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Hypothyroidism and Bladder Function; An Experimental Study
HYPOTHYROIDISM AND BLADDER FUNCTION; AN EXPERIMENTAL STUDY JAMES W. SHERRILL
AND
EATON M. MACKAY
From The Scripps Metabolic Clinic, La Jolla, California
Urological symptoms caused a patient with myxedema and another with a less marked degree of hypothyroidism to seek medical attention. A marked degree of bladder atony was evident in these individuals. Beck has found urological symptoms very frequently in myxedema and Evans as well as Escamilla, Lisser and Shepardson have reported cases of myxedema with an impressive degree of atony of the bladder. The volume of residual urine in our patients attracted our attention to bladder dysfunction in hypothyroidism and prompted the experimental study of the influence of hypothyroidism in the rat upon bladder function which is reported here. An attempt was made to examine the influence of thyroid activity upon bladder tone and hence the functioning of this viscus in a number of different ways. A summary of the methods which gave satisfactory results is presented in the experiments forming table 1. Adult male rats were placed upon a special diet, adequate for maintenance, when they were 170 days old. At 200 days of age one group was thyroidectomized and a third group began to receive 0.1 per cent U. S. P . desiccated thyroid in their diet. Eighty-five days later the first test of bladder tone was carried out. Bladder tone was measured as follows: Each rat was given an intraperitoneal injection of 2 cc per sq. dcm. of body surface of a 20 per cent solution of the radio-opaque compound Hippuran. Radiographs were made of the rat held prostrate on its back at intervals thereafter. The urine containing the iodine compound outlined the bladder. The animals struggled and to some extent this complicated the comparison. The thyroid-fed group particularly were nervous and difficult to keep quiet. They tended to void prematurely, but the outlines of the bladder area in figure 1 show a definite tendency for the thyroidectomized rats to attain a greater bladder volume and to retain the urine longer before voiding than the other groups. This is evident in spite of the somewhat slower urine formation in this group. Presumably this laxity of the bladder wall is a result of hypothyroidism. 34
35
HYPOTHYROIDISM AND BLADDER FUNCTION
When these rats were 480 days old the experiment was terminated. It might be mentioned that while the control and hypothyroid groups TABLE
NUMBER
I 170 days old
L ~Influence of thyroid activity on bladder tone BODY WEIGHT IN GRAMS
j 200 days old j 285 days old j 480 da.ys old
BLADDER
TEST OF BLADDER TONE*
E::M:PTYING
seco
min.
TIME
Control diet 1
2 3 4 5 6 7 8
288 267 264 263 252 251 236 204
335 317 310 270 255 300 270 250
490 450 540 417 480 455 469 390
380 360 418 362 330 370 350 323
Average.,. . . . . . . . . . . . . ........
. .
.. . .. . . . . . . . . . . . .. . . ...
65 44
23 52 34 45 61 50 47
2 5+ 1
3 1
2 2
Thyroidectomized
9 10 11
12 13 14 15 16 Average. ....
286 279 265 260 253 249 234 211 '''
.
. .. . . . . . .
306 326 275 267 286 260 256 266
370 340 304 358 338 360 335 354
.. .. . . . . . . . . . . . . . .
....
504 476 425 405 421 490 425 381
26 30 14 20 12 15 8 35
. ......
20
6
10+ 3 5 4
10+ 6
Fed desiccated thyroid
17 18 19 20 ' 21 22 23 24
285 282 266 254 253 240 231 224
295 300 300 279 268 260 255 251
293 301 294 282 320 254 259 260
43 75 32
285 305 310 264 293
61 40
257
55
Average ...... . . . . . . . . . . . . . . . . . . . . ........... . .... . . . . .
