MENSTRUAL EDEMA WITH INTRACRANIAL

HYPERTENSION (PSEUDOTUMOR CEREBRI)

Report of a Case
E. P E R R Y McCULLAGH, M.D.

Within the past few years considerable interest has arisen in the
occurrence of edema associated with the menstrual period. Such edema
varies from a complaint of "puffiness" which may arouse mild passing
interest of the clinician, to gross visible edema of as much as 14 pounds,
perhaps, associated with severe papilledema and markedly increased
cerebrospinal fluid pressure.
In 1928 Eufinger and Spiegler 1 observed some gain in weight at
the menstrual time in 47 per cent of their subjects. Okey and Stewart 2
found 1 to 3 pounds increase in weight at the menstrual time in 5 of 20
women subjects, and Sweeney 3 reported a gain of 3 pounds or more in
weight, usually premenstrually, in a third of 42 healthy young women
studied. In 1933 Thomas 4 reported 2 cases of massive menstrual edema.
In his first case there was a gain of as much as 12 pounds in weight,
associated with headache, blurred vision and vomiting, and a previous
history of arterial hypertension and albuminuria during pregnancy. In
his second case no significant antecedent illness was noted and kidney
function tests were normal. The menstrual periods were associated with
an increase of as much as 14 pounds in weight, severe headache, "marked
choking of the discs" and "markedly increased" spinal fluid pressure.
In the case reported by Atkinson and Ivy 5 in 1936, there was marked
edema of the feet and legs associated with the menstrual periods. In
their case there was no evidence of abnormal serum protein levels nor
of impaired renal function. Judging from the frequency with which a
similar, although usually milder, picture is seen in clinical practice, this
phenomenon must not be rare.

Premenstrual edema in reported cases has been associated with such

symptoms as a sense of "puffiness", nervousness, emotional instability,
numbness and tingling of the extremities, dizziness, unsteady gait,
blurred vision, diplopia, dulled mental reactions, headache, and vomit-
ing. All symptoms usually are aggravated a week to ten days preceding
the onset of the menstrual flow.
In the title of this report, the term "pseudotumor cerebri" has been
used for the purpose of calling attention to the fact that cases of this
kind may be mistaken for cerebral neoplasms. T h e term "pseudo-
tumor cerebri" is a broad classification, and in general, refers to cases
presenting clinical symptoms and signs of intracranial tumor which,
after complete study, are shown to have none. Such terms as "serous
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 E. PERRY MCCULLAGH, M.D.

meningitis" (Quincke, 18976, Davidoff and Dyke, 1936 7 ), "serous

effusions" (Warrington, 1914 s ), "otitic hydrocephalus" (Symonds,
1931 9 ), and "toxic hydrocephalus" (McAlpine, 193710) have been used
to relate to conditions, some of which may be similar. T h e type of cases
usually included under the term pseudotumor cerebri which are some-
what similar to the case reported here, are those of cerebral edema such
as reported by Sahs and Hyndman 11 . Their cases are more nearly like
some previously called "toxic or otitic" hydrocephalus. Three of their
five cases occurred in children. All had fever, and one had an antecedent
mastoiditis. In these latter respects they differ from such cerebral edema
as is clearly associated with the menstrual cycle. Such cases as those of
Sahs are similar to the ones reported by Gardner 12 in which increased
venous pressure within the skull followed sinus thrombosis. The mech-
anism involved in such cases appears to be different from that present
in the case reported here.

REPORT OF A CASE

T h e patient was referred t o m e b y D r . J. W . S c h o o l n i c of East L i v e r p o o l , O h i o ,

a n d c a m e f o r s t u d y o n F e b r u a r y 16, 1 9 4 0 . S h e w a s a 2 4 y e a r o l d m a r r i e d , w h i t e , w o m a n .
H e r c h i e f c o m p l a i n t s c o n s i s t e d o f h e a d a c h e w h i c h h a d b e e n p r e s e n t f o r five y e a r s a n d
w a s i n c r e a s i n g i n s e v e r i t y ; a n d w i t h i n the p r e c e d i n g t h r e e w e e k s , d i p l o p i a .

