Conditions: Thyroid Diseases
Keywords: Autoimmune disease Graves' Disease Hashimoto's Thyroiditis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 30
Healthy volunteers: no

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.

Arms:
arm 1: 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 arm 2: Pre-operative Standard of Care

Interventions: intervention 1: Prednisone
Intervention descriptions: intervention 1: used to reduce inflammation

Protocol document:
Prot_SAP_000.pdf: 
 
 
 
Randomized Controlled Trial of Preoperative Steroids in 
Autoimmune Thyroid Disease 
NCT04542278 
DOCUMENT DATE: 10/22/2020 


Randomized Controlled Trial of Preoperative Steroids in Autoimmune Thyroid 
Disease 
o 
Dawn Elfenbein, University of Wisconsin, Madison 
o 
Protocol Version Date: April 2020 
o 
Coordinating Center Identification: N/A 
o 
Co-Investigators: Rebecca Sippel, David Schneider, Kristin Long 
o 
Study Coordinator: N/A 
o 
Funding Sponsor: UW-Madison Department of Surgery, American Association of 
Endocrine Surgeons 


Abbreviations: 
AE = adverse event 
ATA = American Thyroid Association 
Ca = Calcium 
FT4 = thyroxine 
HIPAA = Health Insurance Portability and Accountability Act 
Ig = Immunoglobulin 
PHI = protected health information 
PTH = parathyroid hormone 
QoL = quality of life 
RAI = radioactive iodine 
RLN = recurrent laryngeal nerve 
SAE = serious adverse event 
SF-12 = 12 question Short Form Health Survey 
TgAb – Thyroglobulin Antibody 
ThyPRO = thyroid-specific quality of life patient-reported outcome measure for benign thyroid 
disorders 
TNF = tumor necrosis factor 
TPO – Thyroid peroxidase antibody 
TRAb – Thyrotropin Receptor antibody 
TSI – Thyroid Stimulating Ig antibody 
TSH = thyroid stimulating hormone 
 
 


 
 
Project Summary:  
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 small 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 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. 
Background and Significance:  
Graves’ disease and Hashimoto’s thyroiditis are conditions increasingly being treated with 
surgery. High circulating auto-antibody levels in these diseases are correlated with lower quality 
of life (QoL) regardless of thyroid hormone status1-3. A recent randomized trial for patients with 
euthyroid Hashimoto’s disease showed improved QoL and antibody clearance than patients 
treated with levothyroxine alone4. Surgical complications of hypocalcemia and recurrent nerve 
palsy may be higher in autoimmune thyroid conditions as compared to thyroidectomy for benign 
nodules or cancer5, and this is commonly attributed to the greater difficulty of the operation 
because of increased size and inflammation of the thyroid gland6.  
Some clinicians hesitate to recommend thyroidectomy for autoimmune disease without some 
other indication (such as compressive symptoms or indeterminate nodule) because of this 
increased risk of complications. However, the benefit to patients in terms of QoL and antibody-
mediated symptoms resolution may be much greater7 and sustained for these patients than 
previously understood. Instead of focusing on comparing complications rates for different 
indications for thyroid surgery, research is needed to develop strategies that can decrease the 
inherent technical challenges and thus improve surgical outcomes specifically for these 
inflammatory autoimmune conditions.  
A course of steroids is an accepted and proven treatment to calm inflammation in patients with 
subacute thyroiditis8. There is low quality and anecdotal evidence that administering high-dose 
steroids in the perioperative period may make thyroid surgery easier to perform, and the 
American Thyroid Association (ATA) guidelines recommend using steroid in the rapid prep of 
Graves’ thyrotoxicosis9, but whether steroid prep translates into improved surgical outcomes or 
improved time to recovery after surgery for patients with autoimmune thyroid disease is not 
known. The lack of good data in this area represents a critical deficiency in the care of patients 
with autoimmune thyroid disease. Emerging data on the benefits for surgery in this population 
will continue to expand the indications for surgery; consequently, there is an urgent need to 


understand the effects of the use of steroids in the preoperative period on outcomes for patients 
with autoimmune thyroid disease.    
We will be administering a medication to patients – prednisone – which is not a new drug and is 
not investigational. It is an accepted treatment of patients with subacute thyroiditis at similar 
doses to what we are proposing. The regimen recommended by the ATA guidelines for 
treatment of subacute thyroiditis is: Prednisone 40mg x 1-2 weeks followed by gradual taper of 
2-4 weeks9. We propose that the anti-inflammatory effects of this medication that we know are 
effective in non-surgical thyroiditis patients will be beneficial in the immediate pre-operative 
period. 
 
