Carbimazole-Resistant Grave’s Thyrotoxicosis is a Diagnostic and Therapeutic Dilemma, Case Report with Literature Review

Abstract

Background

Carbimazole (CBZ) (or methimazole) is the most used drug inducing and maintaining remission in thyrotoxicosis, especially Grave’s disease (GD). Rarely, situations arise when patients do not respond to recommended or even supratherapeutic doses of CBZ. It poses a challenge to diagnose drug resistance and ultimately manage hyperthyroidism, which can otherwise be fatal if left untreated. Propylthiouracil (PTU) has been used as an alternative in such patients amid increased side effect risks. Additionally, definitive therapy has been recommended with ablation or surgery. However, the best modality of inducing euthyroidism in drug-resistant patients is yet to be established. On literature search, twenty similar cases were found in the literature search. This study summarizes the past literature with addition of a new case of anti-thyroid drug resistant (ATDR) GD.

Case Presentation

A 34-year-old female presented with a 5-day history of progressively worsening fatigue, heat intolerance, sweating, and palpitations. She was diagnosed with GD based on her thyroid function tests (TFTs) and started on CBZ and propranolol. Despite being compliant with CBZ 20 mg once daily and then twice daily, her TFTs remained unchanged for 4 months. However, patient revisited the emergency with continued thyrotoxicosis and unchanged TFTs. Her dose was eventually increased to 20 mg thrice daily, and administration under supervision did not improve her TFTs. The patient was shifted to PTU 150 mg thrice daily with steroids, with minimal improvement. The patient eventually underwent thyroidectomy to avoid long-term PTU use.

Conclusion

ATDR GD is rare and remains a diagnostic and therapeutic challenge. Optimal management should focus on carefully excluding other possibilities and shared decision-making in its management. Most patients may require definitive therapy; hence, arrangements should be made timely with simultaneous attempts to reduce the thyrotoxic state, which otherwise poses a continued threat to patients’ life with potentially serious complications.

Keywords:

• carbimazole
• propylthiouracil
• drug resistance
• thyrotoxicosis
• Grave’s disease

Abbreviations

ATDR, Antithyroid drug resistant; GD, Grave’s disease; ED, Emergency department; HR, Heart rate; CBZ, Carbimazole; PTU, Propylthiouracil; TFTs, Thyroid function tests; SR, Sustained release; BPM, Beats per minute; TSH, Thyroid stimulating hormone; TRAB, TSH receptor antibody; OD, Once daily; TD, Thrice daily; BD, Twice daily; ST, Sinus tachycardia; HPLC, High-pressure liquid chromatography; RAIA, Radio-active iodine ablation.

Ethics Approval and Consent to Participate

This work is original, has not been, and is not under consideration for publication in any other Journal. The study was conducted in full compliance with the principles of the “Declaration of Helsinki”, Good Clinical Practice (GCP) and other relevant guidelines. The Case report was approved by the ethics committee of Medical Research Center (MRC) Qatar. Written informed consent was taken from the patient prior to conducting this work.

Consent to Publication

Written informed consent was taken from the patient prior to publishing this work.

Acknowledgments

The publication of this article was funded by the Qatar National Library.

Author Contributions

Fateen Ata conceptualized and supervised the study. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

None of the authors has any conflict of interest in the publication of this manuscript.

Additional information

Funding

This study was not funded. However, Article processing charges are covered by Qatar National Library.