mr imaging of central diabetes insipidus: a pictorial essay

222 Korean J Radiol 2(4), December 2001

MR Imaging of Central DiabetesInsipidus: A Pictorial Essay

Central diabetes insipidus (DI) can be the outcome of a number of diseasesthat affect the hypothalamic-neurohypophyseal axis. The causes of the conditioncan be classified as traumatic, inflammatory, or neoplastic. Traumatic causesinclude postoperative sella or transection of the pituitary stalk, while infectious orinflammatory causes include meningitis, lymphocytic hypophysitis, and granulo-matous inflammations such as sarcoidosis and Wegener’s granulomatosis.Various neoplastic conditions such as germinoma, Langerhans cell histiocytosis,metastasis, leukemic infiltration, lymphoma, teratoma, pituitary adenoma, cranio-pharyngioma, Rathke cleft cyst, hypothalamic glioma, and meningioma are alsocauses of central DI. In affected patients, careful analysis of these MR imagingfeatures and correlation with the clinical manifestations can allow a more specificdiagnosis, which is essential for treatment.

iabetes insipidus (DI) is a clinical syndrome characterized by the excre-tion of copious volumes of dilute urine combined with the persistent in-take of abnormally large quantities of fluid. There are two general forms

of DI: central (vasopressin-deficient) and nephrogenic (vasopressin-resistant). DI ofcentral origin most often results from lesions in the hypothalamic-neurohypophysealaxis. The differential diagnosis of central DI should include the pathologic processes(e.g. traumatic, infectious or inflammatory, and neoplastic) that involve the structuresnormally found in the pituitary gland or contiguous structures. However, idiopathiccentral DI is diagnosed when central DI occurs in the absence of any alteration that isknown to be responsible for DI (1).

MR imaging provides high-resolution images of the pituitary gland, pituitary stalk,and adjacent structures. The modality’s multiplanar capability allows the diagnosis ofvarious diseases that cause central DI, and thus helps guide its treatment.

In this article, we review the pathophysiology of central DI and the MR features ofneurohypophysis, and demonstrate the MR imaging findings of various pathologic con-ditions that cause central DI.

The Pathophysiology of Diabetes Inspidus and the MR Features ofNeurohypophysis

The neurohypophysis is divided into three parts: the posterior lobe, the pituitarystalk (infundibulum), and the median eminence. These structures derive from thedownward outgrowth of diencephalic neuroectoderm and come into contact with theanterior lobe, which develops upward from stomodeal ectoderm. Antidiuretic hor-mone (ADH) and oxytocin are synthesized in the supraoptic and periventricular nuclei

Ji Hoon Shin, MD1

Ho Kyu Lee, MD1

Choong Gon Choi, MD1

Dae Chul Suh, MD1

Chang Jin Kim, MD2

Sung Kwan Hong, MD3

Dong Gyu Na, MD4

Index terms:Diabetes insipidusMagnetic resonance (MR)

Korean J Radiol 2001;2:222-230Received March 28, 2001; accepted after revision July 30, 2001.

Departments of 1Radiology, 2Neurosur-gery, and 3Internal Medicine, AsanMedical Center, University of UlsanCollege of Medicine; Department of4Radiology , Samsung Medical Center,Sungkyunkwan University College ofMedicine

This paper received a Certificate of Meritaward at the 1999 RSNA ScientificAssembly.

Address reprint requests to:Ho Kyu Lee, MD, Department ofRadiology, Asan Medical Center, 388-1Poongnap-dong, Songpa-ku, Seoul 138-736, South Korea.Telephone : (822) 3010-4325Fax: (822) 476-4719e-mail: [email protected]

D

of the hypothalamus, are transported down along the pitu-itary stalk, and released by exocytosis into the posteriorlobe. The functional state of the neural lobe is thus highlydependent upon the integrity of the pituitary stalk and thehypothalamus. Probably the most common causative de-fect in central DI is failure of ADH release in response tonormal physiologic stimuli, caused by lesions involving thehypothalamic-neurohypophyseal axis.

In most healthy individuals, a normal posterior lobe ap-pears hyperintense on T1-weighted MR images, due tophospholipid or secretory granules contained in pituicytes(Fig. 1) (2). In longstanding DI, this high signal intensity ofthe posterior lobe is absent as a result of failure to synthe-size, transport or store neurosecretory granules. After theadministration of contrast material, the pituitary gland andpituitary stalk enhance homogeneously.

