Prevalence and Predictors of Incidental Thyroid Carcinoma in Patients With Graves' Disease Undergoing Thyroidectomy. (GD)

July 14, 2025 updated by: Saleh Khairy Saleh MD, Minia University

Prevalence and Predictors of Incidental Thyroid Carcinoma in Patients With Graves' Disease Undergoing Thyroidectomy: A Prospective Study.

The prevalence of incidental thyroid cancer (ITC) in Graves' Disease (GD) patients undergoing thyroidectomy appears higher than historically believed, potentially exceeding 10% in large contemporary series, although significant variability exists. The presence of nodules is a strong predictor, while the roles of age, sex, and BMI require clarification. Most ITCs are papillary thyroid microcarcinoma(PTMCs) with generally favorable prognoses, but concerns about aggressiveness persist.

The purpose of the present study is to accurately evaluate the prevalence of incidental thyroid carcinoma (ITC), including microcarcinomas, in a prospectively enrolled cohort of patients undergoing total thyroidectomy for Graves' disease, utilizing standardized pathological examination protocols and secondary outcomes including predictors and histopathological characteristics.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Graves' disease (GD) is the most common cause of hyperthyroidism, affecting approximately 0.5% of the US population.

While definitive treatment often involves radioactive iodine (RAI) or antithyroid drugs (ATDs), thyroidectomy is increasingly utilized, especially for patients with large goiters, compressive symptoms, coexisting suspicious nodules, or contraindications/failure of other therapies.

However, numerous studies over the past few decades have challenged this notion, reporting varying rates of incidental thyroid carcinoma (ITC) discovered in thyroidectomy specimens from GD patients. Understanding the true prevalence and identifying predictors of incidental thyroid cancer (ITC) in this population is crucial for appropriate patient counseling, surgical decision-making, and determining the optimal extent of thyroidectomy.

Identifying factors associated with an increased risk of incidental thyroid cancer in GD patients could help stratify risk and guide management. Several potential predictors in literatures reviews have been investigated, with some conflicting results:

  • Presence of Nodules: The presence of thyroid nodules within the diffuse goiter of GD is a consistently reported risk factor for ITC.
  • Age: Some studies suggest older age is a risk factor. However others, identified younger age as a predictor. This discrepancy requires further investigation.
  • Sex: Male sex has been identified as a risk factor in some studies, although GD is much more prevalent in females.
  • Body Mass Index (BMI): patients with cancer had a higher BMI.
  • Thyroid Autoantibodies and Thyroglobulin: thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibody(TgAbs), and thyroglobulin(Tg) levels but found no statistically significant differences between benign and malignant groups in their cohort undergoing total thyroidectomy for benign diseases. The role of specific GD-related antibodies (e.g., thyroid-stimulating hormone (TSH) receptor antibodies) as predictors requires further study.

The study will enroll approximately 280 patients , utilizing standardized data collection (demographics, clinical history, laboratory, imaging and operative data) and pathological examination protocols. The primary outcome is the prevalence of incidental thyroid cancer (ITC), secondary outcomes including predictors and histopathological characteristics.

Study Type

Observational

Enrollment (Estimated)

280

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
    • Minia
      • Minya, Minia, Egypt, 61519
        • Recruiting
        • Minia university hospital
        • Contact:
        • Sub-Investigator:
          • Rabeh K Saleh, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult patients diagnosed with Graves' disease undergoing total thyroidectomy at Minia University Hospital, a tertiary care center with specialized endocrine surgery services.

Description

Inclusion Criteria:

  • Age 18 years or older.
  • Confirmed diagnosis of Graves' disease based on clinical features (e.g., diffuse goiter, ophthalmopathy if present) and biochemical evidence (suppressed TSH, elevated free T4 and/or T3) and/or positive TSH receptor antibody (TRAb) test.
  • Indication for total thyroidectomy for Graves' disease, based on established guidelines:

Relapse or persistence of hyperthyroidism after a course of antithyroid drugs (ATDs).

Intolerance or adverse reaction to ATDs. Patient preference for surgery over radioactive iodine (RAI) or long-term ATDs. Presence of a large goiter causing compressive symptoms. Coexisting suspicious thyroid nodule(s) on preoperative evaluation. Moderate to severe active Graves' ophthalmopathy where RAI is relatively contraindicated.

  • Patient is scheduled for total thyroidectomy (near-total or subtotal thyroidectomy patients will be excluded).
  • Ability and willingness to provide written informed consent.
  • Ability to understand study procedures and requirements.

Exclusion Criteria:

  • Age less than 18 years.
  • Previous thyroid surgery.
  • Previous neck irradiation.
  • Preoperative diagnosis of thyroid malignancy confirmed by fine-needle aspiration (FNA) cytology (Bethesda V or VI) , the focus is on incidental carcinoma.
  • Inability to provide informed consent (e.g., due to cognitive impairment).
  • Patients undergoing thyroidectomy primarily for reasons other than Graves' disease (e.g., primary indication is large non-toxic MNG).
  • Patients undergoing less than total thyroidectomy (e.g., lobectomy, subtotal thyroidectomy).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Graves' Disease Undergoing Thyroidectomy
Remove of both thyroid lobes and isthmus
Procedure: Total thyroidectomy
Remove of both thyroid lobes and isthmus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of Incidental Thyroid Carcinoma (ITC)
Time Frame: Assessed at the time of final pathology report post-surgery (within 30 days post-operation).Histopathological examination of thyroidectomy specimens using standardized protocols.
The proportion of patients with histologically confirmed incidental thyroid carcinoma, including microcarcinomas, among those undergoing total thyroidectomy for Graves' disease.
Assessed at the time of final pathology report post-surgery (within 30 days post-operation).Histopathological examination of thyroidectomy specimens using standardized protocols.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Histopathological Characteristics of Incidental Thyroid Carcinoma.
Time Frame: Assessed at the time of final pathology report post-surgery (within 30 days post-operation).
Frequency and percentage of ITC characteristics (e.g., histological type, size, stage, multifocality).
Assessed at the time of final pathology report post-surgery (within 30 days post-operation).
Factors Associated with Incidental Thyroid Carcinoma (ITC) Risk.
Time Frame: Assessed at the time of data analysis, approximately 1 year after enrollment completion.
Identification of predictors for incidental thyroid carcinoma (ITC) through univariate and multivariate logistic regression analysis of preoperative clinical, laboratory, imaging, and demographic data. Factors to be assessed include, but are not limited to, presence of nodules, age, sex, and Body Mass Index (BMI).
Assessed at the time of data analysis, approximately 1 year after enrollment completion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Minia University

Investigators

  • Principal Investigator: Saleh K Saleh, MD, Minia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2025

Primary Completion (Estimated)

July 15, 2026

Study Completion (Estimated)

August 15, 2026

Study Registration Dates

First Submitted

July 1, 2025

First Submitted That Met QC Criteria

July 9, 2025

First Posted (Actual)

July 10, 2025

Study Record Updates

Last Update Posted (Actual)

July 17, 2025

Last Update Submitted That Met QC Criteria

July 14, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1574/06/2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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