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hence its richness in mucin (see note 1, p. 942). The connection of
myxoedema with affections of the thyroid was first recognised by Ord 2
in 1878 — an observation which has since been abundantly confirmed.
In 1882, J. L. Keverdin ^ described the symptoms which follow com-
plete removal of the thyroid body for goitre in man, and recognised
these symptoms as identical with those of the disease which had been
described under the name of myxoedema; he accordingly termed
the collection of symptoms " operative myxoedema." ^ The results of
Eeverdin were speedily followed by those of Kocher, who described, in
a large number of cases, similar symptoms as following entire removal
of the thyroid in man.^ Kocher pointed out that the effects are most
marked in young subjects, and that they may not occur at all or
be little manifest as age advances. These observations of Eeverdin
and Kocher led to a renewal of his former experiments by Schiff,^ who
in 1884 published the results of sixty thyroidectomies upon dogs, in all
of which the result was speedily fatal,'' the operation being quickly
followed by the supervention of symptoms — tremors, spasms, and
convulsions — which seemed to point to a serious derangement in the
nutrition of the central nervous system.^ Schiff also discovered the
fact that the symptoms are prevented by a previous graft of a portion
of the gland beneath the skin or into the peritoneal cavity.

Dogs do not show the swollen condition of the connective tissues
which is a characteristic feature after thyroidectomy in man; this
appears to be due to the fact that in them a fatal result usually occurs
too rapidly to allow of the development of the so-called " myxoedema."
They are liable, amongst other symptoms, to a form of conjunctivitis

1 Trans. Clin. Soc. London, 1888, vol. xxi. Suppl. ; Journ. Path, and Bacterial., Edin.
and London, 1892.

' Med.-Chir. Trans., London, 1878. See also Hadden, Brain, London, 1883, p. 193,
and S. Mackenzie, Trans. Clin. Soc. London, 1888 (Report of Committee on Myxo?dema), for
an account of the symptoms of myxoedema in the human subject. For a very full bibliography
of observations on the thyroid and its connection with myxoedema, see Ord, in Allbutt's
"System of Medicine," 1897, vol. iv.

^ Rev. viM. dela Suisse .Rom., Geneve, 1882, p. 539; 1883, ISTos. 4 to 6 ; 1887, pp.
275, 328.

■* Termed also "cachexia strumipriva" and " cachexia thyreopriva. "

5 Arch./. Idin. Chir., Berlin, 1883, Bd. xxix. S. 254.

^ Mev. med. dela Suisse Rom., Geneve, Feb. and Aug. 1884, Bd. xviii. S. 25.

'' Schiff's dogs lived at longest fourteen days, when both lobes were simultaneously
removed ; if the removal was effected in two sittings, at a certain interval apart, the advent
of the characteristic symptoms was delayed or altogether averted.

** These experiments of Schitf have been confirmed by many subsequent observers, but the
literature of the subject is enormous, and only a few papers can here be mentioned — Wagner,
Wien. med. Bl., 1884, S. 25 and 30 ; Sanguirico and Canalis, Arch, per le sc. med., Torino,
1884, tome viii. ; Horsley, Proc. Roy. Soc. Lo7idon, 1884 and 1886, and Brit. Med. Journ.,
London, 1885, vol. i. p. 3 ; 1892, vol. i. p. 267 ; also Festschr. Rudolf Virchow, Berlin,
1891; Fuhr, Arch. f. exjier. Path. u. PharmakoL, Leipzig, 1886, Bd. xxi.; 1889, Bd. xxv. ;
Rogowitsch, Centralhl. f. d. med. Wisscnsch., Berlin, 1886, S. 530, and Arch, de physiol.
norm. et2Mth., Paris, 1888, p. 419 ; Albertoni and Tizzoni, Centralhl. f. d. med. Wissensch.,
Berlin, 1885, S. 419 ; Hoifa, Sitzungsb. d. phvs.-med. Gesellsch. zu Wurzburg, 1887,
S. 104; Ewald, Berl. klin. Wchnschr., 1887, 1889, and 1895; v. Eiselsberg, " Ueber
Tetanie im Anschluss an Kropfexstirpationen," Wien. klin. Wchnschr., 1890 ; Gley,
Arch, de physiol. norm, etpath., Paris, 1892, and subsequent volumes ; Cristiani, ibid., 1893 ;
Langhans, Virchow'' s Archiv, 1892, Bd. cxxviii. S. 400 ; Domenicis, Wien. med. Wchnschr.,
1895, S. 1620 ; G. Rouxeau, Arch, de physiol. norm. etp)ath., Paris, 1897, tome ix. p. 136.


