Ren Fail Downloaded from informahealthcare.com by McMaster University on 12/26/14 For personal use only.
HEMODIALYSIS AND THYROID FUNCTIONS I N CHILDREN James C M Chan, YB Nephrology S e c t i o n Department of P e d i a t r i c s Medical. C o l l e g e o f V i r g i n i a MCV S t a t i o n Box 822 Richmond, VA 23298 W e l l i n g t o n Hung, MD Department of E n d o c r i n o l o g y Children's Hospital National Medical C e n t e r 111 Michigan B l v d , NW Vashington, D . C . 20014
ABSTRACT E v a l u a t i o n of t h y r o i d f u n c t i o n s i n 1 6 c h i l d r e n r e c e i v i n g maint e n a n c e h e m o d i a l y s i s f o r a mean d u r a t i o n o f 1 7 months showed t h a t t h e serum T3, T4 and TSH w e r e below normal c o n c e n t r a t i o n s f o r a g e . However, t h e measurements of t h e s e v a r i a b l e s b e f o r e and a f t e r t h e d i a l y s i s p r o c e d u r e d i d n o t show a n y s i g n i f i c a n t c h a n g e s . The p o s s i b i l i t y t h a t t h e c h r o n i c uremia may g i v e r i s e t o abnormal TSH secret i o n and low T3, T4 c o n c e n t r a t i o n s i s n o t t e s t e d i n t h i s s t u d y .
INTRODUCTION
Prompted by c o n t r a d i c t o r y d a t a o n t h y r o i d f u r
ions i n adults
r e c e i v i n g maintenance h e r n o d i a l y s i s and t h e l a c k of s u c h s t u d i e s i n c h i l d r e n , we e v a l u a t e d t h e e f f e c t o f h e m o d i a l y s i s on t h y r o i d f u n c t i o n s i n 16 c h i l d r e n w i t h end-stage r e n a l f a i l u r e .
387 Copyright 0 1978 by Marcel Dekker. Inc All Rights Reserved Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying. microfilming, and recording. or by any information storage and retrieval system, without permission in writing from the publisher
388
CHAN AND HUNG MATERIALS AND METHODS Sixteen children with a mean duration of 17 months on maintenance
hemodialysis were studied. Their age, sex, duration of dialysis and primary renal diagnosis were presented in Table 1. Blood samples were obtained immediately before and after the 4-5 hour hemodialysis and evaluated for T3, T4, TSB according to the methods of Normura,
Ren Fail Downloaded from informahealthcare.com by McMaster University on 12/26/14 For personal use only.
Pittman and associates (1).
Normal ranges of concentration for the
age groups were previously established by Abbussi et a1 (2).
Serum
protein concentrations were measured by standard methods previously described (3).
Informed parental consent was obtained in each
patient.
TABLE I CHILDREN RECEIVING MAINTENANCE HEMODIALYSIS Primary renal disease
Mean Age at Mean Duration Male Female Start of Dialysis of Dialysis bas> (yrs)
Focal Glomerulosclerosis
12 t 4
18
2
3
Obstructive Uropathies
12 2 2
23
1
1
Chronic Glomerulonephritis
10 2 2
9
1
1
Cystinosis
13 2 4
17
1
1
Anaphylactoid Purpura-Nephritis
8
4
1
-
Medullary Cystic Disease
15
10
-
1
Sickle Cell Nephropathy
17
59
-
1
Wilm's Tumor, Radiation Nephritis
5
11
1
-
Proliferative Glomerulonephritis
6
1
-
1
HEMODIALYSIS AM) THYROID FUNCTIONS I N CHILDREN
389
RESULTS
The T3, T4 and TSH l e v e l s w e r e lower t h a n normal (Figure 1).
There
w a s no d i s c e r n a b l e d i f f e r e n c e f o r any of t h e s e v a r i a b l e s b e f o r e
and a f t e r hemodialysis.
The t o t a l p r o t e i n levels w e r e normal, al-
though t h e mean serum albumin level of 3.3 gmfdl w a s lower than
normal.
Ren Fail Downloaded from informahealthcare.com by McMaster University on 12/26/14 For personal use only.
DISCUSSION
With t h e exception of one a b s t r a c t (4) a l l previous r e p o r t s on t h e thyroid f u n c t i o n s i n hemodialysis d e a l t w i t h d a t a from
adults (5,6,7).
