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Changes in Thyroid Function Test (TFT) Results Due
to Pregnancy N ormal
changes in thyroid function tests during pregnancy include a
transient suppression of thyroid-stimulating hormone and stimulation
of triiodothyronine.[1,2]. Serum total T4 and total T3 steadily
increase during pregnancy to approximately 1.5 times the non-pregnant
level by mid second trimester [3-6]. Whereas serum free T4 and
free T3 gradually decrease during pregnancy [4,7] .
While the values for most thyroid function tests generally lie
within normal non-pregnant ranges. Some investigastors have found free T4
concentrations [8] and TSH [9] to fall below the lower limit of the
normal range using newer assays. Some published reference ranges are
listed in table 1. These discrepencies highlight the
need for each laboratory to develop its own normal ranges in
pregnancy [10].
Table 1. Published Values for Thyroid Function Tests During
Pregnancy
|
Serum
|
Units |
first trimester |
second trimester |
third trimester |
Reference |
| Free T3 |
pmol/L |
3 - 5.7 |
2.8 - 4.2 |
2.4 - 4.1 |
15 |
|
| Free T4 |
ng/dL |
0.86 - 1.87 |
0.64 - 1.92 |
0.64 - 1.92 |
16 |
|
pmol/L |
11.1 - 24.1 |
8.2 - 24.7 |
8.2 - 24.7 |
15 |
| |
ng/dL |
0.86 - 1.77 |
0.63 - 1.29 |
0.66 - 1.12 |
15 |
| |
pmol/L |
11.1 - 22.9 |
8.1 - 16.7 |
8.5 - 14.4 |
15 |
|
| Thyroid
stimulating hormone (TSH) |
µU/mL OR mU/L |
0.2 - 3.5 |
0.2 - 3.5 |
0.2 - 3.5 |
16 |
|
µU/mL OR mU/L |
0.03 - 2.3 |
0.03 - 3.7 |
0.13 - 3.4 |
15 |
Total T4
This test measures the concentration of thyroxine in the serum.
This includes both bound and free hormone.
Elevated estrogen levels during pregnancy cause thyroid binding
globulin (TBG) levels to rise. Because the majority of T4 and T3
circulates bound to TBG the total T4 and total T3 measurements will
also rise, but the levels of free T4 and fee T3 will not be affected.
Hereditary disorders in TBG production, acute liver disease and
medications such as methadone are additional causes of an increased
TBG level.
Total T3
This test measures the concentration of triiodothyronine in the
serum. The T3 is increased in almost all cases of hyperthyroidism and
usually goes up before the T4 does. The T3 is decreased during acute
illness and starvation, and is affected by several medications
including Inderal, steroids and amiodarone.
%T3 Uptake:
This test is performed by adding radiolabeled T3 to a patient’s
serum sample. The labeled T3 binds to serum proteins. A resin is then
added to bind the remaining free labeled T3. The resin is counted for
labeled T3. The value is usually reported as a percent of the total
labeled hormone added. A low resin uptake means that most of the
labeled T3 has been taken up by serum proteins.
Thus conditions associated with an increase in serum proteins such
as pregnancy will cause a low resin uptake, because more labeled T3
binds to proteins and less labeled T3 is available to bind to the
resin. The T4 Uptake is a similar test [11]
FT4
The free T4 (FT4) test measures the concentration of free
thyroxine, the only biologically active fraction, in the serum. The
free thyroxine is not affected by changes in concentrations of
binding proteins.
TSH
Suppression of TSH with an elevation of free T4 is a common
finding during the first trimester of pregnancy [1,11,12]. These
findings are believed to be caused by stimulation of the TSH receptor
by hCG which results in an increase in FT4 and subsequently
suppresses TSH levels [11]. These changes are particularly
pronounced in patients with hyperemesis gravidarum where FT4 levels
may reach 37.6 and TSH may be supressed to undetectable levels [13]
A suppressed TSH with normal FT4 and FT3 can usually be observed
with repeat laboratories q 4 weeks until it normalizes [11].
Additional Considerations in the Interpretation of TFTs [14]:
Are the results a possible lab error ?
Does the patient have a personal or family history of autoimmune disease?
May the result have been caused by a medication?
Does the patient have symptoms or signs consistent with the laboratory diagnosis?