with leucocytic infiltration of the cornea.^ Horsley was the first to
operate upon monkeys. He found that these animals survive the
removal of the thyroid much longer than do dogs, and that in them, as
in man, a " myxoedematous " condition gradually supervenes. They
also pass into a condition which is unmistakably similar to cretinism,
besides which, as in dogs, they are subject to the supervention of muscular
tremors. These, however, may be greatly abated, or their onset delayed,
if the animals are kept in a very warm atmosphere.

It was further found by Allara ^ and by Ewald ^ that no results are
obtainable by thyroidectomy in birds (although it is fatal to reptiles),
and most observers found the same to be the case with rodents and
herbivora generally.^ It is a noteworthy fact that in aged dogs thyroid-
ectomy does not produce the normal symptoms. In man also it is
found that the supervention of operative myxoedema is less frequent as
age advances.^ The absence of the result in birds has never yet been
satisfactorily explained ; but various attempts have been made to
explain the frequent absence of result in herbivora.^ It may be, either
that a portion of the gland has been left behind, or that the animals
were not kept under observation for a sufficient time (Horsley), or
that there existed in the particular case in question accessory thyroids
and parathyroids, separated from the main body and not removed in
the operation. This is the explanation which is given by Gley of the
negative results which usually attend thyroidectomy in rabbits. Gley
states that if in these animals care be taken to remove the accessory
structures as well, the usual symptoms supervene and are very rapidly
fatal.'^ Moreover, he finds that if in young dogs all the parathyroids
are removed, while the main body of the thyroid is left intact, the
symptoms which have been regarded as characteristic of complete
thyroid removal nevertheless supervene, an observation which, if con-
firmed, shows that it is these structures which are physiologically the
more important part of the organ.^

The symptoms which follow thyroidectomy are of two classes —
nervous and metabolic, although we are not able to say that the
nervous symptoms are not produced by metabolic changes in the tissues
of the nervous system ; nor is it certain that the metabolic changes in

^ Gley and Eothon-Duvigneaiid, Arcli. dcfliysiol. norm, etpath., Paris, 1894, p. 101.

^ Sperinientale, Firenze, 1885, p. 281.

^ Ewald and Rockwell, Arch. f. d. gcs. Physiol., Bonn, 1890, Bd. xlvii. S. 160.

^ Sanguirico and Orecchia (abstract in Centralhl. f. Physiol., Leipzig u. Wien, 1887,
Bd. i. S. 587).

^ Bourneville and Bricon {Arch, de ncuroL, Paris, 1886) have shown that the liability
to constitutional symptoms usually ceases at about the thirtieth year.

^According to Hriesacher (^rc/i./. Physiol., Leipzig, 1890, S. 509),the character of the food
in dogs modifies tlie effects of thyroidectomy. Dogs fed M^ith milk bear the operation better
than those fed on flesh, nor do they exhibit, as the latter often do, convulsions after a meal.

'' Compt. rend. Soc. dc bioL, Paris, 1891, pp. 841, 843. See also Edmunds, "Proc. Phys.
Soc," Journ. Physiol., CamlDridge and London, 1895, vol. xviii. Hofmeister {Bcitr. z.
klin. Chir., Tubingen, 1894, Bd. ii. S. 441), and Leonhardt (Virchows Archiv, 1897,
Bd. cxlix. S. 341) have also got positive results in rabbits ; and G. R. Murray has succeeded
in producing symptoms of mj'xoedema in a rabbit from which he had some time previously
removeii the thyroids {Brit. Med. Journ., London, 1896, vol. i. p. '204).

