Thyroid Diseases: Glinoer D

Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D, Mandel SJ, Stagnaro-Green A. · Endocrinology Division, Durand Hospital, Buenos Aires, Argentina. · J Clin Endocrinol Metab. · Pubmed #17948378 links to  free full text

Abstract: OBJECTIVE: The objective is to provide clinical guidelines for the management of thyroid problems present during pregnancy and in the postpartum. PARTICIPANTS: The Chair was selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society. The Chair requested participation by the Latin American Thyroid Society, the Asia and Oceania Thyroid Society, the American Thyroid Association, the European Thyroid Association, and the American Association of Clinical Endocrinologists, and each organization appointed a member to the task force. Two members of The Endocrine Society were also asked to participate. The group worked on the guidelines for 2 yr and held two meetings. There was no corporate funding, and no members received remuneration. EVIDENCE: Applicable published and peer-reviewed literature of the last two decades was reviewed, with a concentration on original investigations. The grading of evidence was done using the United States Preventive Services Task Force system and, where possible, the GRADE system. CONSENSUS PROCESS: Consensus was achieved through conference calls, two group meetings, and exchange of many drafts by E-mail. The manuscript was reviewed concurrently by the Society's CGS, Clinical Affairs Committee, members of The Endocrine Society, and members of each of the collaborating societies. Many valuable suggestions were received and incorporated into the final document. Each of the societies endorsed the guidelines. CONCLUSIONS: Management of thyroid diseases during pregnancy requires special considerations because pregnancy induces major changes in thyroid function, and maternal thyroid disease can have adverse effects on the pregnancy and the fetus. Care requires coordination among several healthcare professionals. Avoiding maternal (and fetal) hypothyroidism is of major importance because of potential damage to fetal neural development, an increased incidence of miscarriage, and preterm delivery. Maternal hyperthyroidism and its treatment may be accompanied by coincident problems in fetal thyroid function. Autoimmune thyroid disease is associated with both increased rates of miscarriage, for which the appropriate medical response is uncertain at this time, and postpartum thyroiditis. Fine-needle aspiration cytology should be performed for dominant thyroid nodules discovered in pregnancy. Radioactive isotopes must be avoided during pregnancy and lactation. Universal screening of pregnant women for thyroid disease is not yet supported by adequate studies, but case finding targeted to specific groups of patients who are at increased risk is strongly supported.

Glinoer D, Rovet J. · No affiliation provided · Thyroid. · Pubmed #19415991 No free full text.

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Glinoer D. · No affiliation provided · J Clin Endocrinol Metab. · Pubmed #16825575 links to  free full text

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Glinoer D. · No affiliation provided · Am J Reprod Immunol. · Pubmed #10836248 No free full text.

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Poppe K, Velkeniers B, Glinoer D, Anonymous00105. · Thyroid Clinic, University Hospital, UZ Brussel, Brussels, Belgium. · Nat Clin Pract Endocrinol Metab. · Pubmed #18506157 No free full text.

Abstract: The thyroid gland and gonadal axes interact continuously before and during pregnancy. Hypothyroidism influences ovarian function by decreasing levels of sex-hormone-binding globulin and increasing the secretion of prolactin. In women of reproductive age, hypothyroidism can be reversed by thyroxine therapy to improve fertility and avoid the need for use of assisted reproduction technologies. For infertile women, preparation for medically assisted pregnancy comprises controlled ovarian hyperstimulation that substantially increase circulating estrogen concentrations, which in turn can severely impair thyroid function. In women without thyroid autoimmunity these changes are transient, but in those with thyroid autoimmunity estrogen stimulation might lead to abnormal thyroid function throughout the remaining pregnancy period. Prevalence of thyroid autoimmunity is significantly higher among infertile women than among fertile women, especially among those whose infertility is caused by endometriosis or ovarian dysfunction. Presence of thyroid autoimmunity does not interfere with normal embryo implantation, but the risk of early miscarriage is substantially raised. Subclinical and overt forms of hypothyroidism are associated with increased risk of pregnancy-related morbidity, for which thyroxine therapy can be beneficial. Systematic screening for thyroid disorders in pregnant women remains controversial but might be advantageous in women at high risk, particularly infertile women.

