Hyperthyroidism in Pregnancy: the Delicate Balance between too Much or too Little Antithyroid Drug

Overt hyperthyroidism during pregnancy is associated with risk of maternal-fetal complications. The antithyroid drugs (ATD) have a potential risk for teratogenic effects and fetal–neonatal hy-pothyroidism. This study evaluated ATD treatment and thyroid function control during preg-nancy, and pregnancy outcome in women with hyperthyroidism. Patients and methods: retro-spective analysis of 36 single fetus pregnancies in 29 consecutive women (median age 30.3 ± 4.7 years) with hyperthyroidism diagnosed before or during pregnancy; a control group of 39 healthy euthyroid pregnant women was used. Results: 26 women had Graves’ disease (GD, 33 pregnan-cies), 1 had a hyperfunctioning autonomous nodule, 2 had gestational transient thyrotoxicosis (GTT). Methimazole (MMI) was administered in 22 pregnancies (78.5%), Propylthiouracil (PTU) in 2 (7.1%), switch from MMI to PTU in 4 (14.2%), no treatment in 8 pregnancies (3 with subclinical hyperthyroidism, 5 euthyroid with previous GD remission before conception). One spontaneous abortion at 5 weeks (3.4% of pregnancies) and 1 premature delivery at 32 weeks with perinatal death in 24h (3.4%) were recorded in 2 of the 8 pregnancies of GD patients diagnosed shortly before (< 6 weeks) or during gestation. In women treated more than 6 months until conception (20 pregnancies): a) median ATD doses were lower than those in women diagnosed shortly before or during pregnancy; b) ATD was withdrawn in 40% of pregnancies in trimester (T) I, all on MMI < 10 mg/day (relapse in 14.2%), and in up to 55% in TIII; c) TSH level was below normal in 37%, 35% and 22% of pregnancies in T I, II and III respectively; FT4 was increased in 5.8% (T I) and sub-normal in 11.75% in TII and III; d) one fetal death due to a true umbilical cord knot was recorded. Hyperthyroidism relapsed postpartum in 83% of GD patients (at median 3 ± 2.6 months). One child had neonatal hyperthyroidism (3.3% of live children in GD women) and a small atrial sept defect (4% of live children in ATD treated women). Mean birth weight did not differ from that of the control group. Conclusion. In hyperthyroid women with long-term ATD control before con-ception, drugs could be withdrawn in TI in a third of them, and fetal complications were rare. Frequent serum TSH and FT4 monitoring is needed in order to maintain optimal thyroid function during pregnancy.

Download Full-text

Hyperthyroidism in Pregnancy: The Delicate Balance between too Much or too Little Antithyroid Drug

Journal of Clinical Medicine ◽

10.3390/jcm10163742 ◽

2021 ◽

Vol 10 (16) ◽

pp. 3742

Author(s):

Monica Livia Gheorghiu ◽

Roxana Georgiana Bors ◽

Ancuta-Augustina Gheorghisan-Galateanu ◽

Anca Lucia Pop ◽

Dragos Cretoiu ◽

...

Keyword(s):