* Gley, Comjjt. rend. Soc. dc hiol., Paris, 1897, p. 181 ; Vassale and Generale, Arch,
ital. de hiol., Turin, 1895 and 1896, tome xxv. p. 459 ; and tome xxvi. p. 61 ; Edmunds,
"Proc. Phys. Soc," Journ. Physiol., Cambridge and London, 1896, vol. xx. ; also Travis.
Path. Soc. London, 1895, 1896, and Journ. Path, and Bacleriol., Edin. and London,
1896, vol. iii. p. 488. Blumenreich and Jacoby {Berl. klin. JFchnschr., 1896, S. 327) state,
on the other hand, that the inclusion or exclusion of parathyroids is immaterial to the
result of thyroidectomy (but cf. Gley, Arch. f. d. yes. PhysioU, Bonn, Bd. Ixvi. S. 308).



the tissues are not consequent on alterations in the nervous system.^
The most characteristic nervous symptoms are those which have been
ah'eady mentioned — muscular tremors, passing gradually into clonic
spasms, and finally into convulsive attacks (tetany) ; there is also apathy
and unsteadiness of gait, and, with the advance of time, the gradual
supervention of a cretinic condition, together with a lowering of the
body temperature and a diminution of cutaneous sensibility. The tremors
also gradually cease. Monkeys die in from five to seven weeks after the
operation. The tremors are of central origin ; they disappear on section
of the motor nerve (Schiff), but not on removal of the cortical brain
area concerned with the movements of the part (Horsley). They also
disappear when a voluntary effort is made, and on reflex irritation. In
monkeys there is extensor paralysis of the upper limb, and there may
occur attacks of functional hemiplegia.^ The attacks are diminished by
administration of potassium bromide.^ The number of red corpuscles
per becomes mark-
edly diminished, while the
white corpuscles tend to
increase in number. The
salivary glands become
swollen and enlarged, and
contain an excess of
mucin. Changes in the
composition of the blood
have also been observed,*
and in the proportions of
the blood gases,^ and de-
generative changes have
been described in the
kidneys.'' It has been
shown that the excita-
bility of the cortex of the
brain, and even of the
lower centres, is increased
in animals which have
suffered from thyroid-
ectomy,^ but with the ^i^. 84.— Monkey deprived of thyroid.— Hoesley.

supervention of the cretinous condition it is diminished.^ The metabolic
changes which occur are most obvious in the connective tissues, and

^ Whitwell {Brit. Med. Journ., London, 1892, vol. i. p. 430) found what he regards as
pathological changes in the nerve-cells of the Rolandic area in a case of myxoederaa. Marked
changes in the nervous elements have also been described as a feature of the condition
of cachexia thyreopriva ; Kopp, Virchow's Archiv, 1892, Bd. cxxviii. S. 290; Langhans,
ibid., S. 318; Capobianco, Internat. Monthly Journ. of Anat. and Physiol., 1894, Bd. xi.
S. 471 (abstract in Ccntralbl. f. Physiol., Leipzig u. Wien, 1893, Bd. vii. S. 112) ; Lorrain
Smith and Pembrey, " Proc. Physiol. Soc," Journ. Physiol., Cambridge and London,
1894, vol. XV.; Quervain, Virchow^s Archiv, 1893, Bd. cxxxiii. S. 481. Vassale and
Donaggio found degeneration in the pyramidal tract (!) of dogs, after extirpation of the
parathyroids {Arch. ital. de biol., Turin, 1896, tome xxvii. p. 129).

^ Horsley, lac. cit.

' Gley, Compt. rend. Soc. de biol., Paris, 1892, p. 300.

* Halliburton, loc. cit. ; Ducceschi, Centralbl. f. Physiol, Leipzig u. Wien, 1895, p.
359, and 1896, p. 217 ; also Arch. ital. de biol., Turin, tome xxvi. p. 209.

5 Albertoni and Tizzoni, loc. cit. (see also p. 943).

^ Rosenblatt, Arch. d. sc. biol., St. P^tersbourg, 1894, p. 53.

"^ Aiitokratotf (abstract in Brain, London, 1890, vol. xxiii. p. 424).

