Pharmacodynamic response to anti-thyroid drugs in Graves’ hyperthyroidism

Ali Abbara; Sophie Clarke; Rosalind Brewster; Alexia Simmonard; Pei Chia Eng; Maria Phylactou; Deborah Papadopoulou; Chioma Izzi-Engbeaya; Amir Sam; Eliza Jonauskyte; Alexander Comninos; Karim Meeran; Tom Kelsey; Waljit Dhillo

doi:10.3389/fendo.2020.00286

Pharmacodynamic response to anti-thyroid drugs in Graves’ hyperthyroidism

Ali Abbara, Sophie Clarke, Rosalind Brewster, Alexia Simmonard, Pei Chia Eng, Maria Phylactou, Deborah Papadopoulou, Chioma Izzi-Engbeaya, Amir Sam, Eliza Jonauskyte, Alexander Comninos, Karim Meeran, Tom Kelsey, Waljit Dhillo

Research output: Contribution to journal › Article › peer-review

Abstract

Objective: Graves' disease is the commonest cause of hyperthyroidism in populations with sufficient dietary iodine intake. Anti-thyroid drugs (ATD) are often used as the initial treatment for Graves' hyperthyroidism, however there is a paucity of data relating the dose of ATD therapy to the effect on thyroid hormone levels, increasing the risk of both over- and under-treatment. We aimed to determine the pharmacodynamic response to the ATD carbimazole.

Design: Retrospective cohort study.

Methods: Participants were patients (n = 441) diagnosed with Graves' disease at Imperial College Healthcare NHS Trust between 2009 and 2018. The main outcome measure was change in thyroid hormone levels in response to ATD.

Results: Baseline thyroid hormone levels were positively associated with TSH receptor antibody titres (P < 0.0001). Baseline free triiodothyronine (fT3) were linearly related to free thyroxine (fT4) levels in the hyperthyroid state (fT3 = fT4^*0.97–11), and fell proportionately with carbimazole. The percentage falls in fT4 and fT3 per day were associated with carbimazole dose (P < 0.0001). The magnitude of fall in thyroid hormones after the same dose of carbimazole was lower during follow up than at the initiation visit. The fall in thyroid hormone levels approximated to a linear response if assessed at least 3 weeks after commencement of carbimazole. Following withdrawal of antithyroid drug treatment, the risk of relapse was greater in patients with higher initial fT4, initial TSH receptor antibody titre, males, smokers, and British Caucasian ethnicity.

Conclusion: We identify a dose-response relationship for fall in thyroid hormones in response to carbimazole to aid in the selection of dose for Graves' hyperthyroidism.

Original language	English
Article number	286
Number of pages	11
Journal	Frontiers in Endocrinology
Volume	11
DOIs	https://doi.org/10.3389/fendo.2020.00286
Publication status	Published - 12 May 2020

Keywords

Graves‘ disease
Anti-thyroid drug (ATD)
Carbimazole
Hyperthyroidism
Anti-thyroid drug therapy

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10.3389/fendo.2020.00286Licence: CC BY

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Copyright © 2020 Abbara, Clarke, Brewster, Simonnard, Eng, Phylactou, Papadopoulou, Izzi-Engbeaya, Sam, Wernig, Jonauskyte, Comninos, Meeran, Kelsey and Dhillo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Final published version, 779 KBLicence: CC BY

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@article{1c312a58476248dca79e3acb45ffad72,

title = "Pharmacodynamic response to anti-thyroid drugs in Graves{\textquoteright} hyperthyroidism",

abstract = "Objective: Graves' disease is the commonest cause of hyperthyroidism in populations with sufficient dietary iodine intake. Anti-thyroid drugs (ATD) are often used as the initial treatment for Graves' hyperthyroidism, however there is a paucity of data relating the dose of ATD therapy to the effect on thyroid hormone levels, increasing the risk of both over- and under-treatment. We aimed to determine the pharmacodynamic response to the ATD carbimazole. Design: Retrospective cohort study. Methods: Participants were patients (n = 441) diagnosed with Graves' disease at Imperial College Healthcare NHS Trust between 2009 and 2018. The main outcome measure was change in thyroid hormone levels in response to ATD. Results: Baseline thyroid hormone levels were positively associated with TSH receptor antibody titres (P < 0.0001). Baseline free triiodothyronine (fT3) were linearly related to free thyroxine (fT4) levels in the hyperthyroid state (fT3 = fT4*0.97–11), and fell proportionately with carbimazole. The percentage falls in fT4 and fT3 per day were associated with carbimazole dose (P < 0.0001). The magnitude of fall in thyroid hormones after the same dose of carbimazole was lower during follow up than at the initiation visit. The fall in thyroid hormone levels approximated to a linear response if assessed at least 3 weeks after commencement of carbimazole. Following withdrawal of antithyroid drug treatment, the risk of relapse was greater in patients with higher initial fT4, initial TSH receptor antibody titre, males, smokers, and British Caucasian ethnicity. Conclusion: We identify a dose-response relationship for fall in thyroid hormones in response to carbimazole to aid in the selection of dose for Graves' hyperthyroidism.",

keywords = "Graves{\textquoteleft} disease, Anti-thyroid drug (ATD), Carbimazole, Hyperthyroidism, Anti-thyroid drug therapy",

author = "Ali Abbara and Sophie Clarke and Rosalind Brewster and Alexia Simmonard and Eng, {Pei Chia} and Maria Phylactou and Deborah Papadopoulou and Chioma Izzi-Engbeaya and Amir Sam and Eliza Jonauskyte and Alexander Comninos and Karim Meeran and Tom Kelsey and Waljit Dhillo",

