The Regulation of Thyroid Function in Pregnancy: Pathways of Endocrine Adaptation from Physiology to Pathology
Daniel Glinoer
Hospital Saint-Pierre, Department of Internal Medicine, Thyroid
Investigation Clinic, Université Libre de Bruxelles,
Belgium
I. Introduction
II. The Regulation of Thyroid Function inNormal Pregnancy
A. The thyroid hormone transport proteins
B. The thyroid hormones
1. Total thyroid hormones
2. Freethyroid hormones
3. Peripheral metabolism of thyroid hormones
C. The serum levels of thyroglobulin (TG)
D. The metabolismof iodine
E. The hypothalamic-pituitary control of thyroidfunction andthe role of
hCG
1. Hypothalamic-pituitary-thyroidaxis (HPTA)
2. Regulation of serum TSH
3. Thyrotropic actionof hCG
F. A global view of thyroidal economy in pregnancy
III. Pathological Alterations of Thyroidal Regulation Associatedwith
Pregnancy
A. IDD
1. Consequences of iodine deficiencyduring pregnancy
2. Assessment of increased thyroidal stimulation
3. Gestational goitrogenesis and its prevention by iodinesupplementation
4. Consequences of iodine deficiency for theoffspring
B. Hypothyroidism and pregnancy
1. Fertility andpregnancy outcome in hypothyroid women
2. Thyroid hormonereplacement in the hypothyroid pregnant woman
3. Subclinicalhypothyroidism in pregnancy
4. Euthyroid autoimmune thyroiddisorders (AITD) and pregnancy
5. AITD and the risk of miscarriage
C. Hyperthyroidism and pregnancy
1. GD in the pregnant woman
2. GTT
3. Hyperemesis gravidarum and hyperthyroidism
IV.Conclusions and Perspectives
This article has been cited by other articles:
M. Boas, J. L. Forman, A. Juul, U. Feldt-Rasmussen, N. E. Skakkebaek, L. Hilsted, M. Chellakooty, T. Larsen, J. F. Larsen, J. H Petersen, et al. Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women
Eur. J. Endocrinol.,
December 1, 2009;
161(6):
903 - 910.
[Abstract][Full Text][PDF]
M. B. Zimmermann Iodine Deficiency
Endocr. Rev.,
June 1, 2009;
30(4):
376 - 408.
[Abstract][Full Text][PDF]
Y. Orito, H. Oku, S. Kubota, N. Amino, K. Shimogaki, M. Hata, K. Manki, Y. Tanaka, S. Sugino, M. Ueta, et al. Thyroid Function in Early Pregnancy in Japanese Healthy Women: Relation to Urinary Iodine Excretion, Emesis, and Fetal and Child Development
J. Clin. Endocrinol. Metab.,
May 1, 2009;
94(5):
1683 - 1688.
[Abstract][Full Text][PDF]
M. Moleti, V. P. Lo Presti, F. Mattina, A. Mancuso, A. De Vivo, G. Giorgianni, B. Di Bella, F. Trimarchi, and F. Vermiglio Gestational thyroid function abnormalities in conditions of mild iodine deficiency: early screening versus continuous monitoring of maternal thyroid status
Eur. J. Endocrinol.,
April 1, 2009;
160(4):
611 - 617.
[Abstract][Full Text][PDF]
M Alvarez-Pedrerol, M Guxens, M Mendez, Y Canet, R Martorell, M Espada, E Plana, M Rebagliato, and J Sunyer Iodine levels and thyroid hormones in healthy pregnant women and birth weight of their offspring
Eur. J. Endocrinol.,
March 1, 2009;
160(3):
423 - 429.
[Abstract][Full Text][PDF]
B. Shields, A. Hill, M. Bilous, B. Knight, A. T. Hattersley, R. W. Bilous, and B. Vaidya Cigarette Smoking during Pregnancy Is Associated with Alterations in Maternal and Fetal Thyroid Function
J. Clin. Endocrinol. Metab.,
February 1, 2009;
94(2):
570 - 574.
[Abstract][Full Text][PDF]
P. Laurberg, C. Bournaud, J. Karmisholt, and J. Orgiazzi Management of Graves' hyperthyroidism in pregnancy: focus on both maternal and foetal thyroid function, and caution against surgical thyroidectomy in pregnancy
Eur. J. Endocrinol.,
January 1, 2009;
160(1):
1 - 8.
