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The effect of castration upon the size of the parathyroid glands and upon the susceptibility to tetania parathyropriva in the albino rat.

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THE E F F E C T OF CASTBATIOW UPON THE STZE OF'
THE PARATHYROID GIAXDS AND UPON THE
SUSCEPTIBILITY TO TETANIA PARATHYROPRIVA I N T H E ALBINO RAT
MILTON D. OVERHOLSER
Department of Anatomy, Den to1 College, New York z:n irsrsity
IKTRODUCTION
I n 1924, 31. M.Hoskins and S. B. Chandler began a series
of parathyroidectomy operations on albino rats. The results
of the operations, as yet unpublished, indicated that before,
during, and for a short period following puberty the albino
rat is markedly susceptible to tetania parathyropriva. Puberty occurs in the rat at about sixty days of age. Their
series included forty-seven operations-twenty-five on rats
from fifty to eighty days of age and the remainder on animals
eighty to one hundred days old. The proportioii of fatal
tetania parathyropriva in the former group was 82 per cent
and in the latter, 45 per cent. On the basis of these results,
it was suggested that a study be made of the effect of castration in the albino rat on the size of the parathyroid glands
and on t,he susceptibility to tctnnia parathyropriva.
In the rat there are only two parathyroid glands. Zuclrerkandl ('03) showed that in this animal oiily the third pharyngeal pouches give rise to parathyroid anlagen. lllore recently,
Rogers ('27) has shoivii that the rat never develops a fourth
pouch--the pouch designated by Znckerkandl as the fourth
being in reality the ultimobranchial body. The two glands
of the rat are very constant in position. They arc embcddecl
either partially or completely in the thyroid lobes near the
dorsolateral border of the superior pole.
30.3
T l J E A X A T O M I C A T . RIECOlZl~, \ - O L
41, KO. :3
I'ARATIIYROIDECTOMY IN ('ASTTIATEI) RATS
305
The results of the present study support tlie belief that
accessory parathyroid t.issne is not common in t.he rat.. This
is, no doubt, due to the fact that there are only two parathyroid a.nlag.cn in t,he rat, while in other species, as pointed out
by Marine ('14), the presence of four separate anlag
Oen enhances the possibilities for abnormal distribution outside the
thyroid area. Those who have found high numbers of accessory parathyroids in the rat ma.y perhaps h a m mistaken for
them somewhat similar-appearing st.rnctures, such as small
isolated sections of serous glands or thymic tissue.
Silvestri ('1.0) report.ed that prcvious removal of the
ova.ries in a.dult guinea-pigs and dogs protec.t.ed t.he anima.ls
from the effec,ts of thyro-paratliyroidcctomy. Massaglia
('11) could not confirm Silvest.ri's work. He found that. previous castmition-about twenty days before thyro-parathyroidectomy in t.hree dogs (one, six, and twelve years old,
respectively)--did not protect the animals from tetany and
death. Also in two female dogs ( t ~ oand seven years old)
removal of t.he ova-ries three to four weeks previous t.0 thyroparathyroidectomy had no amclioratiiig effect on tlie parathyroid-deficie1ic.y symptoms. He concluded that removal of
t.he gonads does not preveiit. tetaiiia parathpropriva. and t.hat
Si.lvestri had not performed complete para.t~hyroidectomyin
his cast.ra.ted animals. ClBret and Glcy ( '11) also report.ed
that previous removal o:f the ovaries i.n adult dogs and rabbits
ha.d no effect. on t.he results of subsequent. thyro-parathyroidectomy.
X o record of the effect of ca?st.ration on the size of the>
parat.liyroid glands has been found in t.hc literature. Gates,
Grant, and Stevens, in a personal communication, state t.liat
castrated ra.bhits subject.cd to nlt.raviolet light do not show
enlargemelit of t'he parathyroid glancls. Grant and Gates
('24) found t1ia.t if normal rabbits were exposed to ult.raviolet.
light an eiilargement of t,hc paratliyroi.ds was abtnincd.
306
MILTON D. OVERHOLSER
M A T E R I A L AKI) ,1TETTIODS
Male albino rats were used in this investigation. They
giwii i-l diet consisting of bread, cracked corn, milk, let,t.uce, and meat.
Ti1 performing pariithyroidectomy in the albino rat, a midvent.ra1 incision mas made in the neck and the thyroid gland
exqmsed. The ope,rat.ion was then continued under gla.sses
which magiiified the field about three times. A parathyroid
gland could usually be seen as a sma.11grayish body partially
c~mbcdtledin the recklish thyroid t,issue along the clorsolateral
border of the superior pole of each lateral lobe. Having been
located, each gland was then grasped with a pair of finepointed forceps and excised by means of iridec.tomy scissors,
t.ogether with the t.hyroid tissue immediately surrounding it.
Wlicii no t r x e of the parathyroid could be seen, we adopted
the pract:ice of removing the t.hyroid lobe on that side, in the
Micf that the parathyroid was completely embedded in the
thyroid tissue and therefore not visible by a superficial inspection. After the ensuing hemorrhage had been controlled
l.)y cott.on pac.ks, the incision was closed with silk threa.d and
washed wit,h 80 per cent alcohol. Infection was not observed
iii any of the cases.
