Iodine and Pregnancy
[Status of iodine nutrition in France: prevention of iodine deficiency in pregnant and lactating women]
Caron P, Glinoer D, Lecomte P, Orgiazzi J, Wemeau JL.
Ann Endocrinol (Paris). 2006 Sep;67(4):281-6. French.
[abstract only]
"Iodine intake varies with age and physiological status: in pregnant and lactating women, recommended iodine intake ranges from 200 to 250 mg/day. Recent epidemiological studies in France demonstrate the presence of moderate iodine deficiency in the majority of pregnant and lactating women. This iodine deficiency induces maternal thyroid hyperplasia and then development of goiter in women, as well as impaired thyroid parameters. Maternal hypothyroxinemia during the first trimester of pregnancy can be associated with abnormal cognitive development and intellectual outcomes in the newborn and the children. According to the recent World Health Organization recommendations for the prevention and control of iodine deficiency in pregnant and lactating women, systematic iodine supplementation is indicated in France: 100 microg/day for women of reproductive age and 200 microg/day in pregnant and lactating women in order to eradicate iodine deficiency during pregnancy and lactation, and prevent the maternal and fetal consequences."
Iodine nutrition requirements during pregnancy.
Glinoer D
Thyroid. 2006 Oct;16(10):947-8.
[citation only]
Miscarriage in women with positive anti-TPO antibodies: is thyroxine the answer?
Glinoer D.
J Clin Endocrinol Metab. 2006 Jul;91(7):2500-2.
[citation only]
Pregnancy and iodine deficiency
Glinoer D
Revised April 2006
"During pregnancy, two fundamental changes take place. There is a significant increase in the renal iodide clearance (by ~1.3- to ~1.5-fold) and, concomitantly, a sustained increment in TH production requirements (by ~1.5-fold), corresponding to increased iodine requirements, from 80 to 120 μg iodide/day. Since the renal iodide clearance already increases in the first weeks of gestation and persists thereafter, this constitutes an unavoidable urinary iodine ‘leakage’ which tends to lower circulating PII levels and, in turn, induce a compensatory increase in the thyroidal clearance of iodide. These mechanisms underline the increased physiologic thyroidal activity during pregnancy. Panel C in Figure 9 indicates that when the daily iodine intake is only 70 μg during pregnancy, and despite an increase in glandular uptake to 60 %, the equilibrium becomes more or less rapidly unbalanced, since the iodide entry resulting from both uptake and recycling is insufficient to fulfill the increased requirements for TH production.
"Calculations show that, in such conditions, ~20 μg of iodine are missing daily and, in order to sustain TH production, the glandular machinery must draw from already depleted intra-thyroidal iodine stores. Thus in about one trimester after conception, the already low intra-thyroidal iodine stores become even more depleted and, when iodine deprivation prevails during the first half, it tends to become more severe with the progression of gestation to its final stages. A second mechanism of iodine deprivation for the mother occurs later in gestation, from the passage of a part of the available iodine from maternal circulation to the fetal-placental unit. The extent of iodine passage has not yet been precisely established. At mid-gestation, the fetal thyroid gland has already started to produce TH, indispensable for the adequate development of the fetus. In summary, augmentation of iodide trapping is the fundamental mechanism by which the thyroid adapts to changes in the iodine supply, and such mechanism is the key to understanding thyroidal adaptation to iodine deficiency. During pregnancy, increased hormone requirements and iodine losses alter the preconception steady-state. When the iodine supply is restricted (or more severely deficient), pregnancy triggers a vicious circle that leads to excessive glandular stimulation."
Thyroid function inside and outside of pregnancy: what do we know and what don’t we know?
Smallridge RC, Glinoer D, Hollowell JG, Brent G.
Thyroid. 2005 Jan;15(1):54-9.
[abstract only]
"A workshop entitled, "The Impact of Maternal Thyroid Diseases on the Developing Fetus: Implications for Diagnosis, Treatment, and Screening," was held in Atlanta, Georgia, January 12-13, 2004. This paper reports on the session that examined the prevalence of thyroid dysfunction in reproductive-age women and the factors associated with abnormal function. For this session the following papers were presented: "Thyroidal Economy in the Pregnant State: An Overview," "The Prevalence of Thyroid Dysfunction in Reproductive-Age Women- United States," and "Risk Factors for Thyroid Disease: Autoimmunity and Other Conditions." These presentations were formally discussed by invited respondents and by others in attendance. Salient points from this session about which there was agreement include the following: physiologic changes associated with pregnancy require an increased availability of thyroid hormones by 40% to 100% in order to meet the needs of mother and fetus during pregnancy. In the first trimester of gestation the fetus is wholly dependent on thyroxine from the mother for normal neurologic development. For the maternal thyroid gland to meet the demands of pregnancy it must be present, disease-free, and capable of responding with adequate stores of iodine. Thyroid autoimmunity is common and may contribute to miscarriages, as well as to hypothyroidism. With sufficient iodine nutrition, autoimmune thyroid disease (AITD) is the most common cause of hypothyroidism. As of 1994, iodine nutrition in the United States appeared to be adequate, but its continued monitoring is essential."
