IATR OGE(NiE I YIP()T IW1DIt1SAl_*

1Y
BNx F. TRF-EMIAINE ITL I INGS, MI).
I lhadl n(ot initeln(led to explain the meaning- of iatrogenic, but
a conv\ersation at the bnreakfast table tlIls miorinon chalniged my
min(l. ()ne colleagtie askedI nme whliat tlis bltusiness of hvpothyroid-
isIll in lactatiing, wvomen wvas all albut. Another scoffed at the first,
statinig th.at obv)iostulv it wvas something allotit gi,vino iodine to
pro(duice hypothyroi(I activity. As most of xon knlow, iatros is the
Greek root imeaning p)hysician. ()ne might fturtlher elaborate by
saving thlat in miany ilnstanices the physician is the uninitenitionial root
of exil. Be that as it miay. the title of the paper is still a little
misleading. In most instances I (ho niot l)elieve physicians actually
reni(ler l)atients l)ermlaneltlv mivxedemato(ius ith the use of thyroid
therapy. It las )eeu l)inte(l o2et lv I )otoi I'ar(juharson.- however,
that the tise of thvr(roild sulbstance (l1Ges inhih)it thle l)rodtlction of
normal thvroil secretion ill 1non-mx xedematous l)atients with hvpo-
mietallolidism. \\hat I would like to imi1ply, is that mnany physicians,
althotughi they dclo not organically supp)ress thyroid secretioln per-
manentlv -itlh thlvroil substance, (0o however, very frecpuienltlI give
patients whose Lasal metabolic rates are low\, the iml)ression that
their tlvroi g ( ldands are functib)nin l1 P(rlv. 'T'lhis impressiol is
ofteni a lastinCg onie, and the l)atienlt tlerl-efore, feels nlot only con-
demined, but actually eagier to take tlvrrold for life. If these people
are nlot in a l)ermanelit state of hyp(othly(roid(nis, they certaily1 tlink
that they are.
\Nhlio are tlese )ec)p}le who seemei s(O temptingly anienal)le to
simple lhormiionial mismanagellment T.heV are people w e all see.
They make til) a very large part of the ilnterniist's I)ractice, especially
lis p)rixate I)ractice. They are mostly femiales, an(l to a certain
extenit thley can be fairlI well gYrotlwed.
tFroin the DI)eartmc: t of Melicine, Vanderbcllt tUniversity School of
Me(dicice, Nashv ille, UTemessec.
This w\ ork.. \\ as spportl(I
t(1 i)art bN tIle John1 1. Howx e Medical Rc-
searclh Ftooi(l.
12
 IATRGGENIC IIYFO1IiYROIDISAI 13
In the first l)lace, there aare those whlo are obese.
In the secolnd )lace, there are those in a(lolescenice, who are
cithier 0)1 le-;e toiligh mlenstr-aiting, or wlho are thlill aidl nlot menl-
struating(, or wlho are 1)0th ol)ese an(l not nmenstruatilln
Thirdlv, there is the groil) of voutng la(lies wlho have finished
school or college or wAho have accomplished a debut, and who are
bidinog their timie awaiting the next exciting step in life which they
tlhliik ideally is imiarria5-e.
Next is the group) of voting la(lies whlio hav iig- attaine(l the
state of ideal miar-ital excitemiienit find it actually nlot So excitinlg to
lhe sad(lled wN-itlh household( clhores, clildlreni and(I a tire(l quarrelsome
mostly absent hutsband.
The old a(lage alout l)asttires appearingl greenier on the otlher
side of the fence applies to the niext group): the la(lies who feel they
have passe(d the marrying age without marryi'ng. Far froml profit-
ing, fromil the exiperience of tlheir hvpometabl)olic Married sisters,
they also seemii to dleclinie ilnto a y pometabolic state.
In reviewing these grouips individiuallv andI collecti velv for a
momiient, it is not (liltctilt to see that lprolbal)lv a comm110on1Ie-
niominiiator is a state of frtistration. tUtler these circtnistanices the
admlni.istration of thlyroid is a st4) gcap at best, uisulllk- unsticcessful
unless accompaniied 1b large (loses of tintlerstanllin, initerest in
eaclh -irl's prol)lemii and associated vitlh the presenice or tlevelop-
ment of insight oni the part of both the patielnt al(il the plhsiciani.
In the pr-esience of stulch a for-ttiitolus (oincidence, thyroid nee(l never
lie administered to paltients falling in one of these grollps.
The ol)ese womain ob\vlotisly eats more tlhaln slhe burns. Slhe
shotil(d tlherefore, eitlher eat less or htirn miore or both. ( )f cotirse
it is llot (tiite as sitple as Doctor Newbir-gh-" would lea(l lis to
believe, however, because behind the btilk of each obese person
stanlds a psychological problem wlhlich nmuist be tunravelledl before
satisfactory re(luctioccurs. \np inyterested lihsicail Catn1 proh-
ably accompldish tli.s better witlotit thyroil therapy. If lhe caniniot,
thlyroid extract will only lie temporarily helpftl.
14 FREDERICK T. BILLINGS, JR.