!Phe excised t,issue was then fixed in Boiiiii’s fluid, cut:
scrially at 10 p, stained with hernatoxylin a.nd eosin, and examined microseopica.lly. I f t.wo complet,e parathyroid glands
were not found, the opera,tion was called incomplete and the
animal discarded.
rl’wo methods of sccnring the glands for size determination
~ w r eused. In the first set of experiments dealing with. the
effect. of castration on the size of the parathyroid glands, the
lalt.ei- were obtained by removing from the neck a block of
t.issiie consist.ing of the trachea and esophagus cut. at the
superior a i d inferior levels of t.he thyroid, together with the
fliy.oitl arid immed:ia.tcly adjacent connect,iw tissue mid
muscles. I n the scc,ond set of esperiment,s, the object of
which was to study .not only the effect: of cast,rat.ion on the
size of t.he parat.hyroid, but. also hlie susc.eptibi1it.y of such
WPIY?
307
PARATHYROIDECTOMY I N GASTRATED RATS
castrated animals to tetania parathyropriva, the glands were
obtained by parathyroidectom>-.
The method of determining the relative size of the parathyroid glands was as follows: The neck-region tissue and
the material removed in the parathyroidectomies were embedded in paraffin, cut serially at 10 v, and stained with
hematoxylin and eosin. The outline of every fifth section of
both parathyroid glands of a given individual was then
drawn under an Edinger projection apparatus at a magnification of eighty. The total area of these outline drawings was
determined in square centimeters by means of a planimeter.
TABLE 1
Xurnber of litters and animals used in determinations of the siae of the
parathyroid
60-da~
75-day
90-day
27
. ..
Total
.-
-
18
26
71
I
-..
83
58
67
"8
44
09
34
__
107
39
29
33
In i
~ ..
.
The figure thus obtained was regarded as the area of the
reconstruction and as representing the size of the parathyroid
gland. By dividing the area of the reconstruction by the
body weight of the animal, a figure was obtained which was
designated the index of the reconstruction and represents
the relative size of the parathyroid gland. The probable
errors of the average figures of the area and of the index of
rcconstruction were calculated in each case.
A comparison of the size of the parathyroid between the
castrated and control animals was made at three ages:
1) sixty days, 2 ) serenty-five days, 3) ninety days. The number of litters and animals in each age series is shown in
table 1.
A4snearly as possible, half of the members of each litter
mere castrated and half kept for controls. The body weight
was takcii at the time of castration and the controls w x e also
weighed a t the corresponding time. The animals were agaiii
weighed at the timc when tlic size of the parathproicl was
cletcrmiiieil. The iiicrcase in body weight was thus ascert aiiicd f o r both castrated and control animals.
The effect of the removal of the parathyroid glands was
cornpared bet.\;5.cciicastrated arid coiitrol mimals iii two a p
series : 1) sixty days, 2) ninety days.
A s showi i i i table 2, of the total of 143 animals in wliic*li
tlir operation of parathyroidectomp was performed, only 112
wc~re taken as being completely parathTvroidcctomized. Of
tlie tliirty ;iiiirnals discarded, twcxity-fonr were incomplctel?T.iR1.I.: 2
.\
lilllbr'l' Of
!fltOl.*
1 0 I d 1 f U l l l b r i' Of
tl)li?>la1S l l W d
;lt
~ J ~ l l ~ l ~ / L 1 / ~ ~ I t ~O l~ ~W~l ~~ l~~ Jf Ol l tl .1\ /
1)~iriitliT'i'oidec,tomi~ed,
as s1ion.n by the hist.ologicta1 examiii;it,ioii of the tissue 1-emoveil. Two died from hemorrhage subsequent. to the operation. Thc remaining foiir exhibited 110
sympt.orns ~11.ateverduring ;in average time of sixt,j--three
h , v s at3 er the operation, althongli the t:issue removed in each
('iis~
sho~v-c?dthat t.hc asual t,wo parathyroid g1aIi.d~had 1)ceii
wm+Letelp excised. !l%cse animals were killed, aiid on hist.olugiea1 examination of the iicck region a n accessoi-y parat l i y w i c l glanrl was fonnd in each case. Tn each of t'he four
~ H S C Sthis accessory gIi111d ~ v a slocated in the posit.ion dewrilwd by Hodiins ;mil Clinncller ( 'as),i.e., cephalad l o tBc~
thyroid glaiicl and dorsal to the cartilage of the larynx. 111
oiie of' t.hc cases a small second accessory parathyroid glantl
wts fonnd dcepl5- emheddecl in. the thyroid tissue.
PAn d TI I TR OI DEC TOMY IN CASTKATED RATS
.