Consider common etiologies first
Example Thyroid Profiles
Normal Profile
|
Test |
Result
|
Units
|
Reference Range |
|
T4 Total |
15.8 |
ug/dl
|
4.5 - 12.0 |
|
T3 Uptake |
18.5 |
% |
24.3 - 39.0 |
|
FT4 Index
|
2.9
|
ug/dl |
1.2 - 4.9 |
|
TSH
|
0.923 |
uIU/ml
|
0.34 - 5.6 |
The TSH, and serum total T4 are within the "normal range for
pregnancy" (approximately 9-18 mg/dl, 120-240 nmol/L). The resin T3
uptake value is reduced as expected during pregnancy
Hyperthyroid
Profile
| Test
|
Result
|
Units
|
Reference Range |
| T4 Total |
27 |
ug/dl |
4.5-12.0 |
| T3 Uptake |
29.6 |
% |
24.3-39.0 |
| FT4 Index |
8.0 |
ug/dl |
1.2-4.9 |
| TSH |
< 0.019 |
uIU/ml
|
0.34-5.6 |
The suppressed TSH, and serum total T4 above the "normal range for
pregnancy" (approximately 9-18 mg/dl, 120-240 nmol/L) are consistent
with hyperthyroidism. The resin T3 uptake value is not reduced as it
should be in pregnancy, and confirms that the suppressed TSH and
elevated thyroxine level are not due pregnancy.
Patterns of Thyroid Function Tests
| TSH
|
FT4
|
FT3
|
Possible Etiologies |
| Low |
Low |
|
- Central
hypothyroidism
- Euthyroid sick syndrome
|
| Normal |
Normal |
- Subclinical hyperthyroidism
|
| Normal |
High |
- T3 -toxicosis.
- Early or relapsing Grave's
- Iodine deficiency
- Solitary nodule
|
| High |
|
- Hashimoto’s
- Grave’s
- Molar pregnancy
- Choriocarcinoma
- Hyperemesis
- Thyrotoxicosis factitia
- Lithium
- Multinodular goiter
- Toxic adenoma
- Thyroid carcinoma
- Iodine ingestion
|
| Normal |
Low |
|
- Hypothyroxinemia
- Severe nonthyroidal illness
(euthyroid sick syndrome)
- Possible secondary hypothyroidism
- Medications
|
| Normal |
|
|
| High |
|
- Euthyroid hyperthyroxinemia
- Thyroid hormone resistance
- Familial dysalbumineic hyperthyroxinemia
- Meds: amiodarone, beta-blockers
- Oral contrast
- Hyperemesis
- Acute psychiatric illness
- Rheumatoid factor
|
| High |
Low |
|
|
| Normal |
|
- Subclinical hypothyroidism
|
| High |
|
- TSH mediated hyperthyroidism
|
REFERENCES
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pregnancy. J Clin Endocrinol Metab 1990;71:276-87.
2. Kol S, et al .Thyroid function in early normal pregnancy:
transient suppression of thyroid-stimulating hormone and stimulation
of triiodothyronine. Gynecol Obstet Invest. 1996;42(4):227-9.
3. Glinoer D. The regulation of thyroid function in pregnancy:
pathways of endocrine adaptation from physiology to pathology.
Endocrinol Rev 1997;18:404-33.
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free iodothyronines during normal pregnancy. Acta Endocrinol
1982;101:531-7.
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variation in thyroid function by iodine supplementation. J Clin
Endocrinol Metab 1993;77:1078-83.
6. Nohr SB et al. Postpartum thyroid dysfunction in pregnant
thyroid peroxidase antibody-positive women living in an area with
mild to moderate iodine deficiency: Is iodine supplementation safe? J
Clin Endocrinol Metab 2000;85:3191-8.
7. Amerlex free triiodothyronine and free thyroxine levels in
normal pregnancy.
Br J Obstet Gynaecol. 1985;92:1234-8.
8. McElduff A Measurement of free thyroxine (T4) levels in
pregnancy.
Aust N Z J Obstet Gynaecol. 1999;39:158-61.
9. Bobrowski RA, et al
Applicability of the third-generation, thyroid-stimulating hormone
assay in pregnancy. J Matern Fetal Med. 1998 ;7:65-7.
10. LMPG: Laboratory Support for the Diagnosis and Monitoring of
Thyroid Disease
National Academy of Clinical Biochemistry 2002
http://www.nacb.org/lmpg/thyroid_lmpg_pub.stm
Accessed 5/1/03
11. Brent GA. Maternal Thyroid function: Interpretation of thyroid
function tests in pregnancy. Clin Obstet Gynecol. 1997;40:3-15.
12. Mori M, et al.Morning sickness and thyroid function in normal
pregnancy.
Obstet Gynecol. 1988 Sep;72(3 Pt 1):355-9.
13. Goodwin TM, Hershman JM.
Hyperthyroidism due to inappropriate production of human chorionic
gonadotropin. Clin Obstet Gynecol. 1997 Mar;40(1):32-44.
14. Supit EJ, et al. Interpretation of Laboratory Thyroid Function
Tests South Med J 95(5):481-485, 2002
15. Panesar Ns, et al. Reference intervals for thyroid hormones in
pregnant Chinese women. Ann Clin Biochem. 2001;38:329-32.
MEDLINE
16. Castracane VD and Gimpel T. Reference Values in Pregnancy for IMMULITE
Assays.DPC Technical Report. 1999. Accessed 10/1/04
Created: 5/1/2003 Mark Curran,M.D. Updated: 11/2/2004 Mark Curran,M.D.
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