^ Horsley, Brit. Med. Jbttx^London, 1892, vol. i. p. 267.


especially in the integument. These tissues become swollen and contain
a superabundance of mucin ;^ the integument especially swells and the
eyelids become puffy, but at the same time the surface becomes dry,
and there is a tendency to the shedding of hairs and of the superficial
epithelium. This hyperplastic change is followed, if the animal remains
alive for a sufficient time, by atrophic changes. The nervous affection
which primarily results is usually accompanied by slight fever. Later
on this passes off, and the temperature becomes reduced even to some
degrees below normal.^

As Schiff originally showed, these effects of thyroidectomy can be
temporarily prevented by a graft of thyroid ; they may also be caused
to disappear either by injection of thyroid juice into a vein or under
the skin,^ or even by taking thyroid juice or raw thyroid by the
mouth. The effects of grafts are to all intents and purposes permanent,
and it has been found, as in the case of the pancreas, that removal of
the graft which has maintained the health of the animal after extir-
pation of its own thyroid, is speedily followed — as with primary removal
of the organ — by the usual symptoms of thyroidectomy. It appears,
however, to be somewhat difficult to ensure the graft taking.^

Theories of action of thyroid extirpation. — Various theories have
been advanced to account for the effects of removal of the gland.
H. Munk ^ held that the effects of removal are due, not to interference
with the functions of the gland, but to interference with adjoining
"nervous structures in the neck. But this, as with the similar theory
propounded to account for the effects of extirpation of the pancreas,
is absolutely negatived if the results of thyroid grafting are to be
accepted. Besides this theory, two others, out of the many which have
been put forward, deserve consideration.*^ Of these the one may be
called the theory of " autotoxication " and the other that of " internal
secretion." The autotoxication theory assumes that there are one or
more toxic substances constantly tending to accumulate in the blood,
and which it is the purpose of the thyroid gland to remove and

^ F. Semon [Brit. Med. Journ., London, 1883, vol. ii. p. 1073) has enunciated a theory
which deserves considei-ation here, to the effect that removal of the thyroid produces an
interference with the full chemical development of the constituents of the connective
tissues, so that these tend to take on an embryonic character ; and it is well known that
excess of mucin is characteristic of embryonic connective tissue.

^ See on this subject, Horsley, Brit. Med. Joiorn., London, 1892; Ughetti, Eiforma
med., Roma, 1890, vol. vi. p. 228.

^ Vassale, Puv. sper. di freniat., Reggio-Emilia, 1890, tome xvi. p. 439 (abstract in
Gentralbl. f. d. med. TFissensch., Berlin, 1891, S. 14) ; and Arch. ital. de hiol., Turin, 1892,
tome xvii. p. 173 ; Gley, Convpt. rend. Soc. de hioL, Paris, 1891, p. 251 ; G. R. Murray,
Brit. Med. Journ., London, 1891, vol. ii. p. 796 ; 1892, vol. ii. p. 449 ; 1893, vol. ii. p.
677 ; Schwarz, Sperimentale, Firenze, 1892, vol. xlvi. ; Arch. ital. de hiol., Turin, tome
xvii. p. 330; Chopinet, Compt. rend. Soc. de bioL, Paris, 1892, p. 602; Brown-Sequard,
Arch, de physiol. norm, et path., Paris, 1892.

■* V. Eiseisberg, Wicn. Iclin. Wchnschr., 1892, S. 81. For a successful case of thyroid
grafting in the human subject, see Macpherson, Edin. Med. Journ., May 1892.

5 Sitzungsh. d. k. Akad. d. JFissensch. zu Berlin, 1887, S. 823, and 1888, p. 1059.
See on the subject of Hunk's experiments, and also on thyroid grafting, Halstead, Johns
Hopkins Hasp. Rep., Baltimore, 1896, p. 373. The bulk of this paper deals with the
hypertrophy of the remaining portion which follows the removal of a part only of the
thyroid. In a recent paper {Virchow's Archiv, 1897, Bd. cl. S; 271) Munk endeavours to
maintain his position. He denies that either cachexia or myxcedema necessarily follows
thyroidectomy, but in this he is at variance with nearly all other experimenters and with
the result of clinical experience.

" For older theories regarding the functions of the thyroid, see Horsley, Brit. Med.
Journ., London, 1892, vol. i. p. 267 et seq.


render innocuous.^ According to this, tlie function of the thyroid
would be primarily excretory. This view is supposed to be sup-
ported by the observation, that the nrine of animals becomes, after
removal of the thyroid, more toxic than that of normal animals,^ and that
the blood is toxic for other animals, and especially for those which have
already had the thyroid removed, although this operation may have
been performed only a short time previously, and before the
symptoms of thyroidectomy have had time to develop. It is not stated
what the probable nature of this substance is, or by what tissues it
may be formed.

