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THE HISTOLOGY OF THE THYROID IN ANIMALS FED ON VARIOUS DIETS.'
By MACKENZIE DOUGLAS.
From the Caneer Hospital &search Instit&e, Brmpton, London, S! W.
(PLATES XXS1.-XXXII.)
IN a paper recently published on the " Glands of Internal Secretion in Pigeons suffering from Beri-beri," Funk and Douglas (1 9 14 3, stated that the changes in the thyroid were difficult to interpret, as the appearances wried so greatly in the different birds, and that this was true also of the normal pigeons examined. Since then I have had an opportunity of examining a large number of thyroids of animals of various kinds, fed on a variety of diets. The object of the present comiuunication is to record the histological appearances found in this investigation. The animals examined were pigeons, fowls, mostly injected with Rous's chick sarcoma, chicks, rats, and rabbits.
PIGEONS.
The largest proportion of animals examined were pigeons, and these may he dealt with first. The thyroids in the pigeon are small bodies, situated in the upper part of the thorax, close to the arteries and reins of the neck, one on each side of the trachea. The thyroids were taken from the animals, in all cases shortly after death, in some cases within a few hours, and in other cases immediately after the animal was killed. The tissues were fixed in sublimate formalin or in zenker. All the animals were kept in the same room, and climatic conditions cannot be responsible for the variations in appearance, because from January to July the change did not vary with the season, and in an animal room the temperature is kept fairly constant. The sex of the animals was noted in some cases, but not in all, as it was soon discovered that the appearance did not differ with the sex. The diif'erence in the appearance of the vesicle, the shapes of the cells, and the amount of colloid present was noted by Baber (1882 I), who considered that these were due to the state of functional activity of
Received August 29, 1914.
342 MACKENZIE DOUGLAS.
the gland a t the time of removal. Chalmers Wabson (1909 3), investi- gating the thyroid in wild rats, found differences similar to those about to be described, and concluded that they represent modifications in structure and function of the gland, which have been induced by dietetic or other factors in the animal’s environment.
The pigeon has been utilised largely in feeding experiments, because i t has been found possible to produce in them a condition which is considered by Funk and others to resemble beri-beri in man, and has been termed by them “pigeon beri-beri.” After feeding pigeons for some time on polished rice, that is, the ordinary commercial rice, free from pericarp which contains the “ vitamines,” the birds lose weight and suddenly develop weakness and assume the characteristic attitudes, with retraction of the head, ataxic gait, and muscular inco- ordination. An examination of the liver, spleen, kidney, and ductless glands showed changes of atrophy, the most remarkable being the very marked atrophy of the thymus. A similar atrophy of the thymus, perhaps not so extreme, but in many cases very marked, has also been noticed in many of the animals in which the beri-beri condition had not developed. It was considered possible that there might be changes also in the thyroid, and a large number of pigeon thyroids have been examined to see what the histological picture is in this condition and with a variety of diets. No common or characteristic appearance was found. In fact, the great difference in the thyroids of animals fed on similar foods and kept under similar conditions was the most remark- able thing noticed. These appearances may be classified under the following heads :-
1. Thyroids with large and medium-sized vesicles full of colloid with little interstitial tissue. The cells lining the vesicles are flattened or a t most only slightly cubical (Plate XXXI. Fig. 2).
2. Thyroids in which the vesicles are not so large and not so distended with colloid, while many of them have little colloid remain- ing. The cells are cubical and tend even to become columnar in shape. In many cases the vesicles have a branched appearance, but in most are round and small. The interstitial tissue is usually greatly increased. Often it happens that a thyroid appears to have two zones, an outer and an inner, the vesicles in the outer ring resembling those of No. 1, while the inner zone has smaller vesicles with less colloid.
3. l%yroids in which the vesicles are small and collapsed with very little or no colloid. In these the interstitial tissue is very small in quantity. The cells lining the vesicles are large and columnar and the distinction between the flattened cell of No. 1 and this variety is very marked (Plate XXXII. Fig. 5).
4. I n many thyroids there is disintegration, either partial or complete. I n the outer zone the vesicles are still well-preserved, while in the centre of the gland the vesicles are breaking up with complete absence oE colloid. But in
In some the two zones are distinct.
