Treatment of maternal hyperthyroidism with antithyroid agents and changes in thyrotrophin and thyroxine in the newborn

Abstract. Eleven pregnant women with concomitant hyperthyroidism were treated with antithyroid drugs. At monthly intervals serum thyroxine (T4) and triiodothyronine (T3) were measured with radioimmunoassay, the Sephadex uptake of radioactive triiodothyronine (T3U) determined and the free T4 and T3 indices calculated (FT4I, FT3I). TSH-binding inhibiting immunoglobulins (TBII) were determined by the radiomembrane assay. Serum TSH and T4 were measured at delivery from cord blood and/or from the newborn infants some days after birth. Serum TSH was significantly elevated in one infant. There was an inadequate post-partal rise in serum T4 concentration in this child and in another who showed only a marginal elevation of TSH. The mothers of these infants were given carbimazole in doses of 30 and 25 mg/day, respectively, at the time of delivery. No significant changes were seen in other infants, the daily doses being 20 mg of carbimazole or less. There was no clinical indication of hypo- or hyperthyroidism in any of the newborn. The TBII were positive in most patients and there was a trend of normalization during treatment. No relationship between the dose of antithyroid drug and the level of TBII could be seen. During treatment the dose was adjusted according to the FT3I values. This seems to be an adequate laboratory test for this purpose.

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FAILURE OF THE TRH TEST TO PREDICT THE CLINICAL COURSE OF PATIENTS IN REMISSION AFTER ANTITHYROID DRUG THERAPY FOR GRAVES' DISEASE

Acta Endocrinologica ◽

10.1530/acta.0.0900018 ◽

1979 ◽

Vol 90 (1) ◽

pp. 18-22

Author(s):

W. J. Irvine ◽

R. S. Gray ◽

A. D. Toft ◽

J. Seth ◽

E. H. D. Cameron

Keyword(s):

Drug Therapy ◽

Clinical Course ◽

Antithyroid Drug ◽

Normal Serum ◽

Antithyroid Drugs ◽

Trh Test ◽

Group I ◽

Antithyroid Drug Therapy ◽

Group Ii ◽

Serum Tsh

ABSTRACT In an attempt to assess the predictive value of the TRH test in patients in remission after stopping antithyroid drugs for thyrotoxicosis, 11 euthyroid patients with a subnormal (group I) and 23 euthyroid patients with a normal serum TSH response to TRH (group II) were followed-up for one year. The mean ± se intervals since the withdrawal of drug therapy were 23.2 ±1.6 and 20.4 ± 0.7 months, respectively, at the outset of the study. Five patients (45 %) from group I and 7 patients (30 %) from group II relapsed during the period of observation. In addition, a change from a subnormal to a normal serum TSH response to TRH and vice versa occurred in some patients. It is not possible to predict by means of the TRH test the subsequent clinical course of patients in remission following antithyroid drug therapy.

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Frequency of Adverse Events of Antithyroid Drugs Administered during Pregnancy

Journal of Thyroid Research ◽

10.1155/2014/952352 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 7

Author(s):

Ai Yoshihara ◽

Jaeduk Yoshimura Noh ◽

Natsuko Watanabe ◽

Kenji Iwaku ◽

Sakiko Kobayashi ◽

...

Keyword(s):

Adverse Events ◽

Pregnant Women ◽

Antithyroid Drug ◽

Antithyroid Drugs ◽

Graves Disease ◽

Newly Diagnosed ◽

Cutaneous Reactions ◽

First Time

The frequency and types of adverse events after initial antithyroid drug (ATD) therapy during pregnancy have never been reported, nor has whether the frequency of adverse events is the same as among nonpregnant subjects ever been investigated. We investigated retrospectively the frequency of adverse events after initial ATD administration to previously untreated Graves’ disease (GD) patients during pregnancy. We reviewed the charts of cases of 91 untreated pregnant women who came to our hospital for the first time and were newly diagnosed with GD during the period between January 1, 1999, and December 31, 2011. Thiamazole (MMI) was used to treat 40 patients and 51 patients were treated with propylthiouracil (PTU). Adverse events occurred in 5 patients (5/40; 12.5%) treated with MMI, and they consisted of cutaneous reactions in 5 patients. Adverse events occurred in five patients (5/51; 9.8%) treated with PTU, and they consisted of hepatotoxicity in two patients and cutaneous reactions in three patients. No patients experienced agranulocytosis or ANCA-related vasculitis. Comparison with the expected rate of adverse events in nonpregnant individuals showed that the frequency of adverse events in pregnant individuals was low.