The regulation of thyroid function during normal pregnancy: importance of the iodine nutrition status.
Glinoer D.
Best Pract Res Clin Endocrinol Metab. 2004 Jun;18(2):133-52. Review.
[abstract only]
"The main change in thyroid function associated with the pregnant state is the requirement of an increased production of thyroid hormone that depends directly upon the adequate availability of dietary iodine and integrity of the glandular machinery. Physiologic adaptation takes place when the iodine intake is adequate, while this is replaced by pathologic alterations when there is a deficient iodine intake. Pregnancy acts typically, therefore, as a revelator of underlying iodine restriction. Iodine deficiency (ID) has important repercussions for both the mother and the fetus, leading to sustained glandular stimulation, hypothyroxinemia and goitrogenesis. Furthermore, because severe ID may be associated with an impairment in the psycho-neuro-intellectual outcome in the progeny-because both mother and offspring are exposed to ID during gestation (and the postnatal period), and because ID is still prevalent today in several European countries-it has been proposed already in the early 1990s that iodine supplements be given systematically to pregnant and breast-feeding women. Particular attention is required to ensure that pregnant women receive an adequate iodine supply, by administering multivitamin tablets containing iodine supplements, in order to achieve the ideal recommended dietary allowance of 200-250 microg iodine/day."
Thyroid autoimmunity and the risk of miscarriage.
Stagnaro-Green A, Glinoer D.
Best Pract Res Clin Endocrinol Metab. 2004 Jun;18(2):167-81.
[abstract only]
"Approximately one-third of all pregnancies end in miscarriage. The etiology of recurrent abortion remains unknown in approximately 50% of all women. In the early 1990s it was discovered that unselected euthyroid women who present with thyroid antibodies (thyroid peroxidase and thyroglobulin) in the first trimester of pregnancy have a two-four-fold increase in their miscarriage rates. The majority of studies investigating women with recurrent abortion have also found a significant increase in thyroid antibody positivity compared with controls. Although the etiology of miscarriage in thyroid antibody women remains unknown, recent data have revealed a potential direct effect of thyroglobulin antibodies on pregnancy loss in a murine model. Uncontrolled studies assessing the effect of levothyroxine on decreasing the miscarriage rate in euthyroid antibody positive women, have demonstrated a decreased miscarriage rate."
Management of hypo- and hyperthyroidism during pregnancy.
Glinoer D.
Growth Horm IGF Res. 2003 Aug;13 Suppl A:S45-54. Review.
[abstract only]
"Pregnancy has profound effects on the regulation of thyroid function, and on thyroidal functional disorders, that need to be recognized, carefully assessed and correctly managed. Relative hypothyroxinemia and goitrogenesis may occur in healthy women who reside in areas with restricted iodine intake, strongly suggesting that pregnancy constitutes a stimulatory challenge for the thyroid. Overt thyroid dysfunction occurs in 1-2% of pregnant women, but mild forms of dysfunction (both hyper- and hypothyroidism) are probably more prevalent and frequently remain unrecognized. Alterations of maternal thyroid function have important implications for fetal and neonatal development. In recent years, particular attention has been drawn to the potential risks for the developing fetus due to maternal hypothyroxinemia during early gestation.Concerning hyperthyroidism, the two main causes of thyrotoxicosis in the pregnant state are Graves’ disease and gestational transient thyrotoxicosis (GTT). The natural history of Graves’ disease is altered during pregnancy, with a tendency for exacerbation during the first trimester, and amelioration during the second and third trimesters. The natural history of the disorder must be considered when treating patients, since antithyroid drugs cross the placenta and can directly affect fetal thyroid function. Algorithms to routinely screen pregnant women for thyroid dysfunction have been proposed in recent years, but these have not yet been implemented systematically, nor have they been the subject of cost-effectiveness analyses."
Thyroid autoimmunity and hypothyroidism before and during pregnancy.
Poppe K, Glinoer D.
Hum Reprod Update. 2003 Mar-Apr;9(2):149-61. Review.