The non-menstruatin-Y fat ad(lolescent w-ill probal)ly imienstruate

satisfactorily, if shie is goillg to, merely witlh careftul olbservation.
If slhe dloesnut solmiethlinig imore comlplicatecd than hypothyroidism
will l)roblalbly he discovered to le lher (liffictiltv.
l interest in the inext grouip, those girls whlo are imlarking
timiie wx ith hated breath hetween dlel)ut and edlding l)ells, dates
hack to lhotuse officer dlays. A friceinl relporte(l to mne with iinterest
that seven of l1er friends, onie after the other, wNere being giv'enl
thyroild by tlheir physicians. They Nwere tire(d anid runll doWn anld
neede(d pel. It seemiie(l ratlher- incre(lilble to imle at the timle that thev
couldl all have incipient mnvxedema. )nring- the couirse of the next
tein y-ears, I have followed the progress of these girls somiie pro-
fessioinallv and some sociallv. All (lisco(itinnie(l thvroidl at the time
of thieir ovo-rria0ge atll have had childl(reln; and now all are tfast joini-
ing(, the next (grrotil) wxhich c ompri ses the hypometalb,olic x oulnlg
housewives. It has een v erv (lifficult to keep those of tlheimi who are
IIIuder my care awvav fr-omll thy-oidl extract.
'T'lhere are many otlher con(litions foir vhich thlyroil is usedI
seemingly oIn a completely emllirical basis. No less an orthopedic
autthority tlhani Doctor Eolwin Cax e1 states in a recenlt article oni the
treatmen1t of clhronic subldeltoid bursitis: Trhie initerni'st slhouil(d re-
viewx the lpatient g-enerally ai(l pssillv l)rescril)e thyxroi(l or other
hormonesllXvlhich in somlle instances appear to b,e ettectiv e." Doctor
Robert (Greenliatti (lisci ngsxii(y the management of uiterinie bleedilng
states: "'thyiroil theralp shlouil(d be administel-rl to all lpatienlts wvith
1m1lilal r- sulil(nl1 mtl a1
hasal metal oliic rate."
'T'lhv lid i's used iii treating sterility inI )tIherxVse ap)parentl
normal x onlen. It is also ad(lnlinistere(l wxith o)ther hormones to con-
trol thir-eatenie(d ahlortiP . No one cain 1eI certaini of its efficacyx under,;
eitlher (If these circumstances.
It x-llildl be fo(loll tsh ixnersal!lv to olec rv the usie of thlyroid in
the treaLtm11enlt of all patients who (11) not havxe iny xedeina, especially
if tlher-e ixs any (lolulIt ats to xv-lhetlheri it might
h1ell.
b1e (_)n the
otlher biail( it sholol(1 be uised lh the physician in all honesty on a
 1ATROGENIC HYPOTHIYROIDISM1 15

trial basis. The patieint shotuld b)e taken into his confidenlce to the
extent that he or she will not forever lose respect for his ur her owii
thvroid secretionis.
The following, histol-ies are those of fouir patients wlho thougl
probably normlal, were made thyroid addicts by tlheir p1ysicians.
eHo*TVM
WT. WOO % IMRt
A SAGE 16
I
MENSES REGULAR THROUGHOUT = o
160 300* 20 oj
S

