Pituitary Hyperplasia Secondary to Thyroid Failure: CT Appearance

469
Pituitary Hyperplasia Secondary to Thyroid Failure:
CT Appearance
John L. Floyd ,1 Robert H. Dorwart,2 Mary Jo Nelson,3 Gary L. Mueller,1 and Monique DeVroede 3
Pituitary hyperplasia in response to primary end-organ failure is well established in the medical literature [1-5]. However, the role of radiology in the evaluation of this phenomenon has been explored only recently. To date, descriptions of
radiographic abnormalities associated with this entity have
included plain-film, tomographic , angiographic, and pneumoencephalographic findings [2-6]. Five patients evaluated with
computed tomography (CT) have been reported [7-9]. In
these cases , older-generation scanners and relatively thick
sections were used; thus , scant data were obtained about
the nature of the enhancing masses. We report two patients
with pituitary hyperplasia secondary to primary hypothyroidism in whom direct coronal, enhanced CT scans demonstrated the nature of the enhancing masses initially and on followup.
Case Reports
Case 1
A 37-year-old woman was admitted to the Wilford Hall USAF
Medical Center Thyroid Clinic with a recent history of headaches ,
generalized fatigue , myalgias , scalp hair loss , a 12.3 kg weight gain ,
and galactorrhea. She had been amenorrheic since discontinuing use
of oral contraceptives about 16 months earlier. Physical examination
revealed hypothyroid facies , dry skin, and periorbital edema . Her
visual fields were normal and no gOiter was palpable. Milky fluid was
expressible from both breasts. The return phase of her Achilles reflex
was prolonged .
Initial laboratory testing revealed thyroxine (T4) of less than 1.0 Ilg/
dl (normal , 4.1-11.2) , thyroid-stimulating hormone (TSH) of greater
than 50 IlU/ml (normal , 0-5.2), and serum prolactin of 28.4 ng/ml
(normal , < 25). After administration of thyrotropin-releasing hormone
(TRH) , TSH remained tonically elevated whereas prolactin increased
slightly. An insulin tolerance test showed intact serum cortisol and
growth hormone responses. Radiographs of the sella were normal ,
but direct coronal CT demonstrated a homogeneously enhancing
pituitary mass with its superior margin extending convexly upward
well above the sella (fig. 1A). Replacement therapy was begun with
levothyroxine 200 Ilg daily; 6 weeks later, serum T4 and TSH were
normal. A follow-up CT scan after 9 weeks of therapy showed a
marked decrease in tumor size (fig . 1B). At that time, the patient was
euthyroid , her galactorrhea had resolved , and regular cyclic menses
returned . On reevaluation 28 months after institution of therapy , she
was clinically well , and repeat follow-up CT confirmed continued
reduction in pituitary size (fig. 1C).
Case 2
A prepubertal 14-year-old girl was referred to the National Institutes
of Health Clinical Center for evaluation of short stature (below the
first percentile). Her development milestones were normal, but for the
past several years she had slept with many blankets and had only
week ly bowel movements. Physical examination revealed a deep
voice, slow speech , delayed reflexes , and dry skin. The thyroid gland
was not palpable.
Serum T4 was low (1.4 Ilg/dl) and TSH elevated (820 IlU/ml). ACTH
test showed an adequate cortisol reserve. No antithyroid or antimicrosomal antibodies were identified . Her visual fields and chromosomes were normal. Radionuclide thyroid scanning showed no technetium uptake in the cervical region , but there was uptake at the
base of the tongue consistent with a lingual thyroid . Skull films
showed marked enlargement of the sella turcica with some erosion
of the dorsum sellae (fig . 2A). Coronal CT revealed an enlarged ,
homogeneously enhancing pituitary gland with an upwardly convex
upper margin (fig. 2B). She was treated with levothyroxine ; after 4
months of therapy , she was thinner and had more active reflexes and
regular bowel movements. Her height increased 5 cm . Repeat CT
demonstrated a reduction in size of the pituitary gland (fig . 2C) .
Discussion
The effect of thyroid hormones (T3 and T4), TSH , and TRH
on the pituitary gland is complex , and the interhormonal
relations are not fully understood . It is known that the fall in
T3 and T4 in primary thyroid failure engenders a response
from the hypothalamic-pituitary feedback loop in a futile attempt to stimulate thyroid hormone production . There is an
accelerated delivery of TRH from the hypothalamus through
the infundibulum and an outpouring of TSH from the pituitary
thyrotrophs [10] . In addition to stimulating TSH release , there
is now clinical and experimental in vivo and in vitro evidence
Received February 8. 1983; accepted after revision August 11 . 1983 .
'Department of Radiology/SGHQRD . Wilford Hall USAF Medical Center. Lackland Air Force Base, San Antonio , TX 78236. Address reprint requests to J . L.
Floyd.
2Department of Radiology . Uniformed Services University of the Health Sciences. Bethesda . MD 20014 .