"In the present review, an attempt was made to describe current knowledge and concepts concerning the complex relationships that link thyroid autoimmunity (TAI) and hypothyroidism with female and male infertility, as well as abnormalities occurring during pregnancy, such as pregnancy loss and maternal and fetal repercussions associated with hypothyroidism. In the case of infertility, although the clinical relevance of TAI is somewhat controversial, when all available information is considered the results strongly suggest that when infertility is due to well-defined female causes, autoimmunity is involved and TAI constitutes a useful marker of the underlying immune abnormality, independently of thyroid function disorders. In the case of pregnancy loss, the vast majority of available studies clearly establish that TAI (even with no overt thyroid dysfunction) is associated with a significant increase in miscarriage risk. To find an association, however, does not imply a causal relationship, and the aetiology of increased pregnancy loss associated with TAI remains presently not completely understood. With regard to maternal repercussions during gestation, the main risk associated with TAI is the occurrence of hypothyroidism and obstetric complications (premature birth, pre-eclampsia, etc.). Thus, systematic screening of TAI and hypothyroidism during early pregnancy, monitoring of thyroid function with/without L-thyroxine treatment and follow-up during post-partum have proved helpful and important in order to manage these patients adequately. Finally, with regard to potential repercussions affecting the offspring, recent evidence suggests that thyroid maternal underfunction, even when considered mild (or subclinical), may be associated with an impairment of fetal brain development. When present only during the first half of gestation, maternal hypothyroxinaemia is a risk factor for impaired fetal brain development, due to insufficient transfer of maternal thyroid hormones to the feto-placental unit. When hypothyroidism is not restricted to the first trimester and worsens as gestation progresses (as in untreated hypothyroidism), the fetus may also be deprived of adequate amounts of thyroid hormones during later neurological maturation and development, leading to poorer school performance and lower IQ."
Feto-maternal repercussions of iodine deficiency during pregnancy. An update.
Glinoer D.
Ann Endocrinol (Paris). 2003 Feb;64(1):37-44. Review.
[abstract only]
"The main changes in thyroid function associated with the pregnant state are increased thyroid hormone requirements. These increased requirements can only be met by a proportional increase in hormone production, that directly depends upon the availability of dietary iodine. When the iodine intake is adequate, normal "physiological" adaptation takes place. When the intake is restricted, physiological adaptation is progressively replaced by pathological alterations, in parallel with the degree of iodine deprivation, leading to excessive glandular stimulation, hypothyroxinemia, and goiter formation. Thus, pregnancy acts typically as a revelator of underlying iodine restriction and gestation results in an iodine deficient status, even in conditions with only a moderately restricted iodine intake, characteristic of many European regions. Iodine deficiency during pregnancy has important repercussions for both mother and fetus, namely thyroid underfunction and goitrogenesis. Furthermore, iodine deficiency may be associated with alterations of the psychoneuro-intellectual outcome in the progeny. The risk of an abnormal progeny’s development is further enhanced because mother and offspring are exposed to iodine deficiency, both during gestation and the postnatal period. Because iodine deficiency is still prevalent in many European regions and remains a subject of great concern, investigators have proposed, since several years, that iodine prophylaxis be introduced systematically during pregnancy, in order to provide mothers with an adequate iodine supply. In areas with a severe iodine deficiency, correcting the iodine lack has proved highly beneficial to prevent mental deficiency disorders. The many actions undertaken to eradicate severe iodine deficiency have allowed to prevent the occurrence of mental retardation in millions young infants throughout the world. In most public health programmes dealing with the correction of iodine deficiency disorders, iodized salt has been used as the preferred strategy in order to convey the iodine supplements to the household. Iodized salt, however, is not the ideal vector in the specific instance of pregnancy (or breastfeeding) or in young infants, because of the necessity to limit salt intake. Hence, particular attention is required in our countries to ensure that pregnant women have an adequate iodine intake, by administering multi-vitamin tablets containing iodide supplements (+125 micro g/d). Finally, it is with some concern that the results of a recent nutritional survey in the USA have disclosed that iodine deficiency, long thought to have been eradicated since many years, may actually show a resurgence, particularly in women in the child-bearing period. This issue needs to be considered seriously by the medical community and public health authorities."
Thyroid dysfunction and autoimmunity in infertile women.
Poppe K, Glinoer D, Van Steirteghem A, Tournaye H, Devroey P, Schiettecatte J, Velkeniers B.
Thyroid. 2002 Nov;12(11):997-1001.
