Thyroid Diseases
Conditions
Keywords
Autoimmune disease, Graves' Disease, Hashimoto's Thyroiditis
Brief summary
This pilot project will randomize a small sample of patients about to undergo surgery for their autoimmune, inflammatory thyroid disease, and determine if a short course of prednisone alters the inflammation of the gland and makes surgery less difficult. It will enroll 30 participants who will each be on study for up to 7 months.
Detailed description
Graves' disease and Hashimoto's thyroiditis are autoimmune conditions affecting the thyroid gland. Surgery to remove the thyroid gland in these patients may be complicated by the inflammatory nature of these diseases. Prednisone is a steroid medication used to decrease inflammation of the thyroid gland in other disease states such as sub-acute thyroiditis, but has not been used systematically to reduce inflammation in patients about to undergo surgery. This is a pilot project that proposes to randomize a small sample of patients about to undergo surgery for their autoimmune, inflammatory thyroid disease, and determine if a short course of prednisone alters the inflammation of the gland and makes surgery less difficult. This could potentially lead to better outcomes for these patients, as well as increased time to recovery and improved quality of life. This project proposes to administer short quality of life surveys at three time points, as well as draw additional labs to measure inflammation and antibody levels at times when patients will already be getting labs drawn for clinical purposes. The purpose of this study is to generate preliminary data from which a larger, blinded, placebo-controlled trial could be designed. These specific aims are: * Determine the benefits and safety of preoperatively administered prednisone for patients with autoimmune thyroid disease undergoing thyroidectomy on: * Difficulty of surgery and rates of surgical complications * Serum autoantibody levels * Longitudinally assess the impact of surgical treatment on QoL in patients with autoimmune thyroid disease Update: Protocol amendment approved on 10-22-2020: Study team decided to omit the aim 'antibody-mediated cytokine levels' from the protocol and consent process as it became cost-prohibitive for processing and storage fees. Cytokine levels are not something typically collected or tracked in the course of clinical care, and may not be relevant. Study can proceed without this aim and will not alter the main outcome measures of antibody levels and difficulty of the operation.
Interventions
DRUGPrednisone
used to reduce inflammation
Sponsors
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
randomized controlled pilot study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Graves' disease or Hashimoto's disease with positive thyroid autoantibodies (Thyroglobulin Antibody \[TgAb\], Thyroid peroxidase antibody \[TPO\], Thyroid Stimulating Ig antibody \[TSI\], and/or Thyrotropin Receptor antibody \[TRAb\]). * Participants will be invited to join the study after the decision has been made to proceed with thyroidectomy as the clinical treatment of their autoimmune thyroid disease.
Exclusion criteria
* Pediatric patients \< 18 * Prior treatment with radioactive iodine (RAI) * Known diagnosis of thyroid cancer * Diabetic patients. * Patients on any immunosuppressive regiment (such as organ transplant patients or patients treated for other autoimmune condition) * Pregnant patients. * Patients being treated for active infection. * Any patient for whom the surgeon feels steroids would provide a clear benefit (ie. Extremely high auto-antibody levels with a very large, inflamed thyroid gland) will be treated according to the clinical judgement of the surgeon. If a surgeon feels steroids are indicated and prescribes them, the patient will not be eligible for the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Thyroid-specific Quality of Life Patient-reported Outcome Measure for Benign Thyroid Disorders (ThyPRO) Score | baseline (2-4 weeks prior to surgery), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op) | The ThyPRO survey is a quality of life measure designed to evaluate how thyroid disease has affected the participant's life. It is a 39-item survey that was scored from 0-4, higher scores indicate worse quality of life. |
