Levothyroxine treatment of mild subclinical hypothyroidism: a review of potential risks and benefits

Therapeutic Advances in Endocrinology and Metabolism

Volumn 7, Issue 1, 2016, Pages 12-23

  Javed, Zeeshan ^a   Sathyapalan, Thozhukat ^b  

^a UNIVERSITY OF HULL   (United Kingdom)

^b UNIVERSITY OF HULL   (United Kingdom)

Author keywords

associated risks; levothyroxine benefits; management; subclinical hypothyroidism; thyroid stimulating hormone

Indexed keywords

AMIODARONE; LEVOTHYROXINE; LIOTHYRONINE; LITHIUM; THYROTROPIN;

CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; COGNITIVE DEFECT; DYSLIPIDEMIA; EXERCISE; FEMALE; GOITER; HASHIMOTO DISEASE; HEART FAILURE; HUMAN; LOSS OF FUNCTION MUTATION; MALE; MATERNAL HYPERTENSION; MOOD DISORDER; OBESITY; POSTPARTUM THYROIDITIS; PREECLAMPSIA; PREGNANCY DIABETES MELLITUS; PREGNANCY OUTCOME; PREMATURE LABOR; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SUBCLINICAL HYPOTHYROIDISM; THYROID CANCER;

EID: 84957811787     PISSN: 20420188     EISSN: 20420196     Source Type: Journal    
DOI: 10.1177/2042018815616543     Document Type: Review

References (103)