T h e h e a d a c h e s w e r e severe, generalized, " p o u n d i n g " h e a d a c h e s associated with a

sense o f n e r v o u s n e s s , faintness a n d m i l d g i d d i n e s s , b u t n o true v e r t i g o . I t w a s e s t a b l i s h e d ,
to o u r c o m p l e t e satisfaction, that they p r e c e d e d a t h y r o i d e c t o m y (to b e described b e l o w )
b y at least t w o y e a r s . H e a d a c h e s o c c u r r e d o n c e o r t w i c e a m o n t h , as a r u l e , a n d v a r i e d
i n d u r a t i o n f r o m o n e d a y t o as l o n g as t h r e e w e e k s . T h e y u s u a l l y a p p e a r e d b e t w e e n t e n
d a y s p r e c e d i n g a n d ten d a y s s u b s e q u e n t to t h e first d a y o f m e n s t r u a l f l o w .

B e g i n n i n g i n D e c e m b e r , 1 9 3 9 , she n o t e d a sense o f pressure i n the h e a d a n d a

" g u s h i n g " noise i n t h e r i g h t s i d e o f t h e head w h i c h seemed to b e synchronous with the
pulse. F o r three weeks before admission she h a d n o t e d s h a d o w s shifting across t h e v i s u a l
field. T h e d i p l o p i a w a s m i l d a n d h a d been continuous except for t w o days during a
three-week period.

I n 1936 she h a d h a d a r i g h t s i d e d p u r u l e n t otitis m e d i a , f o r w h i c h m y r i n g o t o m y w a s

d o n e . C o n t a c t w i t h the p h y s i c i a n w h o a t t e n d e d h e r at that t i m e has e s t a b l i s h e d t h a t
t h e r e w a s n o e v i d e n c e o f l a t e r a l sinus t h r o m b o s i s .

On N o v e m b e r 11, 1 9 3 7 , t h y r o i d e c t o m y w a s p e r f o r m e d e l s e w h e r e f o r s y m p t o m s v e r y
s i m i l a r t o those p r e s e n t o n a d m i s s i o n t o the c l i n i c . H e r s y m p t o m s w e r e n o t r e l i e v e d .
S h o r t l y after this o p e r a t i o n p u f f i n e s s o f the e y e l i d s d e v e l o p e d , a l o n g w i t h p a r e s t h e s i a e
o f the h a n d s , a r e d u c t i o n i n e n e r g y , d r y n e s s o f the skin a n d brittleness o f the nails. I t
h a s a l w a y s b e e n p o s s i b l e t o c o n t r o l these s y m p t o m s b y t a k i n g d e s i c c a t e d t h y r o i d , w h i c h
s h e has u s e d i r r e g u l a r l y s i n c e that t i m e . Basal m e t a b o l i c r a t e d e t e r m i n a t i o n s w e r e n o t
d o n e b e f o r e t h y r o i d e c t o m y . I n A p r i l , 1 9 3 8 , t h e basal m e t a b o l i c r a t e w a s m i n u s 29 p e r
c e n t . S h e h a d t a k e n d e s i c c a t e d t h y r o i d ( L i l l y ) in d o s e s o f 1 ) ^ grains p e r d a y f o l l o w i n g
t h a t finding. T h i s d o s e w a s s u f f i c i e n t to c a u s e a d i s a p p e a r a n c e o f the d r y n e s s o f the skin
a n d nails a n d w a s f o l l o w e d b y loss o f w e i g h t , b u t in spite o f this the h e a d a c h e s a n d r e -
l a t e d s y m p t o m s c o n t i n u e d to b e c o m e m o r e severe. O n J a n u a r y 2 6 , 1 9 4 0 , w h e n t h e h e a d -
a c h e h a d b e e n s e v e r e , t h e b a s a l m e t a b o l i c rate w a s m i n u s 1 p e r c e n t . O n that d a t e
t h y r o i d m e d i c a t i o n w a s s t o p p e d . O n F e b r u a r y 11, the basal m e t a b o l i c r a t e w a s m i n u s
16 p e r c e n t .