Physical Risks 
Prednisone is a common medication prescribed often for inflammatory conditions. A recent 
review found that 1 in 5 adults in this country over 3 years received at least 1 prescription for 
short term use of corticosteroids for various conditions such as allergies, respiratory tract 
infections15. Long term use is associated with severe risks such as fungal, viral or opportunistic 
infections, poorly controlled blood glucose, avascular necrosis, fracture, hypertension, weight 
gain, poor would healing, venous thromboembolism, and risks to a fetus in pregnancy. Risks of 
a short course are generally low, as the risks are dose and duration dependent. Risks of a short 
course (1 week) of prednisone include elevated blood sugar, increased risk of infection, venous 
thromboembolism, and bone fractures. The absolute risks in one well done study showed that 
the 90-day risk of a hospitalization for sepsis after a <30 day course of corticosteroids was 
0.05% compared to 0.02% for non-users. Risk of venous thromboembolism was 0.14% 
compared to 0.09% of non-users, and risk of fracture was 0.51% compared with 0.39% of non-
users. Additionally, there may be side effects of taking the medication such as nausea, 
gastrointestinal upset, appetite changes, mood changes, or insomnia. The risk of wound 
infection for thyroid surgery is low – less than 0.5%, and we will exclude pregnant patients, 
patients with diabetes who are at higher risk of elevated blood glucose, and patients with other 
immunocompromised states. 
 
Specific Aims/Study Objectives:  
We hypothesize that administering a course of steroids to patients with Graves’ or Hashimoto’s 
thyroiditis prior to thyroidectomy will result in a less difficult thyroid operation (measured by a 
previously validated scale) and a lower rate of surgical complications. Furthermore, we 
hypothesize administering steroids will results in faster improvement in antibody levels, antibody 
mediated cytokine levels, and health care quality of life as measured by surveys. 
Over the past 5 years, our group has performed nearly 350 thyroidectomies for Graves’ or 
Hashimoto’s thyroiditis, giving us nearly 70 potential subjects per year. We have extensive 
qualitative methods experience and ability to collect QoL data from our recent clinical trial on 
prophylactic central neck dissection for patients with differentiated thyroid cancer. We 
developed and validated an instrument to quantify the difficulty of thyroid surgery. This project 
will be a small pilot that is a non-blinded, randomized trial of patients of glucocorticoids in 
patients about to undergo surgery for autoimmune thyroid disease. The primary aim of this pilot 
is really feasibility for the definitive trial: determining willingness of participants and clinicians to 


enroll, rates of follow up and response to questionnaires, and time needed for recruitment, 
collection of data and analysis. The specific aims are for the larger, definitive trial, but will be 
assessed for this small pilot.   
These specific aims are: 
• 
Determine the benefits and safety of preoperatively administered prednisone for 
patients with autoimmune thyroid disease undergoing thyroidectomy on: 
o 
Difficulty of surgery6,10 and rates of surgical complications 
o 
Serum autoantibody levels  
• 
Longitudinally assess the impact of surgical treatment on QoL in patients with 
autoimmune thyroid disease 
Outcomes: 
• 
Primary 
o Thyroid difficulty Scale score 
o Autoantibody levels  
o QoL scores (12 question Short Form Health Survey [SF-12], thyroid-specific 
quality of life patient-reported outcome measure for benign thyroid disorders 
[ThyPRO]) 
• 
Secondary 
o Ultrasound doppler quantification of blood flow 
o Surgical complications (parathyroid hormone [PTH] level, recurrent laryngeal 
nerve [RLN] injury) 
Research Design and Methods:  
o 
Study population = 30 patients with autoimmune thyroid conditions referred to the 
University of Wisconsin endocrine surgery clinic for surgical management. 
Patients 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. Once they have decided to proceed with surgery, we will describe the 
study rationale and the risks and benefits to enrolling. We will explain that 
patients will be randomized to take steroids for 1 week prior to surgery, in 
addition to other medications that we give all patients before surgery. If they 
choose not to enroll in the study, their thyroidectomy will proceed as planned. For 
the study, 15 patients will be treated with steroids for 1 week prior to surgery, 15 
will not receive steroids. Both otherwise receive the current standard of 
preoperative care. We are doing a stratified randomization in blocks of four within 
four groups of patients, as determined by category of diagnosis (Graves’ vs. 
Hashimoto’s) and BMI (<35 vs >=35). The small block size will allow for equal 
numbers of control and treatment subjects even if category sizes are small.  
 