| Change in Antibody-mediated Cytokine Levels | baseline (2-4 weeks prior to surgery), up to 4 weeks (Post Operative Day 1), up to 6 weeks (2 weeks post-op), up to 30 weeks (6 months post-op) | Antibody-mediated cytokine levels will be measured using a 10 cytokine panel from Luminex. Cytokines that have been implicated in other autoimmune disease include: IFN-gamma (BR29), IL-6 (BR13), IL-10 (BR22), IL-13 (BR47), IL-15 (BR63), IL-17A (BR42), and VEGF-C (BR38). |
| Change in Short Form Health Survey (SF-12) Mental Component Score (MCS) | baseline (2-4 weeks prior to surgery), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op) | The SF-12 is a 12-item quality of life survey to understand how the participant feels and how well they are able to do their normal activities, it is composed of the mental component score and the physical component score. Each is scored on a scale of 0-100, with higher numbers indicating higher quality of life. |
| Change in Short Form Health Survey (SF-12) Physical Component Score (PCS) | baseline (2-4 weeks prior to surgery), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op) | The SF-12 is a 12-item quality of life survey to understand how the participant feels and how well they are able to do their normal activities, it is composed of the mental component score and the physical component score. Each is scored on a scale of 0-100, with higher numbers indicating higher quality of life. |
| Thyroid Difficulty Scale Score | surgery occurs up to 4 weeks, data collected a conclusion of operation | The surgeon will fill out the Thyroid Difficulty Scale at the conclusion of the operation. This is a 4-item survey to rate the vascularity, friability, mobility, and glandular size of the thyroid. The total possible range of scores from 4-20, higher scores indicate increased difficulty in thyroid surgery |
| Percent Change From Baseline Mean in Autoantibody Levels | baseline measure day of surgery (up to 4 weeks), up to 6 weeks (2 weeks post-op), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op) | Autoantibodies that may be positive include: Thyroglobulin Antibody \[TgAb\], Thyroid peroxidase antibody \[TPO\], Thyroid Stimulating Ig antibody \[TSI\], and/or Thyrotropin Receptor antibody \[TRAb\]. Any that were positive pre-op will be measured at each time point. Baseline level will be 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Surgical Complications: Parathyroid Hormone (PTH) Level | immediately after surgery (baseline for all participants) | PTH is measured right after surgery to determine whether the nearby parathyroid glands were injured during surgery. Low PTH levels immediately after surgery are concerning for symptomatic low calcium levels, either temporarily or permanent, after thyroidectomy. Normal PTH is typically between 20-70. |
| Number of Participants With Surgical Complications: Recurrent Laryngeal Nerve (RLN) Injury | up to 4 weeks (Post Operative Day 1) | — |
| Ultrasound Doppler Quantification of Blood Flow | baseline (2-4 weeks prior to surgery), up to 4 weeks (Post Operative Day 1) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Steroids Participants randomized to the steroid arm will be given a prescription for prednisone 20mg daily for 7 days prior to surgery, otherwise, pre-operative standard of care
Prednisone: used to reduce inflammation | 14 |
| No Steroids Pre-operative Standard of Care | 16 |
| Total | 30 |
Baseline characteristics
| Characteristic | Steroids | No Steroids | Total |
|---|---|---|---|
| Age, Continuous | 39 years STANDARD_DEVIATION 14 | 48 years STANDARD_DEVIATION 15 | 44.0 years STANDARD_DEVIATION 14.7 |
| Body Mass Index | 30 kg/m^2 STANDARD_DEVIATION 4 | 32 kg/m^2 STANDARD_DEVIATION 10 | 31.5 kg/m^2 STANDARD_DEVIATION 7.9 |
| Diagnosis Graves' | 8 Participants | 9 Participants | 17 Participants |
| Diagnosis Hashimoto's | 6 Participants | 7 Participants | 13 Participants |
| Number of Participants with Body Mass Index greater than or equal to 35 | 2 Participants | 3 Participants | 5 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 14 participants | 16 participants | 30 participants |
| Sex: Female, Male Female | 11 Participants | 14 Participants | 25 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 16 |
| other Total, other adverse events | 9 / 14 | 2 / 16 |
| serious Total, serious adverse events | 0 / 14 | 0 / 16 |
Outcome results
Primary
Change in Antibody-mediated Cytokine Levels
Antibody-mediated cytokine levels will be measured using a 10 cytokine panel from Luminex. Cytokines that have been implicated in other autoimmune disease include: IFN-gamma (BR29), IL-6 (BR13), IL-10 (BR22), IL-13 (BR47), IL-15 (BR63), IL-17A (BR42), and VEGF-C (BR38).
