Granulomatous hypophysitis: experience with eight surgical cases of a single center

Clinical profile

The cohort included two men and six women with the mean (±SD) age of 36?±?12.1 years
(range 16–57 years) and reported duration of symptoms ranging from 5 to 24 months.
The most common manifestations of these patients were headache, fatigue, polyuria
and menstrual disorders in females. All six female patients presented with either
menstrual disorders or amenorrhea (case 1, 2, 3, 5, 6, 7). One male patient had erectile
dysfunction (ED) (case 4). Seven of eight patients suffered polyuria (except case
6), and the 24 h output of urine was determined to be about nine liters in one patient
(case 1). The preoperative endocrine level in serum revealed that only two patients
(case 5, 6) had normal levels. Two patients suffered bitemporal hemianopsia (case
1 and 2), and other patients were with normal vision. One was accompanied with eosinophilic
granuloma of the skull (case 2). Additionally, prolactin levels were increased in
all other six patients, four of them were noted to have thyroid axis imbalances (case
1, 2, 3, 4), one was noted to be deficient in the gonadotropin axis (case 1) and two
were deficient in the adrenal axis (case 1, 2) (summarized in Table 1).

Table 1. Clinical and endocrine profiles

All eight patients had a sellar mass extending into the suprasellar region that appearing
on long T1, long T2 and contrast enhanced on MRI. The lesion typically demonstrated
marked, homogenous enhancement (except case 1, 2), although heterogeneous (case 2)
and ring-like enhancement (case 1) was also noted. An abnormally thickened pituitary
stalk was noted in all patients, and the mean size of the seller mass in our patients
was 15.3 mm in the longest diameter (summarized in Table 2).

Table 2. Radiological Profile

Treatment and outcome

All eight patients underwent excision of the lesion via transsphenoidal approach,
except one who had a transcranial approach due to an initial diagnosis of hypophysial
abscess (case 1). Intraoperatively, the surgeon found the difficulty in transsphenoidal
resection due to adhesion of lesions and the dura mater. The appearance of lesions
was mostly gray-white and firm, with a moderate vascular supply. There was no obvious
borderline between delineating the lesion from pituitary tissue. Postoperatively,
six patients still manifested with symptomatic hypopituitarism and underwent treatment
of varying duration involving hormonal replacement therapy, with the exception of
one recovery immediately after surgery (case 6). In one patient hypopituitarism remained
permanent (case 1), and long-term hormone replacement was instituted. Headache resolved
in all patients, diabetes insipidus and menstrual disorders improved or resolved entirely
in all symptomatic patients, one still reported amenorrhea (case 5). The patient with
ED preoperatively had not improved (case 4). And the patients with vision impairment
were both improved after surgery. There were no recurrences of hypophysitis at follow
up postoperatively to date (summarized in Tables 3 and 4).

Table 3. Management and Diagnosis

Table 4. Clinical and Endocrine Outcome

Pathologic profile

A histological diagnosis of granulomatous hypophysitis was obtained in all eight patients
who underwent surgery. Microscopic examination revealed preservation of anterior pituitary
acini separated by inflammatory cells infiltrate exclusively composed of lymphocytes
and plasma cells. Characteristic granulomas formed by epithelioid histiocytes and
multinucleated giant cells were also observed. One case was deemed to be associated
with a Rathke’s cleft cyst (case 2) (summarized in Table 3).

Representative cases

Case 1

A 35-year-old female was admitted to our department presenting with headache, polyuria,
fatigue and menstrual abnormalities for five months. Past medical and family history
were unremarkable. Physical examination showed bitemporal hemianopsia. The preoperative
endocrine levels in serum revealed insufficiency of the thyroid, gonadotropin and
adrenal axes, with increased levels of prolactin. The urine volume per 24 h was about
nine liters. A sellar contrast enhancement MRI was performed (Figs. 1, 2 and 3).