[Abstract][Full Text][PDF]
J. Sanchez-Vega, F. Escobar del Rey, H. Farinas-Seijas, and G. Morreale de Escobar Inadequate iodine nutrition of pregnant women from Extremadura (Spain)
Eur. J. Endocrinol.,
October 1, 2008;
159(4):
439 - 445.
[Abstract][Full Text][PDF]
J. Royer, A. Lefevre-Minisini, G. Caltabiano, T. Lacombe, Y. Malthiery, F. Savagner, L. Pardo, and P. Rodien The Cloned Equine Thyrotropin Receptor Is Hypersensitive to Human Chorionic Gonadotropin; Identification of Three Residues in the Extracellular Domain Involved in Ligand Specificity
Endocrinology,
October 1, 2008;
149(10):
5088 - 5096.
[Abstract][Full Text][PDF]
J. Chevrier, B. Eskenazi, N. Holland, A. Bradman, and D. B. Barr Effects of Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides on Thyroid Function during Pregnancy
Am. J. Epidemiol.,
August 1, 2008;
168(3):
298 - 310.
[Abstract][Full Text][PDF]
F. C. W. Wu, A. Tajar, S. R. Pye, A. J. Silman, J. D. Finn, T. W. O'Neill, G. Bartfai, F. Casanueva, G. Forti, A. Giwercman, et al. Hypothalamic-Pituitary-Testicular Axis Disruptions in Older Men Are Differentially Linked to Age and Modifiable Risk Factors: The European Male Aging Study
J. Clin. Endocrinol. Metab.,
July 1, 2008;
93(7):
2737 - 2745.
[Abstract][Full Text][PDF]
E. E. Wasserman, K. Nelson, N. R. Rose, W. Eaton, J. P. Pillion, E. Seaberg, M. V. Talor, L. Burek, A. Duggan, and R. H. Yolken Maternal Thyroid Autoantibodies during the Third Trimester and Hearing Deficits in Children: An Epidemiologic Assessment
Am. J. Epidemiol.,
March 15, 2008;
167(6):
701 - 710.
[Abstract][Full Text][PDF]
B. Biondi and D. S. Cooper The Clinical Significance of Subclinical Thyroid Dysfunction
Endocr. Rev.,
February 1, 2008;
29(1):
76 - 131.
[Abstract][Full Text][PDF]
M. Alonso, C. Goodwin, X. Liao, D. Page, S. Refetoff, and R. E. Weiss Effects of Maternal Levels of Thyroid Hormone (TH) on the Hypothalamus-Pituitary-Thyroid Set Point: Studies in TH Receptor {beta} Knockout Mice
Endocrinology,
November 1, 2007;
148(11):
5305 - 5312.
[Abstract][Full Text][PDF]
H. Li, K. Richard, B. McKinnon, and R. H. Mortimer Effect of Iodide on Human Choriogonadotropin, Sodium-Iodide Symporter Expression, and Iodide Uptake in BeWo Choriocarcinoma Cells
J. Clin. Endocrinol. Metab.,
October 1, 2007;
92(10):
4046 - 4051.
[Abstract][Full Text][PDF]
P.-C. Huang, P.-L. Kuo, Y.-L. Guo, P.-C. Liao, and C.-C. Lee Associations between urinary phthalate monoesters and thyroid hormones in pregnant women
Hum. Reprod.,
October 1, 2007;
22(10):
2715 - 2722.
[Abstract][Full Text][PDF]
S. L. La'ulu and W. L. Roberts Second-Trimester Reference Intervals for Thyroid Tests: The Role of Ethnicity
Clin. Chem.,
September 1, 2007;
53(9):
1658 - 1664.
[Abstract][Full Text][PDF]
Subsection Reports
J. Clin. Endocrinol. Metab.,
August 1, 2007;
92(8_suppl):
s8 - s47.
[Full Text][PDF]
M. Abalovich, N. Amino, L. A. Barbour, R. H. Cobin, L. J. De Groot, D. Glinoer, S. J. Mandel, and A. Stagnaro-Green Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline
J. Clin. Endocrinol. Metab.,
August 1, 2007;
92(8_suppl):
s1 - s47.