[abstract only]
"A prospective study was undertaken in 438 women (ages, 32 +/- 5 years) with various causes of infertility, and in 100 age-matched (33 +/- 5 years) healthy parous controls with the aim of assessing the prevalence of autoimmune thyroid disease (AITD) and hitherto undisclosed alterations of thyroid function. Female origin of the infertility was diagnosed in 45% of the couples, with specific causes including endometriosis (11%), tubal disease (30%), and ovarian dysfunction (59%). Male infertility represented 38% and idiopathic infertility 17% of the couples. Overall, median thyrotropin (TSH) was significantly higher in patients with infertility compared to controls: 1.3 (0.9) versus 1.1 (0.8) mIU/L. Serum TSH above normal (>4.2 mIU/L) or suppressed TSH (<0.27 mIU/L) levels were not more prevalent in the infertile women than in controls. The prevalence of positive thyroid peroxidase antibody (TPO-Ab) was higher in all investigated women of infertile couples, compared to controls (14% vs. 8%), but the difference was not significant. However, in infertility of female origin, a significant higher prevalence of positive TPO-Ab was present, compared to controls: 18% versus 8%. Furthermore, among the female causes, the highest prevalence of positive antibodies was observed in women with endometriosis (29%). When thyroid antibodies were positive, both hypothyroidism and hyperthyroidism were more frequent in all women of infertile couples and in the women with a female infertility cause, compared to women in the same groups but without positive TPO-Ab. The present study shows that in infertile women, thyroid autoimmunity features are significantly more frequent than in healthy fertile controls and this was especially the case for the endometriosis subgroup."
Potential consequences of maternal hypothyroidism on the offspring: evidence and implications.
Glinoer D.
Horm Res. 2001;55(3):109-14. Review.
[abstract only]
"The adequate functioning of both the maternal and fetal thyroid glands plays important roles to ensure that the fetal neuropsychointellectual development progresses normally. Three sets of clinical disorders ought to be envisaged, potentially leading to impaired brain development: defective glandular ontogenesis (leading to congenital hypothyroidism), maternal hypothyroidism (usually related to chronic autoimmune thyroiditis), and finally iodine deficiency (affecting both the maternal and fetal thyroid functions). The present review will be focused mainly on maternal hypothyroidism, where both the severity and temporal occurrence of maternal thyroid underfunction drive the resulting repercussions for an impaired fetal neuronal development: such clinical situations may take place during early gestation (in women with known but untreated hypothyroidism) or appear only during later gestational stages (in women with thyroid antibodies, who remain euthyroid during the first half of gestation). Recent available evidence and its implications are discussed, as well as our present concepts relating to the complexities of the fetomaternal thyroid relationships, and the potential impact of maternal thyroid function abnormalities on the ideal offspring’s development."
Pregnancy and iodine.
Glinoer D.
Thyroid. 2001 May;11(5):471-81. Review.
[abstract only]
"Hormonal changes and metabolic demands during pregnancy result in profound alterations in the biochemical parameters of thyroid function. For thyroid economy, the main events occurring during pregnancy are a marked increase in serum thyroxine-binding globulin levels; a marginal decrease in free hormone concentrations (in iodine-sufficient areas) that is significantly amplified when there is iodine restriction or overt iodine deficiency; a frequent trend toward a slight rise in basal thyrotropin (TSH) values between the first trimester and term; a transient stimulation of the maternal thyroid gland by elevated levels of human chorionic gonadotropin (hCG) resulting in a rise in free thyroid hormones and decrement in serum TSH concentrations during the first trimester; and finally, modifications of the peripheral metabolism of maternal thyroid hormones. Together, metabolic changes associated with the progression of gestation in its first half constitute a transient phase from preconception steady state to pregnancy steady state. In order to be met, these metabolic changes require an increased hormonal output by the maternal thyroid gland. Once the new equilibrium is reached, increased hormonal demands are maintained until term, probably through transplacental passage of maternal thyroid hormones and increased turnover of maternal thyroxine (T4), presumably under the influence of the placental (type 3) deiodinase. For healthy pregnant women with iodine sufficiency, the challenge of the maternal thyroid gland is to adjust the hormonal output in order to achieve the new equilibrium state, and thereafter maintain the equilibrium until term. In contrast, the metabolic adjustment cannot easily be reached during pregnancy when the functional capacity of the thyroid gland is impaired because of iodine deficiency. The ideal dietary allowance of iodine recommended by World Health Organization (WHO) is 200 microg of iodine per day for pregnant women. In conditions with iodine restriction, enhanced thyroidal stimulation is revealed by relative hypothyroxinernia and goitrogenesis. Goiters formed during gestation may only partially regress after parturition. Pregnancy, therefore, represents one of the environmental factors that may help explain the higher prevalence of goiter and thyroid disorders in women compared with men. An iodine-deficient status in the mother also leads to goiter formation in the progeny and neuropsycho-intellectual impairment in the offspring. When adequate iodine supplementation is given early during pregnancy, it allows for the correction and almost complete prevention of maternal and neonatal goitrogenesis. In summary, pregnancy is accompanied by profound alterations in the thyroid economy, resulting from a complex combination of factors specific to the pregnant state, which together concur to stimulate the maternal thyroid machinery. Increased thyroidal stimulation induces, in turn, a sequence of events leading from physiological adaptation of the thyroidal economy observed in healthy iodine-sufficient pregnant women to pathological alterations affecting both thyroid function and the anatomical integrity of the thyroid gland, when gestation takes place in conditions with iodine restriction or deficiency: the more severe the iodine deficiency, the more obvious, frequent, and profound the potential maternal and fetal repercussions."