Our d a t a i n c h i l d r e n a f t e r a mean d u r a t i o n of 11
months on hemodialysis showed a tendency f o r T3, T4 and TSH t o be below normal l e v e l s f o r corresponding a g e and sex (Figure 1 ) . T h i s observation is i n c o n t r a s t t o t h e d a t a of Neuhaus e t a 1 (81, showing normal mean v a l u e s f o r T4 i n 25 a d u l t p a t i e n t s arter a mean d u r a t i o n of 1 112 y e a r s on maintenance hemodialysis, but i s in agreement with t h a t of Wassner e t al (4) in 9 c h i l d r e n a f t e r 3 months o f hemodialysis. The hypothesis, t h a t t h e kidney may play a r o l e in t h e maintenance of normal T3 l e v e l s (9, lo), and t h a t t h e d a t a documenting subnormal T 3 provides evidence f o r t h e e x i s t e n c e of s u b c l i n i c a l hypothyroidism i n r e n a l f a i l u r e , i s n o t supported by t h e p r e s e n t d a t a i n view of t h e low TSH values.
No d e f i n i t e d a t a a r e a v a i l a b l e
a t p r e s e n t t o s o l v e t h i s problem. S i m i l a r l y , t h e s p e c u l a t i o n t h a t uremia may i n h i b i t t h e p e r i p h e r a l conversion of T4 t o T3 a l s o l a c k d i r e c t s u p p o r t i n g d a t a a t
CHAN AND HUNG
390 CHILDREN (6-17 YRSJ
ADULTS > 1 8 YRS
MALE
FEMALE 150
126
. 0' m
100
E
Ren Fail Downloaded from informahealthcare.com by McMaster University on 12/26/14 For personal use only.
c "
I
4
1%
O
83f42
86f21
94f16
1
'1
5.5a2.3
a
6.0+3.5
w
4
A A 0 0
77fl6
0
58 f 4 7
0
1
8.9&3.4
7.SA3.7
7.3t2.s
I
3.4i2.3
3.912.9
4.5i1.6
PRE-HD
POST-HD
PRE-HD
0
I
4.6r2.3
5.2i3.3
PRE-HD
POST-HD
POST-HD
FIGURE I The pre- and post-dialysis serum T3, T4, and TSH values, in 15 study subjects aged 6-17 years and 1 subject over 18 years of age in comparison to normal values (shaded area) for their respective age group and sex. Normal values established by Abbussi, V., Aceto, T., and Hung, W. (2). Each symbol represents an individual patient receiving maintenance hemodialysis.
39 1
HEMODIALYSIS AND THYROID FUNCTIONS I N CHILDREN
p r e s e n t , although t h e r e i s s u g g e s t i v e evidence t h a t in 6 p a t i e n t s , serum T3 became s i g n i f i c a n t l y e l e v a t e d 1-3 months a f t e r i n i t i a t i o n
of maintenance hemodialysis ( 9 ) , as w e l l as normalization of
T4, T3 and TSH l e v e l s a f t e r r e n a l t r a n s p l a n t a t i o n (9,11,12). The p r e s e n t d a t a f u r t h e r documented a l a c k of d i f f e r e n c e between t h e pre- and p o s - d i a l y s i s values. I n conclusion, i t would appear t h a t t h y r o i d f u n c t i o n s a r e a f f e c t e d
Ren Fail Downloaded from informahealthcare.com by McMaster University on 12/26/14 For personal use only.
by t h e uremic s t a t e (11) b u t , t h a t t h e d i a l y s i s procedure p e r s e does not a l t e r t h e c o n c e n t r a t i o n of T3, T 4 , o r TSH, s i n c e t h e s e remain r e l a t i v e l y constant b e f o r e and a f t e r t h e d i a l y s i s procedure.
However,
t h e cumulative e f f e c t s of s m a l l and u n d e t e c t a b l e changes may result i n chemical hypothyroidism a f t e r long-term hemodialysis (12).
REFERENCES
1. Nomura, S . , Pittman, C.S., Chambers, J . B . , Jr.: Reduced p e r i p h e r a l conversion of thyroxine t o t r i i o d o t h y r o n i n e i n p a t i e n t s w i t h h e p a t i c c i r r h o s i s : J C l i n I n v e s t 56: 643-652, 1975. 2. Abbussi, V., Aceto, T., Hung W.: Thyroid f u n c t i o n i n r e l a t i o n t o age. I n t h e Ross Monogram: Children a r e d i f f e r e n t . 2nd ed. Ross Laboratories, Columbus, Ohio, 1977. Grushkin, C.M., Malekzadeh, M . , e t a l : The adaption 3. Chan, J . C . M . , of hydrogen i o n e x c r e t i o n a s s o c i a t e d w i t h nephron r e d u c t i o n i n post-transplant p a t i e n t s . P e d i a t r R e s 7: 712-718, 1973. 4. Wassner, S.H., Buckingham, B.A., Kershnar, A.K., e t a l : Thyroid f u n c t i o n i n chronic r e n a l f a i l u r e (CRF). P e d i a t r R e s 9: 295, 1975 (abstr)
.