150 F 1 0;
140 200
'
0

130 .10. ME*TA0LI BAAL

I20 100 -20

I
1933 13 1937 139 1941 1943 1945 1947
PATIENT A (FIGURE 1)
Paticuit AI (Figure 1) was a fat sixteen when she first began
taking" thyroi(l 5 grains (ially. She lived in a verv small town whIiere
her widowed motlher vWas the teleplhone operator. In spite of this
large amiotunit of tlvroid, it Nas not unitil lher secon(l year in college
at the age of ninieteeni, that an appreciable weight reduction and
inicrease in l)asal metal)olic rate wvere apparent. She remiiainiedl in
st(to quo unitil 1944 whelne sle went to -New G(iuiea witlh thle Red
Cross, alid for six monfltlhs did wrell witlhout thyroil therapy. A
severe bombing cauise(l a state of exhatustioni. SShe was evactuated
to Atustralia whlere lher- basal metalolic rate was found to l)e low,
but serumn cholesterol levels were 101 and(I 98 mgmis. per celnt. No
thyroid was prescribed, shie wvas allowe(d to rest and thenl enlcotulraged
to leacl a niorm-lal social life. In AManila fotur months later her basal
16 FREDERICK T. BILLINGS, JR.

metabolic rate was -11 per cent. In Korea in 1946 holding a re-
sponsible administrative position, her basal metabolic rate was +17
per cent. After the war she returned to her very small home town.
She remained there a year, less and less inspired, hampered by her
mother. Her b)asal metabolic rate fell to -16 per cent. She was
examined at Vanderbilt University Hospital where she was found
to be normal with basal metabolic rates of -22 and -23 per cent. No
thyroid was prescribed. She went to New York. In a follow-up
communication from her dated October 1950, she stated she was
fine. Weight and menses were normal, and she had not bothered
to have her basal metabolic rate determinations repeated.
GROLESTEROL
mekG ILEt
B $ AGE 38
MEGNESI.REGULAR-WEIGHT NORAL THROUGHOUT
WEIGHT 1340 63
+20
49
La 4
IC
01 - 0
o a
410 A
IL
0
a

200 0

-10

100 -20-

-30-

PATIENT B (FFIGURE 2)
Patienlt B (Figure 2) was thirty-eight when first seen at
Vanderbilt University Hospital. She had been taking thyroid
2' 2 grains daily for fifteen years. She had had five children, the
oldest seventeen years, the youngest eight years. She was born and
reared in New England and never accustomed herself to the softer,
slower southern life. She worked Puritanically hard raising her
 IATROG ENIC HYPOTHYROIDISM 17

childreni, expected strict hard work o)f those aarouindI her, anid hadl no
close female frielnds. Although possessed of far miiore energy thanl are
most housewives, it irritated lher to be tired. Slhe took thyroid un-
successfully to prevent fatigue and because slhe had b)een told that
her low basal metabolic rate was responsible for the fatigue. She
had been told slhe was solmiewhlat anemic aldl l) lght her ownl hlemo-
globinometer to keel) track of tlis. Nhlieni seeni at V-alnderbilt
University Hospital slhe was fouind to be niormiial. Ftigure 2 is self-
explanatory. \Vlheni lher basal metabolic rate was (letermiinied in
B'ostoni or Floricda whlere slhe "relaxed", the values wNere somiiewhat
higher. It was impossible to weani her from thyvroid.
WEIGHT BMR C,g AGE 20

160 +20

+10

140 0

-10

120 -20

-30
THYROID4
GRAINS 3
DAILY 2

1944 1946
P.ATIENT C (FIGURE 3)
pLitit'lot C ( Figture 3) was obese when slhe was twvenitv years
old anid althlough slhe was apl)arently otherwise nlornial anId her
imienistrutal perio(s were regyular, heribasal metabolic rate was -16 per
cent. Thyroid, 4 grains dlaily, was l)rescribled with no clhang,e in the
clinical picture. She was majoring in social psychology at college,
anid was the subject of one of her professor s pulblishedl papers
regarding individuals with low basal metabolic rate and normal
 FREDERICK T. BILLINGS, JR.