Parity as a thyroid size-determining factor in areas with moderate iodine deficiency.
Rotondi M, Amato G, Biondi B, Mazziotti G, Del Buono A, Rotonda Nicchio M, Balzano S, Bellastella A, Glinoer D, Carella C.
J Clin Endocrinol Metab. 2000 Dec;85(12):4534-7.
"Among the factors that may influence thyroid size, pregnancy and its goitrogenic effect have been widely investigated, but thyroid volume and pregnancy have never been compared retrospectively, and there are no data on the possible relationship between thyroid size and parity. The purpose of this work was to evaluate the effects of pregnancy on thyroid volume in a moderate iodine deficiency area, to assess the possibility of a relationship between thyroid size and parity status in healthy females. A group of 208 nongoitrous healthy women underwent thyroid volume estimation by ultrasound examination. All subjects were euthyroid and negative for thyroid autoantibodies. They were assigned to different groups, according to the number of completed pregnancies. Five groups were formed (0, 1, 2, 3, 4 or more term pregnancies). Mean thyroid volume increased progressively among the groups: group 0 (14.8 +/- 0.7 mL); group I (16.0 +/- 0.9 mL); group II (17.1 +/- 0.6 mL); group III (18.2 +/- 0.6 mL); group IV (20.3 +/- 0.9 mL). The increment in thyroid volume was statistically significant between group 0 and groups III (P: < 0.01) and IV (P: < 0.001), and also between group I and group IV (P: < 0. 05). No independent effect of body weight and age on thyroid volume was seen. Our results indicate that, in an area with moderate iodine deficiency, the goitrogenic effect of pregnancy is not fully reversible. Moreover, the statistically significant increase in thyroid volume, observed in relation to parity, is the first clinical demonstration of a cumulative goitrogenic effect of successive pregnancies, providing a strong argument to increase the iodine supply during pregnancy, even in conditions with moderate iodine deficiency."
The potential repercussions of maternal, fetal, and neonatal hypothyroxinemia on the progeny.
Glinoer D, Delange F.
Thyroid. 2000 Oct;10(10):871-87. Review.
[abstract only]
"The adequate functioning of both the maternal and fetal thyroid glands play an important role to ensure that the fetal neuropsycho-intellectual development progresses normally. Three sets of clinical disorders are considered, that may eventually lead to impaired brain development. Firstly, in infants with a defect of glandular ontogenesis (congenital hypothyroidism), the participation of maternal thyroid hormones to the fetal circulating thyroxine environment is normal and, therefore, risk of brain damage results exclusively from the insufficient hormone production by the abnormal fetal thyroid gland. Secondly, when it is only the maternal thyroid gland that is functionally deficient (autoimmune hypothyroidism), the severity and temporal occurrence of maternal underfunction will both drive the resulting consequences for impaired fetal neuronal development. Clinical situations of this type may obviously take place already during early gestation (in women with known but untreated hypothyroidism) or appear only during later gestational stages (in women who have AITD and remain euthyroid during the first half of gestation). Lastly, in conditions with iodine deficiency, both maternal and fetal thyroid functions are affected and, therefore, it is primarily the degree and precocity of the maternal hypothyroxinemia due to iodine deficiency during pregnancy that will drive the potential repercussions for fetal neurological development. In the present review, we summarize available data and develop our present concepts concerning the complex feto-maternal thyroid relationships and the potential impacts of thyroid function abnormalities on the ideal development of the offspring."
What happens to the normal thyroid during pregnancy?
Glinoer D.
Thyroid. 1999 Jul;9(7):631-5. Review.