309
S f t e r pflrathvroidectomy, the animals were closely observed aiid classified in four groups according’t o the degree
of tetania parathyropriva exhibited by each animal. The
classification was as follows : 1)fata,E fetuwy-anima.ls dying
in marked parathyroid tetany within three days (in one case
five days) after the operation ; 2) SC‘LWY tetmy-animals
surviving marked tetany convulsions occurring within t.lircc
days after parathyroidectomy ; 3) wild tptany-animals showing oiilj- mild intermittent tetany ; 4) T ~ Otetaii?p-mimals in
which tetanp was never observed.
Sixteen of the animals t.hat.did not. die in fatal tetaiiy were
killed a t an average t.ime of thirty-one da.ys after t.he qperat.ion. The remaining lived for varioiis lengths of time a.fter
the operation, the average length of life being given in data
to follow. The completeness of the operation in the animals
that did not die in fatal tet.aiiy was proved by one of t.wo
methods : 1) hist,ological examination of the neck region
for acc.essory parathyroid tissue was shown to be negative :
2) observance of decalcification of the incisor t.eet.h,x7hic.h is
typical of parat,hyroid deficiency in the albino ra t,.
PRESEM”4TTON O F DATA
The e f w f of castrat,ion OH th.e size of the parathyrokl .qln.n.ils
Table 3 gives the average figures olitained for the three age
series on parat,hyroid size.
I n the sixty-clay-age series scvcii of the animals were CRStrated at. forty days of age a,iicl the remaining thirtTT-seven a t
t:weiitr days. The figures of thi.s a.ge series show in a. very
striking and concliisive wa.y that. there is no difference in the
size of the parathyroid glands between the castrated a.nd
control animals. They f izrther show t,hat castrat,ion did riot
affect: t.he normal growth in body weight.
In the seventy-five-day-age series two of t.lie animals were
castrated at forty days of a.ge and t.wo at thirt,y daj-s; t.he
remaining twenty-five were castrated at twenty d a p . It will
he noticed that the average body weight. in both t.he c.astrat.es
310
,MILTOX D, OVERHOLSER
TAELP: 3
Asrruge Jigu.re.7 for the three age series on, purnthyroid sizr
.............
....
C.48TllAT1:S
COXTROLS
........
.......
GO-da.>-' 41
29
75-da.y
34
90-day
. . . . . . .
....
G'rains
~
8q.o n .
i
I 111.2 1209.92 5.0: 1.941&.05
~
~
..........
Rrama
106.3 1299.4k14.2 3.5032.2; j
144.4 /264.6+ 3.9. 1.9082.07 j
39
29
33
~
Sq. cm.
I
110.9 211.626.0 1.YGSf.06
105.5 I305.2-19.9 / 3.402-1.20
14'7.1 298.428.2 2.284-1.12
and controls is m i d i below the normal. This was due to the
season of the pear, as it wa.s during the summer season extending from late Nay to early September that the parathyroids of these aiiimals were obtained, and during the snmmer
months a decrease in body weight is usual. The low average
body weight ca.uses in part, at lea.st., the abnormally high
average iiidices of reconstruc.tion shown for this a.ge series.
There is no difference, however, between castrated and c.ontrol
animals in the average body weight or in the average area
an.d average index of rcconst.ruct.ion of the parathyroid
glands.
I n the ninety-day-age series all of t.he animals were c.ast,rat.ed at twenty days of age. The average body weight in
tlie castrates a i i d controls is practically the same, being 144.4
grams in bhe former and 142.1 grams in the 1a.tter. I n this
series, however, the average size of the para.thyroid as measured both by the a.rea and t.he index of reconstruction is
greater iii tile coiitrols than in the castrates. Table 4 shows
tticsc dif€ei*enceswit.11t,lieir probable. errors.
TABLE 1;
T)iffrrc.nces befrrwii. c+ustrates atid controls in u.seruyr area. and
rrconstructioii. f o r the n,iwrty-dag series
...
f~ltO1'1'
. . .
index of
. .
.\ltlC.\ OW Ill<('ONSTIIT-CT ION
1 sI)l,;s O F If li('0 USTI<1.VT I0 s
Sq. crri.
Controls
(';istra.trs
T)i ffercuce
S 8 . 4 2 8.2
264.6 -1 3.9
33.8 -19.0
. . .
2 2 8 4 zk 0.12
1.908 zk 0.0;
. . . . . .
0.376 2 0.14
311
PARATIIYROI~ECTOMY I N CASTllATED RATS
T h e effect of seaso?) on the size of the parathyroid glands
Although the purpose of this study was not to investigate
the effect of seasoii on the size of the parathyroid, nevertheless it is considered advisable to mention what little data
have been accumulated on this point. No detailed evidence
as t o a seasoiial variatioii in the size of the parathyroid caii
be adduced from the data obtained in this investigation. Such
evidence would require measurement of the size of the parathyroid in a large number of animals during each month of
the ycar. Only summer and winter differences can be considered here.
In the sixty-day-age series there is not a sufficient number
of summer animals in either the castrated o r control group
to permit a mathematical comparison between winter and
summer figures.
The seventy-five-day series is a summer one. The high
index of parathyroid size occurring in this series (table 3)
is, no doubt, largely due to the abnormally low average bod?
weight. At an); rate, this factor precludes the use of this
index in any mathematical comparison. The average actual
size of the parathyroid in this series as represented by the
area of reconstruction caiiiiot, of course, be directly compared
with the other age series, but it map indicate an increase in
parathyroid size due to season.