Effect of thyroid juice. — The " internal secretion " theory would
explain the phenomena of extirpation as due to the absence of a
secretion which is formed within the thyroid or parathyroids, and
passes from them into the blood ; a secretion which is necessary for
certain of the metabolic processes of the animal body, and especially
for those connected with the nutrition of the central nervous system
and of the connective tissues. That this view of the function of
the thyroid, which was the one given originally by Schiff, is in the
main the true one, is shown by the fact that beneficial and not
toxic effects follow the exhibition of thyroid juice, both in cases of
thyroidectomy in animals and in myxoedema and other affections in
man. Moreover, extracts of thyroid gland produce distinct physiological
effects in the normal subject.-'^ If a decoction of the gland be injected
into a vein, the blood pressure markedly falls (Fig. 85), although the
beats of the heart remain at about the same rate and of the same
strength as before.* This lowering of the blood pressure is not, however,
peculiar to the thyroid, but occurs with extracts of some other
secreting glands. But it has been shown by G. Oliver,^ that the
exhibition of thyroid juice or other preparations of thyroid seems to
possess a specific tendency to increase the calibre of the radial artery in
the human subject. It would seem, therefore, that the juice of the
thyroid, and extracts which are obtained from the gland, have a distinct
action upon the vascular system. It has further been noticed that feeding
with thyroid tends to cause increased metabolism in the body, accom-
panied by diuresis and diminution of fat, so that it has been proposed as
a cure for obesity.*' Thyroidectomy alters the conditions of the gaseous
exchange,^ and this in all probability by an indirect effect through
the vasomotor system. Lorrain Smith '^ found that in animals which
have been deprived of the thyroid body, the reaction to changes of
temperature is abnormally rapid. When normal animals are exposed to
a cold atmosphere, the production of carbon dioxide becomes increased,
consistently with the increased oxidation which is necessary to cause

^ Horsley, Froc. Roy. Soc. London, 1886, vol. xl. p. 6 ; Brit. Med. Journ., London,
1892 ; Blumeureich and Jacoby, Arch. f. d. ges. Physiol., Bonn, 1896, Bd. xiv. S. 1.

- Laulani(5, Compt. rend. Soc. de bioL, Paris, 1891, p. 307 ; see also Gley, ibid., 1894,
p. 192 ; and Masoin, ibid., p. 105.

^ Gley, Arch, de physiol. norm, etpath., Paris, 1894, p. 484.

^ Oliver and Schiifer, Journ. Physiol., Cambridge and London, 1895, vol. xviii. p. 277.

^ Croonian Lectures, Lancet, London, 13th June 1896.

® Leichtenstern, Deutsche vied. Wchnschr., Leipzig, 1894, No. 50. See on the physio-
logical action of thyroid extract, Ewald, loc. cit. ; Donatti, Virchoiv's Archiv, 1896, Suppl.
Bd. cxliv. S. 253 ; Berkeley, Joh^is Hopkins Hosp. Bull., Baltimore, July 1897. Berkeley
examined the nerve centres of animals which had died from prolonged administration of
thyroid extract, but could find no evidence of any changes in the nerve cells.

7 Michaelsen, Arch. f. d. ges. Physiol., Bonn, 1889, Bd. xlv. S. 622.

^ Journ. Physiol., Cambridge and London, 1894, vol. xvi. p. 378.


an increased production of heat. This increase of carbonic acid does not
take place immediately, but only comes on after a certain period of
time ; the temperature of the body being in the meanwhile maintained
normal by those physical changes which occur in the circulation, and
which allow the quantity of blood brought to the skin, and the amount
of heat thereby lost from the general surface of the body, to be varied.
Now, it is precisely these vasomotor changes which appear to be lack-
ing after removal of the thyroid ; for the production of carbon dioxide
becomes almost immediately increased by exposing thyroidectomised
animals to a low temperature. Cardiac palpitations with increased