Glinoer D. · Department of Internal Medicine and Endocrinology, Thyroid Investigation Clinic, University Hospital St Pierre, 322, Rue Haute, B-1000 Brussels, Belgium. · Public Health Nutr. · Pubmed #18053277 No free full text.

Abstract: OBJECTIVE: To examine the importance of iodine nutrition during pregnancy.DESIGN: Review of existing literature of iodine in pregnancy. SETTING: Population surveys and metabolic studies. SUBJECTS: Pregnant women. RESULTS: The main changes in thyroid function associated with pregnancy are due to an increase in hormone requirements that begin in the first trimester of gestation. This increase can only be met by a proportional increase in hormone production, something that depends directly upon the availability of iodine. When dietary iodine is lacking, an adequate physiological adaptation is difficult to achieve and is progressively replaced by pathological alterations that occur in parallel with the degree and duration of iodine deprivation.CONCLUSIONS: Iodine prophylaxis should be given systematically to women during pregnancy. In most public health programmes dealing with the correction of iodine deficiency disorders, iodised salt has been used as the preferred means to deliver iodine to households. Iodised salt, however, is not the ideal means of delivering iodine in the specific instances of pregnancy, breast-feeding and complementary feeding because of the need to limit salt intake during these periods. In European countries, presently it is proposed that iodine is given to pregnant women and breast-feeding mothers by systematically administering multivitamin tablets containing iodine in order to reach the recommended dietary allowance of 250 microg iodine day-1.

Glinoer D, Abalovich M. · Division of Endocrinology, Department of Internal Medicine, University Hospital Saint Pierre, B-1000 Brussels, Belgium. · BMJ. · Pubmed #17690371 No free full text.

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Glinoer D. · Division of Endocrinology, Department of Internal Medicine, Thyroid Investigation Clinic, University Hospital Saint Pierre, Brussels, Belgium. · Endocr Dev. · Pubmed #17684390 No free full text.

Abstract: 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. In healthy pregnant women, physiological adaptation takes place when the iodine intake is adequate, while this is replaced by pathological alterations when there is a deficient iodine intake. Pregnancy acts typically, therefore, as a revelator of underlying iodine restriction. Iodine deficiency has important repercussions for both the mother and the fetus, leading to hypothyroxinemia, sustained glandular stimulation and finally goitrogenesis. Furthermore, because severe iodine deficiency may be associated with an impairment in the psychoneurointellectual outcome in the progeny, because both mother and offspring are exposed to iodine deficiency during gestation (and the postnatal period), and because iodine deficiency is still prevalent today in several large regions of the world, iodine supplements should be given systematically to pregnant and breastfeeding mothers. Particular attention is required to ensure that pregnant women receive an adequate iodine supply, in order to reach the ideal recommended nutrient intake of 250 microg iodine/day.

Poppe K, Glinoer D, Tournaye H, Devroey P, Schiettecatte J, Haentjens P, Velkeniers B. · Departement of Endocrinology (AZ-VUB), Laarbeeklaan 101--B 1090 Brussels. · Verh K Acad Geneeskd Belg. · Pubmed #17313094 No free full text.

