by Brooke Swearingen, M.D.
NEPTCC Newsletter Volume 22, Issue 1, Fall 2015 [PDF version]
A 30-year-old nulliparous woman presented to MGH at
34 weeks gestation with headaches and visual loss. She was
referred by her ophthalmologist, who documented a bitemporal
field defect with a dense left central scotoma. The visual
loss was progressive, and had worsened in the week prior to
presentation. She had developed headaches three months prior
to admission. The pregnancy was otherwise uncomplicated.
Menses were normal before her pregnancy, and she had no
history of galactorrhea, polyuria/polydipsia or other endocrine
symptoms. Medical history was notable for a deep venous
thrombosis three years ago, and she was being treated with
low molecular weight heparin during the pregnancy. She had
a history of primary hypothyroidism and had been maintained
on 100 μg of thyroxine daily for the past five years. She was
On exam, she did not appear acromegalic or Cushingoid.
There was a dense left central and superior temporal defect,
and a subtle right superior temporal defect. Acuity was 20/30
on the right and 20/800 on the left.
Endocrine testing revealed a 5am cortisol low at 2.3 ug/
dl, prolactin 33 ng/ml (normal <20), TSH 0.09 uIU/ml (normal
0.4-5.0), T4 7.8 ug/dl (normal 4.5-10.9), free T4 low at 0.7 ng/ml
(normal 0.9-1.8). She was begun on steroid replacement with
hydrocortisone and her thyroxine dose was increased.
A noncontrast (because of the pregnancy) MRI was performed.
This demonstrated a 2.3 cm mass arising from the sella,
extending into the suprasellar cistern, with significant chiasm
compression. There was T1 hyperintensity within the central
portion of the mass suggestive of hemorrhage. (Figure 1)
The presumptive diagnosis was pituitary adenoma with
hemorrhage, perhaps related to her heparin requirement,
leading to visual loss. She was seen by the high risk
obstetrics service and the low molecular weight heparin was discontinued prior to planned surgery. Transsphenoidal
exploration was performed after discontinuation of
anticoagulation. At operation, a densely fibrotic mass
was found and biopsied. The T1 hyperintensity seen on
her preoperative MRI proved to be high-protein fluid
within a Rathke’s cleft cyst. Frozen section pathologic
analysis showed fibrotic anterior pituitary with a dense
inflammatory infiltrate composed predominantly of
lymphocytes, consistent with lymphocytic hypophysitis.
Postoperatively, her vision initially improved to 20/25 on
the right and 20/50 on the left, with a smaller central
scotoma. She was maintained on 20 mg of prednisone
daily. Transient diabetes insipidus developed, which
resolved spontaneously after a few days. At 2.5 weeks
post biopsy, (35.5 weeks gestation), she reported
worsening vision on the left despite steroid treatment,
and return of the resolved visual defect on the right. The
prednisone dose was increased to 60 mg daily. She was
admitted for induction of labor, which was unsuccessful
at 48 hours, and she therefore underwent cesarean
section, with delivery of a healthy boy. Postpartum, a
contrast-enhanced MRI was obtained (Figure 2) which
showed the large densely enhancing sellar mass
with persistent chiasm compression. The high dose
prednisone was continued.
On post delivery day one, her vision had begun to improve,
with acuity improved to 20/30 on the left and 20/20 on the
right, and a smaller scotoma. The prednisone was tapered
to 40 mg daily. By two weeks post delivery, formal neuroophthalmologic
exam documented 20/15 vision bilaterally with
full visual fields. A follow-up MRI was obtained which showed
dramatic shrinkage in the inflammatory mass, without
chiasmal compression. (Figure 3)
The differential diagnosis and management
of pituitary disorders during pregnancy is complex.
Possibilities in this case included a previously unrecognized
nonfunctioning pituitary adenoma, with hemorrhage related
to the anticoagulation, leading to rapid expansion and visual
loss, enlargement of a previously unrecognized macro
prolactinoma, or an inflammatory mass. A prolactinoma was
considered unlikely, given the history of normal menses,
absence of galactorrhea, and minimally elevated prolactin
level on hormone testing, and we suspected hemorrhage into
a previously existing tumor. Given the rapid progression and
severity of presentation, a biopsy and possible resection was
felt to be indicated. Pathology showed a dense inflammatory
infiltrate composed predominantly of CD3 positive
lymphocytes with scattered histiocytes and eosinophils,
consistent with hypophysitis.
Hypophysitis can occur in a number of variants, including
adenohypophysitis or infundibulohypophysitis. It is rare,
with an incidence of one in 9 million person-years. It is most
common in peri-partum women, but has been found in men,
non-pregnant women and the elderly. A number of pathologic subtypes exist including lymphocytic, granulomatous,
xanthomatous and IgG4. A subtype associated with the use
of ipilimumab in the treatment of metastatic melanoma
has been recently described. Symptoms typically include
headaches and visual loss from the enlarging mass,
as well as endocrine symptoms from hypopituitarism.
As an autoimmune disorder, it is often associated with
the presence of anti-pituitary antibodies and other
autoimmune disease. Imaging typically demonstrates
homogeneous enhancement in an enlarged pituitary,
without a focal mass lesion. Indications for therapy vary
with the severity of presentation; classic hypopituitarism
without mass effect can be treated with replacement only.
With symptomatic mass effect, definitive diagnosis and
possible transsphenoidal debulking may be necessary,
followed by immunosuppressive treatment with high-dose
glucocorticoids and/or azathioprine. In our case, there was
initial improvement with high-dose prednisone after biopsy,
but dramatic improvement occurred only after delivery,
with resolution of mass effect and improvement in vision.