T h e p a t i e n t h a d h a d t h e c h i l d h o o d diseases w i t h o u t c o m p l i c a t i o n s , a n d t h r e e
y e a r s p r e v i o u s l y a n o n l y p r e g n a n c y e n d e d in a b o r t i o n . H i s t o r y o f t h e s p e c i a l systems

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204
 E. PERRY MCCULLAGH, M.D.

r e v e a l e d n o t h i n g o f i m p o r t a n c e . T h e m e n a r c h e o c c u r r e d a t the a g e o f l O H years, a n d
the menses h a d always been regular within a few days, o c c u r r i n g a b o u t every twenty-
e i g h t d a y s a n d lasting f r o m five to s e v e n d a y s .
N o history suggestive of allergic reactions c o u l d b e established. A slight elevation
o f t e m p e r a t u r e existed f o r t w o o r t h r e e d a y s f o l l o w i n g e n c e p h a l o g r a p h y , but apart f r o m
t h e h i s t o r y o f otitis m e d i a , n o f e v e r w a s k n o w n to h a v e b e e n p r e s e n t a n d there was n o n e
w h i l e she w a s u n d e r o u r o b s e r v a t i o n . T h e r e w a s n o h i s t o r y s u g g e s t i v e of encephalitis.
P h y s i c a l e x a m i n a t i o n r e v e a l e d a r a t h e r s h o r t , stout, s l i g h t l y p a l e y o u n g w o m a n w h o
was agitated and emotional and w e p t frequently. H e r face looked mildly edematous.
H e r h e i g h t w a s 6 3 M i n c h e s , a n d w e i g h t c l o t h e d 150 p o u n d s . H e r t e m p e r a t u r e w a s
9 9 . 2 ° F . , p u l s e r a t e 84, a n d b l o o d pressure 130 m m . systolic a n d 94 m m . d i a s t o l i c .
T h e skin w a s r a t h e r d r y . T h e p u p i l s w e r e e q u a l , r e g u l a r a n d r e a c t e d n o r m a l l y .
T h e r e w a s 3 d i o p t e r s o f p a p i l l e d e m a b i l a t e r a l l y , a n d p e r i m e t r i c fields s h o w e d b i l a t e r a l
e n l a r g e m e n t of the b l i n d spot. E x t r a - o c u l a r muscle m o v e m e n t s w e r e n o r m a l . T h e oral
h y g i e n e w a s g o o d . T h e r e w a s n o l y m p h a d e n o p a t h y . T h e t h y r o i d e c t o m y scar w a s in
g o o d c o n d i t i o n a n d t h y r o i d tissue w a s p a l p a b l e o n b o t h sides o f the n e c k . N o a b n o r m a l i t y
of the heart, chest, a b d o m e n o r pelvis was noted. N e u r o l o g i c a l e x a m i n a t i o n s h o w e d a
s u g g e s t i o n o f r i g h t f a c i a l w e a k n e s s . D e e p reflexes w e r e h y p e r a c t i v e , b u t e q u a l i n the
a r m s a n d legs; s u p e r f i c i a l r e f l e x e s w e r e n o r m a l a n d n o a b n o r m a l reflexes w e r e f o u n d .
O n F e b r u a r y 19, 1 9 4 0 t h e s p i n a l fluid pressure w a s f o u n d t o b e 4 5 0 m m . o f w a t e r .
A t t h a t t i m e D r . A . T . B u n t s m a d e a v e n t r i c u l o g r a m w h i c h s h o w e d t h e v e n t r i c l e s to
b e n o r m a l in size a n d c o n t o u r . B e c a u s e t h e v e n t r i c u l o g r a m s h o w e d n o c a u s e f o r the
i n c r e a s e d i n t r a c r a n i a l pressure, it w a s d e c i d e d that a n e n c e p h a l o g r a m s h o u l d b e m a d e .
I m m e d i a t e l y f o l l o w i n g the first p r o c e d u r e all o b t a i n a b l e c e r e b r o s p i n a l fluid w a s r e -
m o v e d f r o m the l u m b a r s u b a r a c h n o i d s p a c e , t h e r e b e i n g 7 5 c c . p r e s e n t . T h i s w a s r e -