[Abstract][Full Text][PDF]
G. A. Brent Diagnosing Thyroid Dysfunction in Pregnant Women: Is Case Finding Enough?
J. Clin. Endocrinol. Metab.,
January 1, 2007;
92(1):
39 - 41.
[Full Text][PDF]
D. Glinoer Miscarriage in women with positive anti-tpo antibodies: is thyroxine the answer?
J. Clin. Endocrinol. Metab.,
July 1, 2006;
91(7):
2500 - 2502.
[Full Text][PDF]
R. Negro, G. Formoso, T. Mangieri, A. Pezzarossa, D. Dazzi, and H. Hassan Levothyroxine Treatment in Euthyroid Pregnant Women with Autoimmune Thyroid Disease: Effects on Obstetrical Complications
J. Clin. Endocrinol. Metab.,
July 1, 2006;
91(7):
2587 - 2591.
[Abstract][Full Text][PDF]
P. E. Pedraza, M.-J. Obregon, H. F. Escobar-Morreale, F. Escobar del Rey, and G. M. de Escobar Mechanisms of Adaptation to Iodine Deficiency in Rats: Thyroid Status Is Tissue Specific. Its Relevance for Man
Endocrinology,
May 1, 2006;
147(5):
2098 - 2108.
[Abstract][Full Text][PDF]
A. De Leener, L. Montanelli, J. Van Durme, H. Chae, G. Smits, G. Vassart, and S. Costagliola Presence and Absence of Follicle-Stimulating Hormone Receptor Mutations Provide Some Insights into Spontaneous Ovarian Hyperstimulation Syndrome Physiopathology
J. Clin. Endocrinol. Metab.,
February 1, 2006;
91(2):
555 - 562.
[Abstract][Full Text][PDF]
S. Costagliola, E. Urizar, F. Mendive, and G. Vassart Specificity and promiscuity of gonadotropin receptors
Reproduction,
September 1, 2005;
130(3):
275 - 281.
[Abstract][Full Text][PDF]
M.F.G. Verberg, D.J. Gillott, N. Al-Fardan, and J.G. Grudzinskas Hyperemesis gravidarum, a literature review
Hum. Reprod. Update,
September 1, 2005;
11(5):
527 - 539.
[Abstract][Full Text][PDF]
M. B. Hapon, S. M. Varas, G. A. Jahn, and M. S. Gimenez Effects of hypothyroidism on mammary and liver lipid metabolism in virgin and late-pregnant rats
J. Lipid Res.,
June 1, 2005;
46(6):
1320 - 1330.
[Abstract][Full Text][PDF]
J H Lazarus and L D K E Premawardhana BEST PRACTICE NO 184 Screening for thyroid disease in pregnancy
J. Clin. Pathol.,
May 1, 2005;
58(5):
449 - 452.
[Abstract][Full Text][PDF]
J. Oden and I. M. Cheifetz Neonatal Thyrotoxicosis and Persistent Pulmonary Hypertension Necessitating Extracorporeal Life Support
Pediatrics,
January 1, 2005;
115(1):
e105 - e108.
[Abstract][Full Text][PDF]
F. Vermiglio, V. P. Lo Presti, M. Moleti, M. Sidoti, G. Tortorella, G. Scaffidi, M. G. Castagna, F. Mattina, M. A. Violi, A. Crisa, et al. Attention Deficit and Hyperactivity Disorders in the Offspring of Mothers Exposed to Mild-Moderate Iodine Deficiency: A Possible Novel Iodine Deficiency Disorder in Developed Countries
J. Clin. Endocrinol. Metab.,
December 1, 2004;
89(12):
6054 - 6060.
[Abstract][Full Text][PDF]
J. Anselmo, D. Cao, T. Karrison, R. E. Weiss, and S. Refetoff Fetal Loss Associated With Excess Thyroid Hormone Exposure
JAMA,
August 11, 2004;
292(6):
691 - 695.
[Abstract][Full Text][PDF]
K. Poppe, D. Glinoer, H. Tournaye, J. Schiettecatte, P. Devroey, A. van Steirteghem, P. Haentjens, and B. Velkeniers Impact of Ovarian Hyperstimulation on Thyroid Function in Women with and without Thyroid Autoimmunity
J. Clin. Endocrinol. Metab.,
August 1, 2004;
89(8):
3808 - 3812.