51
1
3 2 4
2
* See text for description, weighed almost the same the latter had only 6 per cent body fat in comparison with close to 30 per cent in the controls. The extra
36
JAMES W. SHERRILL AND EATON M. MACKAY
weight in the thyroidectomized animals was undoubtedly due to myxedema. At the end of the experiment the rats were etherized, the abdomen opened and the bladder exposed. A 20-gauge hypodermic needle, connected with a water manometer, reservoir and pressure bulb system, filled with 0.8 per cent NaCl, was thrust through the bladder wall and the pressure raised to 600 mm. in a few seconds. The time TIME IN MINUT ES AFTER DYE INJECTION
2
CONTROLS
3 4
5
9
10
THYROIDECTOMIZED
II
12 13
17 18
THYROID FED
19 20 21
15
30
45
75
105
135
• •• •••• • •••• •• • • • •••• • • •• • • • ...., •
•
····....• , ···-· • --,~• •• •
•
•• •• •
• •
• •• ••• • •· •• • • • •• •
•
Fm. 1
required for the pressure to fall to 200 mm. was recorded in seconds. Naturally, the less tone in the bladder wall the more rapid this pressure fall would be. In table 1 it can easily be seen that this test indicates a much more flaccid bladder wall in the hypothyroid rats. This is evident from the individual observations as well as the averages. In the hyperthyroid group there were several very long pressure falls although the average is similar to that of the controls.
HYPOTHYROIDISM AND BLADDER FUNCTION
After the above test the needle was withdrawn from the bladder and the opened abdominal wall brought together with a hemostat. Some of the rats were kept under ether until they voided. The approximate time before voiding is recorded in table 1. It was definitely longer in the hypothyroid group. Our results demonstrate very clearly the regular occurrence of bladder atony in hypothyroidism in the albino rat. This may be a result of the lack of the well known influence of the thyroid hormone upon the various elements of the nervous system or more likely due to the depressed metabolism of the muscle tissue in the bladder wall similar to the altered function of other tissues. SUMMARY
A.tony of the bladder observed in patients suffering from hypothyroidism stimulated an experimental study of the relation of these conditions in the albino rat. Hypothyroid rats regularly showed bladder atony as measured by the filled area shown by a radio-opaque compound in urine-bladder emptying time and the lowered ability to sustain an artificial increase in the intra-bladder pressure. REFERENCES BECK, H. G.: Association of urologic lesions with hypothyroidism. Endocrinology, 11: 438, 1927. EsCAivIILLA, R. F., H. LISSER AND H. C. SHEPARDSON: Internal myxedema: Report of a case showing ascites, ca.rdiac, intestinal and bladder atony, menorrhagia, secondary anemia and associated carotinemia. Annals Int. Med., 9: 297, 1935-36. EVANS, W.: Case of myxedema with ascites and atony of the bladder. Endocrinology, 16: 409, 1932.
AND
EATON M. MACKAY
From The Scripps Metabolic Clinic, La Jolla, California
Urological symptoms caused a patient with myxedema and another with a less marked degree of hypothyroidism to seek medical attention. A marked degree of bladder atony was evident in these individuals. Beck has found urological symptoms very frequently in myxedema and Evans as well as Escamilla, Lisser and Shepardson have reported cases of myxedema with an impressive degree of atony of the bladder. The volume of residual urine in our patients attracted our attention to bladder dysfunction in hypothyroidism and prompted the experimental study of the influence of hypothyroidism in the rat upon bladder function which is reported here. An attempt was made to examine the influence of thyroid activity upon bladder tone and hence the functioning of this viscus in a number of different ways. A summary of the methods which gave satisfactory results is presented in the experiments forming table 1. Adult male rats were placed upon a special diet, adequate for maintenance, when they were 170 days old. At 200 days of age one group was thyroidectomized and a third group began to receive 0.1 per cent U. S. P . desiccated thyroid in their diet. Eighty-five days later the first test of bladder tone was carried out. Bladder tone was measured as follows: Each rat was given an intraperitoneal injection of 2 cc per sq. dcm. of body surface of a 20 per cent solution of the radio-opaque compound Hippuran. Radiographs were made of the rat held prostrate on its back at intervals thereafter. The urine containing the iodine compound outlined the bladder. The animals struggled and to some extent this complicated the comparison. The thyroid-fed group particularly were nervous and difficult to keep quiet. They tended to void prematurely, but the outlines of the bladder area in figure 1 show a definite tendency for the thyroidectomized rats to attain a greater bladder volume and to retain the urine longer before voiding than the other groups. This is evident in spite of the somewhat slower urine formation in this group. Presumably this laxity of the bladder wall is a result of hypothyroidism. 34
35
HYPOTHYROIDISM AND BLADDER FUNCTION
When these rats were 480 days old the experiment was terminated. It might be mentioned that while the control and hypothyroid groups TABLE
NUMBER
I 170 days old
L ~Influence of thyroid activity on bladder tone BODY WEIGHT IN GRAMS
j 200 days old j 285 days old j 480 da.ys old
BLADDER
TEST OF BLADDER TONE*
E::M:PTYING
seco
min.