p l a c e d b y 85 c c . o f air. R o e n t g e n o g r a m s s h o w e d , in a d d i t i o n t o n o r m a l ventricles,
n o r m a l filling o f the basal cisterns a n d c o r t i c a l s u b a r a c h n o i d p a t h w a y s . D u r i n g the
c o u r s e o f s t u d y , l u m b a r p u n c t u r e w a s p e r f o r m e d s e v e n t e e n times. T h e c e r e b r o s p i n a l
fluid w a s a l w a y s u n d e r i n c r e a s e d pressure, b u t it v a r i e d g r e a t l y , as is s h o w n o n the
a c c o m p a n y i n g chart (Fig. 1).
C e r t a i n b l o o d e x a m i n a t i o n s are s h o w n i n T a b l e 1. B l o o d c h e m i s t r y studies w e r e
d o n e o n fasting b l o o d unless o t h e r w i s e stated.
O t h e r l a b o r a t o r y d a t a w e r e as f o l l o w s : U r i n a l y s i s , r e p e a t e d a t i n t e r v a l s o n n i n e
o c c a s i o n s , s h o w e d n o a b n o r m a l i t i e s . T h e s p e c i f i c g r a v i t y w a s f o u n d to b e as h i g h as
1 . 0 2 9 a n d 1 . 0 3 2 o n v a r i o u s o c c a s i o n s . T h e p H r a n g e d f r o m 5.5 to 7 . 5 .
T h e b l o o d v o l u m e w a s n o r m a l o n M a r c h 11, 1 9 4 0 . O n that d a y h e r s p i n a l fluid
pressure w a s also v i r t u a l l y n o r m a l . T h i s test w a s n o t r e p e a t e d w h e n the spinal fluid
p r e s s u r e w a s h i g h . T h e W a s s e r m a n n a n d K a h n tests o f the b l o o d a n d s p i n a l fluid w e r e
n e g a t i v e . T h e h i g h levels o f b l o o d s o d i u m a r e w o r t h y o f c o m m e n t . I n o u r l a b o r a t o r i e s ,
levels o f b l o o d s o d i u m o n n o r m a l i n d i v i d u a l s r a n g e c o m m o n l y as h i g h as 3 6 0 m g . , b u t
levels as h i g h as those f o u n d i n this case a r e n o t o r d i n a r i l y seen.
E s t r o g e n assays w e r e d o n e o n M a r c h 3 a n d 7 o n 2 4 - h o u r s p e c i m e n s o f u r i n e ; the
first c o n t a i n e d b e t w e e n 10 a n d 20, a n d the s e c o n d less t h a n 10 rat units, a c c o r d i n g to
t h e m e t h o d of G u s t a v s o n a n d D ' A m o u r 1 3 .
U r i n a r y a n d r o g e n s w e r e e s t i m a t e d b y the c a p o n method of M c C u l l a g h and
M c L i n 1 4 , a n d w e r e 14 i n t e r n a t i o n a l units o n M a r c h 2.
T h e spinal fluid p r o t e i n o n several o c c a s i o n s v a r i e d b e t w e e n 30 a n d 35 m g . p e r
100 c c . T h e r e w e r e n o cells a n d n o g l o b u l i n . O n e a c h o f t e n o c c a s i o n s the a m o u n t s o f
v a r i o u s e l e c t r o l y t e s in the s p i n a i fluid w e r e d e t e r m i n e d , a n d n o v a r i a t i o n in t h e m w a s
f o u n d w h i c h a p p e a r e d to b e r e l a t e d to t h e shifts in the p a t i e n t ' s w e i g h t , p a p i l l e d e m a
a n d s p i n a l fluid pressure. T h e c a l c i u m v a r i e d f r o m 5.2 to 5.8 m g . p e r c e n t ; the p h o s -
p h o r u s w a s 1.2 t h r o u g h o u t ; t h e c h l o r i d e s w e r e b e t w e e n 6 4 3 a n d 695 m g . p e r 100 c c . o n
all o c c a s i o n s b u t o n e . S o d i u m w a s b e t w e e n 3 7 3 a n d 398 m g . T h i s s h o w e d s o m e t e n d e n c y
t o b e h i g h e r at the t i m e s w h e n the c e r e b r o s p i n a l fluid pressure w a s h i g h , b u t the shift
o f b o t h s o d i u m a n d p o t a s s i u m levels w e r e n o t o f s u f f i c i e n t e x t e n t o r c o n s i s t e n c e to b e
definitely significant. ( T a b l e 2).

