Genetic Study of Antithyroid Drugs Associated Agranulocytosis

Thionamides, the antithyroid drugs, have been widely used to treat hyperthyroidism1. Side effects are found in 1% - 5% of the patients1. One of the most serious side effect is agranulocytosis, which occurs in 0.1% - 0.3 % of the patients1. This might lead to severe infection and sometimes mortality. The underlying mechanism is unclear. An immune phenomenon may be involved because the antigranulocyte antibodies or lymphocyte sensitized to antithyroid drugs are found in these patients6,7. The recognition of major histocompatibility complex class II peptide complexes by T lymphocytes is central to the development of immune response. According to a report in 1996, the HLA DRB1*08032 allele is strongly associated with susceptibility to methimazole-induced agranulocytosis20.

Recently, there are new techniques for genetics study. We aimed to identify the associated genetic change of the agranulocytosis side effect of antithyroid drugs. First, we will look at the classical human Leukocyte Antigen (HLA) loci, such as HLA-A, -B, -C, -DR, -DQ and -DP. If no significant change is found in the above genes, we will consider whole exon sequencing with next-generation sequencing, Statistic analysis will include appropriate linkage analysis, association study, variation data analysis, pathway analysis. If we can identify the genetic change and perform genetic examinations before prescription, we can avoid the happening of severe side effects.

Study Overview

• Status: Unknown
• Conditions: Agranulocytosis

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Shyang-Rong Shih, PhD; Phone Number: 886-972653337; Email: srshih@ntu.edu.tw
    • Principal Investigator: Shyang-Rong Shih, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Agranulocytosis caused by anti-thyroid drugs

Description

Inclusion Criteria:

• patients with absolute neutrophil count lower than 500/mm3 caused by anti-thyroid drugs

Exclusion Criteria:

• Patients who is younger than 20 years old or older than 85 years old

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Agranulocytosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with anti-thyroid drug related agranulocytosis	The investigators review the chart to see if the patients had anti-thyroid drug related agranulocytosis	within 2 month after taking the drug

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: October 31, 2013
• First Submitted That Met QC Criteria: November 6, 2013
• First Posted (Estimate): November 7, 2013

Study Record Updates

• Last Update Posted (Estimate): November 7, 2013
• Last Update Submitted That Met QC Criteria: November 6, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Leukopenia; Leukocyte Disorders; Agranulocytosis
• Other Study ID Numbers: 201112083RID