menstruation. She (licl d i()t lbegin to lose weight Iutil 1)44 whllenl by
her own admissionl slhe l)hccale miiore satisfied, miiet lher fuiture hus-
banid aniid slhortly tlhereafter became elngcaged anid was miiarried. She
theni had five successive miscarriages followN-ed finally 1y a suiccessful
pregn1ancy. She (lisconitinuie(l thylroi(l therapy at the eni(l of tlle
first trimlester. tler clild nutirse(l satisfactorilv for eight imionths.
She began to take thyroild a-ain after about one N-ear's abstinence.
Althotiugh whein seeln at Vanderl ilt Ulniversitv Hospital in 1950 she
appearedl norn]al, and(1 nio evidlence of hypotlhyroilism was dis-
covered, it vas impossible to wean lher from thyroil. WNlhen a trial
perio(l withlout thvroild was suggeste(l sle clhanlgede p)hsicianIs

D, d' AGE 15 NORMAL PHYSICAL DEVELOPMENT AGE 21

WEIGHT 5 FT-71N. OCCASIONAL MODERATE ASTHMA 6FT.-31N.

150

140

N
120 x

XI---"" BMR
'x

THYROID
EXTRACT
3 ,---"'X
2-
GRAINS I.
DAILY

45 1946 1947 1948

PATIENT D (Fi(;URE 4)

IPaticuzt I) ( Figure 4 ) was a g-anglv boy ot fifteen N-ears when

he hegan to take thliroil, 3 grainis a (lav. He had matured satis-
factorily physically but wvas thotighit to b)e (le elo)ping sb)wlv ill-
tellectually. The onlv son of a divorcee heehadl mil( chrolic asthima
for a number of years. Ile was spoliled alil( slightly owerweight.
 IATROGENIC HYPOTHYROIDISM1 19

The (1lata in Figure 4 was supplied by the boy s maotlher from notes
in lis haVy 1)ook. Excelpt for the fact that he grew fast and
nmatuired at ani a-erage rate intellectually, the general picture did
not clhanige appreciably. W,Vhen seen at Vaanderbilt University
Hospital in 1949, he wvas a normiial tall, thin boy. He lhad lhad trouble
adjusting to being away from home alnd was not doing too well with
lis sttuldies. His miotlher was worrie(l al)out him. All investigations,
inclul(liln xray exaaminations of the skull, wNere normal. His basal
metabolic rate was low. Ile was wealnedl froml thyroid, encouiraged
in his in(lepen(lence, ancd adv ised to eat a better (liet alnd to be
nmre reegular in his habits. lie has (lone well.

Discu ssi10N
Thy-roil is administered in large quantities, in mllost instainces
nllecessarily, bv physicians to patienits all over tlle world. It is
probable that patients witlhouit hypothyroidism who receive thyroid,
thougia henefiting not at all, for the most part suffer little organic
lharm. While taking thyroil, there is prol)alale supl)ression of
niormiial thyroid secretion, wlhiclh rettirns to normal fairly SOOI1 after
thyroid is discontinlued. Doctor HToward Means,4 however has
dlescribe(l the (levelopmen-t of hyvpermetabolism simtl ating precisely
the picture of full blown thyrotoxicosis in a few l)atients receiving
large amounts of thyroid. Wh'lieni the imie(lication was discontinuied
the hypermietal ol sll r egresse(l.
In closincg it shouil(d be re-emiiplhasize(l that although there
seems to be n1o definlite proof that permllanlent organic change is
prodtuce(l in the thyroidl glanid by the a(diinistrationi of thyroid
to hypometal)olic people, vet these people are usually psychologically
so conistituite(l that onice it is iilj)lie(l that thyroild und(ler-secretioni is
the catise of their troubles. they might as well be mvxedematous for
the tenacity, witlh whiclh they clinig to thyroid therapy.

ISI -M ARN

In the liglht of explerience, it is l)oiiited otit that thyroid sub-

stanice adminiistered to patieints, normiial except for low basal nmetab-
20 FREDERICK T. BILLINGS, JR.

olic rates, p)rol)al)ly pro(ltices 1o p)erlmlanent organic dlamiiage. In

admini stering thyroil tili(ler stuch1 circumstances, however, the
physiciani usually overlooks important psychohlogi cal factors. Tlle
use of thyroil to treat hypometabolism in the al)sence of orgalnic
hN-pothyroil functionISlshlould
( e avoi(le(l.