5. Ramirez, G . , Jubiz, W., Gutch, C.F., e t a l : Thyroid a b n o r m a l i t i e s i n r e n a l f a i l u r e : A study of 53 p a t i e n t s on c h r o n i c hemodialysis. Ann I n t e r n Med 79: 500-504, 1973.
6. Oddie, T.H., Flanigan, W . J . , and F i s h e r , D.A.: Iodine and thyroxine metabolism i n anephric p a t i e n t s r e c e i v i n g c h r o n i c p e r i t o n e a l d i a l y s i s . J C l i n Endocr 31: 277-282, 1970.
392
CHAN AND HUNG
7. Koutras, D.A., Marketos, S.G., Rigopoulos, G.A., et al: Iodine metabolism in chronic renal insufficiency. Nephron 9: 55065, 1972. 8.
Neuhaus, K., Baumann, G., Walser, A., et al: Serum thyroxine and thyroxine-binding proteins in chronic renal failure without nephrosis. J Clin Endocrinol and Met 41: 395-398, 1975.
9. Lim, V.S., Katz, A.I., et al: Thyroid dysfunction in chronic renal failure: a study of the pituitary-thyroid axis and peripheral turnover kinetics of thyroxine and tri-iodothyroxine. J Clin Invest 60: 522-534, 1977.
Ren Fail Downloaded from informahealthcare.com by McMaster University on 12/26/14 For personal use only.
10. Spector, D.A., Davis, P.J., Helderman, J.H., Bell, B., Utiger, R.D.: Thyroid function and metabolic state in chronic renal failure. Ann Intern Med 85: 724-730, 1976. 11. Czernichow, P., Dauzet, M.C., Broyer, M., Rappaport R.: Abnormal TSH, PRL and GH response to TSH releasing factor in chronic renal failure. J clin Endocrinol Metab 43: 630-637, 1976.
12. Dandona, P., Newton, D., Platts, MA.: Long-term hemodialysis and thyroid function. Brit Med J 1: 134-136, 1977
HEMODIALYSIS AND THYROID FUNCTIONS I N CHILDREN James C M Chan, YB Nephrology S e c t i o n Department of P e d i a t r i c s Medical. C o l l e g e o f V i r g i n i a MCV S t a t i o n Box 822 Richmond, VA 23298 W e l l i n g t o n Hung, MD Department of E n d o c r i n o l o g y Children's Hospital National Medical C e n t e r 111 Michigan B l v d , NW Vashington, D . C . 20014
ABSTRACT E v a l u a t i o n of t h y r o i d f u n c t i o n s i n 1 6 c h i l d r e n r e c e i v i n g maint e n a n c e h e m o d i a l y s i s f o r a mean d u r a t i o n o f 1 7 months showed t h a t t h e serum T3, T4 and TSH w e r e below normal c o n c e n t r a t i o n s f o r a g e . However, t h e measurements of t h e s e v a r i a b l e s b e f o r e and a f t e r t h e d i a l y s i s p r o c e d u r e d i d n o t show a n y s i g n i f i c a n t c h a n g e s . The p o s s i b i l i t y t h a t t h e c h r o n i c uremia may g i v e r i s e t o abnormal TSH secret i o n and low T3, T4 c o n c e n t r a t i o n s i s n o t t e s t e d i n t h i s s t u d y .
INTRODUCTION
Prompted by c o n t r a d i c t o r y d a t a o n t h y r o i d f u r
ions i n adults
r e c e i v i n g maintenance h e r n o d i a l y s i s and t h e l a c k of s u c h s t u d i e s i n c h i l d r e n , we e v a l u a t e d t h e e f f e c t o f h e m o d i a l y s i s on t h y r o i d f u n c t i o n s i n 16 c h i l d r e n w i t h end-stage r e n a l f a i l u r e .
387 Copyright 0 1978 by Marcel Dekker. Inc All Rights Reserved Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying. microfilming, and recording. or by any information storage and retrieval system, without permission in writing from the publisher
388
CHAN AND HUNG MATERIALS AND METHODS Sixteen children with a mean duration of 17 months on maintenance
hemodialysis were studied. Their age, sex, duration of dialysis and primary renal diagnosis were presented in Table 1. Blood samples were obtained immediately before and after the 4-5 hour hemodialysis and evaluated for T3, T4, TSB according to the methods of Normura,
Ren Fail Downloaded from informahealthcare.com by McMaster University on 12/26/14 For personal use only.