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]). This information is found in the 
patient’s medical record which is available at the time of surgical 
consultation. If a patient has not had antibody levels checked prior (this is 
rare), we can discuss the trial with the patient and draw the first set of 
clinical and research labs. If the clinical labs return that antibody levels 
are negative, we will inform the patient that they are not eligible to 
participate and will withdraw them from the study and discard the 


research serum sample. All patients must first agree to undergo total 
thyroidectomy for their disease before they are even approached about 
the trial.  
 
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. 
 
Subject identification and recruitment. We will identify patients from our 
own clinic who have been referred to us for consideration of 
thyroidectomy as treatment for their autoimmune thyroid disease. Each 
surgeon spends time prior to each clinic looking through their patient list, 
and will flag anyone with an autoimmune thyroid disease coming to 
discuss thyroidectomy as a potential study participant. After the normal 
clinical consult, those patients who choose to undergo thyroidectomy and 
otherwise meet criteria will be given the opportunity to participate in the 
trial. This will all occur in the same physical setting of our UW endocrine 
surgery clinic.  
o 
Because this is a small pilot study done with limited resources and designed for 
feasibility and generating preliminary data, patients and surgeons will not be 
blinded to treatment. The operating surgeon is typically the provider who does 
the preoperative assessment and provides medications and instructions directly 
to the patient, and we lack the resources to coordinate a study-specific 
preoperative visit. 
 
Because participants are not blinded, knowledge of their group 
assignment may affect their behavior. Subject non-blinding should not 
affect our primary outcomes of thyroid difficulty, serum antibody, or 
cytokine levels. It may alter their responses on the QoL surveys, however, 
as steroids can cause a euphoric effect while a person is taking them. 
QoL surveys are to be administered before the study begins, and then not 
again until 6 weeks and 6 months after surgery when subjects are no 
longer taking the steroids, so the effect will be minimal. For secondary 
outcomes, subject non-blinding should not affect ultrasound 
measurements or surgical outcomes. 
 
Because surgeons are not blinded, it is possible that their responses for 
the thyroid difficulty scale will be altered by their knowledge of whether 
the subject took steroids. The logistics of having the patients leave the 
surgeons clinic not knowing their group assignment, then having a 
different researcher assign and provide the medication would be beyond 
the budget and capabilities of our team for this feasibility trial. We feel the 
benefits of ease of enrollment and ability to recruit sufficient patients 
outweigh the possible bias in the thyroid difficulty scale.  
o 
There are no additional collaborating sites – this will all be performed at UW 
Hospitals and Clinics 
o 
Identify information extracted from medical records – demographics, length of 
time of disease, lab values related to thyroiditis disease, indications for surgery, 


surgical data including blood loss and length of operation, postoperative 
laboratory values related to thyroiditis. 
o 
We know that glucocorticoids may decrease Immunoglobulin (Ig)G and IgA levels 
with moderate-to-high dose steroids given over short term. (10-20 percent at one 
week in rheumatoid arthritis  patients)13, therefore we intend to collect serum for 
antibody levels at intervals more frequent than our standard of care.  
o 
Specimen/data collection, handling, storage 
 
Data will be collected electronically (REDCap) on the Institute for Clinical 
and Translational Research (ICTR) secure version of the software and on 
paper. The only data recorded on paper will be the Thyroid difficulty scale 
and the prednisone compliance survey and these will be stored in the PI’s 
office in a locked file cabinet. 
 
All information obtained and associated data files will be confidential and 
will be kept in a locked file or password protected secure departmental 
server through the department of surgery (U:). This server is backed up 
according to standard protocols. All computers used to access this server 
are password protected. The risk of breach of confidentiality regarding 
participation in the study outside of the scope of the research will be 
handled by carefully controlling access to study data only to personnel on 
the research team. 
 
Confidentiality will be protected further by: (1) using a participant log form 
that contains only the minimum necessary protected health information 
(PHI) concerning participants, and storing this log in a locked area when 
not in use, (2) not sharing PHI with any outside institution, (3) coding data 
collection forms with a consecutive participant number that is not derived 
from any participant personal identifiers, and linking that data collection 
form to the participant log, and (4) storing the participant log, the key 
linking the code to the PHI, and data collection forms separately. 
 
