AJR 2004; 182:1560-1562
© American Roentgen Ray Society
Wegener's Granulomatosis Complicated by Central Diabetes Insipidus in a Pediatric Patient
Benjamin M. Muir1,
Rebecca L. Hulett and
Jeffrey G. Zorn
1 All authors: Department of Radiology, The University of Arizona Health
Sciences Center, 1501 N Campbell Ave., PO Box 245067, Tucson, AZ
85724-5067.
Received October 14, 2003;
accepted after revision October 29, 2003.
Address correspondence to R. L. Hulett.
Introduction
Wegener's granulomatosis is a rare vasculitis of unknown cause that is
characterized by focal vasculitis and necrotizing granulomatous lesions
involving the upper and lower respiratory tracts. The kidney is also usually
involved with a focal segmental glomerulonephritis, although there may also be
varying degrees of other histopathologic change. Wegener's granulomatosis was
once a fatal disease, but treatment with chemotherapy and steroids now allows
long-term survival.
Uncommon in adults, Wegener's granulomatosis is especially rare in the
pediatric population. Because of diffuse small-vessel involvement, Wegener's
granulomatosis can have a wide array of clinical manifestations. Neurologic
involvement, although rare at initial presentation, may occur in up to one
third of patients [1].
Pituitary involvement of Wegener's granulomatosis has been described in some
case reports
[2–5].
To our knowledge, ours is the first reported pediatric case of this
disease.
Case Report
An otherwise healthy 13-year-old boy presented to his primary physician
with an ear infection 3 months before his admission and diagnosis of Wegener's
granulomatosis. The infection would not resolve with a variety of antibiotics
and ultimately required drainage of a cyst in the ear. During the same time,
the patient first noted symptoms of polyuria, polydipsia, and weight loss. A
month later, he felt a pain under his left arm. Chest radiography performed at
that time revealed a left upper lobe lung nodule. Purified protein derivative
(tuberculin), blood culture, and coccidioidomycosis serology findings were
negative. Repeated chest radiography was performed a month later and showed an
interval increase in size of the nodule. Again the blood cultures and
coccidioidomycosis serology were negative. Six weeks later, CT of the chest
was performed and indicated another interval increase in size of the left
upper lobe nodule as well as two additional lung nodules; a needle biopsy of
the left upper lobe nodule was attempted unsuccessfully. A month later, bone
scanning was performed to rule out skeletal metastatic disease. The result was
negative.
The patient was admitted a week later for a thorascopic biopsy of one of
the lung nodules and further evaluation of his polyuria and polydipsia. Review
of systems at admission was positive for fatigue, chest pain, cough, and
myalgias. Physical examination revealed dried blood on the nasal turbinates.
Basic laboratory analysis showed a hemoglobin level of 8.4 mg/dL, a hematocrit
of 25.6%, and a urine specific gravity of 1.003. Rheumatologic workup showed
an erythrocyte sedimentation rate of 116 mm/hr, an antineutrophil cytoplasmic
antibody positive to 1:64, and a negative antinuclear antibody. Findings of
lung biopsy were consistent with a diagnosis of Wegener's granulomatosis.
The nephrology and rheumatology teams began treatment with
cyclophosphamide, prednisone, and trimethoprim and sulfamethoxazole (TMP-SMX).
Investigation of the polyuria and polydipsia was performed with a water
deprivation test. The findings were consistent with diabetes insipidus, and
therapy with desmopressin was initiated. The patient had an expected
antidiuretic response to the medication given a diagnosis of diabetes
insipidus. Laboratory analysis for evidence of dysfunction of the anterior
pituitary gland was negative. Unenhanced and constrast-enhanced MRI of the
head, and of the pituitary gland in particular, was ordered to investigate a
pituitary lesion (Fig. 1A,
1B,
1C,
1D,
1E). In view of the patient's
clinical history, the findings were consistent with adeno- and
neurohypophysitis resulting from Wegener's granulomatosis. Findings included
mild diffuse enlargement of the pituitary gland, with a 12-mm height (normal
in pubertal males, 7–8 mm), mild upward convexity, a few foci of
increased T1 signal intensity, more extensive increased T2 signal intensity,
and limited central enhancement with normal peripheral enhancement. MRI
findings were negative for brain or meningeal involvement. The patient
responded relatively well to oral prednisone, TMP-SMX, and desmopressin and to
monthly injections of cyclophosphamide.
View larger version (134K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1A. —13-year-old boy with Wegener's granulomatosis complicated by
diabetes insipidus. Unenhanced T1-weighted sagittal image through pituitary
gland shows diffuse enlargement of gland and pituitary stalk. Some foci of
increased intensity probably represent either blood products or proteinaceous
fluid. Posterior pituitary "bright spot" normally present on T1
image is not seen.
|
|
View larger version (186K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1B. —13-year-old boy with Wegener's granulomatosis complicated by
diabetes insipidus. T2-weighted coronal image through pituitary shows areas of
increased signal intensity that probably reflect edema or ischemia.
|
|
View larger version (99K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1D. —13-year-old boy with Wegener's granulomatosis complicated by
diabetes insipidus. Axial CT images of chest show bilateral cavitary pulmonary
nodules with surrounding inflammatory changes.
|
|
View larger version (116K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1E. —13-year-old boy with Wegener's granulomatosis complicated by
diabetes insipidus. Axial CT images of chest show bilateral cavitary pulmonary
nodules with surrounding inflammatory changes.
|
|
The patient was admitted to the hospital 8 months later for nausea,
vomiting, and headaches, which caused concern about elevated intracranial
pressure, so MRI of the head was performed again. The MRI findings were
negative for elevated intracranial pressure but showed normalization of the
pituitary size and signal. In spite of this radiologic improvement, the
patient continued to require desmopressin for diabetes insipidus at his last
follow-up with this institution, which was approximately 24 months after
diagnosis. Throughout the course of the disease, the patient was free of signs
and symptoms of renal involvement.