1. M.AbalovichA.VazquezG.AlcarazA.KitaigrodskyG.SzumanC.Calabrese. (2013) Adequate levothyroxine doses for the treatment of hypothyroidism newly discovered during pregnancy. Thyroid23: 1479–1483.
2. R.AghiliM.KhamsehM.MalekA.HadianH.BaradaranL.Najafi. (2012) Changes of subtests of Wechsler Memory Scale and cognitive function in subjects with subclinical hypothyroidism following treatment with levothyroxine. Arch Med Sci8: 1096–1101.
3. W.AllanJ.HaddowG.PalomakiJ.WilliamsM.MitchellR.Hermos. (2000) Maternal thyroid deficiency and pregnancy complications: implications for population screening. J Med Screen7: 127–130.
4. M.AndersenA.OlsenJ.MadsenJ.FaberC.Torp-PedersenG.Gislason. (2015) Levothyroxine substitution in patients with subclinical hypothyroidism and the risk of myocardial infarction and mortality. PLoS One10: e0129793.
5. G.AshoorN.MaizM.RotasF.JawdatK.Nicolaides (2010) Maternal thyroid function at 11 to 13 weeks of gestation and subsequent fetal death. Thyroid20: 989–993.
6. I.BaldiniA.VitaM.MauriV.AmodeiM.CarrisiS.Bravin. (1997) Psychopathological and cognitive features in subclinical hypothyroidism. Prog Neuropsychopharmacol Biol Psychiatry21: 925–935.
7. C.BaumgartnerM.BlumN.Rodondi (2014) Subclinical hypothyroidism: summary of evidence in 2014. Swiss Med Wkly144: w14058.
8. H.BehroozM.TohidiY.MehrabiE.BehroozM.TehranidoostF.Azizi (2011) Subclinical hypothyroidism in pregnancy: intellectual development of offspring. Thyroid21: 1143–1147.
9. N.BenhadiW.WiersingaJ.ReitsmaT.VrijkotteG.Bonsel (2009) Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death. Eur J Endocrinol160: 985–991.
10. A.BindelsR.WestendorpM.FrolichJ.SeidellA.BlokstraA.Smelt (1999) The prevalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need for case-finding?Clin Endocrinol50: 217–220.
11. B.Biondi (2007) Cardiovascular effects of mild hypothyroidism. Thyroid17: 625–630.
12. B.BiondiD.Cooper (2008) The clinical significance of subclinical thyroid dysfunction. Endocr Rev29: 76–131.
13. S.BoekholdtS.TitanW.WiersingaK.ChatterjeeD.BasartR.Luben. (2010) Initial thyroid status and cardiovascular risk factors: the EPIC-Norfolk Prospective Population Study. Clin Endocrinol72: 404–410.
14. K.Boelaert (2009) The association between serum TSH concentration and thyroid cancer. Endocr Relat Cancer16: 1065–1072.
15. M.BrennanC.PowellK.KaufmanP.SunR.BahnK.Nair (2006) The impact of overt and subclinical hyperthyroidism on skeletal muscle. Thyroid16: 375–380.
16. G.CanarisN.ManowitzG.MayorE.Ridgway (2000) The Colorado Thyroid Disease Prevalence Study. Arch Intern Med160: 526–534.
17. N.CaraccioE.FerranniniF.Monzani (2002) Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab87: 1533–1538.
18. B.CaseyJ.DasheC.WellsD.McintireW.ByrdK.Leveno. (2005) Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol105: 239–245.
19. S.ChikunguwoS.BrethauerV.NirujogiT.PittS.UdomsawaengsupB.Chand. (2007) Influence of obesity and surgical weight loss on thyroid hormone levels. Surg Obes Relat Dis3: 631–635; discussion 635–636.
20. J.Cleary-GoldmanF.MaloneG.Lambert-MesserlianL.SullivanJ.CanickT.Porter. (2008) Maternal thyroid hypofunction and pregnancy outcome. Obstet Gynecol112: 85–92.
21. N.CorreiaS.MullallyG.CookeT.TunN.PhelanJ.Feeney. (2009) Evidence for a specific defect in hippocampal memory in overt and subclinical hypothyroidism. J Clin Endocrinol Metab94: 3789–3797.
22. C.Dall’astaM.PaganelliA.MorabitoP.VedaniM.BarbieriG.Paolisso. (2010) Weight loss through gastric banding: effects on TSH and thyroid hormones in obese subjects with normal thyroid function. Obesity18: 854–857.
23. M.DaneseP.LadensonC.MeinertN.Powe (2000) Clinical Review 115: Effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J Clin Endocrinol Metab85: 2993–3001.
24. L.De GrootM.AbalovichE.AlexanderN.AminoL.BarbourR.Cobin. (2012) Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab97: 2543–2565.
25. A.De Moura SouzaR.Sichieri (2011) Association between serum TSH concentration within the normal range and adiposity. Eur J Endocrinol165: 11–15.
26. T.Del Ser QuijanoC.DelgadoS.Martinez EspinosaC.Vazquez (2000) [Cognitive deficiency in mild hypothyroidism]. Neurologia15: 193–198.
27. J.DiezP.Iglesias (2004) Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure. J Clin Endocrinol Metab89: 4890–4897.
