| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
Pediatric Endocrinology and Diabetes Unit, Radiology Department (C.G., M.H.), Hôpital Robert Debré, 75019 Paris, France
Address all correspondence and requests for reprints to: Juliane Leger, M.D., Pediatric Endocrinology and Diabetes Unit, Hôpital Robert Debré, 48 boulevard Sérurier, 75019 Paris, France.
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
In conclusion, the natural history of idiopathic isolated central DI with PST is unpredictable. Although germinoma should always be considered during the first 3 yr of follow-up in patients showing isolated DI with PST requiring repeated investigations every 3–6 months, it remains a less frequent etiology for 15% of the cases.
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Using MRI, isolated PS thickening (PST) has been seen in some cases of idiopathic or secondary DI resulting from infiltrative processes (7, 8, 9, 10, 11, 12). In these patients, although not systematically studied, the size of the anterior pituitary could be normal (9), reduced (11), or enlarged (10), with the possible association of isolated or multiple anterior pituitary hormone deficiency (11, 12, 13). To our knowledge no detailed description has ever been made of a large group of patients with DI and PST, and more importantly, the natural history of this condition has not been established.
The first aim of this study was to examine a large group of children with central DI and isolated PST as identified by MRI to better describe the stalk, but also the morphology and function, of the anterior pituitary in this condition. The second aim was to describe the natural course of the disease and a more accurate etiology, rendered possible by the prolonged follow-up of these cases. The results are used to attempt to predict the etiology of this lesion.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Cerebral MRI was performed either at diagnosis of central DI (n = 13) or from 9 months to 7 yr later (n = 13). Most of these latter patients had undergone computed tomography scan evaluation at DI diagnosis, but no PST had been seen. Three patients (Langerhans histiocytosis n = 1) had shown a normal PS at a previous MRI evaluation performed at the time of DI onset, 2.6 ± 1.5 yr before the first MRI showing PST. Repeated MRI evaluations were performed in 24 of the 26 patients, with a mean of 4 ± 2.5 MRI investigations/subject (range, 1–11 MRI). Patients were submitted to clinical and radiological follow-ups of, respectively, 5.5 ± 3.6 yr (range, 0.3–12.3) and 3.0 ± 2 yr (range, 0.6–8.4). Complete anterior pituitary evaluation was carried out in 24 of the 26 patients.
MRI evaluation
All MRI documents were centralized and analyzed retrospectively by the same neuroradiologist who was not initially aware of the etiological diagnosis. Although the patients were submitted to different protocols (different sequences, spin echo or gradient echo; different slice thickness, ranging from 3–5 mm), the data were still included in the study on the condition that sagittal and coronal nonenhanced T1-weighted images of the hypothalamo-hypophyseal tract were available. For 25 patients, MRI was also performed after gadolinium contrast enhancement, which was noted as present or absent.
Various anatomical structures of the hypothalamo-hypophyseal region were assessed initially and at successive MRI investigations to determine any changes taking place throughout the follow-up period.
Measurements were made using the scales provided on the films (accuracy of measurement, 0.5 mm) or using calipers. The diameter and shape of the PS were evaluated. Although large scale normative MRI data for the PS are not available in children, we considered that the stalk was enlarged when a diameter greater than 2.0 mm was measured in at least one portion (proximal, middle, or distal) of the PS (14, 15). PST was always differentiated from the anterior third ventricle recess (16). Images lacking clear demarcation were designated a mass. Because transverse slices were not available for all children, PS diameter was evaluated from sagittal and coronal slices. The height of the anterior pituitary was measured on the sagittal T1-weighted image, perpendicular to the sella turcica base, and was judged to be normal, small, or enlarged based on previously published normative data for children (17).
Anterior pituitary evaluation
Anterior pituitary evaluation included measurement of stimulated plasma GH levels, cortisol at its morning basal level and during insulin-induced hypoglycemia basal free T4 and TSH, and the stimulatory TRH test.
GH deficiency was defined on the basis of a GH peak of less than 10 ng/mL in two pharmacological tests. TSH deficiency was defined as a plasma T4 level of less than 10 pmol/L and/or abnormal TSH stimulation by TRH (normal values for TSH were, respectively, 0.5–6, 14 ± 7, and <8 mU/L for basal, peak, and 120 min post-TRH administration). ACTH deficiency was diagnosed by plasma cortisol values below 60 ng/mL and/or below 150 ng/mL during insulin-induced hypoglycemia.
Evaluation of the pituitary-gonadal axis was achieved mainly by clinical means. Patients were either prepubertal or considered nondeficient when spontaneous pubertal development occurred. Gonadotropin deficiency was suspected in patients who showed no pubertal development at a normal pubertal age, and this was asserted by measurement of plasma sex steroid levels and FSH-LH after GnRH stimulation or after induced puberty.