TARLI.: 5
C o m p w i s o n of cnxvage fig.ures i,t the sutnmev nt1.d winter sire detein&ation.s
the h e t y - d a y series
.
.
-
.
NORMAL AIIX.41.5
. . . . . . . . . . . . .
Snnimrr
19
Urintrr
.
..I
' 14
. . . . .
.
.
.
.
.
\
142.2 1329.4+-15.0'2.446k.17
~
.
.
.
. . . . . . . .
16
142.0 295.6t11.51 2.127t.09
_
... . -.
18
146.F .,237.1
k 5.0 1.71.3-+.00
......
.......
Differonce , 58.5212.71 0.414f.13
'
.................
-'"'142.0 256.42 7.0: i.O642.1!1
,.
......
Differelice
73.0+16.5; 0 . 3 8 2 2 2 8
~
. . . . . . . . . . . . . . . . .
CASTRITLI) AITZIALS
~
. . . . . . .
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
of
~
~
.
.
.
.
.
.
.
.
.
~
-.
.-
312
MILTON 1). OYERHOLSER
Tlic ninety-day series is about equally divided bctwcen
summer and winter material, and a comparison can he made
between summer and winter figures, alt.lioug1i t.lie numlwr of
cases bccomes rather small f o r conclusive mathematical evaluation. The summer group is made up of mat,erial obtained
tliiring the months of Xay, June, and J u l y ; and in the wiiiter
group is placed material secured during t.he months of Oct.ober, November, Janua.ry, and February. Table 5 shows
t2ic figures oht,ained in this comparison. Tt. mill he seei~that
in both normal a i d castra.ted animals the avera.ge area of
i.t~<!oiist.ruc?tioi~
is greater in summer tliaii in wiiit,er. T n t,hc
normal aiiima.1~tlic summer average area of rec.oiistruct.ioii
is 73.0 sq.cm. greater tliaii t.lie winter average (28 per ccnt
increase), with a, probatde error of
3.6.5. This difference
is 4.4 t,imes it.s prohahlc error. In the (xstrated animals tlic
siinirn~raverage area of rc(!oiisti.uc~t~ioii
i s 58.5 sq.cm. grcatci.
tliaii the winter average (24 p e r (rent, increase), with a prohwblo error of -f 1.2.7. This diffcrencc? is 4.6 times its proha1110
cmwr. A H t.o t.he avera.gc index of reconstruction, that of
the siimmer cast.rated a.iiimals is 0.414 greater than that of
i l i c i viiitcr g ~ m i p with
,
R prohahlc error of 2 0.13. This differcncv is t.liree times its probahlc c n o r . Tn the noi.ma1
ani.rnals, however, the summer indc?s is 0.382 greater thari
lh wiiit.cr index, with a. probable error of + 0.28. This dift'(?iwic.e, therefore, caiinot be considcreil mathemnt.icallp
sigriificant.
7'hc c # < > d o f mcfration 0.~1t h e . ~ I i , . ~ C P ) ? ~ l ~ ) i l i tto
:7f
t c f ania parathy ropvizia
'l';iblc Ci gives the resnlt,s obtaincd in the two ape sclries;;.
111 thcl sixty-day series tlic figures show coiwlusi~-clythatcastration did not affect: the suscept.ibilit:- t:o tetania paraif:Iiyropriw. Ti1 tho iiinety-day series the di:ffcrci-tccs i n tlic.
percentages a r e st.ill iiot sigiiific.ant. h shift of t.wo ;iiiimals
iiit,o t:he fa.tal-tciany group, in case of the c!ast.ratcs, o r ii
shift- of t.wo aiiimals oiit, of the fatal-tetanp group, in case of
the controls, woiiltl remove a11>7 seeming difference in the pci.-
PARATHYROIDECTOMY IN CASTRATED RATS
313
centages. I n comparing the two age series, no difference in
the reaction to parathyroidectomy appears between the sixtyand ninety-day animals. The average length of life after
parathyroidectomy in the non-fatal tetany cases is shown to
be somewhat longer in the castrates than in the controls both
in the sixty- and ninety-day series.
TABLE 6
Classification of cases of tetania parathyropriva in animals sixty and ninety
days of age
60- Castrates
day
_
_ Coiitrols
- _ _ _
90- Castrates
day Controls
28 Ill.
26 ~ _
9.
_
29
8.
30 111.
~
39.2% 1. 3.5%114. 50.0%
34.6%
_
_ _1._ .3.8%13.
I-____ 50.0%
27.5% 4. 13.7%115. 51.7%
36.6% ,4. 13.3% 11. 36.6%
2. 7.1% 105 (13 animals)
3. 11.5% 69 (12 animals)
_.