28. V.Fatourechi (2009) subclinical hypothyroidism: an update for primary care physicians. Mayo Clin Proc84: 65–71.
29. E.FioreT.RagoM.ProvenzaleM.ScutariC.UgoliniF.Basolo. (2010) L-Thyroxine-treated patients with nodular goiter have lower serum TSH and lower frequency of papillary thyroid cancer: results of a cross-sectional study on 27,914 Patients. Endocr Relat Cancer17: 231–239.
30. E.FioreP.Vitti (2012) Serum TSH and risk of papillary thyroid cancer in nodular thyroid disease. J Clin Endocrinol Metab97: 1134–1145.
31. R.FlynnS.BonellieR.JungT.MacdonaldA.MorrisG.Leese (2010) Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab95: 186–193.
32. C.FoxM.PencinaR.D’AgostinoJ.MurabitoE.SeelyE.Pearce. (2008) Relations of thyroid function to body weight: cross-sectional and longitudinal observations in a community-based sample. Arch Intern Med168: 587–592.
33. S.Grozinsky-GlasbergA.FraserE.NahshoniA.WeizmanL.Leibovici (2006) Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J Clin Endocrinol Metab91: 2592–2599.
34. J.GusseklooE.Van ExelA.De CraenA.MeindersM.FrolichR.Westendorp (2004) Thyroid status, disability and cognitive function, and survival in old age. JAMA292: 2591–2599.
35. A.HakH.PolsT.VisserH.DrexhageA.HofmanJ.Witteman (2000) Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med132: 270–278.
36. M.HaymartS.GlinbergJ.LiuR.SippelJ.JaumeH.Chen (2009) Higher serum TSH in thyroid cancer patients occurs independent of age and correlates with extrathyroidal extension. Clin Endocrinol71: 434–439.
37. M.Helfandand the US Preventative Services Task Force (2004) Screening for subclinical thyroid dysfunction in nonpregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med140: 128–141.
38. J.HenrichsJ.Bongers-SchokkingJ.SchenkA.GhassabianH.SchmidtT.Visser. (2010) maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the Generation R study. J Clin Endocrinol Metab95: 4227–4234.
39. R.JoffeE.PearceJ.HennesseyJ.RyanR.Stern (2013) Subclinical hypothyroidism, mood, and cognition in older adults: a review. Int J Geriatr Psychiatry28: 111–118.
40. R.JordeK.WaterlooH.StorhaugA.NyrnesJ.SundsfjordT.Jenssen (2006) Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment. J Clin Endocrinol Metab91: 145–153.
41. J.JulvezM.Alvarez-PedrerolM.RebagliatoM.MurciaJ.FornsR.Garcia-Esteban. (2013) Thyroxine levels during pregnancy in healthy women and early child neurodevelopment. Epidemiology24: 150–157.
42. G.Kahaly (2012) Polyglandular autoimmune syndrome type II. Presse Med41: e663–e670.
43. P.KarakostaD.AlegakisV.GeorgiouT.RoumeliotakiE.FthenouM.Vassilaki. (2012) Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. J Clin Endocrinol Metab97: 4464–4472.
44. J.KarmisholtS.AndersenP.Laurberg (2011) Variation in thyroid function in subclinical hypothyroidism: importance of clinical follow-up and therapy. Eur J Endocrinol164: 317–323.
45. S.KimB.LeeJ.LeeS.SongB.KimS.Son. (2011) Preoperative serum thyroid stimulating hormone levels in well-differentiated thyroid carcinoma is a predictive factor for lateral lymph node metastasis as well as extrathyroidal extension in Korean patients: a single-center experience. Endocrine39: 259–265.
46. C.KitaharaE.PlatzP.LadensonA.MondulA.MenkeA.Berrington De Gonzalez (2012) Body fatness and markers of thyroid function among U.S. men and women. PLoS One7: e34979.
47. W.KongM.SheikhP.LumbR.NaoumovaD.FreedmanM.Crook. (2002) A 6-Month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. Am J Med112: 348–354.
48. T.KorevaarM.MediciY.De RijkeW.VisserS.De Muinck Keizer-SchramaV.Jaddoe. (2013a) Ethnic differences in maternal thyroid parameters during pregnancy: the Generation R study. J Clin Endocrinol Metab98: 3678–3686.
49. T.KorevaarS.Schalekamp-TimmermansY.De RijkeW.VisserW.VisserS.De Muinck Keizer-Schrama. (2013b) Hypothyroxinemia and TPO-antibody positivity are risk factors for premature delivery: the Generation R study. J Clin Endocrinol Metab98: 4382–4390.
50. J.KvetnyP.HeldgaardE.BladbjergJ.Gram (2004) Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years. Clin Endocrinol61: 232–238.
51. J.LazarusJ.BestwickS.ChannonR.ParadiceA.MainaR.Rees. (2012) Antenatal thyroid screening and childhood cognitive function. N Engl J Med366: 493–501.
