening on imaging in four of the six patients. Secondary hypothyroidism was identified in four patients (50%). Secondary adrenal insufficiency was noted in one patient (12.5%). Four additional patients were already on highdose glucocorticoids for disease treatment when evaluated at the Mayo Clinic, and their baseline pituitary-adrenal axis was not assessable. IGF-1/GH levels were available in all but one patient, and an abnormally low IGF-1 was found in only one patient, who in fact had panhypopituitarism. Dynamic testing for GH deficiency was not done in any patient. Two patients had panhypopituitarism (cases 2 and 7); one of them had DI, and the other did not. One patient had a mildly elevated prolactin level, and two patients, both of whom had panhypopituitarism, had a low prolactin level. None of the patients reported galactorrhea. Pituitary involvement was noted either at the time of diagnosis of GPA (n ⫽ 4) or within a year (n ⫽ 2) of the diagnosis of GPA in six patients (75%); one of these patients presented with isolated pituitary dysfunction (panhypopituitarism and DI) as the first manifestation of vasculitis and subsequently went on to develop other organ

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manifestations. The remaining two patients had a delayed involvement of the pituitary despite initial response to systemic therapy. The first patient (case 1 in Table 1) presented with a new headache 2 years after the initial diagnosis and had no other signs of disease activity. Head MRI revealed a 1.1-cm sellar mass that progressed despite treatment, prompting a diagnostic excision. Pathology was consistent with granulomatous inflammation. The pituitary mass has not recurred during an 8-year longitudinal follow-up. The second patient (case 7 in Table 1) was noted to have a growing pituitary mass 2 years after initial diagnosis of GPA, despite adequate response to systemic treatment otherwise. Optic chiasm was compromised. Pituitary biopsy was considered but not pursued due to lack of curative potential given the large size of the lesion. The enhancement in the pituitary lesion did, however, improve significantly with intensification of systemic therapy, but its size did not decrease significantly. With the exception of the patients in cases 1 and 7, all other patients had evidence of active disease at other sites when pituitary involvement was diagnosed. Visual field testing was available in five of the eight patients; it was normal in four, and one patient had an initial bitemporal visual field defect that normalized after Table 3.

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6 weeks of aggressive therapy and stayed normal on subsequent follow-ups. Treatment and follow-up All patients with pituitary involvement received remission induction therapy for severe disease consisting of glucocorticoids in combination with either cyclophosphamide or rituximab. Six patients were treated with glucocorticoids and cyclophosphamide, and four of them achieved remission (66.6%). Of the two patients that did not respond to this treatment, one patient (patient 6) was given rituximab, which resulted in disease remission. Two patients (cases 7 and 8) were treated with a combination of glucocorticoids and rituximab for remission induction without a prior trial of cyclophosphamide; both achieved remission that was maintained with periodic rituximab infusions. Improvement in headache was one of the first signs of response to therapy. Mean follow-up duration for all patients was 76 months (range, 18 –132 mo). The systemic disease was noted to be in remission in all the patients at the end of follow-up, albeit with maintenance therapy. The follow-up results are summarized in Table 3. Two patients (25%) had complete resolution of pituitary imaging abnormalities, and three others (37.5%) had

Follow-Up of Pituitary Imaging and Pituitary Hormonal Function

Case No.

Follow-Up Duration, mo

1

120

2

65

3

30 (lost to follow-up)

Pituitary Imaging

Pituitary Function

Systemic Disease

Normalized DI resolved; persistent panhypopituitarism

In remission on maintenance therapy In remission on maintenance therapy

DI and hypogonadism resolved

No evidence of systemic disease on maintenance therapy

Slight increase in prolactin Persistent hypogonadism. DI resolved Normalized

Pituitary biopsy recommended, but patient declined In remission on maintenance therapy

4

128

Changes from sellar surgery: partially empty sella Abnormal: diffuse nonenhancing low T2 signal abnormality throughout the gland Slight increase in size of sellar lesion with stalk displacement upon dose tapering of cyclophosphamide and steroids Size remained stable for 6 mo, then lost to follow-up Normalized

5

132

Sellar mass resolved

DI resolved

6

93

Infundibular thickening decreased, but persistent Normalized

7

20

Persistent panhypopituitarism

8

18

Enhancement of sellar mass significantly decreased, size mildly decreased Decrease in size of sellar mass

Persistent panhypopituitarism and DI

Partial remission of DI

In remission on maintenance therapy Repeated disease flares, necessitating periodic rituximab infusions and highdose steroids In remission, on periodic rituximab infusions In remission, on periodic rituximab infusions