Abstract: In infertile women, the prevalence of thyroid autoimmunity (TAI) is significantly higher compared to that in parous age-matched women. This is especially the case in women with endometriosis and the polycystic ovarian syndrome. TAI does not interfere with normal fetal implantation and comparable pregnancy rates have been observed after assisted reproductive technology (ART) in women with and without TAI. During the first trimester however, pregnant women with TAI carry a significantly increased risk for a miscarriage compared to women without TAI, even when euthyroidism was present before pregnancy. It has further been demonstrated that controlled ovarian hyperstimulation (COH) in preparation for ART has a significant impact on thyroid function, particularly in women with TAI. It is therefore advised to measure thyroid function and detect TAI in infertile women, before ART, and to follow-up these parameters after COH and during pregnancy when TAI was initially present. Women with thyroid dysfunction before or at early gestation stages should be treated with 1-thyroxine to avoid assisted pregnancy or further pregnancy complications. Whether thyroid hormones should be given prior to or during pregnancy in euthyroid women with TAI remains controversial and needs further investigation.

Poppe K, Velkeniers B, Glinoer D. · Department of Endocrinology, Vrije Universiteit Brussel (AZ-VUB), Brussels, Belgium. · Clin Endocrinol (Oxf). · Pubmed #17302862 No free full text.

Abstract: The menstrual pattern is influenced by thyroid hormones directly through impact on the ovaries and indirectly through impact on SHBG, PRL and GnRH secretion and coagulation factors. Treating thyroid dysfunction can reverse menstrual abnormalities and thus improve fertility. In infertile women, the prevalence of autoimmune thyroid disease (AITD) is significantly higher compared to parous age-matched women. This is especially the case in women with endometriosis and polycystic ovarian syndrome (PCOS). AITD does not interfere with normal foetal implantation and comparable pregnancy rates have been observed after assisted reproductive technology (ART) in women with and without AITD. During the first trimester, however, pregnant women with AITD carry a significantly increased risk for miscarriage compared to women without AITD, even when euthyroidism was present before pregnancy. It has also been demonstrated that controlled ovarian hyperstimulation (COH) in preparation for ART has a significant impact on thyroid function, particularly in women with AITD. It is therefore advisable to measure thyroid function and detect AITD in infertile women before ART, and to follow-up these parameters after COH and during pregnancy when AITD was initially present. Women with thyroid dysfunction at early gestation stages should be treated with l-thyroxine to avoid pregnancy complications. Whether thyroid hormones should be given prior to or during pregnancy in euthyroid women with AITD remains controversial. To date, there is a lack of well-designed randomized clinical trials to elucidate this controversy.

Stagnaro-Green A, Glinoer D. · UMDNJ-New Jersey Medical School, Division of Endocrinology and Metabolism, Department of Medicine, 185 South Orange Avenue, MSB C-652, Newark, NJ 07101, USA. · Best Pract Res Clin Endocrinol Metab. · Pubmed #15157834 No free full text.

Abstract: 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.

Glinoer D. · Department of Internal Medicine and Endocrinology, University Hospital Saint Pierre, Thyroid Investigation Clinic, 322, Rue Haute, B-1000 Brussels, Belgium. · Best Pract Res Clin Endocrinol Metab. · Pubmed #15157832 No free full text.

Abstract: 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.

Glinoer D. · Department of Internal Medicine, Thyroid Investigation Clinic, Université Libre de Bruxelles, Centre Hospitalo-Universitaire Saint-Pierre, 322 Rue HAUTE, 1000, Brussels, Belgium. · Growth Horm IGF Res. · Pubmed #12914727 No free full text.

Abstract: 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.

Poppe K, Glinoer D. · Academisch Ziekenhuis, Department of Endocrinology, Laarbeeklaan, Brussels. · Hum Reprod Update. · Pubmed #12751777 links to  free full text

Abstract: 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.

Glinoer D. · Université Libre de Bruxelles, University Hospital Saint-Pierre, Department of Internal Medicine/Endocrinology, Thyroid Investigation Clinic 322, Rue Haute, B-1000 Brussels/Belgium. · Ann Endocrinol (Paris). · Pubmed #12707632 No free full text.

Abstract: 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.

Glinoer D. · Department of Internal Medicine, Thyroid Investigation Clinic, Université Libre de Bruxelles, Centre Hospitalo-Universitaire Saint-Pierre, 322 rue Haute, B-1000 Brussels, Belgium. · Horm Res. · Pubmed #11549871 No free full text.