HISTOLOGY OP TNE THYROID IN ANIMALS. 343
many cases the whole thyroid may show disintegration. In extreme cases, only the framework is left standing out distinctly with no colloid remaining or only slight shreds of it, while the cells are all separated and lying free in the vesicular space. Many of the nuclei are small and dark. The interstitial cells are very few in this type of thyroid.
Many of the last class were fixed shortly or imniediately after the animal’s death before any post-mortem change could have occurred.
Of these 62 had beri-beri. The results of the examination of the thyroids may be tabulated as follows :-
These are the typical cases, but there are stages between.
The thyroids of 150 pigeons were examined.
TABLE I.
Pigeons which developed beri-beri, and
Polished rice did not develop beri-beri . . Foodniixture . . . . . . Casein diet, . . . . . . . Fat diet . . . . . . . Starch diet , . . I
received various treatments
Sugar diet . . . . . . . Polished rice and bread . . . . Food niixturas, with pure butter replacing
the fat Food mixture, with butter extract replacing
the fat Food mixture, with butter from which the
extractives were removed replacing the fat Fat free diet . . . . . . Polished milled cooked rice. . . . Stock . . . . . . . .
Total . . . .
Ul
a - Y
10
4
2
8
4
2
5
... 6
3
... 2
... 1
44
4
23
1
... 1
1
...
... 2
... 1
1
a ...
36
__ 15
17
...
...
...
...
... 3
3
...
...
...
... 2
40
~
7
18
...
...
...
... 2
1
...
...
... 2
...
30
Total.
33
62
3
6
5
3
7
3
11
3
1
3
4
3
150
The numbers of the classes coi~espond with the classification given above.
The food mixture in the above experiments consisted of an arti- ficial diet, whose composition was--casein, 20 ; starch, 33.5 ; sugar, 18 ; fat, 25.5 ; salts, 3. All the three animals developed beri-beri.
344 MACKENZIE DOUGLAS.
The casein diet was composed of casein, 60 ; starch, 1 2 ; sugar, 13 ; fat,
The starch diet had the composition-starch, 60 ; casein, 12 ; sugar, 12 ;
The sugar diet consisted of sugar, 60; casein, 1 2 ; starch, 13 ; fat, 12; Two of the birds with Class I. thyroid had beri-beri and one of those
The
12 ; salts, 4.
fat, 12 ; salts, 4.
salts, 4. of Class IV.
The fat-free diet was casein, 12 ; sugar, 42 ; starch, 43 ; and salts, 4. animals were killed after fourteen days and had not developed beri-beri.
Five of the birds developed beri-beri.
Two of the birds with thyroids of Class I. had beri-beri.
I n the case of the pigeons fed on polished rice and bread there was a lack of colloid, and the cells were columnar in all three examined. Only oue had developed beri-beri, the other two dying before it had time to develop. I n this case it is interesting to note that Funk (1914 8) and others have observed that the addition of carbohydrates to a vitaniine free diet hastened the outbreak of beri-beri.
I n the other cases, butter was used in some cases aa the fa t ; in some, acid extracts of butter ; and in others the butter added minus the extracts.
I n nearly all the pigeons there was considerable loss of weight. From Table I. it will be seen that the onset of beri-beri is not marked by the presence of any type of thyroid. Of the beri-beri pigeons, 18 per cent. had disintegrated or partially disintegrated thyroids as compared with 20 per cent. of all the pigeons taken together.
The first three classes of thyroid are found probably quite inde- pendent of pathological causes and have been found in apparently normal animals. The marked disappearance of colloid in the majority of animals fed on polished rice is the most marked feature in the table. Colloid is generally considered to be the medium for the active part of the secretion.
Oswald (1 897 O) stated that the colloid varies in quantity according to the amount of iodine present in the thyroid. Further investigation on this point will be nmde at a later date.
FOWLS.
The thyroids of five adult 1,1ymouth rock fowls were examined. All these had been injected with Rous’s tumour, and growths were present in five of them. I n fowls one comes across large vesicles and more flattened epithelium than in pigeons, in which cubical epithelium is distinctly more comnion (Plate XXXI. Fig. 1). In the four fowls with tumours two had thyroids of Class I. and two of Class 11,, the vesicles tending in these to be somewhat irregular in shape. In the fowl with no growth the thyroid was of Class I.