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TABLE 1

BLOOD COUNTS AND CHEMISTRY

Date 2/16/40 2/21/40 2/28/40 3/4/40 3/7/40 3/11/40 3/26/40

R e d b l o o d cells 4,400,000 5,140,000

W h i t e b l o o d cells 5,300 6,600

Hemoglobin 84% 91%

Volume 3,816 (26

c c . cells
per K g . )

Sugar 85 m g . (1
hr. p.c.)

Cholesterol 222 m g .

Calcium 10.3 m g . 10.3 m g . 9.8 m g .

4 3 ^ hrs.
p.c.)

Phosphorus 3.2 m g . 4.0 m g .

AY2 hrs.
p.c.)

Chlorides 462 mg. 561 m g .

Sodium 384 m g . 382 mg.

Potassium 17.5 m g . 2 1 . 3 m g .

Proteins 7.9%

Albumin 5.9%

Globulin 2.0%

TABLE 2

S o d i u m a n d P o t a s s i u m L e v e l s o f the C e r e b r o s p i n a l F l u i d

Date Sodium Potassium

mg. /100 cc. mg./100 cc.

F e b r u a r y 28 394 11.0
March 6 387 8.5
14 387 10.2
25 398 10.5
29 398 9.1
April 1 391 8.8
5 10.2
17 373 10.0

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 E. PERRY MCCULLAGH, M.D.

FIGURE 2: April 2, 1940, showing the facial edema present. The hair had been cut in
preparation for surgery. Photograph taken (luring a menstrual period.

T h e hospital stay lasted until A p r i l 18, 1940, a p e r i o d o f 63 days. T h r o u g h o u t most

o f this time it was necessary f r e q u e n t l y to use aspirin, p h e n a c e t i n e a n d c o d e i n e f o r
h e a d a c h e . O c c a s i o n a l l y m o r p h i n e or P a n t a p o n were necessary for pain, a n d barbiturates
f r e q u e n t l y were prescribed as h y p n o t i c s .
T h e course of s o m e of the i m p o r t a n t factors in this case as they c h a n g e d d u r i n g her
hospital stay are presented g r a p h i c a l l y in the a c c o m p a n y i n g chart (Fig. 1).
T h y r o i d m e d i c a t i o n was w i t h h e l d until M a r c h 28. It should b e n o t e d that the
s y m p t o m s had increased steadily previous to her admission and were severe u p to
J a n u a r y 26, w h e n the basal m e t a b o l i c rate was minus 1 per cent. Subsequently, f o l l o w i n g
the menstrual p e r i o d in F e b r u a r y there was a striking fall in spinal fluid pressure, d u r i n g
w h i c h time n o desiccated thyroid was b e i n g given. T h e s e facts, together with the c o n -
sideration that the s y m p t o m s p r e c e d e d t h y r o i d e c t o m y , m a k e it a p p e a r most unlikely
that the subsequent fall in intracranial pressure was d u e to thyroid m e d i c a t i o n .
D e s i c c a t e d thyroid was b e g u n in doses of 2 grains per d a y o n M a r c h 28, 1940 a n d has
been continued.