Abstract: 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.

Glinoer D. · Université Libre de Bruxelles, University Hospital Saint-Pierre, Department of Internal Medicine and Endocrinology, Brussels, Belgium. · Thyroid. · Pubmed #11396705 No free full text.

Abstract: 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.

Glinoer D, Delange F. · University Hospital Saint-Pierre, Department of Internal Medicine-Thyroid Investigation Clinic, Brussels, Belgium. · Thyroid. · Pubmed #11081254 No free full text.

Abstract: 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.

Glinoer D. · University Hospital Saint-Pierre, Department of Internal Medicine, Thyroid Investigation Clinic, Brussels, Belgium. · Thyroid. · Pubmed #10447005 No free full text.

Abstract: 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.

Poppe K, Glinoer D, Tournaye H, Devroey P, van Steirteghem A, Kaufman L, Velkeniers B. · Department of Endocrinology, Vrije Universiteit Brussel, Brussels 1090, Belgium. · J Clin Endocrinol Metab. · Pubmed #12970279 links to  free full text

Abstract: The association between positive thyroid antibodies and an increased miscarriage rate in pregnancies after assisted reproduction technology (ART) remains controversial. We wanted to clarify this issue by performing a prospective cohort study in 234 women by systematically screening for thyroid peroxidase antibodies (TPO-Ab), serum TSH, and free T(4)(FT(4)) before the first ART cycle. Women with overt thyroid dysfunction were excluded. Fourteen percent of the cohort had positive TPO-Ab. Baseline characteristics [age, 33 +/- 5 yr; TSH, 1.6 (0.02-4.1) mU/liter; and FT(4), 12.2 (9.1-18) ng/liter] were comparable to those of the 86% of women without antibodies [age, 32 +/- 5 yr; TSH, 1.3 (0.05-3.6) mU/liter; and FT(4), 11.7 (9.5-16.5) ng/liter]. In the antibody-positive group, the pregnancy rate was 53% vs. 43% in the antibody-negative group, with an odds ratio of 0.67 [95% confidence interval (CI) (0.32-1.41); P = not significant]; however within the group that was pregnant, the miscarriage rate was 53% and 23%, respectively, with an odds ratio of 3.77 [95% CI (1.29-11.05); P = 0.016]. The age of the women was an independent risk factor for miscarriage, odds ratio 1.08 [95% CI (1.03-1.15); P = 0.005]. We conclude that women with positive TPO-Ab before the first ART cycle have a significantly increased risk for miscarriage.

Glinoer D, de Nayer P, Bex M, Anonymous00045. · University Hospital Saint-Pierre (Universite Libre de Bruxelles), Department of Internal Medicine, Thyroid Investigation Clinic, B-1000 Brussels, Belgium. · Eur J Endocrinol. · Pubmed #11331213 links to  free full text