[Abstract][Full Text][PDF]
L. Montanelli, J. J. J. Van Durme, G. Smits, M. Bonomi, P. Rodien, E. J. Devor, K. Moffat-Wilson, L. Pardo, G. Vassart, and S. Costagliola Modulation of Ligand Selectivity Associated with Activation of the Transmembrane Region of the Human Follitropin Receptor
Mol. Endocrinol.,
August 1, 2004;
18(8):
2061 - 2073.
[Abstract][Full Text][PDF]
E. K. Alexander, E. Marqusee, J. Lawrence, P. Jarolim, G. A. Fischer, and P. R. Larsen Timing and Magnitude of Increases in Levothyroxine Requirements during Pregnancy in Women with Hypothyroidism
N. Engl. J. Med.,
July 15, 2004;
351(3):
241 - 249.
[Abstract][Full Text][PDF]
A. Toft Increased Levothyroxine Requirements in Pregnancy -- Why, When, and How Much?
N. Engl. J. Med.,
July 15, 2004;
351(3):
292 - 294.
[Full Text][PDF]
P. Rodien, N. Jordan, A. Lefevre, J. Royer, C. Vasseur, F. Savagner, A. Bourdelot, and V. Rohmer Abnormal stimulation of the thyrotrophin receptor during gestation
Hum. Reprod. Update,
March 1, 2004;
10(2):
95 - 105.
[Abstract][Full Text][PDF]
A. Delbaere, G. Smits, O. Olatunbosun, R. Pierson, G. Vassart, and S. Costagliola New insights into the pathophysiology of ovarian hyperstimulation syndrome. What makes the difference between spontaneous and iatrogenic syndrome?
Hum. Reprod.,
March 1, 2004;
19(3):
486 - 489.
[Abstract][Full Text][PDF]
P. K. Singh, C. A. Parvin, and A. M. Gronowski Establishment of Reference Intervals for Markers of Fetal Thyroid Status in Amniotic Fluid
J. Clin. Endocrinol. Metab.,
September 1, 2003;
88(9):
4175 - 4179.
[Abstract][Full Text][PDF]
G. Smits, O. Olatunbosun, A. Delbaere, R. Pierson, G. Vassart, and S. Costagliola Ovarian Hyperstimulation Syndrome Due to a Mutation in the Follicle-Stimulating Hormone Receptor
N. Engl. J. Med.,
August 21, 2003;
349(8):
760 - 766.
[Full Text][PDF]
F. Arturi, L. Lacroix, I. Presta, D. Scarpelli, B. Caillou, M. Schlumberger, D. Russo, J.-M. Bidart, and S. Filetti Regulation by Human Chorionic Gonadotropin of Sodium/Iodide Symporter Gene Expression in the JAr Human Choriocarcinoma Cell Line
Endocrinology,
June 1, 2002;
143(6):
2216 - 2220.
[Abstract][Full Text][PDF]
R. M. Calvo, E. Jauniaux, B. Gulbis, M. Asuncion, C. Gervy, B. Contempre, and G. Morreale de Escobar Fetal Tissues Are Exposed to Biologically Relevant Free Thyroxine Concentrations during Early Phases of Development
J. Clin. Endocrinol. Metab.,
April 1, 2002;
87(4):
1768 - 1777.
[Abstract][Full Text][PDF]
A. F. Muller, H. A. Drexhage, and A. Berghout Postpartum Thyroiditis and Autoimmune Thyroiditis in Women of Childbearing Age: Recent Insights and Consequences for Antenatal and Postnatal Care
Endocr. Rev.,
October 1, 2001;
22(5):
605 - 630.
[Abstract][Full Text][PDF]
J. Anselmo, T. Kay, K. Dennis, R. Szmulewitz, S. Refetoff, and R. E. Weiss Resistance to Thyroid Hormone Does Not Abrogate the Transient Thyrotoxicosis Associated with Gestation: Report of a Case
J. Clin. Endocrinol. Metab.,
September 1, 2001;
86(9):
4273 - 4275.