[abstract only]
"Hormonal changes and metabolic demands during pregnancy result in profound alterations in the biochemical parameters of thyroid function. For the thyroidal economy, the main events occurring during pregnancy are: a marked increase in serum thyroxine-binding globulin levels; a marginal decrease in free hormone concentrations (in iodine-sufficient conditions) that is significantly amplified when there is iodine restriction or overt iodine deficiency; a frequent trend toward a slight increase in basal thyrotropin (TSH) values between the first trimester and term; a direct stimulation of the maternal thyroid gland by elevated levels of human chorionic gonadotropin (hCG), which occurs mainly near the end of the first trimester and can be associated with a transient lowering in serum TSH; and finally, modifications of the peripheral metabolism of maternal thyroid hormones. Together, metabolic changes associated with the progression of gestation in its first half constitute a transient phase from a preconception steady-state to the pregnancy steady-state. In order to be met, these metabolic changes require an increased hormonal output by the maternal thyroid gland. Once the new equilibrium is reached, increased hormonal demands are maintained until term, probably through transplacental passage of thyroid hormones and increased turnover of maternal thyroxine (T4), presumably under the influence of the placental (type III) deiodinase. For healthy pregnant women with iodine sufficiency, the challenge of the maternal thyroid gland is to adjust the hormonal output in order to achieve the new equilibrium state, and thereafter maintain the equilibrium until term. In contrast, the metabolic adjustment cannot easily be reached when the functional capacity of the thyroid gland is impaired (such as in autoimmune thyroid disease and hypothyroidism) or when pregnancy takes place in healthy women residing in areas with a deficient iodine intake. The ideal dietary allowance of iodine recommended by the World Health Organization (WHO) is 200 microg iodine per day for pregnant women. In conditions with iodine restriction, enhanced thyroidal stimulation is revealed by relative hypothyroxinemia and goitrogenesis. Goiters formed during gestation may only partially regress after parturition. Pregnancy, therefore, represents one of the environmental factors that may explain the higher prevalence of goiter and thyroid disorders in the female population. An iodine-deficient status in the mother also leads to goiter formation in the progeny. When adequate iodine supplementation is given early during pregnancy, it allows for the correction and almost complete prevention of maternal and neonatal goitrogenesis. In summary, pregnancy is accompanied by profound alterations in the thyroidal economy, resulting from a complex combination of factors specific to the pregnant state, which together concur to stimulate the maternal thyroid machinery. Increased thyroidal stimulation induces, in turn, a sequence of events leading from physiological adaptation of the thyroidal economy observed in healthy iodine-sufficient pregnant women, to pathological alterations, affecting both thyroid function and the anatomical integrity of the thyroid gland, when gestation takes place in conditions with iodine restriction or deficiency: the more severe the iodine deficiency, the more obvious, frequent, and profound the potential maternal and fetal repercussions."
Thyroid hyperfunction during pregnancy.
Glinoer D.
Thyroid. 1998 Sep;8(9):859-64. Review.
[abstract only]
"The present report focuses on the two main causes of hyperthyroidism observed in the pregnant state: Graves’ disease (GD) and gestational transient thyrotoxicosis. Together, the prevalence of hyperthyroidism may represent 3% to 4% of all pregnancies, and therefore constitutes an important clinical issue. Concerning GD, the variable presentations of the disease (women under treatment, in remission, or considered cured) and specific alterations occurring in pregnancy are discussed: changes in thyrotropin (TSH) receptor antibody titers, the risk of fetal and neonatal thyrotoxicosis, the outcome of pregnancy in relation to the control of hyperthyroidism, and the treatment of active GD during and after pregnancy with antithyroid drugs. Gestational transient thyrotoxicosis is associated with a direct stimulation of the maternal thyroid gland by human chorionic gonadotropin (hCG), and has been shown to be directly related to both the amplitude and duration of peak hCG values. The syndrome is usually transient, observed at the end of the first trimester, and is frequently associated with emesis. Finally, we propose a global strategy for the systematic screening of hyperthyroidism during pregnancy, based on an algorithm that allows for the diagnosis of both autoimmune and nonautoimmune forms of hyperthyroidism in the pregnant state."
The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology.
Glinoer D.
Endocr Rev. 1997 Jun;18(3):404-33. Review.
"THYROID disorders are observed 4- to 5-fold more frequently in women when compared with men, in particular during the childbearing period. It is therefore not unusual to encounter thyroid function abnormalities during a "routine" laboratory evaluation carried out for pregnant women. One of the aims of the present review is to underscore the rationale that allows for a correct interpretation of these alterations. Furthermore, pregnancy is accompanied by profound alterations in thyroidal economy, resulting from a complex combination of factors specific for the pregnant state: the rise in T4-binding globulin concentrations, the effects of CG on the maternal thyroid, alterations in the requirement for iodine, modifications in autoimmune regulation, and the role of the placenta in deiodination of iodothyronines. Another aim of this review is to discuss the specific role attributed to each factor and delineate the main pathways of thyroidal adaptation, including physiology as well as pathophysiology in the pregnant state. Finally, the third aim is to discuss specific aspects of the management of hypothyroidism (related to established, subclinical, and preclinical hypothyroidism) and hyperthyroidism [both Graves’ disease (GD) and gestational nonautoimmune transient thyrotoxicosis] when associated with pregnancy."
Maternal and fetal impact of chronic iodine deficiency.
Glinoer D.
Clin Obstet Gynecol. 1997 Mar;40(1):102-16. Review.
[citation only]
[Thyroid nodule and cancer in pregnant women]
Glinoer D.
Ann Endocrinol (Paris). 1997;58(3):263-7. Review. French.
