The thyrotrophic role of human chorionic gonadotrophin (hCG) in the early stages of twin (versus single) pregnancies.

OBJECTIVE: Human chorionic gonadotrophin (hCG) is known to possess thyroid-stimulating activity. The aim of the present study was to assess the role of hCG in stimulating the maternal thyroid gland in the early stages of normal gestation. STUDY DESIGN: Thirty euthyroid healthy women were investigated prospectively. In each, conception had been assisted by in vitro fertilization techniques, which allowed for the precise determination of gestational age. Women were subdivided into single (n = 17) and twin (n = 13) pregnancies. Serum intact hCG and its free alpha and beta subunits, TSH and free T4 concentrations were measured at 6, 8, 9, 10, 11, 15, 19, 22 and 32 weeks. RESULTS: In twin pregnancies compared with single pregnancies, peak hCG concentrations (9-11 weeks) were significantly higher (mean +/- SE 171,000 +/- 12,500 vs 65,500 +/- 7600 U/l; P < 0.001), and also much more prolonged. Human CG concentrations above 75,000 U/l lasted for less than 1 week in single, compared with up to 6 weeks in twin pregnancies. Free beta-hCG subunit concentrations paralleled those of intact hCG in both groups. The ratios of free beta-hCG subunit/total hCG were similar in single and twin pregnancies, and did not vary with gestation time. Concerning thyroid function, twin pregnancy was more frequently associated with a lowering of TSH, which was also more profound than in single pregnancies. Furthermore, while free T4 levels remained normal in single pregnancies, they were transiently supranormal (up to 52 pmol/l) in four twin pregnancies. CONCLUSION: In twin pregnancies the placenta produces larger amounts of hCG for a prolonged period of time than in single pregnancies. Both the amplitude and duration of hCG production (i.e. the global exposure of the thyroid gland to hCG) are responsible for increased thyroidal stimulation, leading more frequently to increased free T4 and suppressed TSH levels. The results emphasize the role of hCG in stimulating maternal thyroid function in the first trimester of pregnancy. Even though the production of a variant hCG molecule with potent thyrotrophic activity cannot be excluded, this hypothesis is not required to explain the data. Clinicians should be aware of the frequent occurrence of significant but transient biochemical hyperthyroidism associated with hCG stimulation in the early stages of gestation, particularly in twin pregnancies.

A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects.

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)

Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders.

A prospective study was undertaken in 87 healthy pregnant women with thyroid antibodies and normal thyroid function at initial presentation [asymptomatic autoimmune thyroid disorders (AITD)]. The aims of the study were to assess whether women with AITD constitute a group at risk of developing subclinical hypothyroidism during pregnancy, and whether a mild thyroid function impairment may be associated with obstetrical repercussions. The women investigated were selected among a cohort of 1660 consecutive pregnancies on the basis of 1) no previous history of thyroid disease, 2) euthyroidism at initial presentation, and 3) positive thyroglobulin antibodies and/or thyroid peroxidase antibodies (TPO-Ab). Women with AITD had a basal TSH value significantly higher, albeit still normal, in the first trimester (1.6 vs. 0.9 mU/L; P < 0.001) than that in women with healthy pregnancies used as controls. Despite a 60% average reduction in TPO-Ab titers during gestation, serum TSH remained higher in women with AITD than in controls throughout gestation: at delivery, 40% of the cases had serum TSH levels above 3 mU/L, and 16% had serum TSH levels above 4 mU/L. A TRH test carried out in the days after parturition showed an exaggerated response in 50% of the cases. Furthermore, free T4 concentrations were in the range of hypothyroid values in 42% of the women. Obstetrical repercussions were observed, namely increased rates of spontaneous miscarriage and premature deliveries. In conclusion, women with asymptomatic AITD who are euthyroid in early pregnancy carry a significant risk of developing hypothyroidism progressively during gestation, despite a marked reduction in antibody titers. Hypothyroidism results from the reduced ability of the gland to adjust to the changes in thyroidal economy associated with pregnancy. At the individual level, progression to subclinical hypothyroidism was broadly predictable on the basis of serum TSH levels and TPO-Ab titers in the first trimester. Hence, these parameters provide useful markers to identify women who carry a higher risk, allowing for a close monitoring of thyroid function during pregnancy and the administration of L-T4 in specific cases. Taken together with the known incidences of postpartum thyroiditis and hypothyroidism in women with AITD, the present observations in our opinion justify systematic screening of thyroid autoimmunity during pregnancy.