REFEIRFENCEIS
1. CAVE,F!I)\I N F.: Plain in tile Neck and( Upper E.xtremity. Thl,e -Me(ical
Clilnics of North America. Boston Numher. \\. 1. Saunders Co., 1950.
2. FARQLHi- ARsON. R. 1. and SovIiE.rs, A. H.: Inhibition of the Secretioni of
the Thyroid (Hland by Coiitiniued Inigestioni of Tlhyroid Substance.
Tranisactio us of the Association of American Physicians. 34, 87, 1941.
3. GREENBLATT, ROBiRIT B.: The MIanagement of Functional Uterinie Bleed-
inlg. ]'he d edical Clliics of Nortlh Amiierica. Bostoni Number. W. B.
Saunders Co., 1950.
4. 'EA N s, J. H.: The Thyroil and(l Its Diseases, SecoII(i Edition. J. IB. Lip-
p)incott Company.
5. NEwNVBUR;G, L. H., and(l Joi1 NSTON, M. \W., Thle -Nature of Obesity. Journlal
of Cliilcal Investigation, 8, 197. 1930.

1)I SCUSSION
I)R. ED\vWARD RoSE [Plila., Penniia.]: I slhoul(d like Imiost empliatically to
say amleni to Dr. Billings remarks all(I to add another groul) of individuals
to tlhose wholm lhe hIas menltionied; thlat is, the chlild or adolescent who, be-
cau1se of obesity (r fatigabilitv, is subj'ected to a basal metabolism test which
is fotull sollmewhat low, aii( is tlheni put on (ltesiccate(i thyroid, with the
samle train (of unfortunate events tlhat I)r. 1Billings lhas (lescribe(l.
D)esiccated thlvroid, I believe, L)r. Billii-gs, is ussually niot truly a thyroid
extract, althoug-li tlhere a-e a few p)rel)aratiolls oln the market which cani be
called( extracts. Th'le preparation most oftell utsed( is. of courI-se, the dried
whole thyroid glanl, but this )revl)aration, 1 matter by what niame we call
it, is one of the imiost abused ituems i the p)harmuacol)oeia, amid whien one eni-
couLnters a patient like olie of tllose D)r. ,illiings lhais described(, who has been
startedI vears before oni tlis substance, it is oftell most (littictlt, somitetimiles
almiiost impossible, to pmr()prly evalutatk, the imilhi-erit funictio:lal capacity of
that patient's own thyroild glal fOr manvy nmilthis after the medication h1as
been withdrawn.
 IATROGENIC HYFOTHIYROIDIM21 21
hI adlditioll to the seXveral w eli-recoy-ize( causes 0f 1hy iolletalilisiIll,
asi(de frona chronic tln roil lailure, tlhi- remainls a g roup of patients wX ith
persistently los metabolic rates, soIImetines wX ithout Svyllptollms, s(omletimies
W ith a groupl ot symptomlls, wXXhich I)r. \Willard Thompson (lescribed well a
number of vears ago iiiler the name of idiopathic hypometabolism, and to
tllis group) of p)atients we mulLlst still, unIfortutnately, apply the terIml idiopatllic.
If Xwe may extenid Albright's hypothesis of pseui(lolhy)oparathyroidisll, some
of tlheum nmay possibil prosve, w-ith tie aid of mo(lei-ii mimetlio(ds of studying tliy-
r(ii(i functi](:n, to be examples of p)erip)hleral tissue resistan1ce to ani outp)ut of
XXwhat siouild i)e a niormiial amiiouinit of tinyroild iorm)ionle.
D)R. RoI* RF I L. I EXVY [ NCw York, Nesw Yorkk T11 Xe unise use of tllh-
roid( me(licationi ind(uces not onlys a state of dependency uiponi tllis drug, but,
in somiie indiXvi(duals xX itlh onIv sliglht loswerinlg of muetaholic rate, may catuse
the development of paroxysmal auricular filbrillati)n. As Dr. Blillings lhas
intimatedi, it is sometimes rlificult to (lissuci(le the latient, as XX-ell as llis
illhysiciall, that the administratiPo of tiy roid is unmecessary. The patient is
convinced that hie feels b)etter Xwhen hle takes it; the (loctor is iniflueniced by
the level of the metabolic rate.
Ofteni the best that canl be (lonie utoler suclh circutmistanices is to reco miienid
oXXering of the dose. Thlis mav suffice to (1o aXay Xith the paroxysms ; but
complete cessation of therai)v mav he necessary to accomnlplislh the desired
result.
I)R. R-X LY I
IFEC R F.I1M0M IIiONARSN [ Toronito, Cala]d : Mr. P'resident,
Xwhen I sass Dr. Billings' title, I Xwollndere(l w hlether lhe Xwas going to talk
ai)out the iltrog-lenic effects of su-go-esting that these people halve hlylpotllyroid-
isi, or hlether lhe wXas goilng to (edscribe tle del)ressionl in function of tlle
tlvyroi(I g laii(i Xhile tliev are taking it.
I have seell a nutlmler of people sswho becamle very anixious aiout tile per-
sistent loXw metaiolic rates tlat w ere (lemiollstratterI even svhen they took in-
creasing dolses of thvyroid aoild accordmigl\, thaex \vlclderedl Xhether thev hiad
soi0le serolus disease tilat losere(l tleir blasal rate in spite of the adiministra-
tionI of tlnvroid.
Tile blasal metab)olic rate (if tlesc people Call he raisedl tIlImp)orarilv but it
teni(Is to CO11t black to tile formleir les-el and, as I)r. Billings p illted out, X-lieni
the thyroid is (liscolltillue(l it oftel falls temporarily ileloss the forimier level,
amId tletll tley mlay hlave somle symI11uptoms of mllild hly pothyroidisin. It is ratlher
imitem-estiilg, loswever, as p)oiIlted ()tt bI I)r. Peters' group ill Ness Has el, tlat,
if oIle keleps ()11 g isilg tilyroidl ill larger (loses, (lle fild(Is tlhat the tilyroid gliald
hlas really soIlle activity. It 11may liot iie maki-lg tilivron(I hlorImlonie, bhut thli
ireselee (If tlle intact tihyroid glam(l hlas a oIllmeostatic infltmence. Omle can
fee(l iIIcr asitlg aillutmits alld i-eatcl a (lose, if onie goes v ery slosslv, of six
 FREDERICK T BILLINGS, JR.