Time frame: baseline (2-4 weeks prior to surgery), up to 4 weeks (Post Operative Day 1), up to 6 weeks (2 weeks post-op), up to 30 weeks (6 months post-op)
Population: Investigators did not collect cytokines, as originally planned, as they did not have the storage space or equipment they initially thought.
Primary
Change in Short Form Health Survey (SF-12) Mental Component Score (MCS)
The SF-12 is a 12-item quality of life survey to understand how the participant feels and how well they are able to do their normal activities, it is composed of the mental component score and the physical component score. Each is scored on a scale of 0-100, with higher numbers indicating higher quality of life.
Time frame: baseline (2-4 weeks prior to surgery), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Steroids | Change in Short Form Health Survey (SF-12) Mental Component Score (MCS) | baseline | 39.4 score on a scale | Standard Deviation 11 |
| Steroids | Change in Short Form Health Survey (SF-12) Mental Component Score (MCS) | 6 weeks post-op | 46.7 score on a scale | Standard Deviation 15.7 |
| Steroids | Change in Short Form Health Survey (SF-12) Mental Component Score (MCS) | 6 months post-op | 43.4 score on a scale | Standard Deviation 16.4 |
| No Steroids | Change in Short Form Health Survey (SF-12) Mental Component Score (MCS) | baseline | 35.3 score on a scale | Standard Deviation 17.6 |
| No Steroids | Change in Short Form Health Survey (SF-12) Mental Component Score (MCS) | 6 weeks post-op | 38.6 score on a scale | Standard Deviation 19.3 |
| No Steroids | Change in Short Form Health Survey (SF-12) Mental Component Score (MCS) | 6 months post-op | 40.3 score on a scale | Standard Deviation 22.5 |
Primary
Change in Short Form Health Survey (SF-12) Physical Component Score (PCS)
The SF-12 is a 12-item quality of life survey to understand how the participant feels and how well they are able to do their normal activities, it is composed of the mental component score and the physical component score. Each is scored on a scale of 0-100, with higher numbers indicating higher quality of life.
Time frame: baseline (2-4 weeks prior to surgery), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Steroids | Change in Short Form Health Survey (SF-12) Physical Component Score (PCS) | baseline | 41.5 score on a scale | Standard Deviation 10.4 |
| Steroids | Change in Short Form Health Survey (SF-12) Physical Component Score (PCS) | 6 weeks post-op | 47.4 score on a scale | Standard Deviation 14.4 |
| Steroids | Change in Short Form Health Survey (SF-12) Physical Component Score (PCS) | 6 months post-op | 50.2 score on a scale | Standard Deviation 15.8 |
| No Steroids | Change in Short Form Health Survey (SF-12) Physical Component Score (PCS) | baseline | 43.2 score on a scale | Standard Deviation 18.1 |
| No Steroids | Change in Short Form Health Survey (SF-12) Physical Component Score (PCS) | 6 weeks post-op | 42.7 score on a scale | Standard Deviation 20.9 |
| No Steroids | Change in Short Form Health Survey (SF-12) Physical Component Score (PCS) | 6 months post-op | 44.2 score on a scale | Standard Deviation 24.2 |
Primary
Change in Thyroid-specific Quality of Life Patient-reported Outcome Measure for Benign Thyroid Disorders (ThyPRO) Score
The ThyPRO survey is a quality of life measure designed to evaluate how thyroid disease has affected the participant's life. It is a 39-item survey that was scored from 0-4, higher scores indicate worse quality of life.
