Hypothyroxinemia and pregnancy.
OBJECTIVE
To evaluate the peer-reviewed literature on iodine deficiency and hypothyroxinemia in pregnancy.


METHODS
We review published studies on isolated hypothyroxinemia in pregnancy, methodology of free thyroxine (T4) assays, impact of iodine deficiency on free T4 levels, and status of ongoing prospective randomized trials of isolated hypothyroxinemia during pregnancy.


RESULTS
Hypothyroxinemia during pregnancy is common. Studies have demonstrated the pivotal role exerted by maternal T4 on fetal brain development and the negative impact of hypothyroxinemia on neurobehavioral performance in offspring. Two intervention studies have demonstrated a positive effect on neurodevelopment in children of mothers promptly supplemented with iodine compared with the neurodevelopment in children of nonsupplemented mothers. Free T4 assays presently in clinical use have limitations. Preliminary results of the Controlled Antenatal Thyroid Study (CATS) are somewhat mixed, and the National Institutes of Health Maternal Fetal Medicine Thyrotropin Study (TSH Study) will be completed in 2015. Knowledge regarding the impact of isolated hypothyroxinemia has progressed, but major questions remain. An optimal diagnostic test for free T4 during pregnancy (accurate, inexpensive, and widely available) remains elusive. Trimester-specific normative data and normal ranges from different geographic regions do not exist.


CONCLUSIONS
Data published to date are insufficient to recommend levothyroxine therapy in pregnant women with isolated hypothyroxinemia. Adequate iodine intake should be recommended before conception and early in pregnancy.
Division of Endocrinology, V. Fazzi Hospital, 73100, Lecce, Italy. dr.negro@libero.it
Roberto
R
Negro
Offie P
OP
Soldin
Maria-Jesus
MJ
Obregon
Alex
A
Stagnaro-Green
D001774:Blood Chemical Analysis / Q000379:methods; D002648:Child; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D007455:Iodine / Q000172:deficiency; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000453:epidemiology / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D013960:Thyroid Function Tests / Q000379:methods; D013974:Thyroxine / Q000097:blood / Q000172:deficiency
D007455:Iodine; D013974:Thyroxine
J Clin Invest. 2003 Apr;111(7):1073-82
12671057
J Clin Endocrinol Metab. 2008 Jul;93(7):2616-21
18413422
Am J Clin Pathol. 1997 Oct;108(4):417-21
9322595
Public Health Nutr. 2007 Dec;10(12A):1554-70
18053280
Clin Chem. 1989 Jul;35(7):1362-6
2758578
Clin Endocrinol (Oxf). 2003 Sep;59(3):282-8
12919150
Trends Endocrinol Metab. 2007 Nov;18(9):338-43
17962037
Thyroid. 2007 Apr;17(4):303-11
17465859
Clin Chem. 2007 May;53(5):985-8
17395710
Clin Chem. 2003 Sep;49(9):1531-5
12928239
J Clin Invest. 1990 Sep;86(3):889-99
2394838
Clin Chem. 2009 Jul;55(7):1380-8
19460839
J Clin Endocrinol Metab. 2010 Jul;95(7):3207-15
20427488
Public Health Nutr. 2007 Dec;10(12A):1606-11
18053287
Thyroid. 2005 Aug;15(8):917-29
16131334
Thyroid. 2003 Oct;13(10):959-64
14611705
Eur J Clin Nutr. 1998 May;52(5):351-5
9630385
Best Pract Res Clin Endocrinol Metab. 2004 Jun;18(2):225-48
15157838
J Clin Endocrinol Metab. 2002 Apr;87(4):1768-77
11932315
Clin Chem Lab Med. 2003 Jul;41(7):942-7
12940522
Thyroid. 2009 May;19(5):511-9
19348584
Eur J Endocrinol. 1996 Apr;134(4):443-8
8640295
J Clin Endocrinol Metab. 1993 Dec;77(6):1719-22
8263162
J Clin Endocrinol Metab. 2006 Jul;91(7):2587-91
16621910
J Clin Endocrinol Metab. 2004 Jul;89(7):3117-28
15240580
J Clin Endocrinol Metab. 1995 Jan;80(1):258-69
7829623
Clin Chem. 2010 Jun;56(6):912-20
20395623
Clin Biochem. 1992 Apr;25(2):77-87
1623581
Am J Obstet Gynecol. 1991 Feb;164(2):482-5
1992688
Endocrinology. 2004 Sep;145(9):4037-47
15087434
Clin Endocrinol (Oxf). 2010 Jun;72(6):825-9
19878506
J Clin Endocrinol Metab. 2010 Sep;95(9):4227-34
20534757
N Engl J Med. 1999 Aug 19;341(8):549-55
10451459
J Clin Endocrinol Metab. 2004 Dec;89(12):6054-60
15579758
Thyroid. 1997 Oct;7(5):749-54
9349578
Clin Lab. 2004;50(9-10):581-4
15481634
Clin Endocrinol (Oxf). 1999 Feb;50(2):149-55
10396355
J Clin Endocrinol Metab. 2009 Sep;94(9):3234-41
19567536
Am J Obstet Gynecol. 2009 Mar;200(3):260.e1-6
19114271
N Engl J Med. 2010 Feb 18;362(7):590-9
20089957
J Clin Endocrinol Metab. 2000 Nov;85(11):3975-87
11095417
Thyroid. 2008 Nov;18(11):1207-14
19014327
Eur J Endocrinol. 2009 Apr;160(4):611-7
19179457
J Endocrinol Invest. 1991 Jan;14(1):1-9
2045620
N Engl J Med. 2010 Jun 10;362(23):2224; author reply 2225-6
20558375
Clin Chem. 2008 Apr;54(4):642-51
18258669
Pediatrics. 2006 Jan;117(1):161-7
16396874
J Clin Endocrinol Metab. 1993 Oct;77(4):1078-83
8408456