to eiglht. and occeasionallx miore. eirains of (lesiccated thyroi(l per day without
maintaining a raise Ietabolisill rate.gAt first the lbasal metabolism rises,
the lhorimionial iodinie--it von can nise that termi-also rises, tlleni the tlhyroid,
actilm,'g sliX\-iN a(lj Usts both blaiSl Metabolic rate and lhorimionial io(linle almiost
to the initial lev el; bnt somiie paticlnts, oil dosage of four to six or eighit
-raiins per day, are niot able to accomplishi the liolmneostasis andcl stiffer svmlip-
toml.s of lwpertliyroisill.
D)R. BILL INGS Closing] : The olie thing- I w outld like to say, directly
commnientimig 0lm the coiitributioni each Of the discussors has ila(le, is that
this 11111) 0, ati'iits woUld be a very initeresting one to investigate more
th1oronghlvX wx ith radioactive iodinie and Vi it11iirotein-bound iodinie studies.
Hoxxexer, thlev are all so constitutionally set ti) and(I usnally so psychologically
mixe(l-tip that if at anx- tlime they are suibjected to granidiose medical and
scienltific investigations, imistea(l of helping themii, oIIe lhindCiers tlhem'i anld puts
the hypothyroid stig-ma more deeply UpOnl themii.
D)r. YoumIIaiis commI11ien1tedI on1 tlis problem in a (liiseissiin siiailar to this
at Vami(lerbilt ami(I sug--ested thlit these stti(lies be carried otit. I mildly
objected for the reasolns I have stated, anld lhe said, "NN'ell, of course, you
canniot make ani om1elet witliout breaking Some eggs." and(lit appears that
before this problem is conmpletely settled, a fewx eggs inay have to be broken.