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John P Gibbs, MD
Medical Director,
Kerr-McGee
(retired)
A recent analysis of NHANES
2001-2002 data reported:
An association between altered thyroid function
(↑ TSH, ↓total T4) and increasing urine
perchlorate concentration among females age
12 and older.
800
715
700
9% of all samples < 100 µg/L
600
512
475
500
408
400 330 342
272
300 239
210
176
200 162
104 120 115
100 65
1 2 3 4 5
Quintile
NHANES: National Health And Nutritional Survey
Maternal Perchlorate Dose Estimates from Tellez et al
100%
90%
80%
Cumulative Percent
70%
Antofagasta
60%
Chanaral
50%
Taltal
40%
RfD
30%
NOEL
20%
10%
0%
0.00001 0.0001 0.001 0.01 0.1
p-
N Mean N Mean N Mean val
ue*
Thyroglobulin
58 4.32 45 3.67 57 3.67 0.32
(ng/ml)
T3 (ng/dL) 35 79 42 73 28 82 0.03
Thyroglobulin
30 16.8 36 14.0 28 18.1 0.29
(ng/ml)
*Kruskal-Wallis
Maternal Free T4 vs Weeks Gestation
( Includes first and second prenatal visits )
2
Mixed Model Repeated Measures Regression of Free T4 w ith
Maternal Age and Weeks Gestation* , N=307, Variance =
Antofagasta Taltal Chanaral 0.01444
The dashed lines below are the 10th and 90th percentiles on
Reference Range
Non-Pregnant
* Init ial regression using repeat ed measuresincluded a cit y ef f ect (p=0 1543) mat ernal age (p=0 004)
Free T4, ng/dL
1.25
0.75
0.5
0.25
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestation
We accept that general iodine nutrition correlates with thyroid
function in the extremes of excess or deficiency BUT ….
Urine ClO4- - - - -
Coefficients
I- - ClO4-are such that -both TSH- & free T4
Interaction - -
decrease with increasing spot urine iodine levels
Ln(TSH) Weeks gestation - - - -
Urine I- - - .0000730 0.0254
Urine ClO4- - - - -
I- - ClO4- Interaction - - - -
Urinary Iodine: µ/L vs µ/g-creat
For the most part, the graphics that I am
going to show appear very similar for both
measures
All graphics of based on the study of
pregnant women in Chile are based on
urine iodide (µ/L)
Spot Urine Iodine Cumulative Distribution
First Prenatal Second Prenatal
100%
C u m u la tiv e P e rc e n ta g e
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
0 100 200 300 400 500 600 700 800 900 1000
N was small
Free T4 (gestation corrected) vs Urine Iodine Categorized by Urine Perchlorate
2.0
1.8
1.6
1.4
1.2
fre e T 4
1.0
0.8
0.6
0.4
0.2
0.0
0 100 200 300 400 500 600 700 800 900 1000
Urine Iodine, mcg/L
Free T4 (gestation corrected) vs Urine Iodine Categorized by Urine Perchlorate
≥100
2.0
1.8 Free T4 does not decrease with
1.6 decreasing iodine for those women
with urine perchlorate ≥100 µ/L
1.4
1.2
fre e T 4
1.0
0.8
0.6
0.4
0.2
0.0
0 100 200 300 400 500 600 700 800 900 1000
Urine Iodine, mcg/L
TSH vs Urine Iodine Categorized by Urine Perchlorate
<10 10-19 20-49 50-99 ≥100
10
1
T S H
0.1
0 100 200 300 400 500 600 700 800 900 1000
Urine Iodine, mcg/L
TSH vs Urine Iodine Categorized by Urine Perchlorate
≥100
10
1
T S H
0.1
0 100 200 300 400 500 600 700 800 900 1000
Urine Iodine, mcg/L
Free T4, Controlled for age & gestation, Categorized by Urine
Iodine
<100 100-199 200-399 >400 mean T4
2.0
1.8
1.6
1.4
1.2
fre e T 4
1.0
0.8
0.6
0.4
0.2
0.0
0 100 200 300 400 500 600 700 800 900 1000
Urine Perchlorate, mcg/L
Free T4, Controlled for age & gestation, Categorized by Urine
Iodine
<100 100-199 200-399 >400 mean T4
2.0
1.8
1.6 Free T4 does not decrease with
1.4 increasing perchlorate for those
1.2 women with urine iodine < 100 µ/L
fre e T 4
1.0
0.8
0.6
0.4
0.2
0.0
0 100 200 300 400 500 600 700 800 900 1000
Urine Perchlorate, mcg/L
TSH Categorized by Urine Iodine
<100 100-199 200-399 >400 log mean TSH
10
1
T S H
0.1
0 100 200 300 400 500 600 700 800 900 1000
Urine Perchlorate, mcg/L
TSH Categorized by Urine Iodine
<100 100-199 200-399 >400 log mean TSH
10
1
T S H
0.1
0 100 200 300 400 500 600 700 800 900 1000
Urine Perchlorate, mcg/L
We accept that general iodine nutrition correlates with thyroid
function in the extremes of excess or deficiency BUT ….
100%
C u m u la tiv e P e rc e n ta g e
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
0 100 200 300 400 500 600 700 800 900 1000
700
* 134 subjects had a spot urine iodine determination at their first
prenatal visit 578
600
500
Median Urine Iodine, ug/L
343
400
279
300
204
200 128
100
0
1 2 3 4 5
Quintile
Comparison of First Prenatal Iodine Distribution with
Subsequent Urine Iodine Distribution
700
* 134 subjects had a spot urine iodine determination at their first
prenatal visit and at least one more spot urine iodine
600 determination at the second prenatal visit or post partum visit. If 578
two additional tests were obtained, the average of the two was
used
500
Median Urine Iodine, ug/L
400
343
204
200
128
100
0
1 2
Quintile 3 Prenatal 4
at First 5
Visit
First Prenatal Maternal Iodine compared with Second Prenatal and Postpartum
Iodines
1000
Io d in e ,
900
R2 < 0.0001
800
S e c o n d P re n a ta l o r P o s tp a rtu d m
700
600
u g /L
500
400
300
200
100
0
0 200 400 600 800 1000 1200