3National lnstitutes of Health . Bethesda. MD 20014.
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FLOYD ET AL.
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Fig. 1. -Case 1. A, Initial direct coronal CT scan. Homogeneously enhancing pituitary mass with suprasellar extension. B, After 9 weeks of. thyroid hormone
replacement therapy. Marked reduction in pituitary mass . C, Coronal reconstruction from thin-section axial CT scan 28 months after Initiation of treatment.
Persistent reduction in size of pituitary mass.
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Fig. 2. -Case 2. A, Lateral radiograph . Marked enlargement of sella turcica and erosion of dorsum sellae. B, Initial direct coronal CT scan. Enlarged ,
homogeneously enhancing pituitary gland. C, After 4 months of thyroid hormone replacement therapy. Marked reduction in size of pituitary gland.
that TRH also accelerates the delivery of prolactin by the
pituitary lactropes (11 , 12]. Galactorrhea and amenorrhea
may fi rst bring the patient to medical attention . This "hormonal
overlap" may possibly involve gonadotropins and growth hormone as well (3] .
The morphologic respon se of the pituitary to hypothyroidism has been studied extensively in mice (1, 13J and in man
(2]. Initially there is degranulation of the thyrotrophs and hyperplasia of the adenohypophysis. The hyperplastic pituitary
at this stage can be successfully transplanted only to thyroidectomized mice; it will not grow in a normal host (13] .
Through transplantation of cell suspensions of hyperplastic
pituitary cells into thigh muscles of succeeding generations
of hypothyroid mice, autonomous tumors have been produced (1]. Whether pituitary hyperplasia secondary to endorgan endocrine failure may undergo transformation to an
autonomously functioning tumor in man is debatable; such a
case has not been documented at this time.
The CT appearance of the adult pituitary has been described (14, 15]. Normally, it is 7-8 mm in maximum height
and is completely confined within the sella ; it is generally
somewhat larger in women. Its upper surface is usually concave downward or flat, but may be convex upward , particularly in adolescent girls , in whom the pituitary also may be
somewhat larger than in adults (16]. The normal pituitary
gland is heterogeneous on CT, contain ing small «3 mm)
lucencies on contrast-enhanced scans ; these areas correspond to "loose" tissue containing cells of decreased or
absent granularity (17J.
The initial appearance of the pituitary was similar in our two
cases. There was upward convexity of the superior margin
of the gland and substantial suprasellar extension . Contrast
enhancement was relatively uniform throughout the gland.
This appearance (a homogeneously enhancing , enlarged pituitary on thin-section coronal CT) and a clinical picture compatible with hypothyroidism suggests pituitary hyperplasia.
Pituitary adenomas are typically heterogeneous, with areas
of low density mixed with areas of enhancement (14 , 15].
Lymphoid adenohypophysitis is a rare autoimmune disorder
that results in pituitary insufficiency and may present as an
enhancing mass and be associated with hypothyroidism (18J.
The CT findings in our patients lend support to previous
reports that pituitary hyperplasia secondary to longstanding
primary thyroid failure can be reversed with oral thyroid
hormone replacement (2, 5, 7-9]. We also describe the CT
appearance of pituitary hyperplasia on thin-section (1.5 mm),
direct coronal, enhanced scans . It is imperative that radiologists be familiar with this phenomenon since proper treatment
is thyroid hormone replacement rather than surgery or radiotherapy .
REFERENCES
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CT OF PITUITARY HYPERPLASIA
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471
Fig . 3 .- A and B. Coronal and sagittal reconstructions at time of initial evaluation. Pituitary is
enlarged . with suprasellar upward bowing of its
superior margin. C and D. After 6 months of thyroid
hormone replacement therapy . Pituitary now has
normal appearance concomitant with patient' s clinical improvement.
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Addendum
Since this article was submitted for publication , we have
seen another patient with similar clinical and radiographic
findings , substantiating the conclusions of the foregoing report:
Case 3
After a normal pregnancy and delivery , a 25-year-old physician
failed to resume normal menses and had perSistent galactorrhea
although she was not breast-feeding . She had been easily fatigued
but attributed this to the demands of her work and the new child .
Endocrinologic evaluation demonstrated no significant physical abnormalities other than galactorrhea. Serum prolactin was elevated
(43 .2 ngjml), thyroid hormone levels were in the hypothyroid range,
and serum TSH was 20 times the normal upper limit for our laboratory .
Thin-section axial CT of the sella with sagittal and coronal reconstruction demonstrated suprasellar upward bowing of the superior margin
of the enlarged pituitary (figs . 3A and 3B) . She was treated with
levothyroxine , 200 p.gjday . Six months after institution of therapy ,
her clinical and laboratory abnormalities had resolved ; repeat CT of
the sella demonstrated a pituitary of normal size and configuration
(figs . 3C and 3D).

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