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Human foetal prolactin but not thyrotropin secretion is decreased by bromocriptine

Acta Endocrinologica ◽

10.1530/acta.0.1120035 ◽

1986 ◽

Vol 112 (1) ◽

pp. 35-42 ◽

Cited By ~ 7

Author(s):

Elio Roti ◽

Giuseppe Robuschi ◽

Alessandro Alboni ◽

Lorenzo d'Amato ◽

Mara Montermini ◽

...

Keyword(s):

Cord Blood ◽

Pregnant Women ◽

Maternal Serum ◽

Time Interval ◽

Placebo Administration ◽

Human Foetus ◽

Tsh Secretion ◽

Small Inhibition ◽

Serum Tsh

Abstract. In the adult, dopamine inhibits prolactin (Prl) secretion and less so thyrotropin (TSH) release. Little information is available concerning the role of dopaminergic stimuli in the regulation of TSH and Prl secretion in the term human foetus. The dopamine agonist, bromocriptine (5 mg), or placebo were randomly administered orally to 120 pregnant women during labour. Maternal and foetal cord blood was obtained at parturition and analyzed for Prl, TSH, T4, T3 and rT3 concentrations. Since the time of parturition is unpredictable, maternal and cord blood hormone values were grouped at intervals of time from the time of bromocriptine or placebo administration to delivery. Hormone values were compared between the bromocriptine and placebo groups by two-way analysis of variance (ANOVA). Bromocriptine markedly inhibited maternal serum Prl conentrations compared to values in the placebo treated women (P < 0.001) and this decrease was more marked as the time interval between bromocriptine administration and delivery increased (P < 0.001, regression analysis). Cord blood Prl was also significantly lower in newborns whose mothers received bromocriptine (P < 0.001). Bromocriptine significantly inhibited maternal serum TSH concentrations as compared to values in women treated with placebo (P < 0.006). In contrast, bromocriptine administration did not affect cord blood TSH concentrations. These findings suggest that bromocriptine crosses the term human placenta and suppresses foetal Prl secretion. In contrast to the small inhibition of TSH secretion in pregnant women, bromocriptine does not affect foetal TSH secretion suggesting that regulation of TSH secretion in the term foetus may not be under dopaminergic control.

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The Increased Trend of Medical Treatment for Thyroid Diseases during Pregnancy: A 13-Year National Study

European Thyroid Journal ◽

10.1159/000515125 ◽

2021 ◽

pp. 1-7

Author(s):

Suvi Turunen ◽

Marja Vääräsmäki ◽

Maarit Leinonen ◽

Mika Gissler ◽

Tuija Männistö ◽

...

Keyword(s):