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improvement of imaging abnormalities. The improvement in imaging was noted rather rapidly after institution of therapy, with resolution occurring within months. Patient 1 had diagnostic removal of the sellar mass due to unresponsiveness to the initial medical therapy and did not have recurrence after the surgery. Patient 2 had persistently abnormal imaging and pituitary dysfunction despite remission of systemic disease. She did, however, have resolution of DI. Patient 3 had progressive pituitary enlargement with optic chiasmal compression; biopsy and pituitary decompression were recommended, but not pursued, and the patient was lost to follow-up after 30 months. DI was resolved in four of six patients (67%), improved in one, and was persistent in one patient despite systemic therapy. The resolution of DI did not always coincide with improvement in anterior pituitary dysfunction; two patients had resolution of both the DI and anterior pituitary dysfunction, and the other two had resolution of DI alone with persistent anterior pituitary hormone deficiencies. Also, resolution of DI did not always coincide with improvement in imaging findings; in fact, three of our patients recovered from DI with persistent imaging abnormalities. On the other hand, the one patient with persistent DI had normalization of pituitary imaging during follow-up. The outcome of anterior pituitary dysfunction was less favorable. Secondary hypogonadism persisted in four of seven patients (57%), and secondary hypothyroidism persisted in three of four patients (75%). At the time of the last follow-up, three of seven patients remained glucocorticoid-dependent.

Discussion In this study, we describe the largest case series of pituitary involvement in GPA from a single center, illustrating the variable clinical presentation, treatment response, and functional outcomes. First reported in 1953 (5), pituitary involvement in GPA is rare, with less than 50 patients documented in the English literature to date, representing less than 1% of all GPA cases (6). Neurological complications, mainly in the form of peripheral nervous system involvement, have been reported in 22–54% of the patients with GPA (7). Central nervous system involvement including pachymeningitis and cerebral vasculitis has been reported at rates varying from 7–18% (8). Three different pathogenic mechanisms have been suggested for pituitary involvement in GPA: vasculitis affecting the pituitary vessels, contiguous involvement of the pituitary from granulomatous masses originating in the ENT tract, and/or granulomatous inflammation originating in situ (9).

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The low prevalence of pituitary disease in our patient cohort resonates with the previous reports in the literature. However, it is certainly likely that a greater proportion of patients had subclinical pituitary involvement that was never diagnosed due to the lack of adequate pituitary imaging. A previous review (10) of all cases in the English literature between 1966 and 2006 reported 23 patients with an average age of 38.1 years (range, 13–71 y), with 74% female patients. In contrast, the average age of our patients was 48 years, and there was no sex predilection. Pituitary disease in GPA was suspected on the basis of abnormal neuroimaging and/or symptoms of pituitary hormone deficiencies. Tissue diagnosis from the pituitary was required in only one patient in our series. Histological confirmation of pituitary involvement in patients with GPA is only necessary if other etiologies of a pituitary mass need to be excluded. This is the case when pituitary disease is the only disease manifestation (11), or pituitary disease is unresponsive to immunosuppressive therapy for severe GPA that controls other systemic disease manifestations well. It is important for clinicians to be aware of the potential for pituitary involvement in this disease in order to avoid unnecessary surgery in these patients. Secondary hypogonadism was the most common (87.5%) endocrinopathy in our patients, closely followed by DI (75%). The latter, a result of posterior pituitary dysfunction, is the most commonly reported endocrinopathy in GPA patients in the singular case reports and may very well be the presenting feature of the disease (11–14). It has been described in more than 90% of the patients with pituitary disease, with nearly two-thirds of them having isolated posterior pituitary dysfunction and the remainder having concomitant anterior pituitary hormone deficiencies (10). The high rate of secondary hypogonadism observed in our study may also be the result of alternative pathologies affecting the hypothalamic-pituitarygonad axis, including long-term glucocorticoid use and chronic illness itself. We also cannot exclude that mild DI was not clinically recognized in the two patients that were reported as not having it. Thus, DI may very well have been the most common endocrinopathy in our series as well. As is the case in our series, isolated anterior pituitary dysfunction is less common and is almost always accompanied by DI (12, 15, 16). Isolated anterior pituitary dysfunction was noted in one of our patients (12.5%) and has been previously reported in about 13% of the patients with pituitary dysfunction due to GPA (7). Panhypopituitarism has previously been reported in about 25% of patients with pituitary involvement (11, 12, 17, 18), which again is comparable to our experience. Hyperprolactinemia, due to compression of the pituitary stalk, was seen in one patient but has previously been reported in about half