It is highly likely that these measures will result in avoidance of breach of 
confidentiality outside of the research. In addition, the data to be collected 
are not sensitive to participants. 
o 
Study Procedures: 
 
Eligible patients will have a diagnosis of autoimmune thyroiditis, positive 
auto-antibodies, and an indication or preference for surgical treatment 
with a total thyroidectomy. This will be a randomized, non-blinded pilot 
study, and all patients who are eligible will be given the opportunity to 
participate.  
 
Preoperative Testing: All randomized patients will undergo our current 
standard of care pre-operative testing, which includes a clinic ultrasound 
and laboratory testing of thyroid function and autoantibody levels. All 
study patients will be directed to complete the online quality of life surveys 
(SF-12 and ThyPRO) prior to surgery. Each survey will take 
approximately 10-20 minutes to complete. Patients randomized to the 
steroid arm will be given a prescription for prednisone 20 mg daily for 7 
days prior to surgery. Patients will be instructed to take the prednisone 
once a day, in the morning, with food. All patients (steroid or not) will 
receive our standard instructions for TUMS and saturated iodine (in 
Graves’ disease) if indicated. Our current standard of care for patients 
with Graves’ disease is to take 1-2 drops of saturated iodine solution 


twice a day and 1000mg of TUMS three times a day for the 7 days 
leading up to surgery. There is no consistent regiment for TUMS or 
saturated iodine for patients with Hashimoto’s in our clinic, but it is up to 
the clinical judgement of the surgeon whether to use these medications 
on an individual basis. There are no interactions of these medications 
with prednisone, and administration or non-use of these medications does 
not exclude anyone from participating in the trial.   
 
Day of Surgery: Surgeon will repeat the ultrasound in the operating room 
to compare area of blood flow. As part of the clinical workup, each 
surgeon always performs thyroid ultrasound using our GE Logiq clinic 
equipment, and this includes a single image using “doppler” mode to 
measure blood flow. Surgeons then do an ultrasound once the patient is 
positioned in the operating room to verify incision placement, and for 
study patients we will save one “Doppler” image for comparison purposes 
to the preop image. While the single image is unique to this study, 
performing the ultrasound is part of our routine clinical care and saving 
one additional image takes 10 seconds and confers no additional risk. 
There is no charge for this image and it will be uploaded with the clinical 
image to the radiology digital storage system for the surgeons to compare 
blood flow from before and after steroid administration. Research specific 
blood draw (15mL) will occur at the time of IV placement and sent for 
antibody levels. Patients will be asked whether they took their course of 
steroids as described and we will record their answers. If they report not 
taking it as directed, their narrative reasons for not doing so will be 
recorded. Total thyroidectomy will be performed using standard 
techniques in all patients potentially eligible for randomization. An open 
technique will be used to remove the entire thyroid including pyramidal 
lobe and all visible thyroid tissue. Care will be taken to visualize and 
preserve both recurrent laryngeal nerves and to preserve all parathyroids 
in situ. All removed specimens will be carefully examined for any 
parathyroid tissue and any devascularized or resected normal parathyroid 
glands will be confirmed by frozen section and autotransplanted into the 
sternocleidomastoid muscle, as per our standard of care. The surgeon 
will then fill out the “Thyroid Difficulty Scale” at the conclusion of the 
operation, either by the surgeon entering it directly into the secure 
RedCap project or recording their answers on paper that is coded and 
entered later. If on paper and coded, surgeons will store the paper 
separately from any PHI related to that subject and will destroy the paper 
as soon as it is entered into the database.  
 
2 weeks postoperatively: Patients are all seen in clinic 10-14 days after 
surgery and calcium and PTH hormone levels are checked as per our 
standard of care. Research specific labs of antibody levels will be 
checked for our study patients (15-45 mL, depending on individual 
antibody profiles of subjects).  
 
6 weeks postoperatively: Patients are all given a lab slip to have thyroid 
stimulating hormone (TSH) and thyroxine (FT4) drawn to check 
levothyroxine dosing as per our standard of care, as well as checking 
antibodies to monitor for treatment success. This can be done at a lab of 
their choosing. Patients will be sent an electronic link to fill out the quality 
of life surveys (SF-12 and ThyPRO).  


 
6 months postoperatively: Patients have TSH and FT4 drawn again to 
check levothyroxine dosing as per our standard of care, as well as 
checking antibodies to monitor for treatment success. Again, this can be 
drawn at the lab of their choice. Patients will be sent an electronic link to 
fill out the quality of life surveys (SF-12 and ThyPRO).  
 