TIME
Control diet 1
2 3 4 5 6 7 8
288 267 264 263 252 251 236 204
335 317 310 270 255 300 270 250
490 450 540 417 480 455 469 390
380 360 418 362 330 370 350 323
Average.,. . . . . . . . . . . . . ........
. .
.. . .. . . . . . . . . . . . .. . . ...
65 44
23 52 34 45 61 50 47
2 5+ 1
3 1
2 2
Thyroidectomized
9 10 11
12 13 14 15 16 Average. ....
286 279 265 260 253 249 234 211 '''
.
. .. . . . . . .
306 326 275 267 286 260 256 266
370 340 304 358 338 360 335 354
.. .. . . . . . . . . . . . . . .
....
504 476 425 405 421 490 425 381
26 30 14 20 12 15 8 35
. ......
20
6
10+ 3 5 4
10+ 6
Fed desiccated thyroid
17 18 19 20 ' 21 22 23 24
285 282 266 254 253 240 231 224
295 300 300 279 268 260 255 251
293 301 294 282 320 254 259 260
43 75 32
285 305 310 264 293
61 40
257
55
Average ...... . . . . . . . . . . . . . . . . . . . . ........... . .... . . . . .
51
1
3 2 4
2
* See text for description, weighed almost the same the latter had only 6 per cent body fat in comparison with close to 30 per cent in the controls. The extra
36
JAMES W. SHERRILL AND EATON M. MACKAY
weight in the thyroidectomized animals was undoubtedly due to myxedema. At the end of the experiment the rats were etherized, the abdomen opened and the bladder exposed. A 20-gauge hypodermic needle, connected with a water manometer, reservoir and pressure bulb system, filled with 0.8 per cent NaCl, was thrust through the bladder wall and the pressure raised to 600 mm. in a few seconds. The time TIME IN MINUT ES AFTER DYE INJECTION
2
CONTROLS
3 4
5
9
10
THYROIDECTOMIZED
II
12 13
17 18
THYROID FED
19 20 21
15
30
45
75
105
135
• •• •••• • •••• •• • • • •••• • • •• • • • ...., •
•
····....• , ···-· • --,~• •• •
•
•• •• •
• •
• •• ••• • •· •• • • • •• •
•
Fm. 1
required for the pressure to fall to 200 mm. was recorded in seconds. Naturally, the less tone in the bladder wall the more rapid this pressure fall would be. In table 1 it can easily be seen that this test indicates a much more flaccid bladder wall in the hypothyroid rats. This is evident from the individual observations as well as the averages. In the hyperthyroid group there were several very long pressure falls although the average is similar to that of the controls.
HYPOTHYROIDISM AND BLADDER FUNCTION
After the above test the needle was withdrawn from the bladder and the opened abdominal wall brought together with a hemostat. Some of the rats were kept under ether until they voided. The approximate time before voiding is recorded in table 1. It was definitely longer in the hypothyroid group. Our results demonstrate very clearly the regular occurrence of bladder atony in hypothyroidism in the albino rat. This may be a result of the lack of the well known influence of the thyroid hormone upon the various elements of the nervous system or more likely due to the depressed metabolism of the muscle tissue in the bladder wall similar to the altered function of other tissues. SUMMARY
A.tony of the bladder observed in patients suffering from hypothyroidism stimulated an experimental study of the relation of these conditions in the albino rat. Hypothyroid rats regularly showed bladder atony as measured by the filled area shown by a radio-opaque compound in urine-bladder emptying time and the lowered ability to sustain an artificial increase in the intra-bladder pressure. REFERENCES BECK, H. G.: Association of urologic lesions with hypothyroidism. Endocrinology, 11: 438, 1927. EsCAivIILLA, R. F., H. LISSER AND H. C. SHEPARDSON: Internal myxedema: Report of a case showing ascites, ca.rdiac, intestinal and bladder atony, menorrhagia, secondary anemia and associated carotinemia. Annals Int. Med., 9: 297, 1935-36. EVANS, W.: Case of myxedema with ascites and atony of the bladder. Endocrinology, 16: 409, 1932.