CHICKS.
The thyroids of twenty-two chicks were examined ; of these twelve were fed on special diets, while the other ten were injected with
HISTOLOGY OR THB THYROID IN ANIMALS. 345
Rous’s tumour, alcoholic extract of Rous’s tumour, or with Rous’s tumour plus some arsenical compound (Plate XXXI. Fig. 3,and Plate XxliII. Fig. 5).
The seven chicks on ordinary laboratory diet had special feeding, but for periods varying from two to several weeks had been on ordin- ary food, so that they must be considered as chicks on normal food.
The noticeable point is, that in chicks also, we meet with appear- ances, histologically quite different, in animals under very similar conditions.
i I .
B O C
1 2 2
1 ... 1 ... 1 ... 1 ...
... 1
e E s 3 1 s
_ _ ~ -
. . . . . . 1
6 , 3
TABLE 11.
C h i k
1
1
1
1 .
... 1
. . . . . .
7
Fed on ordinary chicken food . . . Injected with Rous’e turnour . . . Injected with alcoholic extract of Rous’s
Injected with Rons’e tnmour and various
Fed on fermented barley . . . .
turnour
arsenical compounds
Fed on ungerminated Larlcy . . . Fed on polished rice, red rice, cod-liver oil
Fed on polished rice, red rice, and cod-liver unextracted, and egg yolk
oil unextracted
Total . . . .
- f G
3
-
...
... 4
...
...
...
...
- c
__
Total.
23
RATS.
The thyroids of rats were examined at intervals after feeding. This was to decide the point as to whether these changes might not be due to changes in the gland and its cells, corresponding to those seen in liver cells. notices in wild rats that it was possible to get thyroids of Class I. in animals in which the stomach was full, and also when it was empty. The investigation in this case confirmed that observation. In the rat the most common appearance ie that of a thyroid with cubical cells and not much dis- tension of the vesicles with colloid. This waa observed in the majority of these normal rats, whether the animal had recently fed or time had been allowed to elapse to let the stomach and small intestine empty themselves. A number of rats, also on special diets, were examined, and also a few which had tumours growing in them.
Chalmers Watson (1909
346 MACKENZIE DOUGLAS.
TABLE 111.
Rats.
Fed on ordinary laboratory diet of bread . Rat embryo . . . . . . Rat with spontaneous tumour . . . Injected with rat carcinoma . . .
Injected with niouse chondroma . . . Injected with rat sarcoma; fed for three weeks on sterilieed food
Food mixture with fat in form of pure butter
Food mixtnrc with fat in form of margarine.
Food mixture with fat in form of acid ex-
Food mixture + lard + ether extract of yolk tracted butter
of egg __
Total . . . .
CI
mm 5
3
_-
...
... I
...
...
...
... 1
... .. -
5
4 m U
S
G __ 25
1
...
... 1
... 1
...
...
1
29
ri U U
m m 0
5
2
...
...
...
...
...
...
...
...
...
2
1
... 1
...
...
1
1
1
2
4
11
Total.
31
1
1
1
1
1
2
I
3
5
--
45
In many of the rats on special diets there was considerable loss of weight, and, as in the pigeons, there seems to be some association between the weakened animal and the degeneration of the thyroid.
RABBITS.
I have had the opportunity of examining the thyroids of several rabbits injected with the Streptococcus .rhciimaticits, and found that in them the thyroids have mostly fair-sized vesicles, with abundant colloid contents and lining cells of cubical type. In one animal with an abscess in the abdominal wall, the causal organism of which wae not determined, the colloid had entirely disappeared. The vesicles were collapsed and the cells columnar (see Plate XXSZI. Fig. 6).
Farrant (1914 *) has recently attempted to diflerentiate diseases by the effects on the thyroid. The experimental evidence on this point was based on the histological appearances of thyroids of guinea-pigs, injected with different organisms. His results were extremely inter- esting. Some of the animals which I have examined had either abscesses or some septic condition, but the causal organism was not followed out in each case, and no distinctive changes were noticed in those cues observed. That the thyroid has some function in the production of immunity is quite possible, and must be borne in mind
HISTOLOGY OF THE THYROID IN ANIMALS. 347
in considering its histology. On the other hand, care has to be taken in interpreting the results, as the appearance of thyroids of animals under exactly similar conditions is so diflerent that it would be necessary to have a large number of aninids inoculated with the same organism or toxin. Further, if in artificially fed animals the condition of the animals, e.g., cachexia, is of importance, the dose and virulence of the toxin and the reaction of the animal must be taken into consideration.