Time point 
Procedures (all standard of 
care) 
Labs (italics are current standard of care, 
black are study specific and in the budget) 
Surveys (study 
specific) 
Preop 
clinic visit 
(2-4 
weeks 
preop) 
Ultrasound with color doppler 
quantification of blood flow, 
vocal fold ultrasound 
Ca, PTH, TSH, FT4, Tg, TgAb, TSI, TPO, 
TRAB  
SF-12, ThyPRO 
Day of 
Surgery 
Repeat ultrasound with color 
doppler 
TgAb/TPO/TSI/ TRAB for any that were 
positive preop 
Thyroid difficulty 
scale (surgeon) 
2 weeks 
postop 
Clinical voice assessment, 
vocal fold ultrasound 
Ca, PTH, TgAb/TSI/TPO/TRAB if they were 
positive 
  
6 weeks 
postop 
Laryngoscopy if clinically 
indicated  
TSH, FT4, Tg, TgAb/TSI/TPO/TRAB if they 
were positive 
SF-12, ThyPRO 
6 months 
postop 
TSH, FT4, TgAb/TSI/TPO/TRAB if they were 
positive 
SF-12, ThyPRO 
o 
Study Drug: 
 
Rx will be provided to patients randomized to steroid prep group for 
“Prednisone 20mg tabs. Sig: Seven days before your scheduled surgery, 
Take 1 tab (20mg) daily in the morning for 7 daysTake with food. Disp: 7 
tabs. Refills: none” 
 
Patients will fill this at the UW American Center outpatient pharmacy at no 
charge, no drug accountability procedures are required for this 
commercially available drug that is being used in the standard of care 
dosing and route. 
 
Concomitant medications allowed/disallowed: No other steroids or 
immunosuppressive medications, No antibiotics, antitubercular drugs, or 
anti-fungals. No anticoagulants. Caution in many anti-seizure 
medications. 
 
No placebo 
 
While chronic systemic steroids may impair wound healing, there is 
literature to support that acute (< 10 days), high-dose systemic 
corticosteroid use has no clinically significant effect on wound healing14  
 
The prednisone dose is within the accepted guidelines for rapid prep for 
Graves’ disease patients, and is considered a moderate dose. It is 
expected to contribute negligible increased risk for wound complications 
in this population where wound infection rates are already extremely low 
(less than 0.5%). 
• 
Data and Safety Monitoring Plan: 
o 
This is a study that involves randomizing patients to receive a prescription drug, 
therefore is greater than a minimal risk study.  It is using a commonly prescribed 
medication for a short duration and has been shown to have a low incidence of 
adverse events at these doses and durations. Prednisone is already prescribed 


in a subset of similar patients to our population outside the context of a trial 
(Graves’ disease requiring rapid surgical prep). Potential problems will be 
monitored and handled by the primary surgeon, clinic staff and principal 
investigator. This is appropriate given the small number of participants (15 
subjects will receive the intervention drug), single site, and low risk medication. 
We will not assemble a formal external Data and Safety monitoring committee..  
o 
Dr. Elfenbein will be notified by the enrolling surgeon each time a subject enrolls 
in the trial and of any protocol deviations. Adverse events from the study 
medication will be reported immediately. We anticipate that the manner in which 
subjects will report adverse events is by (1) directly notifying the principal 
investigator as directed in the informed consent document, (2) calling our clinic 
staff who will notify Dr. Elfenbein, or (3) by reporting side effects and amount of 
drug taken on the drug compliance survey on the day of surgery. 
o 
Protocol violations and deviations, side effects, and adverse events will be noted 
in the secure RedCap database. 
o 
A monthly clinical research meeting occurs among our group to discuss all 
clinical research, and this study will become a standing item on our agenda 
during the duration of the trial for any surgeon to discuss possible adverse events 
or concerns 
o 
Given low rates of wound infection in this population, any wound infection 
requiring treatment with antibiotics in the steroid group will be considered an 
adverse event (AE) and will be investigated immediately by the principal 
investigator and operating surgeon, and reported to the IRB within 14 business 
days If a wound infection requires an operation, it is considered a serious 
adverse event (SAE), although it is not immediately life threatening or debilitating 
to other subjects, so also will be reported with 14 business days to the IRB.  If a 
second wound infection requiring antibiotics or surgery  occurs in the steroid 
treated group, enrollment will immediately cease and it will be reported as a SAE 
in the same 14 day timeframe, when we will closely scrutinize these cases with 
the help of the IRB to determine whether it is safe to proceed. Monitoring for 
wound infections will occur in the context of our usual clinical care. We will see 
every wound in person at the postoperative visit, but otherwise we rely on 
patients self-reporting to alert clinic staff if they have concerns (redness, warmth, 
drainage) about their incisions. No specific study-specific instructions will be 
given to study subjects, we will simply ask them to call the clinic staff if they have 
any concerns, and clinic staff will be trained to immediately notify Dr. Elfenbein if 
a study patient reports wound complications.  
• 
Statistical Considerations: Provides an explanation as to why the number of subjects 
was chosen and the means for analyzing data will meet the specific aims/study 
objectives 
o 
As a small pilot, feasibility study, the size of 30 is based on our estimate of a 
realistic recruitment rate for the future definitive trial. We see approximately 70 
potential subjects in our clinics per year, and our listed exclusion criteria are rare 
in our population. We estimate that fewer than one fourth will not meet criteria, 
and an additional one fourth may decline to participate. From the patient 
perspective, enrollment involves only answering QoL surveys and possibly taking 
a medication 1 week prior to surgery, the risks and effort are not much greater, 
which is why we estimate a generous rate of inclusion. We are giving ourselves 1 
year to enroll all 30 patients (with an additional 6 months to collect follow up 
data).  Our biostatistics team has already been engaged and feels this is an 
aggressive but realistic expectation. For all primary aims, data will be analyzed 