[abstract only]
"Most thyroid nodules discovered during pregnancy are benign. In this article, we propose a pragmatic attitude for the diagnosis and treatment of such nodules, insisting particularly on the importance of thyroid echography and fine needle aspiration. For women who have successfully been treated for thyroid cancer before pregnancy, we discuss the adaptation of thyroxine substitution when they become pregnant, the obstetrical and fetal risks (spontaneous miscarriage, fetal abnormalities of the thyroid gland and others), and also potential later risks for the child, in relation with previous radioactive iodine administration to the mother. Finally, we evoke more difficult questions, such as the rare instances in which thyroid cancer is discovered during pregnancy, pregnancy occurring during the months immediately following radioiodine treatment, and exceptional cases where therapeutic radioiodine was inadvertently given during pregnancy."
[Thyroid changes in the pregnant woman]
Glinoer D.
Rev Med Brux. 1996 Sep;17(4):210-3. French.
[abstract only]
"In Belgium the iodine intake is restricted and even marginally insufficient. During pregnancy, the insufficient iodine supply is associated with chronic stimulation of the thyroid gland, leading to the development of gestational goiters and to an increased risk of foetal goitrogenicity. Also, approximately one third of pregnant women exhibit relative hypothyroxinemia. Moreover, women who present chronic autoimmune thyroiditis and in whom thyroid function is normal at the onset of pregnancy carry a significant risk of developing thyroid insufficiency during gestation. In conclusion, healthy pregnant women should be given the benefit of iodine supplementation, both during pregnancy and breastfeeding. This will allow them to maintain a well adapted thyroid function, prevent goitrogenicity, and ensure adequate foetal hormone production. For women with autoimmune thyroiditis, thyroid function should be closely monitored during pregnancy and the slightest indication of thyroid insufficiency should prompt the administration of thyroid hormone substitution."
A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects.
Glinoer D, De Nayer P, Delange F, Lemone M, Toppet V, Spehl M, Grun JP, Kinthaert J, Lejeune B.
J Clin Endocrinol Metab. 1995 Jan;80(1):258-69.
[abstract only]
"One hundred and eighty euthyroid pregnant women were selected at the end of the first trimester of gestation on the basis of biochemical criteria of excessive thyroid stimulation, defined as supranormal serum thyroglobulin (TG > 20 micrograms/L) associated with a low normal free T4 index (< 1.23) and/or an increased T3/T4 ratio (> 25 x 10(-3)). Women were randomized in a double blind protocol into three groups and treated until term with a placebo, 100 micrograms potassium iodide (KI)/day, or 100 micrograms iodide plus 100 micrograms L-T4/day. Parameters of thyroid function, urinary iodine excretion, and thyroid volume were monitored sequentially. Neonatal thyroid parameters, including thyroid volume by echography, were also assessed in the newborns from mothers of the three groups. In women receiving a placebo, the indices of excessive thyroid stimulation worsened as gestation progressed, with low free T4 levels, markedly increased serum TG and T3/T4 ratio. Serum TSH doubled, on the average, and was supranormal in 20% of the cases at term. Urinary iodine excretion levels were low, around 30 micrograms/L at term. The thyroid volume increased, on the average, by 30%, and 16% of the women developed a goiter, confirming the goitrogenic stimulus associated with pregnancy. Moreover, the newborns of these mothers had significantly larger thyroid volumes at birth as well as elevated serum TG levels. In both groups of women receiving an active treatment, the alterations in thyroid function associated with pregnancy were markedly improved. The increase in serum TSH was almost suppressed, serum TG decreased significantly, and changes in thyroid volume were minimized (group receiving KI) or almost suppressed (group receiving KI combined with L-T4). Moreover, in the newborns of the mothers in the two groups receiving an active treatment, serum TG was significantly lower, and thyroid volume at birth was normal. The effects of therapy were clearly more rapid and more marked in the group receiving a combination of T4 and KI than in the women receiving KI alone. The differences could be partly attributed to the slightly higher amount of iodine received by women in the combined treatment. However, the main benefits of the combined treatment were almost certainly attributable to the hormonal effects of the addition of L-T4. Furthermore, the study demonstrated that the administration of T4 did not hamper the beneficial effect of iodine supplementation. In conclusion, the present work emphasizes the potential risk of goitrogenic stimulation in both mother and newborn in the presence of mild iodine deficiency. (ABSTRACT TRUNCATED AT 400 WORDS)"
Goiter and pregnancy: a new insight into an old problem.
Glinoer D, Lemone M.
Thyroid. 1992 Spring;2(1):65-70.
[abstract only]
"Evidence is presented that pregnancy constitutes a goitrogenic stimulus, particularly in conditions with a restricted or even a marginally low iodine intake. In a series of studies carried out in a large cohort of pregnancies in the Brussels area, the authors show that an increase in thyroid volume is observed in a majority of pregnant women, leading to goiter formation at delivery in 9% of the cases. Furthermore, increments in thyroid volume were correlated with biochemical evidences of functional stimulation of the thyroid, such as an elevation in serum TG levels, preferential T3 secretion, and slight increases in basal TSH at delivery. Hence, the association of biochemical features of thyroidal stimulation with volumetric changes in the gland strongly suggests that pregnancy truly induces goitrogenesis rather than vascular swelling ("intumescence") alone, at least in conditions with a low iodine intake. Finally, preliminary data from this laboratory, as well as recently published data from other investigators, suggest that goiter formation during pregnancy can easily be prevented by increasing the iodine supply during pregnancy."