Antithyroid antibodies underlying thyroid abnormalities and miscarriage or pregnancy induced hypertension.

OBJECTIVE: To assess whether asymptomatic abnormalities, including thyroid auto-antibodies, were associated with an abnormal miscarriage rate or a poor obstetric outcome. DESIGN: Prospective study of thyroid auto-antibodies and thyroid function in an unselected obstetric population. SETTING: Saint-Pierrie Hospital, Brussels, Belgium. SUBJECTS: Seven hundred and thirty consecutive pregnant women attending the antenatal clinic. MAIN OUTCOME MEASURES: Miscarriage and pregnancy induced hypertension. RESULTS: Elevated antithyroperoxidase (TPO-Ab) and antithyroglobulin (TG-Ab) antibody titres are associated with an increased miscarriage rate. Also, asymptomatic thyroid abnormalities, mainly abnormal echo-structure but not antithyroid antibodies, are associated with pregnancy induced hypertension. CONCLUSION: The presence of thyroid auto-antibodies during pregnancy constitutes a marker of increased risk of miscarriage and poor obstetric prognosis.

Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions.

A prospective study was undertaken during pregnancy in 120 euthyroid women presenting with mild thyroid abnormalities (TA): 11 with a past history of thyroid disorder, 44 with goiter, 20 with nodules, and 45 with thyroid autoantibodies. The aims of the study were to assess whether the pattern of thyroid alterations during gestation was different in women with TA compared to that in healthy control pregnant subjects and to evaluate possible obstetrical and neonatal repercussions. The overall prevalence of underlying subtle thyroid abnormalities in the cohort was 17%, probably as the result of the environmental moderately low iodine intake. Despite the intrinsic heterogeneity of the four groups of women with TA, the adaptation of the thyroid to the stress of pregnancy was different from that of the control subjects. Noteworthy were 1) the marked elevation of serum thyroglobulin in women with past history of thyroid disorder, goiter and thyroid nodules; 2) the increase in goiter size in a third of the goitrous women, associated with biochemical evidence of functional stimulation of the gland; 3) the indirect evidence of partial thyroidal autonomy in goitrous patients; and 4) the increase in the number and size of thyroid nodules during gestation. Taken together, the data indicated that pregnancy was associated with a greater thyroidal risk in patients with TA compared to healthy subjects. In relation to thyroid autoimmunity, most patients remained euthyroid during gestation, but in a few cases, TSH was elevated at delivery, suggesting diminished thyroidal reserve. Also, 40% of newborns from mothers with thyroid autoimmunity had elevated thyroid peroxidase antibody titers at birth, and there was a highly significant correlation between maternal and neonatal thyroid peroxidase antibody titers. Finally, thyroid autoimmunity was clearly associated with an increased risk of spontaneous abortion (13.3 vs. 3.3%; P less than 0.001). Thyroid function in newborns from mothers with TA was normal and not different from that in controls; similarly, obstetrical features were similar in patients with TA and control subjects. In conclusion, pregnancy is associated with a greater thyroidal risk in women with TA, thereby emphasizing a potential link between pregnancy and thyroid disorders. It is recommended that patients with known, even subtle, thyroid abnormalities be closely monitored during pregnancy, in particular those with a goiter, nodules, or thyroid autoimmunity, especially in areas with a moderately low iodine intake, where the prevalence of mild thyroid disturbances is high.