Pregnant Women ◽

Drug Prescription ◽

Antithyroid Drug ◽

Fold Increase ◽

Study Data ◽

National Study ◽

Antithyroid Drugs ◽

Thyroid Disorders ◽

Medical Birth Register ◽

Hormone Use

Objective: Thyroid dysfunction affects up to 5–7% of all pregnancies. The rates of thyroid hormone use in nonpregnant population have substantially increased in recent years. The aim of this study was to assess possible changes in the use of levothyroxine substitution and antithyroid drugs over time in pregnant women. Methods: The study data consisted of all singleton pregnancies (N = 736,873) between 2004 and 2016 in Finland collected from the Finnish Medical Birth Register. The Prescription Register and Special Refund Entitlement Register provided information on levothyroxine and antithyroid drug purchases. The annual rates of levothyroxine and antithyroid drug prescription redemptions were explored to estimate changes in exposure rates to thyroid medication from 2004 to 2016. Joinpoint regression analyses were performed to explore interannual variability in levothyroxine and antithyroid drug treatment. Results: There was more than a five-fold increase in levothyroxine use during the study period; in 2004, 1.1% of pregnant women had levothyroxine treatment, and by 2016, the prevalence increased to 6.2%. In addition, we observed a slight increase in antithyroid medication during pregnancy, but antithyroid drug use during pregnancy overall was very rare. In 2004, 0.05% of pregnant women used antithyroid drugs, and by 2016, this percentage had increased to 0.14%. Conclusions: Our study shows that the rate of levothyroxine use in pregnancy has markedly increased. This suggests that tracing and screening relevant patients and awareness of thyroid disorders on pregnancy and their significance for the pregnancy outcome have increased and the threshold to treat thyroid disorders has declined.

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Prenatal Phthalates Exposure and Cord Thyroid Hormones: A Birth Cohort Study in Southern Taiwan

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18084323 ◽

2021 ◽

Vol 18 (8) ◽

pp. 4323

Author(s):

Po-Chin Huang ◽

Pao-Lin Kuo ◽

Wei-Hsiang Chang ◽

Shu-Fang Shih ◽

Wan-Ting Chang ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormones ◽

Cord Blood ◽

Pregnant Women ◽

Phthalate Metabolites ◽

Cord Serum ◽

Serum T4 ◽

Southern Taiwan ◽

Hormone Homeostasis ◽

Serum Tsh

Background: The regulation of thyroid hormones in the early stages of gestation plays a crucial role in the outcome of a pregnancy. Furthermore, thyroid hormones are fundamental for the fetal development of all organs, including endocrine hormone changes in uterus. Endocrine disrupting chemicals have been shown to have an effect on thyroid hormone homeostasis in newborns, which affects their later development. Few studies have proposed how phthalates could alter thyroid function through several mechanisms and the possible effects on thyroid hormone homeostasis of phthalates on pregnant women. However, the effects of cord blood phthalates and prenatal phthalate exposure on thyroid hormones in newborns remain unclear. Objectives: We aim to follow up on our previous established subjects and determine the correlation between phthalate exposure and thyroid hormones in pregnant women and newborns. Materials and methods: We recruited 61 pregnant women from the Obstetrics and Gynecology Department of a medical hospital in southern Taiwan and followed up. High performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was used to analyze urine samples for five phthalate metabolites. Serum levels of thyroid hormones were analyzed using electrochemoluminescence immunoassay (ECLIA) method. We used Spearman and Pearson correlation coefficients to evaluate the correlation between each phthalate metabolites in serum and the thyroid hormone levels in fetus and parturient. Finally, multiple logistic regression was used to explore the relationship between hormones and their corresponding phthalate metabolites in cord blood. Results: High MBP in cord blood was correlated with negative cord serum TSH in newborns (r = −0.25, p < 0.06). By using multiple linear regression after adjusting for potential confounders (gestational and maternal age), cord serum MBP levels showed a negative association with cord serum TSH (β = 0.217, p < 0.05), cord serum T4 (β = 1.71, p < 0.05) and cord serum T4 × TSH (β = 42.8, p < 0.05), respectively. Conclusion: We found that levels of cord serum TSH and T4 in newborns was significantly negatively associated with cord serum MBP levels after adjusting for significant covariate. The fall in TSH in newborns may potentially be delaying their development.

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Graves'-Basedow disease in pregnancy

Nuklearmedizin ◽

10.1055/s-0037-1616612 ◽

2015 ◽

Vol 54 (03) ◽

pp. 106-111 ◽

Cited By ~ 5

Author(s):

S. L. Andersen ◽

P. Laurberg

Keyword(s):

