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Interpretation of Thyroid Function Tests During Pregnancy

The thyroid gland is normally regulated by thyroid-stimulating hormone (TSH), also called thyrotropin, which is secreted by the pituitary. TSH stimulates the thyroid gland to produce and release the thyroid hormones thyroxine (T4) and triiodothyronine (T3) . T4 and T3 are released from the thyroid into the bloodstream, where they are bound to the serum proteins thyroxine-binding prealbumin, (also called transthyretin), albumin, and thyroxine-binding globulin (TBG). TBG normally accounts for about 75% of the bound hormones. About 0.03% of the total serum T4 and 0.3% of the total serum T3 are free. Only free T4 and T3 are metabolically active.

By a negative feedback mechanism increased levels of free thyroid hormones (T4 and T3) inhibit TSH secretion from the pituitary, whereas decreased levels of T4 and T3 cause an increase in TSH release from the pituitary. TSH secretion is also influenced by thyrotropin-releasing hormone (TRH) synthesized in the hypothalamus. TRH causes release of TSH (Figure 1).
Changes in Thyroid Function Test (TFT) Results Due to Pregnancy

Normal 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
  • Normal
High
  • Euthyroid hyperthyroxinemia
  • Thyroid hormone resistance
  • Familial dysalbumineic hyperthyroxinemia
  • Meds: amiodarone, beta-blockers
  • Oral contrast
  • Hyperemesis
  • Acute psychiatric illness
  • Rheumatoid factor

High Low
  • Primary hypothyroidism
Normal
  • Subclinical hypothyroidism
High
  • TSH mediated hyperthyroidism

REFERENCES

1. Glinoer D et al. Regulation of maternal thyroid function during 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.

4. Weeke J et al. A longitudinal study of serum TSH and total and free iodothyronines during normal pregnancy. Acta Endocrinol 1982;101:531-7.

5. Pedersen KM, et al. Amelioration of some pregnancy associated 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.


Copyright © 2003-2009 by San Gabriel Valley Perinatal Medical Group, Inc. All rights reserved. www.peridocs.com . Reproduced with permission.
 



 

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