Abstract: OBJECTIVE: In Graves' hyperthyroidism treated with antithyroid drugs (ATD), the overall relapse rate reaches 30-50% following ATD discontinuation. Conflicting results have previously been reported with regard to the usefulness of combining ATD with thyroxine (l-T4), and thereafter maintaining l-T4 treatment after ATD withdrawal. Also, clinicians are in search of useful parameters to predict the risk of a recurrence of hyperthyroidism after ATD treatment. DESIGN: Eighty-two consecutive patients (70 women and 12 men; mean age 36 years) with a first episode of Graves' hyperthyroidism were investigated prospectively; they were treated with ATD for a total of 15 months, combined with l-T4 (for at least 12 months) after they had reached euthyroidism, with the aim of maintaining serum TSH below 2.5 mU/l during the combined therapy. Following ATD discontinuation, the patients were randomly assigned (double-blind placebo-controlled trial) to taking 100 microg/day l-T4 (vs placebo) for an additional year. METHODS: The following determinations were carried out at initial diagnosis: serum total T4 and tri-iodothyronine (T3), free T4 and T3, TSH, TSH-receptor antibodies (TSHR-Ab), thyroid scintigraphy and echography. During ATD treatment, serum free T4 and T3 and TSH concentrations were recorded after 1 (optional), 2, 4, 6, 9, 12 and 15 months, and echography at the end of ATD treatment. During the randomized trial, serum free T4 and T3 and TSH concentrations were checked every 3 months (or until a recurrence). TSHR-Ab titers were measured at initial diagnosis, after 6 months with ATD, and at the end of ATD treatment. RESULTS: l-T4 administration, both during and after ATD treatment, did not improve the final outcome and recurrence rates were similar in placebo and l-T4-treated patients (30%). Two parameters were identified that might be useful to help predict recurrence risks after ATD: (i) positive TSHR-Ab (at the end of ATD treatment) was significantly associated with a greatly increased recurrence risk; and (ii) despite the relatively small number of patients who were smokers, regular cigarette smoking was shown, for the first time, to be significantly associated with an increased recurrence risk. Also, the deleterious effect of smoking was shown to manifest its impact independently of TSHR-Ab titers at the end of ATD treatment. Thus, compared with the overall 30% recurrence risk, non-smoking patients with a negative TSHR-Ab (at the end of ATD) had a lower (18%) recurrence risk; smoking patients with negative TSHR-Ab (at the end of ATD) had a 57% recurrence risk; non-smoking patients with positive TSHR-Ab (at the end of ATD) had a high (86%) recurrence risk; the recurrence risk was 100% in those few patients who both smoked and maintained a positive TSHR-Ab at the end of ATD treatment. CONCLUSIONS: The present study confirmed that l-T4 administration during and after ATD withdrawal did not improve remission rate. Two factors, namely positive TSHR-Ab at the end of ATD treatment and regular smoking habits may represent clinically useful (albeit not absolute) predictors of the risk of recurrence in patients with Graves' hyperthyroidism treated with ATD. However, due to the relatively small number of smoking patients in the present cohort, this conclusion needs to be confirmed by a larger study.

Glinoer D. · Département de Médecine Interne, C.H.U. Saint-Pierre, U.L.B. · Rev Med Brux. · Pubmed #11068483 No free full text.

Abstract: Graves' disease (GD) patients treated with antithyroid drugs (ATD) have overall relapse rates of 30-50% after ATD discontinuation. Conflicting data have been reported with regard to the usefulness of adding thyroxine (I-T4) during and after ATD treatment. Also, clinicians are still in search of useful factors to predict remission/recurrence after ATD withdrawal. Eighty two consecutive patients were treated with ATD for 15 months, combined with 12 months of I-T4. Then, patients were randomized (placebo-controlled double blind protocol) to continuing I-T4 versus a placebo for one year. RESULTS: I-T4 administration during and after ATD treatment did not affect favorably the outcome, the final recurrence rate being 31%, in both placebo and I-T4 groups. Two factors were identified as independent and synergistic markers of a significantly increased risk of recurrence after ATD withdrawal: smoking and TSH receptor antibodies (TSHR-Ab) remaining positive at the end of ATD. Non smoking patients with a negative TSHR-Ab (end ATD) had a low (18%) recurrence risk, while smoking patients also with a negative TSHR-Ab had a higher (57%) recurrence risk. Non smoking patients with a positive TSHR-Ab (end ATD) had a 86% recurrence risk. Finally, smoking patients with a positive TSHR-Ab (end ATD) all recurred within 6 months. CONCLUSIONS: 1) T4 administration after ATD withdrawal does not improve recurrence rates; 2) two parameters, smoking and positive TSHR-Ab (at end ATD), were valid--albeit not absolute-predictors of the risk of recurrence in ATD-treated patients with Graves' disease.

Saussez S, Glinoer D, Chantrain G, Pattou F, Carnaille B, André S, Gabius HJ, Laurent G. · Laboratory of Anatomy, Faculty of Medicine and Pharmacy, University of Mons-Hainaut, Mons, Belgium. · Thyroid. · Pubmed #18630998 No free full text.