Thyroid Function ◽

Antithyroid Drug ◽

Antithyroid Drugs ◽

Premature Delivery ◽

Control Group ◽

Neonatal Hypothyroidism ◽

Fetal Complications ◽

Neonatal Hyperthyroidism ◽

And Control

Overt hyperthyroidism (HT) during pregnancy is associated with a risk of maternal–fetal complications. Antithyroid drugs (ATD) have a potential risk for teratogenic effects and fetal–neonatal hypothyroidism. This study evaluated ATD treatment and thyroid function control during pregnancy, and pregnancy outcome in women with HT. Patients and methods: A retrospective analysis of 36 single fetus pregnancies in 29 consecutive women (median age 30.3 ± 4.7 years) with HT diagnosed before or during pregnancy; a control group of 39 healthy euthyroid pregnant women was used. Results: Twenty-six women had Graves’ disease (GD, 33 pregnancies), 1 had a hyperfunctioning autonomous nodule, and 2 had gestational transient thyrotoxicosis (GTT). Methimazole (MMI) was administered in 22 pregnancies (78.5%), Propylthiouracil (PTU) in 2 (7.1%), switch from MMI to PTU in 4 (14.2%), no treatment in 8 pregnancies (3 with subclinical HT, 5 euthyroid with previous GD remission before conception). In the 8 pregnancies of GD patients diagnosed during gestation or shortly before (<6 weeks), i.e., with fetal exposure to uncontrolled HT, there was 1 spontaneous abortion at 5 weeks (3.4% of all ATD-treated pregnancies), and 1 premature delivery at 32 weeks with neonatal death in 24 h (3.4%); 1 child had neonatal hyperthyroidism (3.3% of live children in GD women) and a small atrial sept defect (4% of live children in ATD treated women). In women treated more than 6 months until conception (20 pregnancies): (a) median ATD doses were lower than those in women diagnosed shortly before or during pregnancy; (b) ATD was withdrawn in 40% of pregnancies in trimester (T)1, all on MMI < 10 mg/day (relapse in 14.2%), and in up to 55% in T3; (c) TSH level was below normal in 37%, 35% and 22% of pregnancies in T1, T2 and T3 respectively; FT4 was increased in 5.8% (T1) and subnormal in 11.75% in T2 and T3; (d) no fetal birth defects were recorded; one fetal death due to a true umbilical cord knot was registered. Mean birth weight was similar in both ATD-treated and control groups. Hyperthyroidism relapsed postpartum in 83% of GD patients (at median 3 ± 2.6 months). Conclusion: In hyperthyroid women with long-term ATD treatment before conception, drugs could be withdrawn in T1 in 40% of them, the thyroid function control was better, and pregnancy and fetal complications were rarer, compared to women diagnosed during pregnancy. Frequent serum TSH and FT4 monitoring is needed to maintain optimal thyroid function during pregnancy.

Download Full-text

Maternal Thyroid Function, Use of Antithyroid Drugs in Early Pregnancy, and Birth Defects

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-01343 ◽

2019 ◽

Vol 104 (12) ◽

pp. 6040-6048 ◽

Cited By ~ 6

Author(s):

Stine Linding Andersen ◽

Louise Knøsgaard ◽

Jørn Olsen ◽

Peter Vestergaard ◽

Stig Andersen

Keyword(s):

Thyroid Function ◽

Birth Defects ◽

Early Pregnancy ◽

Antithyroid Drug ◽

Maternal Blood ◽

Antithyroid Drugs ◽

Birth Cohorts ◽

Increased Risk ◽

Maternal Thyroid

Abstract Context Antithyroid drug (ATD) therapy in early pregnancy is associated with birth defects, but more data are needed to substantiate the risk associated with different types of ATD. Furthermore, the role of abnormal maternal thyroid function per se remains unclarified. Objective To evaluate the risk of birth defects associated with the use of ATD in an extended nationwide cohort and the role of abnormal maternal thyroid function in birth cohorts including stored maternal blood samples from early pregnancy. Participants Danish pregnant women and their live-born children, including 1,243,353 children from a Nationwide Register-Based Cohort (NRBC), 1997 to 2016; 8830 children from the Danish National Birth Cohort (DNBC), 1997 to 2003; and 14,483 children from the North Denmark Region Pregnancy Cohort (NDRPC), 2011 to 2015. Main Outcome Measures Birth defects diagnosed before 2 years of age. Results In the NRBC, altogether 2718 (0.2%) children had been exposed to ATD in early pregnancy. The overall frequency of birth defects was 6.7% (95% CI, 6.7% to 6.8%) in nonexposed children and higher after exposure to methimazole/carbimazole (9.6%; 95% CI, 8.2% to 11.2%) and propylthiouracil (8.3%; 95% CI, 6.7% to 10.3%). On the other hand, the frequency of maternal thyroid dysfunction in early pregnancy was similar in the random cohort and in cases of birth defect in the DNBC (12.4 vs 12.6%, P = 0.8) and the NDRPC (15.1 vs 15.4%, P = 0.8). Conclusions Results corroborate an increased risk of birth defects associated with the use of ATD in early pregnancy and suggest that abnormal maternal thyroid function is not a major risk factor for birth defects.