using a mixed model two-way analysis of variance examining the effects of the 
treatment group. When appropriate, t-tests comparing the steroid prep vs non-
steroid prep groups will be performed. Our WISOR biostatistics core will perform 
this analysis using SAS statistical software. This supplemental data analysis will 
then be used to obtain a sample size calculation for our future study.  
o 
There is no planned interim analyses for this short study  
o 
The data will be analyzed in an “intent-to-treat” fashion with groups being 
analyzed based on their initial group and not on whether or not they report taking 
the steroid medication. However, if large numbers of patients report not taking 
the medication as directed, this is very important information for our future larger 
study and we will record patient responses and reasons for this. 
o 
Drop-outs are not expected in high numbers for this population. Everyone who 
undergoes thyroidectomy requires levothyroxine therapy postoperatively, and we 
follow all of our patients very closely for at least 6 weeks. It is possible that the 6 
month data will be more challenging to obtain, and that is also very important 
information to know in this feasibility trial. 
• 
Data and Record Keeping: Addresses how data will be captured, protected, and shared 
with others 
o 
The Principal Investigator will manage the study data 
o 
Data confidentiality will be assured by coding and storing electronic data on 
password protected Department of Surgery servers, storing coding keys and data 
separately, as previously described.  Data will be destroyed 10 years after 
publication of study findings. 
 
• 
Bibliography & References Cited:  
1. Ott J, Promberger R, Kober F, et al. Hashimoto's thyroiditis affects symptom load and 
quality of life unrelated to hypothyroidism: a prospective case-control study in women 
undergoing thyroidectomy for benign goiter. Thyroid : official journal of the American 
Thyroid Association. 2011;21(2):161-167. 
2. Bektas Uysal H, Ayhan M. Autoimmunity affects health-related quality of life in 
patients with Hashimoto's thyroiditis. Kaohsiung J Med Sci. 2016;32(8):427-433. 
3. Frohlich E, Wahl R. Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in 
Thyroid and Extra-Thyroidal Diseases. Front Immunol. 2017;8:521. 
4. Guldvog I, Reitsma LC, Johnsen L, et al. Thyroidectomy Versus Medical Management 
for Euthyroid Patients With Hashimoto Disease and Persisting Symptoms: A 
Randomized Trial. Ann Intern Med. 2019;170(7):453-464. 
5. Thomusch O, Sekulla C, Billmann F, Seifert G, Dralle H, Lorenz K. Risk profile analysis 
and complications after surgery for autoimmune thyroid disease. The British journal of 
surgery. 2018;105(6):677-685. 
6. Schneider DF, Mazeh H, Oltmann SC, Chen H, Sippel RS. Novel thyroidectomy 
difficulty scale correlates with operative times. World journal of surgery. 
2014;38(8):1984-1989. 
7. Mirallie E, Borel F, Tresallet C, et al. Impact of total thyroidectomy on quality of life 
at 6 months: the prospective ThyrQoL multicentre trial. European journal of 
endocrinology / European Federation of Endocrine Societies. 2019. 


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