Time frame: baseline (2-4 weeks prior to surgery), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op)
Population: Not all participants provided survey data for all time points.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Steroids | Change in Thyroid-specific Quality of Life Patient-reported Outcome Measure for Benign Thyroid Disorders (ThyPRO) Score | Baseline | 2.03 score on a scale |
| Steroids | Change in Thyroid-specific Quality of Life Patient-reported Outcome Measure for Benign Thyroid Disorders (ThyPRO) Score | 6 weeks post-op | 1.47 score on a scale |
| Steroids | Change in Thyroid-specific Quality of Life Patient-reported Outcome Measure for Benign Thyroid Disorders (ThyPRO) Score | 6 months post-op | 1.29 score on a scale |
| No Steroids | Change in Thyroid-specific Quality of Life Patient-reported Outcome Measure for Benign Thyroid Disorders (ThyPRO) Score | Baseline | 1.95 score on a scale |
| No Steroids | Change in Thyroid-specific Quality of Life Patient-reported Outcome Measure for Benign Thyroid Disorders (ThyPRO) Score | 6 weeks post-op | 1.05 score on a scale |
| No Steroids | Change in Thyroid-specific Quality of Life Patient-reported Outcome Measure for Benign Thyroid Disorders (ThyPRO) Score | 6 months post-op | 0.99 score on a scale |
Primary
Percent Change From Baseline Mean in Autoantibody Levels
Autoantibodies that may be positive include: Thyroglobulin Antibody \[TgAb\], Thyroid peroxidase antibody \[TPO\], Thyroid Stimulating Ig antibody \[TSI\], and/or Thyrotropin Receptor antibody \[TRAb\]. Any that were positive pre-op will be measured at each time point. Baseline level will be 1.
Time frame: baseline measure day of surgery (up to 4 weeks), up to 6 weeks (2 weeks post-op), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Steroids | Percent Change From Baseline Mean in Autoantibody Levels | surgery to 2 weeks post op | 0.81 percent change from baseline mean | Standard Deviation 0.8 |
| Steroids | Percent Change From Baseline Mean in Autoantibody Levels | surgery to 6 weeks post-op | 0.43 percent change from baseline mean | Standard Deviation 0.23 |
| Steroids | Percent Change From Baseline Mean in Autoantibody Levels | surgery to 6 months post-op | 0.12 percent change from baseline mean | Standard Deviation 0.04 |
| No Steroids | Percent Change From Baseline Mean in Autoantibody Levels | surgery to 2 weeks post op | 0.78 percent change from baseline mean | Standard Deviation 0.24 |
| No Steroids | Percent Change From Baseline Mean in Autoantibody Levels | surgery to 6 weeks post-op | 0.54 percent change from baseline mean | Standard Deviation 0.28 |
| No Steroids | Percent Change From Baseline Mean in Autoantibody Levels | surgery to 6 months post-op | 0.24 percent change from baseline mean | Standard Deviation 0.24 |
Primary
Thyroid Difficulty Scale Score
The surgeon will fill out the Thyroid Difficulty Scale at the conclusion of the operation. This is a 4-item survey to rate the vascularity, friability, mobility, and glandular size of the thyroid. The total possible range of scores from 4-20, higher scores indicate increased difficulty in thyroid surgery
Time frame: surgery occurs up to 4 weeks, data collected a conclusion of operation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Steroids | Thyroid Difficulty Scale Score | 9.8 score on a scale | Standard Deviation 3.8 |
| No Steroids | Thyroid Difficulty Scale Score | 9.75 score on a scale | Standard Deviation 4 |
Secondary
Number of Participants With Surgical Complications: Recurrent Laryngeal Nerve (RLN) Injury
Time frame: up to 4 weeks (Post Operative Day 1)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Steroids | Number of Participants With Surgical Complications: Recurrent Laryngeal Nerve (RLN) Injury | 2 Participants |
| No Steroids | Number of Participants With Surgical Complications: Recurrent Laryngeal Nerve (RLN) Injury | 2 Participants |
Secondary
Surgical Complications: Parathyroid Hormone (PTH) Level
PTH is measured right after surgery to determine whether the nearby parathyroid glands were injured during surgery. Low PTH levels immediately after surgery are concerning for symptomatic low calcium levels, either temporarily or permanent, after thyroidectomy. Normal PTH is typically between 20-70.
Time frame: immediately after surgery (baseline for all participants)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Steroids | Surgical Complications: Parathyroid Hormone (PTH) Level | 52 pg/mL | Standard Deviation 43 |
| No Steroids | Surgical Complications: Parathyroid Hormone (PTH) Level | 38 pg/mL | Standard Deviation 30 |
Secondary
Ultrasound Doppler Quantification of Blood Flow
Time frame: baseline (2-4 weeks prior to surgery), up to 4 weeks (Post Operative Day 1)
Population: Investigators were unable to come up with a system to quantify doppler flow, so data were not collected