D u r i n g the hospital stay, an a t t e m p t was m a d e to c o n t r o l the intake of certain

electrolytes and w a t e r . T h e f o o d was w e i g h e d to the f r a c t i o n o f a g r a m a n d the e l e c t r o -
lyte c o n t e n t was c a l c u l a t e d . T h i s was difficult in itself a l t h o u g h s o m e degree of success
was attained. It was clearly r e c o g n i z e d that the level o f s o d i u m and chlorides still r e -
m a i n e d too high to b e e x p e c t e d to cause diuresis in itself. T h e water intake, h o w e v e r , was

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FIGURE 3 : A u g u s t 18, 1941. P h o t o g r a p h taken during a menstrual p e r i o d .

i n c o n s t a n t , the p a t i e n t b e h a v i n g f o r m o s t o f the t i m e v e r y u n l i k e a g u i n e a p i g a n d m u c h
m o r e like a h u m a n f e m a l e . T h e u r i n a r y o u t p u t w a s m e a s u r e d as a c c u r a t e l y as p o s s i b l e ,
b u t s h o w e d n o c l e a r c o r r e l a t i o n to the rise a n d fall o f spinal fluid pressure a n d b o d y
w e i g h t . T h e l o w e s t u r i n a r y v o l u m e s w e r e 6 0 0 to 9 0 0 c c . M a r c h 2 t o 7, w h e r e a s a m o u n t s
of 2000 were f o u n d o n M a r c h 22 and 24; 1900 o n April 1; and 2100 a n d 2000 on April 5
a n d 6 respectively.

W h e n the p o t a s s i u m i n t a k e w a s first i n c r e a s e d , as s h o w n o n t h e c h a r t , it w a s s u s -
p e c t e d that this m i g h t b e c a p a b l e o f m a i n t a i n i n g the l o w levels o f spinal fluid pressure
w h i c h w e r e o b s e r v e d o r of d e p r e s s i n g t h e m f u r t h e r . W e a t t e m p t e d to test this b y
c h a n g i n g to a l o w p o t a s s i u m , h i g h s o d i u m intake, b u t n o s i g n i f i c a n t e f f e c t w a s seen.
F o l l o w i n g this the p o t a s s i u m w a s a g a i n i n c r e a s e d to h i g h levels b y a d d i n g p o t a s s i u m
c h l o r i d e . It w a s a p p a r e n t that this t o o h a d little e f f e c t f o r the s p i n a l fluid pressures r o s e
d u r i n g its a d m i n i s t r a t i o n to the v e r y h i g h levels s h o w n . O n M a r c h 31 after p r e o p e r a t i v e
o r d e r s h a d b e e n w r i t t e n a n d s u b t e m p o r a l d e c o m p r e s s i o n s e e m e d i m m i n e n t , it w a s
u r g e d that o b s e r v a t i o n b e e x t e n d e d b e y o n d o n e m o r e m e n s t r u a l p e r i o d . W e t h e n
w o n d e r e d w h e t h e r the c h l o r i d e i o n m i g h t b e the i m p o r t a n t o n e , o r w h e t h e r the shift
w a s d u e to o t h e r f a c t o r s a s s o c i a t e d w i t h the menses. T h e s a m e d o s e o f p o t a s s i u m c h l o r i d e
w a s t h e r e f o r e m a i n t a i n e d until t h e m e n s t r u a l flow b e g a n a n d d u r i n g the t i m e it w a s
b e i n g g i v e n there w a s a striking fall in spinal fluid pressure a n d in b o d y w e i g h t , a m o u n t -
i n g t o ten p o u n d s in e i g h t d a y s . O n A p r i l 17 the p o t a s s i u m c h l o r i d e w a s d i s c o n t i n u e d
a n d p o t a s s i u m nitrate in doses o f 8 g r a m s p e r d a y w a s s u b s t i t u t e d . T h e spinal fluid
p r e s s u r e h a d a l r e a d y fallen f r o m 6 1 0 m m . to 3 0 0 m m . o f w a t e r .

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 E. PERRY MCCULLAGH, M.D.