Maternal and neonatal thyroid function at birth in an area of marginally low iodine intake.
Glinoer D, Delange F, Laboureur I, de Nayer P, Lejeune B, Kinthaert J, Bourdoux P.
J Clin Endocrinol Metab. 1992 Sep;75(3):800-5.
[abstract only]
"Thyroid function was evaluated in cord serum of healthy full-term newborns and compared to that of mothers immediately after parturition. The study was carried out in an area without overt iodine deficiency, but with a marginal iodine supply (less than 100 micrograms/day in 80% of women). The aim of the study was to delineate the interrelationships between the thyroid statuses of mother and child at birth. Maternal thyroid function was characterized at delivery by relative hypothyroxinemia; increased T3/T4 ratios, indicating preferential T3 secretion; slightly increased TSH levels within the normal range in 97% of women; increased serum thyroglobulin (TG) values, which were above normal in 60% of women; and also goiter formation in almost 10% of women. The findings indicated glandular stimulation and confirmed our earlier reports that pregnancy constitutes a stress for the maternal thyroid economy, enhanced by the limited availability of iodine in the diet. By contrast, newborns showed a strikingly distinct pattern: there was no relative hypothyroxinemia and free T4 levels were significantly higher than in the respective mothers (19.4 vs. 14.7 pmol/L; P less than 0.001). In spite of these differences, however, mean neonatal TSH and TG levels were significantly higher than maternal values, respectively 6.0 vs. 1.9 mU/L for TSH (P less than 0.001) and 70 vs. 40 micrograms/L for TG (P less than 0.001). Furthermore, neonatal TG and TSH levels increased in parallel and were highly correlated with maternal data, suggesting a regulatory link between both thyroid economies. The results suggested that the common regulatory link is the limited availability of the iodine supply. In conclusion, the present study demonstrates that even in conditions with a marginally low iodine intake, pregnancy constitutes a stimulus for both the maternal and newborn thyroids. Changes in both groups are associated and the abnormalities in TSH and TG are amplified in the newborns. The TSH and TG alterations at birth in full-term healthy newborns, associated with similar alterations in maternal thyroid function, provide evidence for a common stimulatory factor, relative iodine deficiency. The data emphasize the hypersensitivity of neonatal thyroid function to marginal iodine deficiency and point to the need to increase the iodine supply in groups at risk, such as women during pregnancy, and also newborns in the perinatal period."
Regulation of maternal thyroid during pregnancy.
Glinoer D, de Nayer P, Bourdoux P, Lemone M, Robyn C, van Steirteghem A, Kinthaert J, Lejeune B.
J Clin Endocrinol Metab. 1990 Aug;71(2):276-87.
[abstract only]
"A prospective study was undertaken in 606 healthy women during pregnancy to evaluate the changes occurring in maternal thyroid economy as a result of 1) the increased thyroid hormone-binding capacity of serum, 2) the effects of increased levels of hCG on TSH and on the thyroid, and 3) a marginally low iodine intake in the population (50-75 micrograms/day). Four main features were observed. First, thyroidal activity adjusted to the marked increase in serum T4-binding globulin: pregnancy was accompanied by an overall reduction in the T4/T4-binding globulin ratio, with lower free T4 and T3 levels, although in most cases free hormone levels remained within the normal range. The adjustment of thyroidal output of T4 and T3 did not occur similarly in all subjects. In approximately one third of the women, there was relative hypothyroxinemia, higher T3/T4 ratios (presumably indicating preferential T3 secretion), and higher, although normal, serum TSH concentrations. Second, high hCG levels were associated with thyroid stimulation, both functionally (lower serum TSH) and anatomically (increased thyroid size). The data are consistent with a TSH-like effect of hCG on the thyroid. Hence, regulation of the maternal thyroid is complex, resulting from both elevated hCG (mainly in the first half of gestation) and increasing TSH (mainly in the second half of gestation). Third, a significant increase in serum thyroglobulin levels was observed throughout gestation, especially during the last trimester. Fourth, increased thyroid volume was common, and goiter formation not uncommon (goiter was found in 9% of women at delivery). In conclusion, the alterations in maternal thyroid function during gestation are intricate and far from fully understood. In areas of marginally low iodine intake, gestation is associated in a significant number of women with relative hypothyroxinemia, increased thyroglobulin, and enlarged thyroid."