Pittman and associates (1).
Normal ranges of concentration for the
age groups were previously established by Abbussi et a1 (2).
Serum
protein concentrations were measured by standard methods previously described (3).
Informed parental consent was obtained in each
patient.
TABLE I CHILDREN RECEIVING MAINTENANCE HEMODIALYSIS Primary renal disease
Mean Age at Mean Duration Male Female Start of Dialysis of Dialysis bas> (yrs)
Focal Glomerulosclerosis
12 t 4
18
2
3
Obstructive Uropathies
12 2 2
23
1
1
Chronic Glomerulonephritis
10 2 2
9
1
1
Cystinosis
13 2 4
17
1
1
Anaphylactoid Purpura-Nephritis
8
4
1
-
Medullary Cystic Disease
15
10
-
1
Sickle Cell Nephropathy
17
59
-
1
Wilm's Tumor, Radiation Nephritis
5
11
1
-
Proliferative Glomerulonephritis
6
1
-
1
HEMODIALYSIS AM) THYROID FUNCTIONS I N CHILDREN
389
RESULTS
The T3, T4 and TSH l e v e l s w e r e lower t h a n normal (Figure 1).
There
w a s no d i s c e r n a b l e d i f f e r e n c e f o r any of t h e s e v a r i a b l e s b e f o r e
and a f t e r hemodialysis.
The t o t a l p r o t e i n levels w e r e normal, al-
though t h e mean serum albumin level of 3.3 gmfdl w a s lower than
normal.
Ren Fail Downloaded from informahealthcare.com by McMaster University on 12/26/14 For personal use only.
DISCUSSION
With t h e exception of one a b s t r a c t (4) a l l previous r e p o r t s on t h e thyroid f u n c t i o n s i n hemodialysis d e a l t w i t h d a t a from
adults (5,6,7).
Our d a t a i n c h i l d r e n a f t e r a mean d u r a t i o n of 11
months on hemodialysis showed a tendency f o r T3, T4 and TSH t o be below normal l e v e l s f o r corresponding a g e and sex (Figure 1 ) . T h i s observation is i n c o n t r a s t t o t h e d a t a of Neuhaus e t a 1 (81, showing normal mean v a l u e s f o r T4 i n 25 a d u l t p a t i e n t s arter a mean d u r a t i o n of 1 112 y e a r s on maintenance hemodialysis, but i s in agreement with t h a t of Wassner e t al (4) in 9 c h i l d r e n a f t e r 3 months o f hemodialysis. The hypothesis, t h a t t h e kidney may play a r o l e in t h e maintenance of normal T3 l e v e l s (9, lo), and t h a t t h e d a t a documenting subnormal T 3 provides evidence f o r t h e e x i s t e n c e of s u b c l i n i c a l hypothyroidism i n r e n a l f a i l u r e , i s n o t supported by t h e p r e s e n t d a t a i n view of t h e low TSH values.
No d e f i n i t e d a t a a r e a v a i l a b l e
a t p r e s e n t t o s o l v e t h i s problem. S i m i l a r l y , t h e s p e c u l a t i o n t h a t uremia may i n h i b i t t h e p e r i p h e r a l conversion of T4 t o T3 a l s o l a c k d i r e c t s u p p o r t i n g d a t a a t
CHAN AND HUNG
390 CHILDREN (6-17 YRSJ
ADULTS > 1 8 YRS
MALE
FEMALE 150
126
. 0' m
100
E
Ren Fail Downloaded from informahealthcare.com by McMaster University on 12/26/14 For personal use only.
c "
I
4
1%
O
83f42
86f21
94f16
1
'1
5.5a2.3
a
6.0+3.5
w
4
A A 0 0
77fl6
0
58 f 4 7
0
1
8.9&3.4
7.SA3.7
7.3t2.s
I
3.4i2.3
3.912.9
4.5i1.6
PRE-HD
POST-HD
PRE-HD
0
I
4.6r2.3
5.2i3.3
PRE-HD
POST-HD
POST-HD
FIGURE I The pre- and post-dialysis serum T3, T4, and TSH values, in 15 study subjects aged 6-17 years and 1 subject over 18 years of age in comparison to normal values (shaded area) for their respective age group and sex. Normal values established by Abbussi, V., Aceto, T., and Hung, W. (2). Each symbol represents an individual patient receiving maintenance hemodialysis.