Traumatic Lesions

Transection of the Infundibular StalkPost-traumatic central DI can be caused by any type of

head trauma, in particular by motor vehicle accidents.Clinically, severe head trauma may cause anterior pituitaryinsufficiency and/or DI, and when this occurs, it is fre-quently associated with skull fractures and other neurologi-cal abnormalities. While the immediate onset of DI is be-lieved to result from direct injury to the posterior lobe, itsdelayed onset is caused by transection of the stalk, sinceADH stored in the posterior lobe is able to maintain its

function over a period of time (3). In most cases, DI devel-ops a few days after stalk transection and is commonlytransient (Fig. 2). In addition to the absence of the high sig-nal intensity normally seen in the posterior lobe, an ectopicbright spot in the proximal stump of the transected, retract-ed proximal stalk or hypothalamus can occasionally beidentified.

Postoperative SellaAn association between transient DI and postoperative

sella is not uncommon. The reported incidence of this is upto 60%, and it appears to represent selective damage tothe posterior lobe without concurrent damage to the hypo-thalamic neurosecretory nuclei (4). Permanent DI aftertranssphenoidal hypophysectomy has been reported to oc-cur in 0.4 3% of cases (5), and is usually caused by pitu-itary stalk injury. Fortunately, permanent DI is not a par-ticularly disabling deficit because hormone replacement isa satisfactory treatment. MR imaging shows marked struc-tural distortion and an area of high signal intensity in thepituitary fossa, with an associated mass effect on T1-weighted images within two weeks of surgery. This mostlikely represents methemoglobin accumulation due to he-morrhage in the surgical bed, a fairly typical feature of ear-ly postoperative sella (4).

MR Imaging of Central Diabetes Insipidus

Korean J Radiol 2(4), December 2001 223

Fig. 1. Sagittal T1-weighted MR image shows the normal anato-my of the sella turcica and juxtasellar region. The anterior lobe(thick arrow), posterior lobe (open arrow), pituitary stalk (thick ar-rowhead), optic chiasm (open arrowhead), mamillary body (M),and clivus (C) are indicated.

Fig. 2. Transection of the pituitary stalk caused by a fall in a 17-year-old male. The signs and symptoms of DI developed twomonths after trauma. Sagittal T1-weighted MR image (600/15) re-veals diffuse atrophy of the pituitary gland (arrows). The high sig-nal intensity normally seen in the posterior lobe is absent, and thenormal pituitary stalk is not seen. Two foci of high signal intensityanterior and posterior to the pituitary fossa represent the fat mar-row of the sella turcica.

Infectious or Inflammatory Lesions

Tuberculous MeningitisTuberculosis is one of the common infective causes of

central DI. The infiltrative nature of tuberculous meningitiscan result in damage to the hypothalamic-neurohypophy-seal axis leading to central DI (4). MR imaging reveals auniformly thickened pituitary stalk, as seen in other granu-lomatous diseases, and diffuse meningeal enhancement, es-pecially in the basal cistern (Fig. 3).

Epidemic Hemorrhagic FeverKorean hemorrhagic fever, more commonly known in

the Western world as epidemic hemorrhagic fever, is anacute disease caused by viruses belonging to the genusHantavirus (6). It is characterized clinically by fever, circu-latory collapse, hemorrhage, and renal failure. In fatal cas-es, necrosis of the anterior lobe often develops, and theremay be occasional hemorrhage at this location. The even-tual result is atrophic change in the pituitary gland.Depending on the location and stage of the hemorrhageand the severity of the disease, the signal intensity of thehemorrhagic area varies (6). DI is a very uncommon symp-tom in patients with epidemic hemorrhagic fever, though itcan result when atrophic change extends into the pituitarystalk (Fig. 4).

Lymphocytic HypophysitisIn the last few years, a broad spectrum of presentation of

the condition known as lymphocytic hypophysitis has beenestablished. The entity is not confined to the anterior lobebut can involve the posterior lobe and pituitary stalk (7).

Furthermore, both men and women may be affected, andthe condition is thus not necessarily related to pregnancy.According to the anatomical site and severity of the in-flammatory process, lymphocytic hypophysitis may besubclassified as lymphocytic adenohypophysitis, lympho-cytic infundibuloneurohypophysitis, or necrotizing in-fundibulohypophysitis (8). The first and second of theseare distinctly different entities, and are probably caused bydifferent autoimmune processes (9). It has been reportedthat in lymphocytic infundibuloneurohypophysitis, inflam-mation is localized in the nerurohypophyseal system and

Shin et al.