The results from the MR scans were then compared with the clinical and endocrinological histories. Results are expressed as the mean ± SD.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
As shown in Table 1
, patients were
subdivided into groups according to the etiology of the disease:
germinoma (n = 4), Langerhans’ histiocytosis (n = 5), or
idiopathic (n = 17) when no evidence of autoimmune, infiltrative,
or infectious disorders was found up to the last evaluation.
|
-fetoprotein were detectable in serum and
cerebrospinal fluid in one case. A diagnosis of Langerhans’ histiocytosis with multisystem disease including skeletal involvement was made an average of 6.4 ± 4.3 yr before (n = 4) and 4.4 yr after (n = 1) the onset of DI. Among the nine patients showing recognized causes of DI and PST, a clear etiology was reported in four patients at the time of diagnosis, all of them showing Langerhans’ histiocytosis.
During the follow-up period, most patients were studied in the absence of any treatment other than desmopressin and substitutive anterior pituitary hormone therapy when necessary.
MRI findings
All 26 patients had lost the hyperintense signal normally
generated by a normal neurohypophysis on MRI T1-weighed images. As
shown in Table 1
, the PS enlargement noted at the first evaluation
varied from 2.2–9.0 mm. The lesion was restricted to the proximal
level of the PS near the median eminence in 10 patients, to the middle
of the PS in 6 patients, and to the distal level for only 2 patients
(Fig. 1). The entire stalk was involved
in 8 patients. A normal, small, or enlarged anterior pituitary gland
was found in, respectively, 12, 8, and 6 patients. The MRI findings at
the final evaluation (n = 24), 3.0 ± 2 yr after the initial
MR presentation, are described in Table 1.
|
and 2, among the 24
patients for whom more than 1 MRI was performed, 8 showed no change in
the image of the stalk or the pituitary. Two of them had histiocytosis,
and the other 6 had idiopathic central DI. As shown in Table 2, a
profound modification of PS size was seen in 16 patients. For 6
patients, the stalk became increasingly enlarged, measuring 6.6 ±
4.5 and 15 ± 11 mm, respectively, at the first and last
evaluations after 1.8 ± 1.6 yr of follow-up. During the same
period, anterior pituitary size was increased in 2 of these 6 cases and
remained stable in the other 4. In addition, the presence of a growing
suprasellar mass with progressively enlarging PS was demonstrated in
these 6 patients. For 4 of them, a suprasellar mass invading the PS and
the floor of the third ventricle was shown to be a germinoma by
surgical biopsy. In 1 case, the intrasellar content was normal at the
first MRI, but was already larger than normal in the 3 other cases. The
etiology of the so-called suprasellar mass of the 2 other patients
(patients 18 and 22) remained unknown at the final clinical evaluations
performed, respectively, 7.8 and 12.3 yr after DI onset (Fig. 2 for patient 18). In these 2 patients,
hypoplasia of the adenohypophysis has been present since the first
evaluation, and the PS lesion has been stable for 6.3 ± 3.2
yr.
|
|
for patient 23); in fact, 1 of these 5
patients exhibited an extremely thin PS (patient 19). In 6 of the same
10 patients, a modification of anterior pituitary height (
1 mm) was
seen after 1.2 ± 0.6 yr of MRI follow-up (with reduced anterior
pituitary size, n = 5; Table 2).
The PST signal characteristics after contrast material administration
also changed over time, as all patients presented enhanced PST at the
first MRI evaluation, but the enhancement was no longer present after
2.9 ± 1.8 yr of follow-up in five patients with idiopathic DI
(Table 1).
Endocrine evaluation
An analysis of anterior pituitary function in 24 of the 26
patients with DI led to their subclassification into 3 groups: group I
patients with isolated central DI (n = 3; all idiopathic), group
II patients with associated GH deficiency (n = 14; germinoma,
n = 1; histiocytosis, n = 3; idiopathic DI, n = 10), and
group III patients with associated multiple hormone deficiencies (GH
deficiency plus abnormality of at least one other anterior pituitary
hormone; n = 7; germinoma, n = 3; histiocytosis, n = 1;
idiopathic DI, n = 3; Table 1).
The presence of suprasellar mass invading the PS was related to multiple hormone deficiency. Enlargement of the anterior pituitary gland was observed in six patients at the time of diagnosis (germinoma, n = 3; Langerhans’ histiocytosis, n = 1; idiopathic, n = 2). Among the four patients in whom germinoma was later demonstrated, three initially showed an enlargement of the intrasellar content. The presence of a normal or small anterior pituitary gland was not clearly related to either clinical histories or laboratory values.