Download Full-text

A STUDY OF THE ANTITHYROID EFFECT OF TOLBUTAMIDE

Journal of Endocrinology ◽

10.1677/joe.0.0250343 ◽

1962 ◽

Vol 25 (3) ◽

pp. 343-350 ◽

Cited By ~ 3

Author(s):

G. HANNO ◽

H. K. AWWAD

Keyword(s):

Thyroid Function ◽

Mode Of Action ◽

Salivary Secretion ◽

Inhibitory Effect ◽

Drug Dose ◽

Term Treatment ◽

Antithyroid Drugs ◽

Total Drug ◽

Long Term Treatment

SUMMARY The mechanism of the antithyroid effect of tolbutamide was investigated by studying its effect on thyroid iodine trapping, the salivary secretion of 131I and the organic binding of thyroid 131I. No inhibitory effect was noted on iodine trapping. After prolonged therapy a defect in the organic binding of 131I was observed in some cases. There was a significant correlation between thyroid function as measured by the 2 hr. neck:thigh ratio and the total drug dose in patients on long-term treatment. Recovery of the gland from this defect after withdrawal of the drug seemed to be slower than the recovery from other antithyroid drugs having the same mode of action.

Download Full-text

LONG-TERM CONTROL OF THYROTOXICOSIS WITH THE BETA-BLOCKER SOTALOL - A MODEL OF UNTREATED HYPERTHYROIDISM?

Acta Endocrinologica ◽

10.1530/acta.0.0870734 ◽

1978 ◽

Vol 87 (4) ◽

pp. 734-742 ◽

Cited By ~ 6

Author(s):

Peter Wahlberg ◽

Sten-Anders Carlsson

Keyword(s):

Thyroid Hormone ◽

Thyroid Function ◽

Beta Blocker ◽

Clinical Symptoms ◽

Symptom Control ◽

Hormone Secretion ◽

Antithyroid Drugs ◽

Beta Blockade ◽

Trh Stimulation

ABSTRACT Five patients with hyperthyroidism and no goitre were treated only by beta blockade with sotalol. All but one became clinically euthyroid, although the thyroid hormone values in their sera remained high. The TSH response to intravenous TRH remained absent. One patient had fluctuating thyroid hormone values, one has had borderline values for 20 months, one had a hormonal recovery within 6 months, one became clinically thyrotoxic and was switched to carbimazole, and one who had first been treated with carbimazole and had a relapse of high hormone values at 3 months and of clinical symptoms within 9 months after cessation of carbimazole treatment became clinically euthyroid with beta blockade. Sotalol offers a symptom control of hyperthyroidism without lowering the thyroid function, and thus makes it possible to study the long-term hormonal pattern of hyperthyroidism without suppression of thyroid hormone secretion. The results show that the course of hyperthyroidism may vary in duration and pattern. TRH stimulation may cause none or a small TSH response even when the disease is in hormonal remission. The cause of this phenomenon is discussed. The duration of hyperthyroidism cannot be forecast by present methods, and this should be borne in mind when patients are treated with antithyroid drugs for this disorder.

Download Full-text

Effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with graves’ disease

Italian Journal of Pediatrics ◽

10.1186/s13052-021-00999-5 ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Yanyan Hu ◽

Yulin Man ◽

Xuemei Sun ◽

Yongzhen Xue

Keyword(s):