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of the patients (8, 13, 19 –21). Interestingly, we did not see any association between hyperprolactinemia and the presence of DI, as may have been expected on the basis of pituitary stalk involvement in both the processes. Visual deficits were seen in 40% of our patients, compared to the 17% reported in previous literature (8). As described in our series, when pituitary dysfunction is the presenting feature of GPA, there is, typically, simultaneous evidence of other organ involvement, most commonly ENT (7). However, isolated pituitary dysfunction as a presentation of GPA has been described (11). Pituitary disease more commonly occurs several months or years (varying from 2 mo to 15 y) (10) after the initial diagnosis of the vasculitis (11, 19, 22), sometimes even when the disease is thought to be quiescent systemically (23, 24). It is not clear whether this truly represents isolated pituitary disease vs unreported subtle symptoms in other organ systems. Pituitary disease is often diagnosed based on head imaging pursued to investigate headache, visual symptoms, and/or sinusitis. All the patients in our series had abnormal pituitary imaging, with the most common finding being sellar mass with peripheral enhancement, areas of central necrosis, and stalk thickening. These findings are not specific for pituitary involvement due to GPA, but certainly provide strong circumstantial evidence in the right clinical context. Radiological abnormalities have previously been reported in more than 90% of patients with pituitary involvement due to GPA (10). The ones with normal head imaging had either a normal MRI (25, 26) or a normal head computed tomography that was not followed by a MRI (18, 27). In those with an imaging abnormality, the most common finding was pituitary enlargement, described in as many as 80% of the patients. The pituitary enhancement on MRI varies between a heterogeneous and a homogeneous pattern. As seen in our patients, cystic changes in the pituitary, infundibular thickening with contrast enhancement, and absence of the normal hyperintense signal in the pituitary on T1-weighted images have also been commonly reported (10, 13, 22). These imaging findings in a patient with GPA should raise the suspicion regarding pituitary involvement. In our series, pituitary involvement in GPA was treated with standard remission induction regimens for severe GPA consisting of high-dose glucocorticoids combined with either cyclophosphamide or rituximab. The remission rate of systemic disease with the cyclophosphamidebased regimen was 66.6%, whereas the remission rate in three cases who received rituximab was 100%. In a previous retrospective review of 23 patients with pituitary disease due to GPA reported in the English literature between 1966 and 2006, 65% of the patients were treated with a cyclophosphamide-based regimen, with a relapse

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rate of 27% occurring at a median of 10.5 months (range, 7–36 mo). Induction treatment without cyclophosphamide was associated with a relapse in 50% of the patients at a median of 4.5 months (range, 4 –18 mo) (10). There have been isolated reports of excellent response with highdose glucocorticoids alone (19), but the durability of response would be questionable, and the side effects of longterm treatment would be unacceptable. Our experience seems to be in line with the success rate reported in cumulative case reports on the use of cyclophosphamidebased therapy for pituitary disease in GPA. Rituximab has been shown to be of benefit for treatment of severe GPA refractory to cyclophosphamide therapy, and it has recently been approved for remission induction in severe ANCA-associated vasculitides based on results from a large randomized controlled trial (28 –30). There is not much experience with the use of rituximab in pituitary GPA, but isolated case reports do support its use in refractory disease (15). Our limited experience with it in pituitary GPA presented here seems to be consistent with published reports on this agent in GPA, but further evaluation would be beneficial. Unfortunately, randomized controlled trials are not feasible in this small subset of patients with GPA. It is not clear whether pituitary involvement in GPA portends a worse prognosis of the disease. The fact that pituitary disease can develop despite good control of the vasculitis in other organs (23, 24) suggests the possibility of relative resistance to certain immunosuppressive agents. The patients in our series had a variable recovery of pituitary function with treatment. Despite the high rate of systemic disease remission on maintenance therapy, 62.5% of the patients were left with residual pituitary hormonal deficits. Previous experience has similarly indicated residual deficits in 48% of the patients despite remission of systemic disease (10). Surprisingly, posterior pituitary disease was reversible in 83% of patients affected by DI, as brought out by resolution of symptoms and/or discontinuation of vasopressin therapy. This is in contrast to the previous experience where reversal of neurohypophyseal DI has been considered extremely rare (31). In contrast, anterior pituitary dysfunction appears less likely to be reversible and is therefore perhaps a marker of more advanced pituitary disease. Our experience clearly indicates that pituitary dysfunction may persist despite normalization or improvement in head imaging (12, 15, 23, 27), and that there is a potential for irreversible pituitary damage or subclinical pituitary disease. Conversely, we also observed that pituitary function may improve despite persistent imaging abnormalities. Therefore, follow-up should include both imaging and pituitary function assessment. Also, as was our expe-

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rience, in treatment-responsive cases, there is usually a rapid resolution of pituitary imaging abnormalities, occurring within a few months of treatment (19). We recognize the limitations of a retrospective study design. However, our series of patients with this rare complication of an uncommon, potentially life-threatening disease still provides valuable information to the practicing endocrinologist about the presentation and management challenges of these patients. Conclusion Pituitary involvement can occur in a very small subset of patients with GPA. It typically presents as pituitary hormonal dysfunction and/or abnormal sellar imaging. Pituitary disease is usually accompanied by other organ involvement, most commonly ENT, but on rare occasions can be an isolated finding. It appears to respond well to remission induction therapy for severe GPA, be it cyclophosphamide- or rituximab-based. Rituximab is the preferred agent if the pituitary disease is a presentation of a relapse of GPA or if it occurs or progresses while the patient is on cyclophosphamide. Pituitary hormone deficiencies may persist despite adequate response in systemic disease and resolution of head imaging findings. DI is potentially reversible in a large proportion of these patients.

Acknowledgments Address all correspondence and requests for reprints to: Dr Ekta Kapoor, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail: [email protected]. Disclosure Summary: The authors have nothing to declare.

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Pituitary dysfunction in granulomatosis with polyangiitis: the Mayo Clinic experience.

Pituitary involvement in granulomatosis with polyangiitis (GPA) has been described in case reports. The aim of this study was to describe the clinical...
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