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
DI is relatively common in patients with Langerhans’ histiocytosis, with a reported prevalence of up to 50% of cases (18, 19, 20, 21). It can occur before, concurrently with, or many years after other multisystem manifestations of the disease that lead to the diagnosis of histiocytosis (18). Anterior pituitary dysfunction, less common, is most often manifested by GH deficiency in these patients (22, 23). Some of the clinical features of the disease, such as skin and bone defects, are known to spontaneously fluctuate (24), and in the absence of clinical features, the disease is probably underdiagnosed. The natural history of the hypothalamo-pituitary disease is thought to be triggered by infiltration of the hypothalamo-pituitary region. Increased sensitivity of imaging methods has shown that the normal high intensity signal of the posterior pituitary, associated with a thickened PS, is absent in patients with histiocytosis-associated DI (18, 21, 23, 25, 26). Moreover, although homogeneous enhancement of the normal PS with gadolinium is common (27), these patients demonstrated a pronounced enhancement of the thickened stalk (25, 26). In one of our patients with evidence of systemic involvement of histiocytosis, MRI performed before and after the onset of DI showed the successive loss of the normal high intensity signal followed by the appearance of the thickened PS and its pronounced enhancement. Although progression from partial to complete DI has been reported (18, 28), the recovery of posterior pituitary function is rare (18, 21), and no resolution of PS enlargement has been spontaneously reported in patients with histiocytosis and DI. Nevertheless, thickening of the PS with contrast enhancement was found to regress in some patients after chemotherapeutic treatment (21) or irradiation to the lesion (23). These latter patients had showed massive involvement of the hypothalamo-pituitary region. In this study, we have shown spontaneous reduction of PS enlargement in one patient with Langerhans’ histiocytosis.
Germinoma should be suspected in all patients with DI and PST even when neurological and ophthalmological symptoms are absent. From anatomical findings, the primary site of germinomas in the hypothalamo-neurohypophyseal axis seems to be from the posterior lobe of the pituitary gland to the stalk (29). DI is the initial symptom in the majority of cases, and anterior pituitary dysfunction is frequently associated (30, 31). The course of germinoma is usually dramatic, with the tumor progressing rapidly; within 1.3 yr after PST identification by MRI and within 2.5 yr of the initial DI diagnosis in our patients. These findings reflect those reported previously (12). Thus, MRI plays an important role in the identification of small germinoma.
PST with an identical aspect has also been reported in adult patients with idiopathic DI who do not have and never have had germinoma, Langerhans’ histiocytosis, sarcoidosis, or infectious granuloma. A biopsy performed in some of these patients demonstrated lymphocytic inflammation (9, 10). Some of these cases may be caused by infiltration due to lymphocytic infundibuloneurohypophysitis even if no evidence of organ-specific autoimmunity is found (9). Some patients with idiopathic DI have circulating antibodies to vasopressin neurosecretory cells, which also suggests a possible immunological basis for the disease (32, 33). Although DI was the presenting feature and persisted along with the absence of a hyperintense signal in the neurohypophysis, the PST was seen by repeated MRI studies to sometimes regress spontaneously in our children. PS enlargement has been found to regress in adult patients during follow-up, either spontaneously or after glucocorticoid treatment (9, 10, 34, 35). Biopsy samples revealed chronic inflammation with infiltration of lymphocytes and plasma cells (9, 10). In six of our patients presenting an idiopathic form of DI with PST, a spontaneous decrease in anterior pituitary size was demonstrated. This sequence of events may be compatible with the autoimmune hypothesis of idiopathic DI with lymphocytic infundibuloneurohypophysitis and adenohypophysitis. It would be useful in these cases to perform repeated immune tests for antibodies against vasopressin cells and other organs.
It is interesting to note that some patients with a long MRI follow-up showed a progressive increase in the PST during the first 1.8 ± 1.5 yr of follow-up, with evidence of a mass lesion in two cases, although the adenohypophysis was always hypoplasic. For these children, the etiology is not clear, but germinoma is unlikely, as the DI occurred 7.8 and 12.3 yr before the final evaluation, and the normal course of a germinoma is far more rapid. The possibility of autoimmune disease or other infiltrative process cannot be excluded even in these cases.
A change in contrast enhancement was also observed during MR follow-up studies in five of the children with idiopathic DI and PST. This may have been due to secondary vascular changes, as seen in patients with hypophysitis, who also show a decrease in enhancement (35). It has been suggested that during the acute stage of inflammation, conventional MR images were able to show up anatomical abnormalities, such as pituitary enlargement or thickening of the stalk, but after regression of the disease, the abnormality would only be detectable by the dynamic study showing abnormal enhancement (35).