Thyroid Function ◽

Oral Prednisolone ◽

Pulse Therapy ◽

Antithyroid Drugs ◽

Control Group ◽

Thyroid Peroxidase ◽

Graves Disease ◽

Thyroid Antibodies ◽

Free Triiodothyronine ◽

Glucocorticoid Treatment

Abstract Background Glucocorticoid treatment is used in children with Graves’ disease (GD) only in cases of exophthalmos. The purpose of this study was to observe the effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with GD. Methods Twenty children who were treated by intravenous methylprednisolone pulse therapy (MPT) followed by oral prednisolone administration and antithyroid drugs were included in the pulse group. Twenty children who were treated with antithyroid drugs alone were included in the control group. Serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and thyrotropin receptor antibodies (TRAb) were recorded at baseline and 10 days, 30 days, and 60 days after treatment. Results Significant differences in FT3, FT4, TSH, TPOAb, TGAb, and TRAb levels were found in the pulse group and the control group from baseline to follow-up time points (all p < 0.05). On the 30th day, the TRAb level in the pulse group was significantly lower than that in the control group (p = 0.023). However, the level of TRAb rose on the 60th day. For values of TRAb at baseline, 10 days, and 60 days after treatment, there were no significant differences respectively between the pulse group and the control group (all p > 0.05). No significant differences were observed in FT3, FT4, TSH, TPOAb, and TGAb levels between the pulse group and the control group (all p > 0.05). Conclusions The results suggested that the effect of intravenous MPT followed by oral prednisolone on TRAb level was temporary in children with GD. Glucocorticoid pulse therapy was not beneficial for the sustained recovery of thyroid function.

Download Full-text

Thyroid Function and Human Reproductive Health

Endocrine Reviews ◽

10.1210/er.2009-0041 ◽

2010 ◽

Vol 31 (5) ◽

pp. 702-755 ◽

Cited By ~ 504

Author(s):

G. E. Krassas ◽

K. Poppe ◽

D. Glinoer

Keyword(s):

Thyroid Function ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Controlled Ovarian Hyperstimulation ◽

Male Reproduction ◽

Antithyroid Drugs ◽

Premature Delivery ◽

Ovarian Hyperstimulation ◽

Autoimmune Thyroid ◽

The Impact

Via its interaction in several pathways, normal thyroid function is important to maintain normal reproduction. In both genders, changes in SHBG and sex steroids are a consistent feature associated with hyper- and hypothyroidism and were already reported many years ago. Male reproduction is adversely affected by both thyrotoxicosis and hypothyroidism. Erectile abnormalities have been reported. Thyrotoxicosis induces abnormalities in sperm motility, whereas hypothyroidism is associated with abnormalities in sperm morphology; the latter normalize when euthyroidism is reached. In females, thyrotoxicosis and hypothyroidism can cause menstrual disturbances. Thyrotoxicosis is associated mainly with hypomenorrhea and polymenorrhea, whereas hypothyroidism is associated mainly with oligomenorrhea. Thyroid dysfunction has also been linked to reduced fertility. Controlled ovarian hyperstimulation leads to important increases in estradiol, which in turn may have an adverse effect on thyroid hormones and TSH. When autoimmune thyroid disease is present, the impact of controlled ovarian hyperstimulation may become more severe, depending on preexisting thyroid abnormalities. Autoimmune thyroid disease is present in 5–20% of unselected pregnant women. Isolated hypothyroxinemia has been described in approximately 2% of pregnancies, without serum TSH elevation and in the absence of thyroid autoantibodies. Overt hypothyroidism has been associated with increased rates of spontaneous abortion, premature delivery and/or low birth weight, fetal distress in labor, and perhaps gestation-induced hypertension and placental abruption. The links between such obstetrical complications and subclinical hypothyroidism are less evident. Thyrotoxicosis during pregnancy is due to Graves’ disease and gestational transient thyrotoxicosis. All antithyroid drugs cross the placenta and may potentially affect fetal thyroid function.