52. J.LazarusR.BrownC.DaumerieA.Hubalewska-DydejczykR.NegroB.Vaidya (2014) 2014 European Thyroid Association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J3: 76–94.
53. J.LeeP.BuzkovaH.FinkJ.VuL.CarboneZ.Chen. (2010) Subclinical thyroid dysfunction and incident hip fracture in older adults. Arch Intern Med170: 1876–1883.
54. T.LepoutreF.DebieveD.GrusonC.Daumerie (2012) Reduction of miscarriages through universal screening and treatment of thyroid autoimmune diseases. Gynecol Obstet Invest74: 265–273.
55. C.LiZ.ShanJ.MaoW.WangX.XieW.Zhou. (2014) Assessment of thyroid function during first-trimester pregnancy: what is the rational upper limit of serum TSH during the first trimester in Chinese pregnant women?J Clin Endocrinol Metab99: 73–79.
56. Y.LiZ.ShanW.TengX.YuY.LiC.Fan. (2010) Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25–30 months. Clin Endocrinol72: 825–829.
57. D.LiuF.JiangZ.ShanB.WangJ.WangY.Lai. (2010) A cross-sectional survey of relationship between serum TSH level and blood pressure. J Hum Hypertens24: 134–138.
58. M.MainentiP.VigarioP.TeixeiraM.MaiaF.OliveiraM.Vaisman (2009) Effect of levothyroxine replacement on exercise performance in subclinical hypothyroidism. J Endocrinol Invest32: 470–473.
59. J.MarchalH.Maurice-StamN.IkelaarF.KlouwerK.VerhorstertM.Witteveen. (2014) Effects of early thyroxine treatment on development and growth at age 10.7 years: follow-up of a randomized placebo-controlled trial in children with Down’s Syndrome. J Clin Endocrinol Metab99: E2722–2729.
60. R.MarwahaS.ChopraS.GopalakrishnanB.SharmaR.KanwarA.Sastry. (2008) Establishment of reference range for thyroid hormones in normal pregnant Indian women. BJOG115: 602–606.
61. A.MonzaniF.ProdamA.RapaS.MoiaV.AgarlaS.Bellone. (2013) Endocrine Disorders in childhood and adolescence. Natural history of subclinical hypothyroidism in children and adolescents and potential effects of replacement therapy: a review. Eur J Endocrinol168: R1–R11.
62. F.MonzaniN.CaraccioM.KozakowaA.DardanoF.VittoneA.Virdis. (2004) Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study. J Clin Endocrinol Metab89: 2099–2106.
63. F.MonzaniV.Di BelloN.CaraccioA.BertiniD.GiorgiC.Giusti. (2001) Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol Metab86: 1110–1115.
64. S.Mooijaart (2012) Subclinical thyroid disorders. Lancet380: 335; author reply 336–337.
65. R.NegroA.SchwartzR.GismondiA.TinelliT.MangieriA.Stagnaro-Green (2010a) Increased pregnancy loss rate in thyroid antibody negative women with TSH Levels between 2.5 and 5.0 in the first trimester of pregnancy. J Clin Endocrinol Metab95: E44–E48.
66. R.NegroA.SchwartzR.GismondiA.TinelliT.MangieriA.Stagnaro-Green (2010b) Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. J Clin Endocrinol Metab95: 1699–1707.
67. R.NegroA.Stagnaro-Green (2014) Diagnosis and management of subclinical hypothyroidism in pregnancy. BMJ349: g4929.
68. A.NyrnesR.JordeJ.Sundsfjord (2006) Serum TSH is positively associated with BMI. Int J Obes30: 100–105.
69. N.OchsR.AuerD.BauerD.NanchenJ.GusseklooJ.Cornuz. (2008) Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med148: 832–845.
70. J.ParleL.RobertsS.WilsonH.PattisonA.RoalfeM.Haque. (2010) A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: the Birmingham elderly thyroid study. J Clin Endocrinol Metab95: 3623–3632.
71. A.ParsaikB.SinghR.RobertsS.PankratzK.EdwardsY.Geda. (2014) Hypothyroidism and risk of mild cognitive impairment in elderly persons: a population-based study. JAMA Neurol71: 201–207.
72. S.PearceG.BrabantL.DuntasF.MonzaniR.PeetersS.Razvi. (2013) 2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J2: 215–228.
73. P.PerrosR.MccrimmonG.ShawB.Frier (1995) Frequency of thyroid dysfunction in diabetic patients: value of annual screening. Diabet Med12: 622–627.
74. S.RazviL.IngoeG.KeekaC.OatesC.McmillanJ.Weaver (2007) The beneficial effect of l-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab92: 1715–1723.
75. S.RazviA.ShakoorM.VanderpumpJ.WeaverS.Pearce (2008) the influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: a metaanalysis. J Clin Endocrinol Metab93: 2998–3007.
76. S.RazviJ.WeaverT.ButlerS.Pearce (2012) Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Arch Intern Med172: 811–817.
77. V.ReutersP.TeixeiraP.VigarioC.AlmeidaA.BuescuM.Ferreira. (2009) Functional capacity and muscular abnormalities in subclinical hypothyroidism. Am J Med Sci338: 259–263.