Fig. 4. Epidemic hemorrhagic fever in a 52-year-old man. Sagittalfat-suppressed T1-weighted MR image (600/20) shows diffuse at-rophy of the pituitary gland. The focal high signal intensities ob-served (arrows) suggest hemorrhage in the pituitary gland, whichmay occur in the course of this disease.

Fig. 3. Tuberculous meningitis in a 10-year-old boy with multiple cranial nervepalsy. A, B. Contrast-enhanced axial (A) andcoronal (B) T1-weighted MR images(600/20) depict enhancement of the uni-formly thickened pituitary stalk (arrows)and diffuse leptomeningeal enhance-ment in the basal cistern. Strong en-hancement of the bilateral thickenedthird nerves (arrowheads in A) and se-vere communicating hydrocephalus arenoted. Tuberculous meningitis was con-firmed by cerebrospinal fluid analysis.

A B

forms a mass lesion in the posterior lobe and/or pituitarystalk, whereas MR imaging and histologic studies haveshown that the anterior lobe is spared (9). However, simul-taneous involvement of the anterior adenophysis has beenreported (10), and in this situation, the term ‘lymphocyticinfundibulohypophysitis’ is more appropriate than ‘lym-phocytic infundibuloneurohypophysitis’ (Fig. 5) (10).

Granulomatous InflammationGranulomatous diseases such as sarcoidosis, Wegener’s

granulomatosis and Churg-Strauss syndrome can involvethe hypothalamic-neurohypophyseal axis, and result incentral DI. MR imaging reveals a uniformly thickened pitu-itary stalk, with occasional involvement of the adjacent hy-pothalamus or pituitary gland. The development of neu-rosarcoidosis is primarily leptomeningeal and vascular in

nature and most commonly involves the meninges, cranialnerves, hypothalamus, infundibular stalk and pituitarygland. Wegener’s granulomatosis is a disease characterizedby necrotizing vasculitis and granulomatous inflammationof the upper and lower respiratory tracts, together withglomerulonephritis. DI is a very rare complication, the pre-sumed mechanism of which is thought to be either hypo-thalamic vasculitis or direct granulomatous involvement,or both. Churg-Strauss syndrome, known as allergic granu-lomatosis and angiitis, is characterized by systemic vasculi-tis, extravascular granulomas, and eosinophilia, which oc-cur in patients with bronchial asthma and allergy (11). MRimaging reveals diffuse swelling of the pituitary stalk, adja-cent hypothalamus, and pituitary gland, which enhancesstrongly after the injection of contrast material (Fig. 6), afinding similar to that of other granulomatous diseases.



Fig. 5. Lymphocytic infundibulohy-pophysitis in a 43-year-old man. A. Sagittal T1-weighted MR image(500/25) depicts an isointense masscomprising the hypothalamus, the pitu-itary stalk, and the pituitary gland (ar-rows). The posterior lobe no longershows high signal intensity. B. Contrast-enhanced sagittal T1-weighted MR image (500/25) showsstrong enhancement of the mass (ar-rows). Lymphocytic infundibulohy-pophysitis was pathologically proven.

A B

Fig. 6. Churg-Strauss syndrome in a 38-year-old man.A. Sagittal T1-weighted MR image(600/15) reveals an isointense mass in-volving the hypothalamus, pituitary stalkand pituitary gland (arrows). The posteri-or lobe no longer shows high signal in-tensity. Prominent mucosal thickening ofthe sphenoid sinus is apparent. B. Contrast-enhanced sagittal T1-weighted MR image (600/15) demon-strates strong enhancement of the mass(arrows), and there is a non-enhancingportion. The thickened mucosa of thesphenoid sinus is intensely enhanced,representing sphenoid sinusitis (arrow-heads). Churg-Strauss syndrome waspathologically proven.

A B

Neoplastic Lesions

GerminomaIn Asian countries, germinoma is the most common in-

tracranial tumor accompanied by central DI, especially inchildren. Since the hypothalamic-neurohypophyseal axis isone of the most common sites from which a germinomaoriginates, DI occurs frequently. Because a hypothalamic-pituitary area lesion is too subtle to be detected during theearly stages of suprasellar germinoma, idiopathic centralDI is sometimes diagnosed. In such cases, but where a ger-minoma is still suspected, follow-up MR imaging is there-fore necessary, especially in teenage boys. In typical cases,MR imaging clearly demonstrates a thickened pituitarystalk with or without a lobulated pineal mass (Fig. 7). In

patients with germinoma, the response to chemotherapyand radiotherapy is usually dramatic.