[Abstract][Full Text][PDF]
R. C. Smallridge and P. W. Ladenson Hypothyroidism in Pregnancy: Consequences to Neonatal Health
J. Clin. Endocrinol. Metab.,
June 1, 2001;
86(6):
2349 - 2353.
[Full Text][PDF]
F DELANGE Iodine deficiency as a cause of brain damage
Postgrad. Med. J.,
April 1, 2001;
77(906):
217 - 220.
[Abstract][Full Text]
G. Morreale de Escobar, M. Jesús Obregón, and F. Escobar del Rey Is Neuropsychological Development Related to Maternal Hypothyroidism or to Maternal Hypothyroxinemia?
J. Clin. Endocrinol. Metab.,
November 1, 2000;
85(11):
3975 - 3987.
[Abstract][Full Text]
J.-M. Bidart, L. Lacroix, D. Evain-Brion, B. Caillou, V. Lazar, R. Frydman, D. Bellet, S. Filetti, and M. Schlumberger Expression of Na+/I- Symporter and Pendred Syndrome Genes in Trophoblast Cells
J. Clin. Endocrinol. Metab.,
November 1, 2000;
85(11):
4367 - 4372.
[Abstract][Full Text]
M. T. Kilbane, R. A. Ajjan, A. P. Weetman, R. Dwyer, E. W. M. McDermott, N. J. OHiggins, and P. P. A. Smyth Tissue Iodine Content and Serum-Mediated 125I Uptake-Blocking Activity in Breast Cancer
J. Clin. Endocrinol. Metab.,
March 1, 2000;
85(3):
1245 - 1250.
[Abstract][Full Text]
A. F. Muller, A. Verhoeff, M. J. Mantel, F. H. de Jong, and A. Berghout Decrease of Free Thyroxine Levels after Controlled Ovarian Hyperstimulation
J. Clin. Endocrinol. Metab.,
February 1, 2000;
85(2):
545 - 548.
[Abstract][Full Text]
C. Herzmann, J. K. Torrens, G. M. de Escobar, F. E. del Rey, M. Fukushi, K. Honma, K. Fujita, J. G. Hollowell, P. L. Garbe, D. T. Miller, et al. Maternal Thyroid Deficiency during Pregnancy and Subsequent Neuropsychological Development of the Child
N. Engl. J. Med.,
December 23, 1999;
341(26):
2015 - 2017.
[Full Text]
T. W. Furlanetto, L. Q. Nguyen, and J. L. Jameson Estradiol Increases Proliferation and Down-Regulates the Sodium/Iodide Symporter Gene in FRTL-5 Cells
Endocrinology,
December 1, 1999;
140(12):
5705 - 5711.
[Abstract][Full Text]
C. R. Fantz, S. Dagogo-Jack, J. H. Ladenson, and A. M. Gronowski Thyroid Function during Pregnancy
Clin. Chem.,
December 1, 1999;
45(12):
2250 - 2258.
[Abstract][Full Text][PDF]
A. Caixàs, M. Albareda, A. García-Patterson, J. Rodríguez-Espinosa, A. de Leiva, and R. Corcoy Postpartum Thyroiditis in Women with Hypothyroidism Antedating Pregnancy?
J. Clin. Endocrinol. Metab.,
November 1, 1999;
84(11):
4000 - 4005.
[Abstract][Full Text]
R. D. Utiger Maternal Hypothyroidism and Fetal Development
N. Engl. J. Med.,
August 19, 1999;
341(8):
601 - 602.
[Full Text]
P. Rodien, C. Bremont, M.-L. R. Sanson, J. Parma, J. Van Sande, S. Costagliola, J.-P. Luton, G. Vassart, and L. Duprez Familial Gestational Hyperthyroidism Caused by a Mutant Thyrotropin Receptor Hypersensitive to Human Chorionic Gonadotropin
N. Engl. J. Med.,
December 17, 1998;
339(25):
1823 - 1826.
[Full Text][PDF]
V. J. Pop, L. H. Maartens, G. Leusink, M. J. van Son, A. A. Knottnerus, A. M. Ward, R. Metcalfe, and A. P. Weetman Are Autoimmune Thyroid Dysfunction and Depression Related?
J. Clin. Endocrinol. Metab.,
September 1, 1998;
83(9):
3194 - 3197.
[Abstract][Full Text]