78. N.RodondiD.AujeskyE.VittinghoffJ.CornuzD.Bauer (2006) Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis. Am J Med119: 541–551.
79. N.RodondiD.Bauer (2013) Subclinical hypothyroidism and cardiovascular risk: how to end the controversy. J Clin Endocrinol Metab98: 2267–2269.
80. N.RodondiW.Den ElzenD.BauerA.CappolaS.RazviJ.Walsh. (2010) Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA304: 1365–1374.
81. M.RozingJ.Houwing-DuistermaatP.SlagboomM.BeekmanM.FrolichA.De Craen. (2010) familial longevity is associated with decreased thyroid function. J Clin Endocrinol Metab95: 4979–4984.
82. E.SimonsickA.NewmanL.FerrucciS.SatterfieldT.HarrisN.Rodondi. (2009) Subclinical hypothyroidism and functional mobility in older adults. Arch Intern Med169: 2011–2017.
83. M.SkarulisF.CeliE.MuellerM.ZemskovaR.MalekL.Hugendubler. (2010) Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance. J Clin Endocrinol Metab95: 256–262.
84. L.SomwaruC.RariyA.ArnoldA.Cappola (2012) the natural history of subclinical hypothyroidism in the elderly: the Cardiovascular Health Study. J Clin Endocrinol Metab97: 1962–1969.
85. C.SpencerJ.HollowellM.KazarosyanL.Braverman (2007) National Health and Nutrition Examination Survey III thyroid-stimulating hormone (TSH)-thyroperoxidase antibody relationships demonstrate that TSH upper reference limitsmaybe skewed by occult thyroid dysfunction. J Clin Endocrinol Metab92: 4236–4240.
86. A.Stagnaro-GreenM.AbalovichE.AlexanderF.AziziJ.MestmanR.Negro. (2011) Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid21: 1081–1125.
87. S.StanickaK.VondraT.PelikanovaP.VlcekM.HillV.Zamrazil (2005) Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy. Clin Chem Lab Med43: 715–720.
88. P.SuK.HuangJ.HaoY.XuS.YanT.Li. (2011) Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China. J Clin Endocrinol Metab96: 3234–3241.
89. M.SurksJ.Hollowell (2007) Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab92: 4575–4582.
90. M.SurksE.OrtizG.DanielsC.SawinN.ColR.Cobin. (2004) Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA291: 228–238.
91. A.SvareT.NilsenB.AsvoldS.ForsmoB.ScheiT.Bjoro. (2013) Does thyroid function influence fracture risk? Prospective data from the Hunt2 study, Norway. Eur J Endocrinol169: 845–852.
92. K.ToulisA.Stagnaro-GreenR.Negro (2014) Maternal subclinical hypothyroidsm and gestational diabetes mellitus: a meta-analysis. Endocr Pract20: 703–714.
93. T.TrioloT.ArmstrongK.McfannL.YuM.RewersG.Klingensmith. (2011) Additional autoimmune disease found in 33% of patients at type 1 diabetes onset. Diabetes Care34: 1211–1213.
94. C.TudelaB.CaseyD.McintireF.Cunningham (2012) Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol119: 983–988.
95. E.Van den BoogaardR.VissenbergJ.LandM.Van WelyJ.van der PostM.Goddijn. (2011) Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Hum Reprod Update17: 605–619.
96. M.VanderpumpW.TunbridgeJ.FrenchD.AppletonD.BatesF.Clark. (1995) The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham survey. Clin Endocrinol43: 55–68.
97. H.VerloopM.LouwerensJ.SchoonesJ.KievitJ.SmitO.Dekkers (2012) Risk of hypothyroidism following hemithyroidectomy: systematic review and meta-analysis of prognostic studies. J Clin Endocrinol Metab97: 2243–2255.
98. H.VillarH.SaconatoO.ValenteA.Atallah (2007) Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev: CD003419.
99. V.VirginiL.WijsmanN.RodondiD.BauerP.KearneyJ.Gussekloo. (2014) Subclinical thyroid dysfunction and functional capacity among elderly. Thyroid24: 208–214.
100. J.WalshA.BremnerM.BulsaraP.O’LearyP.LeedmanP.Feddema. (2005) Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med165: 2467–2472.
101. K.WilsonB.CaseyD.McIntireL.HalvorsonF.Cunningham (2012) subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol119: 315–320.
102. Y.YanZ.DongL.DongF.WangX.YangX.Jin. (2011) Trimester- and method-specific reference intervals for thyroid tests in pregnant Chinese women: methodology, euthyroid definition and iodine status can influence the setting of reference intervals. Clin Endocrinol74: 262–269.
103. L.YassaE.MarquseeR.FawcettE.Alexander (2010) Thyroid hormone early adjustment in pregnancy (the THERAPY) trial. J Clin Endocrinol Metab95: 3234–3241.