Fig. 85. — Effect in the dog upon the blood pressure of the intravenous injection of decoc-
tion of thyroid. Time in seconds. The line above the time tracing is the abscissa
of the mercurial manometer.

pulse frequency, often accompanied by a feeling of giddiness, may
sometimes be produced by large doses of fresh thyroid ; after a time
glycosuria and increase of urea appear.^ Experiments upon the effect
of thyroid feeding on metabolism have been made by various observers.^
Eichter^ found in man no marked effect on nitrogenous metabolism,
but Bleibtreu and Wendelstadt and also Eoos got a distinct increase
of excreted nitrogen during thyroid feeding. Schondorff obtained an
increased excretion of nitrogen during the first eight days (in dog) ;
after that, N-balance was maintained, while the body-fat was greatly
diminished in amount. The sodium chloride and phosphoric acid were
also somewhat increased. Bettmann "^ states that thyroid feeding tends
to produce "alimentary glycosuria" (see p. 881).

^ Georgiewsky, Centralbl. f. d. mcd. JVissensch., Berlin, 1895, Bd. xxvii.

2 Napier, Lancet, London, 1893, vol. ii. p. 805; Vermehren,i)cMtec7ic med. Ifc/iwsc/w. , Leipzig,
1893, No. 11 ; Bemng, Miinehen. med. Wchnschr., 1895, S. 464 ; Bleibtreu and Wendelstadt,
Deutsche med. JVchnschr., Leipzig, 1895, S. 346; Mediger, Diss., Greifswald, 1895
(abstract in Ceniralbl. f. Nervenh. u. Psychiat., Coblenz u. Leipzig, Bd. xviii. S. 289) ;
Lanz, Deutsche m,vd. Wchnschr., Leipzig, 1895, S. 597 ; Irsal, Vas, and Gara, ihid., 1896,
Bd. xxii. S. 439 ; Schondorff, Arch. f. d. ges. PMjsiol., Bonn, 1896, Bd. Ixiii. S. 423;
Gluzinski and Lemberger, Centralbl. f. innereMed., Leipzig, Bd. xviii. S. 90 ; Roos, Ztschr.
f. physiol. Chem., Strassburg, 1895,'Bd. xxi. S. 19; and 1896, Bd. xxii. S. 18; Giirber,
Sitzungsb. d. phys.-med. Gesellsch. zu Wurzburg, 1896, S. 101.

3 Centralbl. f. innere Med., Leipzig, 1896, S. 65.

4 Berl. Mill. Wchnschr., 1897, S. 518.


That the thyroid gland yields an internal secretion which subserves a
useful purpose within the body, appears to follow conclusively from these
data, and the effects which follow thyroidectomy are probably due to
the loss of that secretion. Whether the gland also possesses the
function of destroying toxic products of metabolism which would other-
wise tend to accumulate in the blood, a function which has been
attributed to it by some authors, is a point the evidence regarding
which is at present insufficient.

On account of its extreme vascularity and its direct connection with
the vessels which supply blood to the head, the thyroid has also been
regarded as exercising a regulatory function on the blood supply to the
brain, — short-circuiting by vaso-dilatation the cerebral blood flow, or vice
versd. This view, which was long previously enunciated by J. Simon,^
has been of late again brought into prominence by Stahel,^ whose
opinion is supported by that of Waldeyer,^ both of whom approach
the subject from the anatomical standpoint. More recently the matter
has been the subject of physiological experimentation by Cyon,* who
finds that the nerves passing to the thyroid contain powerful vaso-
dilatators, and that their stimulation may greatly lower the pressure in
the carotid. Cyon further states that they are called into action
very easily on excitation of the cut ends of the vagi, of the depressors,
or of the cardiac branches of the recurrent laryngeal nerves. After
removal of the gland, the excitability of these nerves is diminished, but
it is increased by the administration of thyroid preparations.

The mode of connection which unquestionably exists between turg-
escence of the thyroid and the other nervous and vascular symptoms
which characterise Graves's disease (exophthalmic goitre), is still quite
obscure. This affection is not, like ordinary goitre and myxoedema, bene-
fited by thyroid feeding ; but various observers have obtained consider-
able benefit by administration of the uncooked thymus of young animals.^

The Pituitaky Body.

The next organ the internal secretion of which we may shortly con-

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 132 of 147)