_
2. 6.8% 90 (18animals)
4. 13.3%1 48 (13 animals)
~
T h e effect of season. o n the susceptibility t o tetania
parathyropriva
Although it was not primarily intended to make a study of
the effect of season on the susceptibility to tetania parathyropriva, the data gathered on this point are presented. Only
summer and winter comparisons can be made here. The summer series includes those animals that were parathyroidectomized during the months of May, June, July, and August,
and the winter series includes those parathyroidectomized
during the months of October, November, December, January,
and February.
Table 7 shows the figures obtained in comparing summer
and winter parathyroidectomies in both the sixty- and ninetyday series. The simmer group in the sixty-day series is a
small one, but it shows that there is a marked rise in fatal
tetany during the summer months. No difference appears
between the castrates and controls in either the winter o r
summer groups. I n the ninety-day series, also, there is an
314
MILTON D. OVERHOLSER
increase in f a t d tetany in the aummer group. No significant
difference appears between the castrates and controls in either
the winter or summer groups.
TABLE 7
Comparison of results in aummer and winter parathyroidectomies in the aixty-
AQE
SERIES
21
21
60-day
II Castrate;
1 Controls
I
I
14
12
90-day
~
19.0%i
4.7%ji4. 66.6% 2.
4.7% 13. 61.9%, 3.
4.
4.
1.
19.0% 1.
7.
5.
100%
100%
2.
3.
14.2% 3. 21.4%
25.0% 1. 8.37'
~
I
.. ..
. ...
~
I
i
6. 40.0%1 1. 6.6%
8. 44.4% 3. 16.6%
I :::: I
1i
li
9.5%
14.2%
....
....
8. 57.1% 1. 7.1%
4. 33.3% 4. 33.3%
7. 46.6% 1.
7. 38.8%
6.6%
....
TABLE' 8
Average index of parathyroid siae of all the fatal and severe tetany casea
compared with the average index of all the mild and no-tetany cases
I
FATAL AND SEVERE TETANY CASES
!
60-dayl
gO-day,
4
11
MILD AND NO-TETANY CASES
Grams
'
100.9
138.9
60-day
16
90-day
_ _
1.8752.08 ~ _ _ _ 17
(33)
P a r t B -Controls
102.3 '
138.2 2.3662.15
(129.2),
60-day
9O-daY
;:
(29)
1
I
Gram
1.875k.08
1.7912.04 1.7915.04
(129.8)
0.0842.09
104.5
153.6
_
_
110.8
2.366f.15
154.7 1.6752.05 1.6752.05
0.6912.16
(130.4)
i
PARATIIY1~OII)ECTOMY IN CASTRATED BATS
315
In the winter groups no significant difference in susceptibility to fatal tetany appears between the sixty- and ninetyday series. In the summer groups the ninety-day animals
may be less susceptible to fatal tetany than those sixty days
of age. However, the summer sixty-day group is small, and
in a larger series the percentage of fatal tetany would no
doubt be somewhat lower.
Relation of parathyroid size t o degree of tetania
parathyropr i v a
No correlation between the size of the gland and the number
of days of survival after parathyroidectomy was found. I n
table 8 the average index of the size of the parathyroid of all
the combined fatal and severe tetany cases is cornpared with
the average index of all the combined mild and no-tetany
cases. Part A gives the figures for the castrates and part R,
for the controls. I n the castrated animals there is no difference in the average index of the size of the parathyroid in
fatal and severe tetany cases on the one hand and mild and
no-tetany cases on the other. In the control animals, however, there is a significant difference. The average index of
the size of the parathyroid in fatal and severe tetanp cases
0.16) greater than the average
is 0.691 (probable error,
index in mild and no-tetany cases. This difference is 4.3
times as great as its probable error.
It will also be noticed in table 8 that when the average body
weights in the mme age series are compared, the mild and
no-tetany eases are heavier than the fatal and severe tetany
cases in both castrates and controls.
DISCUSSION OF DATA
The sixty-, seventy-five-, and ninety-day-age series in which
the size of the parathyroid gland is compared between castrated and normal animals are sufficiently large for mathematical treatment (table 3). The sixty- and seventy-five-day
series show clearly that castration did not affect the size of
316
MILTOX D. OVERHOLSER
the parathyroid at these ages. The almost ideiitical averages
lictwccii castrates aiitl controls in both of these series makc
tiii,.; point coiiclusive. The average indices of tlic size of tlli!
parathyroid ill tlie seventy-five-day series are abnormally high
aiid do riot truly represent the relative size of the parathyroid
for this age. This is largely due to the fact that a majority
of the aiiimals (both castrates a i d controls) were helon- normill in hotly Lveight, because of a seasoiial effect. Sinw tho
series is a summer oiie, the high indices are also probably d u t h ,
in part, to ail increase in the actual size of the parathyroid.
The latter caiiiiot be proved, however. The data obtained
from the iiinety-day series appear, tit first, to give a different
wsult (tahle 4). Tlie arcrage area of the recoiistrnctioii of‘
t h o parathyroid iii tlie c.oiitrols is 33.8 sq.cm. grentcr. t l i n i i
that of the castrates. Tliis differencc is X i times as great
as its prohahlc error. However, ill tlic relative size of tlw
parathyroid, as exzpresseci by the iiides of reconstruction, t l i c h
awragc of the controls is 0.376 greater thwri tiitit o f tlic
castrates, which ciifferciicc is only 2.6 times its probable PI*K*OI*.