Fig. 1. A coronal T1-weighted image (left) revealed a iso/hypo-intense sellar lesion with
a su-prasellar extension. A gadolinium enhanced image (right) demonstrated an enhancing
lesion with a hypointense center

Fig. 2. T1-weighted coronal (left) and sagittal (right) MRI with contrast demonstrated an
intra-sellar and suprasellar mass lesion and thickening of the pituitary stalk with
ring-like enhancement

Fig. 3. Coronal T1-weighted with contrast MRI showed ‘bright spot’ in tuber cinereum of the
hypothalamus

According to semiology, disease history and radiological characteristics, the patient
underwent a craniotomy via subfrontal approach due to the initial diagnosis of hypophysial
abscess. Intraoperatively, a sellar cystic lesion was noted with moderate vascular
supply. Visualization of the lesion revealed yellow fraction pus within the cyst and
milky-white wall (Fig. 4 left). After the lesion was resected, a histological examination revealed necrotizing
granulomas composed of perinecrotic epithelioid histiocytes, lymphocytes and occasional
multinucleate giant cells (Fig. 4 right).

Fig. 4. The image of the lesion at operation (left). The image of histological examination
(right) revealed necrotizing granulomas composed of perinecrotic epithelioid histiocytes,
lymphocytes and occasional multinucleate giant cells

The postoperative MRI showed the lesion was disappeared (Fig. 5). However, the symptoms of polyuria and hypopituitarism were still present. Fortunately,
the patient responded well to a pharmacological dose of hormonal replacement. Dose
reduction resulted in exacerbation of her symptoms after one year. Finally, we decided
to administer long-term hormonal replacement to control her symptoms.

Fig. 5. T1-weighted coronal (left) and sagittal (right) MRI with contrast demonstrated the
sel-lar/suprasellar mass lesion was disappeared 3 months after surgery

Case 2

A 57-year-old female was admitted to our department complaining of polyuria, weight
loss and a menstrual disorder for the past 24 months. Past medical and family history
were unremarkable. The preoperative serum endocrine levels revealed thyroid and adrenal
axis insufficiencies, but increased of levels of prolactin. A sellar contrast enhancement
MRI, regular cerebral MRI and plain brain X ray were performed (Figs. 6, 7 and 8).

Fig. 6. Sagittal T1-weighted (left) and contrast (right): A tumor-like lesion involving the
pitui-tary distinct enhancement up to the suprasellar region. Extension of mass along
a thickened pitui-tary stalk into the hypothalamus

Fig. 7. Coronal T1-weighted (left) and contrast (right): Sellar/suprasellar mass, isointense
T1 and hyper/hypo-intense in T2 to white matter, with mass effect on the undersurface
of the optic chiasm. Mass demonstrates heterogenous enhancement

Fig. 8. Axonal T2 (upleft) and T1 (upright) MR showed the iso/hyper-intensity lesion in the
left parital skull. Advanced cerebral plain X ray (down) confirmed the skull lesion
(yellow circle)

According to semiology, disease history and radiological manifestations, the preoperative
diagnosis of the patient was pituitary adenoma with Rathke’s cleft cyst and an eosinophilic
granuloma of the skull. Transsphenoidal surgery was therefore planned for the intrasellar
lesion and a craniotomy was deemed appropriate for the skull lesion, these two surgeries
were performed under one anesthesia session. Intraoperatively, the surgeon also found
difficulty in resection of the intrasellar lesion due to dural adhesion. Mass visualization
revealed a gray-white color and firm appearance, moderate vascular supply, and a lack
of obvious borderline between the lesion and pituitary tissue. Both intracranial and
skull lesions were completely resected, with a histological examination confirming
the diagnosis (Fig. 9).

Fig. 9. The image of histologic examination and relative MR (upleft). A: Rathke’s cleft cyst; B: show granulomatous hypophysitis of epitheloid macrophages and multinucleated giant
cells. C: Eosinophilic granuloma of the skull. HE stain showing granuloma with epitheloid
macrophages and multinucleated giant cells

The postoperative sellar MRI revealed the lesion as resolved (Fig. 10). Additionally, the symp-toms of polyuria and hypopituitarism state improved. Hormone
replacement dosage was gradually diminished until she received a dose of hormonal
replacement for 1 year. Symptom resolution was reported after surgery.

Fig. 10. T1-weighted sagittal (left) and with contrast (right) MRI demonstrated the sel-lar/suprasellar
mass lesion was disappeared 3 months after surgery