Discussion
Although Wegener's granulomatosis is rare in adults, once an adult has the
disease, neurologic involvement is common; no large pediatric case series
exists to establish the incidence in children. In a large series of 324
patients [1], approximately one
third were found to have neurologic complications of Wegener's granulomatosis.
These complications consisted primarily of peripheral nervous system disease,
such as peripheral and cranial neuropathy. Central nervous system disease in
that series was much less common and included ophthalmoplegia, cerebrovascular
accidents, seizures, and cerebritis
[1]. Three mechanisms have been
considered for central nervous system involvement: invasion by nasal or
paranasal granulomas, development of remote granulomas, and cerebral
vasculitis [6].
Central diabetes insipidus resulting from Wegener's granulomatosis is a
rare clinical entity, with only a handful of case reports in the literature.
Furthermore, central diabetes insipidus usually presents after pulmonary or
kidney involvement and is rarely the presenting symptom
[7]. Diabetes insipidus is the
most common manifestation of Wegener's granulomatosis with pituitary disease.
However, a few case reports tell of Wegener's granulomatosis involving the
anterior pituitary gland and resulting in hyperprolactinemia or
panhypopituitarism [3,
5,
7]. Routine screening for
anterior pituitary dysfunction has been recommended in patients with Wegener's
granulomatosis and secondary diabetes insipidus because steroid
immunosuppressive treatment may mask their signs
[3].
MR findings in Wegener's granulomatosis of the pituitary have been
previously described in several case reports. The normal posterior pituitary
has an area of high intensity on T1-weighted images. Regardless of the cause,
nearly all cases of diabetes insipidus lose the posterior pituitary
"bright spot" [8].
Other findings of granulomatous hypophysitis include a thickened pituitary
stalk, a diffusely enlarged gland, and extension of enhancement to the optic
chiasm [4]. Involvement of the
anterior lobe may result in a T1-weighted hyperintensity that is presumably
due to hemorrhagic elements
[5]. Contrast studies may show
a paucity of central enhancement in the anterior pituitary
[5]. These MR findings
previously described by other authors mirror those in our patient. The T1
intense foci in our patient may represent blood or proteinaceous fluid. The
more extensive T2 intense foci may represent edema or ischemia. Our patient
exhibited no evidence of anterior pituitary dysfunction in spite of the
obvious abnormalities on MRI. The two patients reported by Katzman et al.
[5], who had T1-weighted
hyperintensity and decreased central enhancement of the anterior pituitary,
both had laboratory-proven anterior pituitary dysfunction.
Several previous case reports have documented normalization of pituitary MR
findings after patients with Wegener's granulomatosis have undergone
immunosuppressive therapy
[2–4,
7]. In some instances, the
improvement in MR findings mirrored a clinical improvement in diabetes
insipidus [2,
7]. In spite of the improvement
seen on MRI, other patients have had persistent diabetes insipidus
[3,
4].
To our knowledge, ours is the only reported case of Wegener's
granulomatosis complicated by diabetes insipidus in a pediatric patient. Our
case shows the usefulness of MRI in the evaluation of clinically apparent
diabetes insipidus, and it shows how MRI can be used to monitor progress in
the treatment of hypophysitis.
References
- Nishino H, Rubino FA, DeRemee RA, Swanson JW, Parisi JE.
Neurological involvement in Wegener's granulomatosis: an analysis of 324
consecutive patients at the Mayo Clinic. Ann Neurol1993; 33:4
–9[Medline]
- Czarnecki EJ, Spickler EM. MR demonstration of Wegener
granulomatosis of the infundibulum, a cause of diabetes insipidus.
Am J Neuroradiol1995; 16[4 suppl]:968
–970[Abstract]
- Garovic VD, Clarke BL, Chilson TS, Specks U. Diabetes insipidus and
anterior pituitary insufficiency as presenting features of Wegener's
granulomatosis. Am J Kidney Dis2001; 37:E5[Medline]
- Goyal M, Kucharczyk W, Keystone E. Granulomatous hypophysitis due
to Wegener's granulomatosis. Am J Neuroradiol2000; 21:1466
–1469[Abstract/Free Full Text]
- Katzman GL, Langford CA, Sneller MC, Koby M, Patronas NJ. Pituitary
involvement by Wegener's granulomatosis: a report of two cases. Am
J Neuroradiol 1999;20:519
–523[Abstract/Free Full Text]
- Drachman DA. Neurological complications of Wegener's
granulomatosis. Arch Neurol1963; 8:145
–155[Abstract/Free Full Text]
- Miesen WM, Janssens EN, van Bommel EF. Diabetes insipidus as the
presenting symptom of Wegener's granulomatosis. Nephrol Dial
Transplant 1999;14:426
–429[Abstract/Free Full Text]
- Elster AD. Modern imaging of the pituitary.
Radiology1993; 187:1
–14[Free Full Text]
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
Top
Introduction
Case Report