Download Full-text

Effect of triiodothyronine on thyroid function after stopping long-term treatment of thyrotoxicosis with antithyroid drugs

Metabolism ◽

10.1016/0026-0495(67)90022-4 ◽

1967 ◽

Vol 16 (8) ◽

pp. 741-743 ◽

Cited By ~ 2

Author(s):

W.Donald Alexander ◽

Ronald McG. Harden ◽

Donald McLarty ◽

Paul McGill

Keyword(s):

Thyroid Function ◽

Term Treatment ◽

Antithyroid Drugs ◽

Long Term Treatment

Download Full-text

Effects of Glucocorticoid Pulse Therapy on Thyroid Function and Thyroid Antibodies in Children with Graves’ Disease

10.21203/rs.3.rs-110598/v1 ◽

2020 ◽

Author(s):

Yanyan Hu ◽

Yulin Man ◽

Xuemei Sun ◽

Yongzhen Xue

Keyword(s):

Thyroid Function ◽

Oral Prednisolone ◽

Pulse Therapy ◽

Antithyroid Drugs ◽

Control Group ◽

Thyroid Peroxidase ◽

Graves Disease ◽

Thyroid Antibodies ◽

Free Triiodothyronine ◽

Intravenous Methylprednisolone Pulse

Abstract Objective The purpose of this study is to observe the effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with Graves’ disease (GD).Methods Twenty children who were treated by intravenous methylprednisolone pulse therapy (MPT) followed by oral prednisolone administration and antithyroid drugs were included in the pulse group. Twenty children who were treated with antithyroid drugs alone were included in the control group. Serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and thyrotropin receptor antibodies (TRAb) were recorded at baseline and 10 days, 30days, and 60 days after treatment. Results Significant differences in FT3, FT4, TSH, TPOAb, TGAb, and TRAb levels were found in both groups from baseline to follow-up time points (all P<0.05). On the 30th day, the TRAb level in the pulse group was significantly lower than that in the control group (P=0.023). However, the level of TRAb rose on the 60th day. For values of TRAb at baseline, 10 days, and 60 days after treatment, there were no significant differences respectively between the two groups (all P>0.05). No significant differences were observed in FT3, FT4, TSH, TPOAb, and TGAb levels between the two groups (all P>0.05). Conclusion Our results suggest that the effects of intravenous MPT followed by oral prednisolone on TRAb level are temporary in children with GD. It is not helpful to the sustained recovery of thyroid function.

Download Full-text

Management of Graves' hyperthyroidism in pregnancy: focus on both maternal and foetal thyroid function, and caution against surgical thyroidectomy in pregnancy

Acta Endocrinologica ◽

10.1530/eje-08-0663 ◽

2009 ◽

Vol 160 (1) ◽

pp. 1-8 ◽

Cited By ~ 92

Author(s):

Peter Laurberg ◽

Claire Bournaud ◽

Jesper Karmisholt ◽

Jacques Orgiazzi

Keyword(s):

Drug Therapy ◽

Thyroid Function ◽

Antithyroid Drug ◽

Autoimmune Disorder ◽

Antithyroid Drugs ◽

Graves Disease ◽

Limited Effect ◽

Antithyroid Drug Therapy ◽

Maternal Thyroid ◽

In Pregnancy

Graves' disease is a common autoimmune disorder in women in fertile ages. The hyperthyroidism is causedby generation of TSH-receptor activating antibodies. In pregnancy both the antibodies and the antithyroid medication given to the mother pass the placenta and affect the foetal thyroid gland. Thyroid function should be controlled not only in the mother with Graves' hyperthyroidism but also in her foetus.The review includes two cases illustrating some of the problems in managing Graves' disease in pregnancy.Major threats to optimal foetal thyroid function are inadequate or over aggressive antithyroid drug therapy of the mother. It should be taken into account that antithyroid drugs tend to block the foetal thyroid function more effectively than the maternal thyroid function, and that levothyroxin (l-T4) given to the mother will have only a limited effect in the foetus.Surgical thyroidectomy of patients with Graves' hyperthyroidism does not lead to immediate remission of the autoimmune abnormality, and the combination thyroidectomy+withdrawal of antithyroid medication+l-T4 replacement of the mother involves a high risk of foetal hyperthyroidism.ConclusionAntithyroid drug therapy of pregnant women with Graves' hyperthyroidism should be balanced to control both maternal and foetal thyroid function. Surgical thyroidectomy of a pregnant woman with active disease may lead to isolated foetal hyperthyroidism.

Download Full-text