Langerhans Cell Histiocytosis Although isolated Langerhans cell histiocytosis of the

central nervous system is rare, central nervous system in-volvement as part of the systemic process is common. Thisusually takes the form of neuroendocrine disturbances in-volving the hypothalamic-neurohypophyseal axis. The ab-sence of normal high signal intensity of the posterior lobe,associated with a thickened pituitary stalk, although non-specific for Langerhans cell histiocytosis, should, becauseof frequent systemic involvement, prompt further studiessuch as chest radiography, bone scanning, and temporalbone CT (Fig. 8) (12).

Shin et al.


Fig. 7. Germinoma in a 29-year-old man. A. Initial contrast-enhanced sagittal T1-weighted MR image (600/15) depictsmild thickening and homogeneous en-hancement of the pituitary stalk. In addi-tion, small nodular enhancing lesions areseen in the pineal gland outlet of thefourth ventricle (arrows). B. Contrast-enhanced sagittal T1-weighted MR image (480/14) obtainedone year later, without treatment, showsa marked increase in the size and inho-mogeneous enhancement of those le-sions, and also of the pituitary gland (ar-rows). The focal enhancing lesion seenwithin the fourth ventricle appears to becerebrospinal seeding. Germinoma waspathologically proven.

A B

Fig. 8. Langerhans cell histiocytosis in a15-year-old boy. A. Sagittal T1-weighted MR image(600/15) demonstrates a uniformly thick-ened pituitary stalk (arrow). The posteri-or lobe no longer shows high signal in-tensity. B. Contrast-enhanced sagittal T1-weighted MR image (600/15) showsstrong enhancement of the lesion (ar-row). The high signal intensity in thesphenoid sinus presumably representsfat marrow associated with poorpneumatization. Langerhans cell histio-cytosis was pathologically proven.

A B

MetastasisMetastases to the pituitary-hypothalamic axis account for

1% of sellar masses. Breast cancer metastases are mostcommon, followed by those from gastrointestinal carcino-ma (4). About 20% of these metastases to the pituitary-hy-pothalamic axis are diagnosed clinically, with DI as themain presenting symptom (13). DI of a transient naturemay represent metastases to the posterior lobe of the pitu-itary, without significant encroachment on the supraopticand periventricular nuclei of the hypothalamus. At MR, adestructive and inhomogeneously enhancing intrasellarand suprasellar lesion, with involvement of the adjacentstructure, can be observed (Fig. 9).

LeukemiaDI is a rare complication of acute leukemia, despite the

fact that perihypophyseal leukemic infiltrates are found atautopsy in 46% of such patients. In describing the patho-genesis of DI in patients with leukemia, two main histolog-ic findings have been mentioned: diffuse leukemic infil-trates of the neurohypophysis, and thrombosis of the smallvessels in the hypothalamic nuclei and neurohypophysis(14). MR may reveal thickening of the pituitary stalk, withor without adjacent hypothalamic enlargement (14).

LymphomaPrimary lymphoma of the central nervous system is seen

either in immunocompetent patients, or in those with hu-man immunodeficiency virus (HIV) infection or in otherimmunocompromised states. It can cause DI by directly de-stroying hypothalamic ADH-producing neurons or seedingthe third ventricle with lymphomatous cells (15). At MR,



Fig. 9. Metastasis from lung cancer in a41-year-old man. A. Contrast-enhanced sagittal T1-weighted MR image (600/16) depicts themarkedly enhancing thickened medianeminence and pituitary stalk, and lessenhancing posterior lobe (arrows). Theposterior lobe no longer shows high sig-nal intensity, and the normally enhancedanterior lobe (arrowhead) is compressedand displaced anteriorly by the enlargedposterior lobe. B. Contrast-enhanced sagittal T1-weighted MR image (600/23) obtainedtwo months after radiotherapy showsnear disappearance of the lesion. Theclinical symptoms of DI were also muchimproved.

A B

Fig. 10. Primary intraventricular lym-phoma (non-Hodgkin’s lymphoma) in a77-year-old woman. A. Sagittal T1-weighted MR image(600/15) depicts multiple masses in thehypothalamus, floor and posterior wall ofthe third ventricle and septum pellucidum(arrows). The posterior lobe no longershows high signal intensity. B. Contrast-enhanced sagittal T1-weighted MR image (600/15) showsstrong enhancement of the above men-tioned lesions and of the superior portionof the fourth ventricle (arrows), indicatinglymphomatous involvement. Lymphomawas pathologically proven.