O n A p r i l 9, 1940, A . P. L . ( A y e r s t ) w a s b e g u n o n the basis o f i m p r o v e m e n t r e -

p o r t e d i n T h o m a s ' 4 case m e n t i o n e d a b o v e . I f a n y m e d i c a t i o n c a n b e said t o h a v e i n -
fluenced t h e c o u r s e o f this disease, it w a s A . P . L . I t w a s c o n t i n u e d f r o m that t i m e u n t i l
J u n e , 1 9 4 1 , as s h o w n b e l o w . F o r m o s t o f the t i m e it w a s u s e d i n c o n j u n c t i o n w i t h a l o w
s o d i u m d i e t , d e s i c c a t e d t h y r o i d in doses o f 2 g r a i n s d a i l y ; p o t a s s i u m n i t r a t e , 6 to 8 g r a m s
p e r d a y w a s c o n t i n u e d f o r m a n y m o n t h s . W h e n t h e p o t a s s i u m n i t r a t e w a s first d i s c o n -
t i n u e d in J u n e , 1940, the s y m p t o m s r e c u r r e d , A . P. L . h a v i n g b e e n r e d u c e d at the s a m e
t i m e . L a t e r , it w a s a p p a r e n t t h a t the s y m p t o m s w e r e v e r y w e l l c o n t r o l l e d w i t h o u t the
use o f p o t a s s i u m nitrate, p r o v i d e d a d e q u a t e doses o f A . P . L . w e r e g i v e n .

A.P.L. Daily Potassium nitrate

Date in international orally in grams Progress
units per day

4/9/40 600
4/17 6.0
4/23 500 8.0
5/2 Menses began
5/3 Papilledema, 1 to 2 diopters
5/13 500 8.0 D i s c s h a z y . S p i n a l fluid pressure 2 3 0 m m .
6/3 500 8.0
6/4 8.0 Menses began
6/6 250 Discontinued O p t i c fundi normal
6/15 H e a d a c h e s r e c u r r e d a n d b e c o m i n g se-
vere. Face puffy.
7/3 500 8.0 Menses. Visible edema
8/1 Discontinued 8.0 Fundi marginal blurring. Menses. N o
e d e m a . R e m a i n e d w e l l u n t i l m e n s e s in
September, when edema and headache
recurred.
9/26 250 Discontinued Fundi normal
alternate days
10/- 250
daily begun Discontinued E d e m a a n d h e a d a c h e 10 d a y s p r e -
menstrual.
11/8 250 Discontinued Menstrual period symptom-free
250 Discontinued M e n s e s r e m a i n e d r e l a t i v e l y free o f e d e m a ,
h e a d a c h e a n d n o visual b l u r r i n g r e -
curred.
6 / 9 / 4 1 250 discontinued.
Stilbestrol, mg.
per day begun
9 / 1 8 / 4 1 A . P . L . u s e d f o r 10 Symptoms minimal. Fundi oculi normal.
d a y s in J u l y . N o n e B y this d a t e the p a t i e n t ' s w e i g h t h a d
since. N o p o t a s s i u m f a l l e n g r a d u a l l y to 129 p o u n d s .
n i t r a t e . Stilbestrol
orally, y 2 m g . 5
days preceding and
succeeding menses.

TREATMENT AND SUBSEQUENT COURSE

D e s i c c a t e d t h y r o i d , 2 g r a i n s p e r d a y , a n d a l o w s o d i u m d i e t a n d fluids l i m i t e d to
a p p r o x i m a t e l y 1200 cc. per d a y have b e e n c o n t i n u e d throughout. A placental extract
c o n t a i n i n g estriol g l u c u r o n i d e ( E m m e n i n ) w a s u s e d o r a l l y in d o s e s o f 1 d r a m f o u r t i m e s
d a i l y f o r t w o m o n t h s f o l l o w i n g S e p t e m b e r 26, 1 9 4 0 , a n d n o i m p r o v e m e n t c o u l d b e s e e n
t o f o l l o w it.

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 MENSTRUAL EDEMA

O n S e p t e m b e r 30, 1941 the p a t i e n t w a s seen a g a i n . S h e h a d c o n t i n u e d the use o f

stilbestrol as o u t l i n e d above but h a d f o l l o w e d n o o t h e r t h e r a p y . W i t h i n the past
m o n t h h e a d a c h e s h a v e i n c r e a s e d , a n d v i s i b l e e d e m a r e c u r r e d w i t h the last m e n s t r u a l
p e r i o d . H e r o p t i c discs s h o w e d n o e v i d e n c e o f pressure a n d h e r u r e a c l e a r a n c e test
s h o w e d 9 0 a n d 83 p e r c e n t c l e a r a n c e i n e a c h o f t w o h o u r s , the b l o o d u r e a b e i n g 33 m g .
per cent.