39 1
HEMODIALYSIS AND THYROID FUNCTIONS I N CHILDREN
p r e s e n t , although t h e r e i s s u g g e s t i v e evidence t h a t in 6 p a t i e n t s , serum T3 became s i g n i f i c a n t l y e l e v a t e d 1-3 months a f t e r i n i t i a t i o n
of maintenance hemodialysis ( 9 ) , as w e l l as normalization of
T4, T3 and TSH l e v e l s a f t e r r e n a l t r a n s p l a n t a t i o n (9,11,12). The p r e s e n t d a t a f u r t h e r documented a l a c k of d i f f e r e n c e between t h e pre- and p o s - d i a l y s i s values. I n conclusion, i t would appear t h a t t h y r o i d f u n c t i o n s a r e a f f e c t e d
Ren Fail Downloaded from informahealthcare.com by McMaster University on 12/26/14 For personal use only.
by t h e uremic s t a t e (11) b u t , t h a t t h e d i a l y s i s procedure p e r s e does not a l t e r t h e c o n c e n t r a t i o n of T3, T 4 , o r TSH, s i n c e t h e s e remain r e l a t i v e l y constant b e f o r e and a f t e r t h e d i a l y s i s procedure.
However,
t h e cumulative e f f e c t s of s m a l l and u n d e t e c t a b l e changes may result i n chemical hypothyroidism a f t e r long-term hemodialysis (12).
REFERENCES
1. Nomura, S . , Pittman, C.S., Chambers, J . B . , Jr.: Reduced p e r i p h e r a l conversion of thyroxine t o t r i i o d o t h y r o n i n e i n p a t i e n t s w i t h h e p a t i c c i r r h o s i s : J C l i n I n v e s t 56: 643-652, 1975. 2. Abbussi, V., Aceto, T., Hung W.: Thyroid f u n c t i o n i n r e l a t i o n t o age. I n t h e Ross Monogram: Children a r e d i f f e r e n t . 2nd ed. Ross Laboratories, Columbus, Ohio, 1977. Grushkin, C.M., Malekzadeh, M . , e t a l : The adaption 3. Chan, J . C . M . , of hydrogen i o n e x c r e t i o n a s s o c i a t e d w i t h nephron r e d u c t i o n i n post-transplant p a t i e n t s . P e d i a t r R e s 7: 712-718, 1973. 4. Wassner, S.H., Buckingham, B.A., Kershnar, A.K., e t a l : Thyroid f u n c t i o n i n chronic r e n a l f a i l u r e (CRF). P e d i a t r R e s 9: 295, 1975 (abstr)
.
5. Ramirez, G . , Jubiz, W., Gutch, C.F., e t a l : Thyroid a b n o r m a l i t i e s i n r e n a l f a i l u r e : A study of 53 p a t i e n t s on c h r o n i c hemodialysis. Ann I n t e r n Med 79: 500-504, 1973.
6. Oddie, T.H., Flanigan, W . J . , and F i s h e r , D.A.: Iodine and thyroxine metabolism i n anephric p a t i e n t s r e c e i v i n g c h r o n i c p e r i t o n e a l d i a l y s i s . J C l i n Endocr 31: 277-282, 1970.
392
CHAN AND HUNG
7. Koutras, D.A., Marketos, S.G., Rigopoulos, G.A., et al: Iodine metabolism in chronic renal insufficiency. Nephron 9: 55065, 1972. 8.
Neuhaus, K., Baumann, G., Walser, A., et al: Serum thyroxine and thyroxine-binding proteins in chronic renal failure without nephrosis. J Clin Endocrinol and Met 41: 395-398, 1975.
9. Lim, V.S., Katz, A.I., et al: Thyroid dysfunction in chronic renal failure: a study of the pituitary-thyroid axis and peripheral turnover kinetics of thyroxine and tri-iodothyroxine. J Clin Invest 60: 522-534, 1977.
Ren Fail Downloaded from informahealthcare.com by McMaster University on 12/26/14 For personal use only.
10. Spector, D.A., Davis, P.J., Helderman, J.H., Bell, B., Utiger, R.D.: Thyroid function and metabolic state in chronic renal failure. Ann Intern Med 85: 724-730, 1976. 11. Czernichow, P., Dauzet, M.C., Broyer, M., Rappaport R.: Abnormal TSH, PRL and GH response to TSH releasing factor in chronic renal failure. J clin Endocrinol Metab 43: 630-637, 1976.
12. Dandona, P., Newton, D., Platts, MA.: Long-term hemodialysis and thyroid function. Brit Med J 1: 134-136, 1977