The use of PS biopsy with its attendant risk should be reduced by careful follow-up MR studies. In a series of nine patients with DI and PST, transphenoidal biopsy of the PST performed in seven of nine patients showed a germinoma (12). In the present study of cases of DI with PST, only 15% of the subjects to date have presented with germinoma. We think that PS biopsy is not to be recommended if the PST is well limited and the lesion less than 7 mm, as patients with isolated idiopathic PST may show spontaneous resolution of the stalk lesion (9, 34, 35). However, the presence of pituitary enlargement associated with anterior pituitary deficiencies should lead to stronger suspicion of germinoma. Repeated cerebral MRI and research of the tumor marker hCG in serum and cerebrospinal fluid (30) should be performed every 3–6 months during the first 3 yr after the onset of DI (frequency depending of the presence of a progressively enlarging PS) to rapidly establish the diagnosis before the development of a larger tumor leading to visual and neurological symptoms. Surgical biopsy should be reserved for those cases in which PS enlargement extends progressively on both sides of the stalk. After 3 yr of follow-up of these idiopathic patients, a malignant process is unlikely, but careful clinical and dynamic MRI evaluation should be performed every year during the next 2 yr and every 2–5 yr thereafter (depending of the importance and the evolutivity of the lesion) as the etiological diagnosis of these child patients remains to be determined in most cases.
In conclusion, the natural history of idiopathic isolated central DI with PST is unpredictable. Recovery of pituitary function has not been seen, and hypothalamo-pituitary MR findings may vary from complete recovery to a persistent mass on the hypothalamo-pituitary axis. Infiltrative disorders such as Langerhans histiocytosis are probably underdiagnosed even after a long course of the disease due to the lack of a reliable marker. Although the presence of germinoma must always be researched during the first 3 yr of follow-up of a child showing isolated DI with PST with repeated investigations every 3–6 months, it must be emphasized that it remains an infrequent etiology, which in this series concerns 15% of the cases.
|
Footnotes |
|---|
con, France); H. Bony-Trifunovic (Amiens, France);
R. Brauner, I. Netchine, and R. Rappaport (Necker, Paris, France); S.
Cabrol and M. C. Raux-Demay (Trousseau, Paris, France); H.
Crosnier (Saint Germain en Laye, France); and V. Sulmont (Reims,
France). 
Received October 22, 1998.
Revised February 12, 1999.
Accepted February 26, 1999.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  S. N. Saleem, A.-H. M. Said, and D. H. Lee Lesions of the Hypothalamus: MR Imaging Diagnostic Features RadioGraphics, July 1, 2007; 27(4): 1087 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Ikema and N Takasu Serial T1-weighted magnetic resonance imaging changes in a patient with central diabetes insipidus, possibly due to lymphocytic infundibuloneurohypophysitis Eur. J. Endocrinol., December 1, 2005; 153(6): 989 - 990. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Maghnie and C. Malattia Timing of Pituitary Stalk Assessment in Langerhans Cell Histiocytosis: "When" Is Sometimes More Important than "What" J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4166 - 4166. [Full Text] [PDF]
|
|
|
|
|
|
M. Maghnie, M. Altobelli, N. di Iorgi, E. Genovese, G. Meloni, M. L. Manca-Bitti, A. Cohen, and S. Bernasconi Idiopathic Central Diabetes Insipidus Is Associated with Abnormal Blood Supply to the Posterior Pituitary Gland Caused by Vascular Impairment of the Inferior Hypophyseal Artery System J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1891 - 1896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Donadieu, M.-A. Rolon, I. Pion, C. Thomas, F. Doz, M. Barkaoui, A. Robert, A. Deville, F. Mazingue, M. David, et al. Incidence of Growth Hormone Deficiency in Pediatric-Onset Langerhans Cell Histiocytosis: Efficacy and Safety of Growth Hormone Treatment J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 604 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. De Bellis, A. Colao, A. Bizzarro, F. Di Salle, C. Coronella, S. Solimeno, A. Vetrano, R. Pivonello, G. Pisano, G. Lombardi, et al. Longitudinal Study of Vasopressin-Cell Antibodies and of Hypothalamic-Pituitary Region on Magnetic Resonance Imaging in Patients with Autoimmune and Idiopathic Complete Central Diabetes Insipidus J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3825 - 3829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Maghnie, G. Cosi, E. Genovese, M. L. Manca-Bitti, A. Cohen, S. Zecca, C. Tinelli, M. Gallucci, S. Bernasconi, B. Boscherini, et al. Central Diabetes Insipidus in Children and Young Adults N. Engl. J. Med., October 5, 2000; 343(14): 998 - 1007. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