COMMENT

T h e mechanism involved in the production of menstrual edema is

not clearly understood. Rccent studies in hormonal metabolism do
afford some insight, however, into the process. The many points of
interest cannot be discussed here, but a few of the salient ones may be
recalled. T h e chief consideration is the fact that many of the steroid
hormones have the power to cause retention of sodium, chloride, other
electrolytes and water in the body. The adrenal cortical hormone
desoxycorticosterone has a very powerful effect in this regard and no
physician who has watched critically the effect of this hormone on the
fall in hematocrit level and the rise in body weight of patients with
Addison's disease could fail to be impressed. So great is this power that
this hormone, if used in excessive amounts, may cause pulmonary edema
and death. Thorn 13 has shown that the same type of action exists for
estrone, estradiol, testosterone and progesterone. Such effects for
testosterone propionate have also been shown by Kenyon 16 , and for
testosterone propionate and methyl testosterone by me 17, 18. The fact
that this power is not relegated to the estrogens alone, but to testosterone
and progesterone as well, is interesting to consider here in view of the
fact that both of these substances have been recommended for the
therapy of phenomena similar to menstrual edema. Thorn 19 feels that
the hormones of the adrenals and gonads may, under certain conditions,
" a c t as precipitating factors in the production of edema". Whether a
change in rate of excretion of these substances is a factor of importance
is not certain. Such a mechanism has been suggested by Frank23. Further
discussion as to the mode of action of pregnancy urine extract in cases
of this kind would at present be more philosophical than scientific.

Various forms of treatment have been suggested. In Thomas' 4 ease,

calcium lactate and calcium gluconate were helpful and pregnancy
urine extract produced spectacular improvement. In the case of Atkinson
and Ivy 5 , desiccated thyroid, ammonium nitrate, potassium chloride,
calcium gluconate and viosterol failed. G o o d results were obtained at
first with pregnancy urine extract, but these could not be repeated.
Finally, a good result was obtained with an estrogenic placental extract
(Emmenin) which contains estriol glucuronide. Thorn 19 recommends
absolute restriction of sodium chloride in the diet for seven to ten days
preceding the onset of menstruation, plus 10 cc. of a 20 per cent solution
of potassium citrate in fruit juice two or three times daily.
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 E. PERRY MCCULLAGH, M.D.

Frank20 reported good results in overcoming premenstrual tension

with the use of magnesium sulfate by mouth, and recommended roent-
gen ray castration. In one case of severe premenstrual tension with
neurologic signs, we prescribed roentgen therapy to the ovaries, with
good results.
Hormones have been used for their antagonistic effect on estrogens
and good results have been reported by Israel21 following the pre-
menstrual administration of progesterone, and Greenblatt 22 has used
testosterone propionate successfully for the same purpose. Whether
these later affect premenstrual molimina by virtue of hormonal action
not dependent upon electrolyte response is not clear.
More recently Greenhill and Freed ' 3 ascribed premenstrual distress
to retention of water in the tissues, and report excellent results following
the qualitative restriction of sodium chloride, plus the oral administra-
tion of 1.0 gm. of ammonium chloride three times per day. In some of
our cases apparently similar to the one reported above, subtemporal
decompression has been necessary to prevent blindness.
M u c h more experience is needed in the management of menstrual
edema before an accurate evaluation of the various types of therapy can
be made.
SUMMARY AND CONCLUSIONS

Observations are reported on a case of menstrual edema with in-

creased intracranial pressure (pseudotumor cerebri).
Hypothyroidism was a complicating feature, but the use of desiccated
thyroid failed to control the recurrent edema.
Potassium citrate, sodium chloride, potassium chloride, and
Emmenin appeared to influence the course of the disease little, if at all.
Potassium nitrate in doses of 8 grams daily may have been of some value.
A. P. L. (Ayerst), a pregnancy urine extract, in large doses appears
to have had a distinct influence upon the disease.
T o the time of writing, the patient remains almost completely
symptom-free, but there are evidences of mild exacerbations.

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