A B

an enhancing mass can be seen in the pituitary stalk, hypo-thalamus, thalamus, basal ganglia, or periventricular whitematter (Fig. 10). Lymphomatous spread to the cere-brospinal fluid is, however, rare.

TeratomaIntracranial teratomas are defined as benign tumors

which contain well-differentiated elements derived fromthe three germinal layers and have a predilection for themidline, that is, the pineal region, the third ventricle, andthe infundibulochiasmal region. On rare occasions, in-

tracranial suprasellar teratomas extend into the pituitaryfossa, with enlargement of the sella turcica, thereby result-ing in visual disturbance, DI, and hypopituitarism. At T1-and T2-weighted MR imaging, high signal intensities repre-senting fat components can be seen in sellar and suprasel-lar areas.

Other TumorsPituitary adenoma and craniopharyngioma are less com-

mon causes of central DI. The former usually shows homo-geneous signal intensity, with occasional hemorrhage.

Shin et al.


Fig. 11. Pituitary adenoma in a 42-year-old man. A. Sagittal T1-weighted MR image(600/15) shows marked thickening of thepituitary stalk (arrows). The posteriorlobe, displaced by the lesion, is seen asseveral foci of high signal intensity (ar-rowheads).B. Contrast-enhanced sagittal T1-weighted MR image (600/15) demon-strates homogeneous mild enhancementof the thickened pituitary stalk, which ex-tends into the pituitary fossa and dis-places the normal pituitary gland to theleft side. Due to strong enhancement,the displaced and compressed pituitarygland is seen as multiple foci of high sig-nal intensity (arrows). Although the masswas found to completely encircle the pi-tuitary stalk, at surgery the two wereseparated easily. Pituitary adenoma waspathologically proven.

A B

Fig. 12. Craniopharyngioma in a 34-year-old man. A. Sagittal T1-weighted MR image (600/15) shows a large lobulated mass (arrows) involving the suprasellar area and hypothalamus.The posterior lobe no longer shows high signal intensity. B, C. Contrast-enhanced sagittal (B) and coronal (C) T1-weighted MR images (600/15) show strong enhancement of the solid compo-nent of the tumor (arrows), which also has a smaller cystic component (arrowhead in C). Craniopharyngioma was pathologically proven.

A B C

Rarely, pituitary adenoma can surround and compress thepituitary stalk, resulting in DI (Fig. 11). Several explana-tions have been proposed as to how ectopic pituitary tissuearises. Some have suggested that because the anterior lobeoriginates embryonically from Rathke’s pouch, pituitarycells may be deposited along the route of embryologic de-velopment of the pituitary gland. Such remnants may be-come foci of a pituitary adenoma. A craniopharyngiomaappears as a rather inhomogeneous mass commonly associ-ated with cyst formation (Fig. 12). A Rathke cleft cyst hasnon-enhancing, well-defined walls, and the observed MRsignal intensity, which depends on the intracystic proteinconcentration, varies. Most commonly, a Rathke cleft cystshows a high signal intensity on T1-weighted images andiso- to low signal intensity on T2-weighted images, relativeto gray matter, reflecting a high protein concentration inthe cystic fluid (Fig. 13). Large hypothalamic/chiasmaticgliomas and meningiomas also can cause DI.

SUMMARY

The multiplanar capability of MR imaging plays an im-portant role in the assessment of the hypothalamic-pitu-itary area and in determining the underlying cause of cen-tral DI. Although a wide spectrum of disease processesmay cause central DI, MR imaging, particularly when cou-pled with clinical information, can help provide a morespecific diagnosis.

AcknowledgementsWe are very grateful to Bonnie Hami, M.A., of the De-

partment of Radiology, University Hospitals of Cleveland(U.S.A.), for her editorial assistance.

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Fig. 13. Rathke cleft cyst in a 59-year-old woman. A. Sagittal T1-weighted MR image(600/15) depicts a well-defined, homoge-neous high signal intensity mass (ar-rows) in the sella turcica and extendinginto the suprasellar cistern. B. Axial T2-weighted (3500/99) MR im-age indicates that the mass is isointenserelative to gray matter (arrows), reflectingthe high protein concentration of the cys-tic fluid. A Rathke cleft cyst was patho-logically proven.

A B

Shin et al.


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mr imaging of central diabetes insipidus: a pictorial essay

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