note = "The Section of Endocrinology and Investigative Medicine was funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7- HEALTH- 2009- 241592 EuroCHIP grant and was supported by the NIHR Biomedical Research Centre Funding Scheme. AA was supported by an NIHR Clinician Scientist award. SC was supported by an NIHR Clinical Lectureship. AC was supported by the NHS and BRC. WD was supported by an NIHR Research Professorship (RP-2014-05-001).",

year = "2020",

month = may,

day = "12",

doi = "10.3389/fendo.2020.00286",

language = "English",

volume = "11",

journal = "Frontiers in Endocrinology",

issn = "1664-2392",

publisher = "Frontiers",

}

TY - JOUR

T1 - Pharmacodynamic response to anti-thyroid drugs in Graves’ hyperthyroidism

AU - Abbara, Ali

AU - Clarke, Sophie

AU - Brewster, Rosalind

AU - Simmonard, Alexia

AU - Eng, Pei Chia

AU - Phylactou, Maria

AU - Papadopoulou, Deborah

AU - Izzi-Engbeaya, Chioma

AU - Sam, Amir

AU - Jonauskyte, Eliza

AU - Comninos, Alexander

AU - Meeran, Karim

AU - Kelsey, Tom

AU - Dhillo, Waljit

N1 - The Section of Endocrinology and Investigative Medicine was funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7- HEALTH- 2009- 241592 EuroCHIP grant and was supported by the NIHR Biomedical Research Centre Funding Scheme. AA was supported by an NIHR Clinician Scientist award. SC was supported by an NIHR Clinical Lectureship. AC was supported by the NHS and BRC. WD was supported by an NIHR Research Professorship (RP-2014-05-001).

PY - 2020/5/12

Y1 - 2020/5/12

N2 - Objective: Graves' disease is the commonest cause of hyperthyroidism in populations with sufficient dietary iodine intake. Anti-thyroid drugs (ATD) are often used as the initial treatment for Graves' hyperthyroidism, however there is a paucity of data relating the dose of ATD therapy to the effect on thyroid hormone levels, increasing the risk of both over- and under-treatment. We aimed to determine the pharmacodynamic response to the ATD carbimazole. Design: Retrospective cohort study. Methods: Participants were patients (n = 441) diagnosed with Graves' disease at Imperial College Healthcare NHS Trust between 2009 and 2018. The main outcome measure was change in thyroid hormone levels in response to ATD. Results: Baseline thyroid hormone levels were positively associated with TSH receptor antibody titres (P < 0.0001). Baseline free triiodothyronine (fT3) were linearly related to free thyroxine (fT4) levels in the hyperthyroid state (fT3 = fT4*0.97–11), and fell proportionately with carbimazole. The percentage falls in fT4 and fT3 per day were associated with carbimazole dose (P < 0.0001). The magnitude of fall in thyroid hormones after the same dose of carbimazole was lower during follow up than at the initiation visit. The fall in thyroid hormone levels approximated to a linear response if assessed at least 3 weeks after commencement of carbimazole. Following withdrawal of antithyroid drug treatment, the risk of relapse was greater in patients with higher initial fT4, initial TSH receptor antibody titre, males, smokers, and British Caucasian ethnicity. Conclusion: We identify a dose-response relationship for fall in thyroid hormones in response to carbimazole to aid in the selection of dose for Graves' hyperthyroidism.

AB - Objective: Graves' disease is the commonest cause of hyperthyroidism in populations with sufficient dietary iodine intake. Anti-thyroid drugs (ATD) are often used as the initial treatment for Graves' hyperthyroidism, however there is a paucity of data relating the dose of ATD therapy to the effect on thyroid hormone levels, increasing the risk of both over- and under-treatment. We aimed to determine the pharmacodynamic response to the ATD carbimazole. Design: Retrospective cohort study. Methods: Participants were patients (n = 441) diagnosed with Graves' disease at Imperial College Healthcare NHS Trust between 2009 and 2018. The main outcome measure was change in thyroid hormone levels in response to ATD. Results: Baseline thyroid hormone levels were positively associated with TSH receptor antibody titres (P < 0.0001). Baseline free triiodothyronine (fT3) were linearly related to free thyroxine (fT4) levels in the hyperthyroid state (fT3 = fT4*0.97–11), and fell proportionately with carbimazole. The percentage falls in fT4 and fT3 per day were associated with carbimazole dose (P < 0.0001). The magnitude of fall in thyroid hormones after the same dose of carbimazole was lower during follow up than at the initiation visit. The fall in thyroid hormone levels approximated to a linear response if assessed at least 3 weeks after commencement of carbimazole. Following withdrawal of antithyroid drug treatment, the risk of relapse was greater in patients with higher initial fT4, initial TSH receptor antibody titre, males, smokers, and British Caucasian ethnicity. Conclusion: We identify a dose-response relationship for fall in thyroid hormones in response to carbimazole to aid in the selection of dose for Graves' hyperthyroidism.

KW - Graves‘ disease

KW - Anti-thyroid drug (ATD)

KW - Carbimazole

KW - Hyperthyroidism

KW - Anti-thyroid drug therapy

U2 - 10.3389/fendo.2020.00286

DO - 10.3389/fendo.2020.00286

M3 - Article

SN - 1664-2392

VL - 11

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

M1 - 286

ER -

Pharmacodynamic response to anti-thyroid drugs in Graves’ hyperthyroidism

Abstract

Keywords

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