Side Effects ◽

Birth Defects ◽

Thyroid Dysfunction ◽

National Study ◽

Antithyroid Drugs ◽

Upper Limit ◽

Special Concern ◽

Maternal Thyroid ◽

Toxic Reactions ◽

Serum Tsh

SummaryThyroid hormones are essential development factors and maternal thyroid dysfunction may cause pregnancy complications and diseases in the fetus/child. In the present review we discuss new data on the incidence of Graves'-Basedow disease (GBD) in and around pregnancy, and how hyperthyroidism may affect the risk of spontaneous abortion and stillbirth.A special concern in pregnant women is the potential side effects from the use of antithyroid drugs (ATDs). One type of side effects is the allergic/toxic reactions to the drugs, which seem to be similar in and outside pregnancy, and another is that ATDs tend to over treat the fetus when the mother with GBD is made euthyroid. To avoid fetal hypothyroidism, the lowest possible ATD dose should be used to keep maternal thyroid function at the upper limit of normality with low serum TSH. Birth defects after the use of methimazole (MMI) (or its prodrug carbimazole) have been considered to be very rare, and no risk has previously been associated with the use of propylthiouracil (PTU). However, a recent Danish national study found that 1/30 of children exposed to MMI in early pregnancy had birth defects associated with this, and many defects were severe. PTU exposure was associated with defects in 1/40, and these defects were less severe. Proposals are given on how to reduce the risk of ATD associated birth defects.

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Oxygen Consumption in Platelets of Newborn Infants before and after Stimulation by Thrombin.

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647969 ◽

1976 ◽

Vol 35 (03) ◽

pp. 712-716 ◽

Cited By ~ 3

Author(s):

D. Del Principe ◽

G Mancuso ◽

A Menichelli ◽

G Maretto ◽

G Sabetta

Keyword(s):

Oxygen Consumption ◽

Cord Blood ◽

Umbilical Cord ◽

Newborn Infant ◽

Umbilical Cord Blood ◽

Newborn Infants ◽

O2 Consumption ◽

Adult Control ◽

Healthy Newborn ◽

Before And After

SummaryThe authors compared the oxygen consumption in platelets from the umbilical cord blood of 36 healthy newborn infants with that of 27 adult subjects, before and after thrombin addition (1.67 U/ml). Oxygen consumption at rest was 6 mμmol/109/min in adult control platelets and 5.26 in newborn infants. The burst in oxygen consumption after thrombin addition was 26.30 mμmol/109/min in adults and 24.90 in infants. Dinitrophenol did not inhibit the burst of O2 consumption in platelets in 8 out of 10 newborn infants, while the same concentration caused a decrease in 9 out of 10 adult subjects. Deoxyglucose inhibited the burst in O2 consumption in newborn infant and adult platelets by about 50%. KCN at the concentration of 10−4 M completely inhibited basal oxygen consumption but did not completely inhibit the burst after thrombin. At the concentration of 10−3 M, it inhibited both basal O2 consumption and the burst in infants and adult subjects.

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Faculty Opinions recommendation of Impact of lithium on efficacy of radioactive iodine therapy for Graves' disease: a cohort study on cure rate, time to cure, and frequency of increased serum thyroxine after antithyroid drug withdrawal.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2813959.2479058 ◽

2010 ◽

Author(s):

Furio Pacini ◽

Stefania Marchisotta

Keyword(s):

Cohort Study ◽

Radioactive Iodine ◽

Drug Withdrawal ◽

Antithyroid Drug ◽

Graves Disease ◽

Radioactive Iodine Therapy ◽

Cure Rate ◽

Serum Thyroxine

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Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low

European Journal of Clinical Pharmacology ◽

10.1007/s00228-021-03122-z ◽

2021 ◽

Author(s):

E. Heinonen ◽

M. Blennow ◽

M. Blomdahl-Wetterholm ◽

M. Hovstadius ◽

J. Nasiell ◽

...

Keyword(s):

Cord Blood ◽

Pregnant Women ◽

Plasma Concentrations ◽

Relative Difference ◽

Interindividual Variation ◽

Therapeutic Drug ◽

Cytochrome P450 Enzyme ◽

Second Trimester ◽

P450 Enzyme ◽

Placental Passage

Abstract Purpose Sertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants. Method Pregnant women with moderate untreated depression were recruited in 2016–2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed. Results Nine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers’, measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants. Conclusion Placental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment. Trial registration The trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.

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