CONCLUSIONS. 1. There are no characteristic appearances in the pigeon in the
condition of beri-beri. 2. In pigeons fed on polished rice, the tendency is for the
disappearance of colloid from the vesicles of the thyroid. These animals are, for the most part, not so well nourished as normal birds.
3. The histological appearances do not represent different stages of secretion, comparable to those of secreting glands engaged in the process of digestion.
4. Under similar conditions and in animals fed on similar diets, the appearances in the thyroid differ very markedly. One observes all stages, from the type with large vesicles, full of colloid with flattened cells, to that of a thyroid with no colloid and columnar-shaped cells. Also the thyroid may be wholly or partially disintegrated.
5. The variation, in appearance, of the thyroid seems to depend to some extent on the nutrition, and is thus only in this way de- pendent on the diet.
REFERENCES. 1. E. C. BABER . . . . . Phil. Tram., London, 1881, vol. clxxii.
2. C. FUNK AND M. DOUQLAS Journ. PhpioZ., London, 1914, vol. xlVii.
3. C. WATHON . . . . . Quart. Journ. Exper. Physiol., London, 1909, vol. ii. p. 383.
4. R. FARRANT . . . . . Brit. Med. Journ., London, 1914, vol. i. p. 470; Lancet, London, 1914, vol. i. p. 680
5. C. FUNK AND VON SCHOX- .Journ. Pliysiol., London, 1914, vol. xlviii.
p. 577.
p. 475.
BORN p. 328. 6. SWALE VINCENT . . . . “Internal Secretion and the Ductless Glands,”
London, 19 12.
1912.
Bd. lxxxix. S. 373.
7. A. BIEDL . . . . . . “The Internal Secretory Organs,” London,
8. C. FUNK . . . . . . Ztschr. f. phyeiob. Chent., Strassburg, 1914,
9. OSWALD. . . . . . . Ibid., 1897, Bd. xxiii. S. 306.
DESCRIPTION OF PLATES XXX1.-XXXII. PLATE XXXI.
Fro. 1.-Thyroid of fowl, injected with Rous’s tumour. The vesicles are large and dis- tended with colloid. The lining cells are flattened and there is little interstitial tissue. ( x 86.)
348 HISTOLOGY OF THE THYROID IN ANINALS.
FIG. 2.-Thyroid from a pigeon with beri-beri. The vesicles are not so large as in Fig. 1, and not distended, but still there is abundant colloid. There is also some increase in the interstitial tissue, and the cells are slightly cubical. ( x 85.)
FIG. %.-Thyroid of a chick, showing the vesicles fairly large, with large amount of colloid and little intcrstitial tissue. The cells are cubical. This chick had had various artificial diets, but for some time had been on the ordinary laboratory diet. ( x 250.)
PLATE XXsII.
FIG. 4.-Thyroid of a pigeon fed on polished rice. Beri-beri had not developed. The colloid has disappeared or is rcpresented only by strands. The lining cells are large and columnar in shape, and there is very little interstitial tissue. ( x 250.)
The chick had lost weight. The vesicles are disintegrated. The colloid has disappeared and the cells lining the vesicles have separated and are lying free in the lumen. Hany of the nuclei are pyknosed and degenerating. This is a type found in inany animals, but not so advanced as often seen.
The colloid has disappeared and the cells lining the vesicles are large and columnar. There is very littlc interstitial tissue. ( x 250.)
Fro. 5.-Thyroid of a chick, with a large Rons’s tumour growing.
( x 250.) FIG. &-Thyroid of a rabbit with abscess.
JOUMAL OF PATHOLOOY.-VOL. SIX. PLATE XXXI.
We. 1.
FIG. 2.
FIG. 8.
JOURNAL OF PATHOLOQY.-VOL. XIX.
FIQ. 4.
FIG. 6.
PLATE XXXII.
FIG. 6.