‘I’liv cluestioii iiow arises iis to whether thcse differences arc
mathematically sigiiificaiit. The curves of the figures wv
plotted for both the area aiici index of reconstruction. 111
each case thc curves were sltewd to the right, but the distribution of the figures ~ v a smuch better in thc ciirves of the
i i i c l i c c x ‘[’hc index of the parathyroid sizc is tlicreforr tlw
pi.cfcralh figorci iii rnaltiiip tlic comparisons between castrates
; ~ n dcontrols. A difference between two arcrages \diicli is
oiil>- 2.6 times its prohble error cannot, with ccrtaintr, bc
wilsitlcrcvi t o be sigiiificaiit, except pperliaps in a prfectI!distributctl series wlicrc normal ciirv(~sare o1)taiiicvl. This
tlitf‘t~i-c~uco,
in tlic t w o n\-ci*ap:.esi i i i d e ~ *cotisidoixf i o i i , wliiccli i h
2.6 tixncs i i s large a s its ~)i-obal)lc
( b i ~ o i . , a.onld ai*ise 1))- awitlcnt aloiic i.95 timw out of ;I liuiicl~-edsimilar trials.’ I t
seems much safer, tlicrcforc, to regard this diffci.eiicc1 as tluc
to (~liaiiwsampling. rii this particular i iivest iga t ioii diffei-’ I’mirl, R i i ~ i i i o n d ,1923. Iritrotluctioii t o nit’dkiil 1 1 i i 1 1 1 1 ~ i~i nt nd s t i l t i s t i n , 11. L‘1h
I\‘. 13. Sn uiirl(Lr\ (’ciiiil):iiiv.
eiices due to chance sampliiig may be very a.pt to occur, due
to a. possible seasonal iiifluence on t,he size of the parathyroid.
Regarding the effect of season on the size of the parathvroid, the figures presented are inconclusive, due to the small
number of cases. Only t.he ninety-day animals could be divided into summer and wint.er groups (t.able 5). The figures
obtained ha17e already been poiiit.ed out (p. 312). A seasonal
variat.ioii in the size of the parathyroid no doubt occurs. It
has been shown t.o occur in the endocrine organs (parathpvoids not mentioned specifically) of the rabhi.t by Brown,
Pea.rce, and Van Allen ( ’24), a.nd particularly in the case of
the thyroid and testis in pigeons by Riddle ( ’25). The marked
rise in the blood-calcium curve during the summer months in
pigeons, as shown h p Riddle and Reinhart ( ’as), indicates an
increased activity of the pa.rat.liyroidand possibly an increa.se
in it,s size during t,hese mont,Tis. Grant, and Gates ( ’24) found
a decrease in the normal size of t,he parathyroids of rabbits
from Xovemher t o February.
It is considered t.hat t.hc data in this study indicate that an
iiicreasc in the size of the parathyroid owurs during the summer months as compared with the size found during t.he
winter months. Conclusions as to a difei.entia1 response
between castrates mid controls t.o t.he sea.sona1 variation in
the size of tlie pi\riltllvroid caiinot be drawn from the present
c1at.a. Ry referring to t.able 5 it will now be soen that in the
ninety-(lay normal animds there are five more in t.he summer
gi-oul? t . h n in the winter groiip, while in the castrates there
are t.mo mow in the winter gronp t.hari in t.lie summer. This
nncqual seasonal distribut.ion of t.he samples between castrates and controls in the nii1ot.y-day-sizeseries may therefore
account. for t.he differences in the a.verage figures obtained in
this series, as discussed above.
Castration also did not affect the susceptibility to t.etania
parathpropriva. in the two a.ge series &died (t,ahle 6). In
the sixt.y-day series the figures in t.he castrates and controls
are practically identical. I n the ninety-day series the differences in the ppcrcentagcs ohtaiiicd arc not significant when the
318
MILTON D. OVEIiHOLSER
size of the series is considered, and when it can be shown t,hat
R shift of two a.nimals in or out of the fatal-t,etany group
will remove the differcnces. The non-fat.al tct.aiiy cases iii
t,he castrates survived longer, on the average, t1ia.n similar
cases in llie codrols. Wliet.hemrthis fact is significant. or not
cannot be said.
The a.rialysis of the effect of, season on the degree of susccptibi1it.y t.o tcta,nia parathyropriva shows that fatal tetany
increases during t.he summer mont.hs (t.able '7). This confirms
similar resn1t.s obt.aincd by Hammett ( '27). The cause of this
snmmcr inc.rease in fa.t.al tetany may be correlated with several factors, such as : 1) a subaverage nutrit.iona1 sta.tus:
2 ) t.he actual temperature increase; 3) increase in t.hc size
a,nd activity of the parathyroid. Regarding the subaverage
nutritional status, Hammet.t. ( '27) found the average body
weight of rats dying in tetai1i.a parathyropriva was less than
that of those tha.t survived parathyroid tetany. This point.
is confirmed in the present investigation (table 8). During
the hot summer season a decrease in body weight was observed in many of the animals used in tshi.swork. The actual
increase in temperature may aggravate the symptoms. Dragstedt, Phillips, and Snclan ('23) showed that tet.any could be
induced in parathyroidectomized dogs, that had becn kept,
tet,any-free on a carbohydrate diet, by exposure to high temperature. It is probable that a summer increase in the size
and activity of the parathyroid acc0unt.s largely for the increased susceptibility t,o fatal tetania parat,hpropriva.