Abstract: BACKGROUND: Since the histological expression of galectins is increased in thyroid carcinoma, determination of their serum levels may provide useful preoperative information. The goal of this study was to determine if a difference in galectin serum levels could be detected between benign and malignant nodular thyroid diseases. DESIGN: Using validated ELISAs, the concentrations of several galectins were prospectively measured in serum samples from 30 healthy individuals and preoperatively in 90 patients with thyroid disease. Seventy-one patients had multiple thyroid nodules (MTN), 13 patients had a single thyroid nodule (STN), and 6 patients had Graves' disease. Nine of 71 patients with MTN had fine-needle aspiration biopsy (FNAB) of their nodules and in 7 patients a "benign" diagnosis was made, in 0 patient a "malignant" diagnosis was made, and in 2 patients a "suspicious" diagnosis was made. Six of 13 patients with STN had FNAB of their nodules and in 2 patients a "benign" diagnosis was made, in 3 patients a "malignant" diagnosis was made, and in 1 patient a "suspicious" diagnosis was made. RESULTS: Thyroid disease was associated with higher levels of galectins-1 and -3 compared to normal subjects. Using a threshold value of 3.2 ng/mL as a cut-off point, the measurement of serum galectin-3 separated micro- and macropapillary thyroid carcinoma (PAP_CA) from patients with nonmalignant thyroid disease with 74% specificity, 73% sensitivity, 57% positive predictive value, and 85% negative predictive value. Elevated serum galectin-3 concentrations (>3.2 ng/mL) detected 87% of macropapillary thyroid carcinomas and 67% of micropapillary thyroid carcinomas. CONCLUSIONS: Serum levels of galectins-1 and -3 are relatively high in patients with thyroid malignancy but there is considerable overlap in serum galectin-3 concentrations between those with benign and malignant nodular thyroid disease and, to a lesser extent, between those with and without nodular thyroid disease.

Caron P, Glinoer D, Lecomte P, Orgiazzi J, Wémeau JL. · Département d'Endocrinologie des CHU de Toulouse, Bruxelles, Tours, Lyon, Lille. · Ann Endocrinol (Paris). · Pubmed #17072231 No free full text.

Abstract: 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.

Tondeur M, Glinoer D, Sand A, Verelst J, Ham H. · Radioisotope Department, CHU Saint-Pierre, Brussels, AZ Jan Palfijn and UZ, Ghent, Belgium. · Clin Endocrinol (Oxf). · Pubmed #16886961 No free full text.

Abstract: OBJECTIVE: When using radioiodine for hyperthyroidism there is no consensus regarding the administration of fixed or calculated doses. Guidelines do not specify the preferable approach or the parameters to use to calculate the dose. Therefore, the dose might be quite different with regard to the chosen procedure. This study was undertaken to evaluate the variability of the amount of radioiodine administered in Belgium in various cases of hyperthyroidism. DESIGN AND PATIENTS: Twenty-one Belgian nuclear medicine physicians received summarized clinical files from 10 patients suffering from overt hyperthyroidism (n = 7) or subclinical hyperthyroidism (n = 3). Five patients had homogeneous goiters, one had multinodular goiter, and four had hot nodule. Participants had to determine the radioiodine dose (millicuries, mCi) they would give in each case. RESULTS: Proposed doses varied between 2 mCi and 25 mCi. Mean proposed dose for nodular disease was 10.71 mCi; it was 6.79 mCi for homogeneous goiter. For individual cases, a difference between the lowest and the highest dose of more than 17 mCi was observed in more than 50% of the cases. CONCLUSIONS: We believe that more precise guidelines are mandatory, underlying uncertainties, controversies but recommending however, as minimal and maximal doses to administer, as well as clinical and biological parameters, if any, to be taken into account in order to modulate these doses.