The analysis of the figures regarding the relation bet,wecn
t,lic sizc? of parathyroid an.d the degree of susceptibility t.o
pnra.thyroid teta.ny bears 011 the a.bovo point. It. was found
t;liitt in normal animals tlic fatal and severe t.et,a.npcases posscissetl, 011 Olie awrage, larger parathyroids than thc mild and
no-tetany cases (table 8). This difference is 4.3 ti.mes ;is
grcat. as its probable error. I n the castrated a.nimals this relation did not hold, the average index of the parathyroid
lwing the same in bot,h classes of reac,tion. This lat.ter fact
n1.a;~
be d u e to t.he insufficieiicy of the data o r to tlic fact, that
PAKATHPROIUECTOMY I N CASTRATED RATS
319
castration has disturbed the normal size relationsliip between
the size of the parathyroid and the clcgrce of susceptibility
to tctaiiia parathyropriva. Of interest in this connection are
the unpublished results of Gates, Grant, slid Stevens. They
found that if castrated adult rabbits were subjected to ultraviolet light there was no enlargement of the parathyroids.
Exposure of normal rabbits to ultraviolet light causes an
increase in the size of the parathyroids (Grant and Gates,
'24). I t seems safe to eoncliide, hov-ever, that in normal animals high susceptibility to fatal and severe tetania parathyropriva is correlated with large-sized parathyroids.
Finally, the results obtained in this investigation and the
unpriblished results obtained by Hoskins and Chandler will
be compared. This refers to normal animals. Their series
of paratliyroidcctomies consisted of forty-sewii operations,
tw-eiit~-fiveon rats from fifty t o eighty days of age and t,he
remainder on animals eighty to one hundred days old. Fatal
tetany occurred in 82 per cent of the animals in the former
group and in 45 per cent of the latter group. All of these
operations were performed during the warm spring months
of the Arlransas climate. In this study the proportion of
fatal tetaiiy was about 35 per cent in both the sixty- and
ninety-day series (table 6). These series, however, were
made up of unequal proportioiis of winter and summer operations. The sixty-day series was preponderantly composed of
winter operations which would lower the per cent of fatal
tetaiip. The ninety-clay series was about equally divided between summer and winter operations. If the summer sixt;vday group is compared with the summer ninety-day group
(table 7 ) , it is seen that the percentages of fatal tetaiiy correspond in general with those obtained by Hoskins and
Chandler iii their two age groups. Thus the inflnence of age
on the per cent of fatal parathyroid tetany may be strongly
modified by a seasonal effect. This influence of season on
the susceptibility to tetania parathyropriva cannot be too
stroiigly emphasized.
THE AFATO~UICAT,RECORD, VOI,. 41, so. 3
320
SUMMAPP AXD COX(%U&IONB
1. The size of t.he parathyroid gland was compared betwceii
castrated aiid c:oiitrol animals in three age series: 1) sixty
days, 2) gerenty-five days, 3) ninety days. Castration does
iiot affect thc relat.ive size of tho paratligroid to n matlicmatically sigiiificaiit extent in any of tlie series.
2. The size of t.he parathyroid gland was compared betwecw
winter a d summer groups in the ninety-day seriew. Thc
data indicate an increase in tlie size of the pamt.h;rroicl chiring
the summer season as compared with winter.
3. Tho susceptibility to t.etaiiia paratliyropriva was comparod het8wccii castrated and control animals in two t t g !
ecries: 1) sixty days, 2) iliuety days. No sigiiificaiit (1itTcreiice .iu msceptihility appears bctween the castrates aucl m i trols in either of the series.
4. The data on the susceptibility to tetania paratliyroprivtt
w r e analyzed for a seasonal effect. It was fouiid that SLIMceptibility to fatal tetaiiy increasea during the summer scasoii.
HS compared with winter, in botli castrates and controls.
8. Tlie data were amlyzed for a relation betweeii the deprw
of tetaiiia parathyroprivtt and the size of the parathyraid.
.In the noimal animals fatal and ~ e v c r ctetanq- is corrckited
with a large reltitiw size of the parathyroid. 1.11 castratod
animals no relation is ahowii hy t.he data.
6. Auimal~that show fatal ~ i i dsewrc tct.ttiiy MI'C', 011 thc
ttverag(?,of IO~ITCI'
lmdy weight tlictn tliow that slim- mild aiitl
1 1 0 tc!ttirig.
32 1
1,lTEHATURE CTTED
BROWX,
IT. H., PE:AR(T, L., AND VANA L L E X , c‘. M. 1924 Seasonal changes in
organ weights and their relation to meteorological ronditions. Pror.
8oc. Expor. Yiol. and Med., vol. ?l, pp. 373-3i5.
(‘LhRET, If., ET GLEY, E. 1911 Ovariertomic et thpro-parathyroidectoinie. COIIlpt.
Rend. Soc. de Biol., T. 70, lip. 470-472.
1911 ISouvrIle note sur Ies effcts ilc la th~ro-~~arathyroidcctoni~ii~~
apres orariectoniie. Ibicl., T. SO, pp. 1019-1020.
I)ILAOBTI“,D~I*,
I,. R., PHILLIPS,
K., ASD SLrDns, A . c‘. 1923 Exciting factors i n
cxperimental tetanp jn dogs. AIII. ,Tour. Physiol., vol. 65, pp. 503-.5ll.
EEKDHEIY,
5 . 1906 Zur Anatomic der Kirmeiitlerirate bci Ratte, Kaninrhrn.
und Tgrl. Anat. Anz., Rd. 29, 8. 609-623.
FAKSER,
E., USD KLINGNR, It. 1920 Experiiiientelle I!ntersurhungrn iiher Tetanic.. Mitt. a. d. Grcnzgeb. d. Mect. u. Elhir., Kd. 32, S. 353-373.
GRANT,a . 13. R., A N D G A m s . F. F. 1924 The rff’ect on the external parathproitl
glands of the esposurt. of ralibitn to ultra-! i o k t light. .Tour. Gen.
Physiol., \ o l . 6 , 1’1). 1335-645.
H m x r r r , F. S. l!Ei Stur1it.s of tlie thyroid apyamtns. XLVII1. Agc, Sex,
weight and season a s lethal factors i n conditions of parathyroid and
thyroid deficicncp. En(locrinology, ~ o l11, pp. 117-124.
I L o s s r ~ s ,M. M., ASD (’HASDLLR, S. €3. l!E5 A4ccc~sorypttrathyoids in t h r rat.
Anat. Xtv., 101. 30, p p !%-98.
KVROKA\VA,
K. 1925 Histologiral studics of normal and pathological human
parath-poitl glands. Japan M d . World, rol. 5 , pp. 241-251.
JI $RISE. T) 1914 Otmcrvationq oii tcataii) in (logs: rclation of the parathyroids
t o t h r thyroid; to agr ; arcessor? parathyroids, pregnancy, lactation ;
eflert of calriuin salts, etc-. Jour. kkper. Illed., rol. 19, pp. 89-105.
> I . ~ s s ~ ( : ~ , I A , A. ( I , 1911 A ~iropnsito t l i esatrnzioiw (* tiropariitiroiclcc.tonii:i.
Oazz. d. OYl)., ‘1’. 32, 1’. 4”“.
KIcIior.As, J . S.,A ~ I X\\IN(~LA,
)
XI’. \Y. l!E3 k’ur:itli,vrnid extirpation in the coat.
T’roc. Soc. Rxlwr. Biol. ant1 >led., rol. 21, pp, 160-161.
~IIDI)I,P:.
OS(’AR 192.5 Stntlirs 011 the physiology o f rcyroduction in hirtls. X S .
Reciprocal sizc clinngen of gon:idr :rnd thywids in rclation to ~ ( * : I S O I I
and ovulation ratc in pigrons. Am. Jour. Physiol., vol. 73, pp. 5-16.
I ~ I I ~ I., 0..
I AS]) I ~ ~ ! , I N ~ I ~ KN‘.
T . i i . 1Mi Htutlics o i i the physiology of reproduction in birds. SXT. BlooiI c;ilciuin c.liaiigex in thr rcproductivc cycle..
h i d . , vol. 7 6 , pi). 660-6i6.
Ronci<\. T!?. M. l%!7 ‘I’hcs fatc of tho ~i1titi~oI~r:iii~lii:~l
1)otly i i r ttiv whit$&I:ct
(Mux norvcgicus :iIl)iniis). A n i . .Tour. Anat., vol. 38, pp. 349-366.
H i ~ a r i ~ oS.,
, A K D JAYFE:, HENRY1,. 1923 On t h r wcurrrnce of accessory paratliyrnids and thvir rekition t o survival of : ~ n i n i a l:iftvr
~
parnth>roidectoniy. Endocrinolog~,vol. 7, pp. i 2 0 - i 2 3 .
S i i . V E : s w r . 1’. 1910 (‘astr:tziono v tirop:irntiroitlectoiiii:i.
I I T’olirliniro, T. 1 7 ,
pp. 1571-1574.
‘i’o~oriK I ’ , ‘1’. 1911 <Jhcr tlic paratlipreoprirc VrrPnderung des Rattenzahnes.
Frankfurt. Ztsclir. f . Path., Rd. 7, 8. 349-294.
1903 Die Entwirkelung der Srhilddriisr und drr Tlivnius bri
Z : I - I ~ K E I { R A N D LE.
,
dw ILittc. .inst. FTcftr, Bd. 21, 8. 1-28.
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