Thyroidectomy for Graves' Disease or Amiodarone-induced Thyrotoxicosis: Is it Still Necessary to Achieve a Preoperative Euthyroid State? - A Prospective Observational Multicenter European Study (GRATES)
Conditions: Graves Disease, Amiodarone-Induced Thyrotoxicosis, Thyroidectomy
Sponsor: Andrea Goldmann

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 1/19 
 
Research plan/Protocol for HRO: 
Further use of biological material and health-related personal data for research 
pursuant to Articles 32 and 33 HRA 
 
Title of the research project 
Thyroidectomy for Graves' Disease or Amiodarone-induced Thyrotoxicosis: Is it 
still necessary to achieve a preoperative euthyroid state? – A prospective 
observational multicenter European study 
 
 
 
Name and address of the project leader and sponsor 
Goldmann Andrea, MD  
Leading physician of the Endocrine Surgery Unit  
Clinic for Visceral and Thoracic Surgery  
Winterthur Cantonal Hospital  
Brauerstr. 15  
CH-8400 Winterthur  
  
e-mail: andrea.goldmann@ksw.ch  
telephone: +41 052 266 24 19 
 
 
Confirmation of the project leader and the sponsor 
With my signature, I attest that all information in this protocol is correct and that I will 
comply with the information I have given and with national legislation, namely data 
protection law. 
 
 
Project leader and sponsor: 
 
 
 
Place, date 
 
Signature 
 
 
 
 
  
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 2/19 
Local project leader at the local center/site: 
 
Local Project Leader:  
 
Demarchi Marco Stefano, MD  
Senior physician  
Thoracic and Endocrine Surgery  
University Hospitals of Geneva  
Rue Gabrielle Perret-Gentil 4  
CH-1211 Geneva  
  
e-mail: rdeh@hcuge.ch  
telephone: 0223727862   
 
 
 
 
Place, date 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 3/19 
 
Local Project Leader: 
 
Clerici Thomas MD  
Leading physician of the Endocrine Surgery Unit  
Clinic for General, Visceral, Endocrine Surgery and Transplantation   
St. Gallen Cantonal Hospital  
Rorschacher Str. 95  
CH-9000 St. Gallen  
  
e-mail: Thomas.Clerici@kssg.ch  
telephone: +41 71 494 13 12 
 
 
 
 
Place, date 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 4/19 
Local Project Leader: 
 
Kaderli Reto, Prof., MD,  
Leading physician of University Center of Endocrine Surgery 
Clinic of Visceral Surgery and Medicine 
University Hospital Bern 
Inselspital 
CH-3010 Bern  
 
e-mail: reto.kaderli@insel.ch 
telephone + 41 (0)31 632 5900 
 
 
  
Place, date 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 5/19 
Local Project Leader: 
 
Kern Beatrice, MD,  
Senior physician Visceral Surgery 
Clarunis- University Abdominal Center 
St. Claraspital 
Postfach 
4002 Basel 
 
e-mail: beatrice.kern@clarunis.ch 
telephone +41 61 777 75 06 
 
 
  
Place, date 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 6/19 
Local Project Leader: 
 
Grafen Franziska, MD,  
Deputy Chief Surgeon 
General, Vascular and Visceral Surgery 
Spital Limmatal 
Urdorferstrasse 100 
8952 Schlieren  
 
 
e-mail: franziska.grafen@spital-limmattal.ch 
telephone +41 44 733 11 11 
 
 
 
  
Place, date 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 7/19 
Local Project Leader: 
 
Matter Maurice, Prof., MD,  
Chief Surgeon Visceral Surgery 
Lausanne University Hospital (CHUV)  
Rue du Bugnon 21 
CH-1011 Lausanne  
 
 
e-mail: Maurice.Matter@chuv.ch 
telephone +41 21 314 1111 
 
 
 
  
Place, date 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 8/19 
Local Project Leader: 
 
Köberle-Wührer Roswitha, MD,  
Senior Surgeon Visceral Surgery 
Cantonal Hospital Baselland 
Reinstrasse 26 
4410 Liestal 
 
e-mail: roswitha.koeberle-wuehrer@ksbl.ch 
telephone +41 61 925 25 25 
 
 
 
  
Place, date 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 9/19 
Local Project Leader: 
 
Peloni Giuseppe, MD 
Senior Surgeon  
Regional Hospital Mendrisio 
Via Alfonso Turconi 23 
6850 Mendrisio 
 
e-mail: Giuseppe.Peloni@eoc.ch 
telephone +41 91 811 31 11 
 
 
 
  
Place, date 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 10/19 
Local Project Leader: 
 
Robert Mechera, PhD, MD 
Senior Consultant Visceral Surgery and Endocrine Surgery 
Regional Hospital of Männedorf 
Asylstrasse 10 
8708 Männedorf 
 
e-mail: r.mechera@spitalmaennedorf.ch 
telephone +41 44 922 2512 
 
 
 
  
Place, date 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 11/19 
 
Abbreviations 
HRA  
Human Resarch Act 
HRO  
Human Research Ordinance 
AIT 
 
Amiodarone-induced Thyrotoxicosis 
EU 
 
European Union  
TSH  
Thyroidea stimulating Hormone 
fT3 
 
free triiodothyronine 
fT4 
 
free thyroxine 
ICU 
 
intensive care unit 
 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 12/19 
1. Background 
Thyrotoxicosis is the clinical condition associated with excessive thyroid hormone 
activity, usually due to inappropriately high levels of circulating thyroid hormones. The 
clinical presentation is variable, ranging from asymptomatic to life-threatening 'thyroid 
storm'. Symptoms include weight loss, heat intolerance and palpitations [1].  
Thyrotoxicosis can result from diffuse alterations of the thyroid gland, such as Graves' 
disease and Amiodarone-induced thyrotoxicosis (AIT). This poses a considerable 
challenge across multiple medical specialties, spanning endocrinology, cardiology, and 
anesthesiology.  
Graves' disease is a widespread endocrine disorder that affects approximately 1% of 
the population. Treatment strategies vary based on clinical presentation and patient 
preferences, with options ranging from medical management to thyroidectomy [2,3].  
Amiodarone is a class III antiarrhythmic drug used to treat supraventricular and 
ventricular arrhythmias, and to maintain sinus rhythms after cardioversion of atrial 
fibrillation [4]. Its prescription has become more common in recent decades. However, 
the medication comes with the risk of precipitating severe thyrotoxicosis, which, if left 
untreated, can be fatal. [2, 4, 5, 6]. Discontinuing the medication may not always be 
feasible.  
Under medical treatment for thyrotoxicosis (using thionamides or glucocorticoids), 
attaining euthyroidism can frequently be challenging to achieve, prompting 
consideration of definitive treatment through thyroidectomy [7,8].  
Thyroidectomy for Graves' disease or AIT presents unique disease-specific challenges, 
potentially resulting in elevated perioperative complication rates when compared to 
other indications [8]. According to current guidelines, it is recommended to attain a 
euthyroid state prior to surgery to mitigate perioperative risks, despite the inconclusive 
evidence supporting this approach [2]. Nevertheless, data from retrospective studies 
show that between 21-51% of patients undergo surgery when euthyroidism is not stable 
or cannot be achieved [9-12]. 
The EUROCRINE® registry offers a valuable opportunity to assess the morbidity linked 
to thyroidectomy for Graves' disease and AIT, considering both euthyroid and 
hyperthyroid states. This prospective, observational study aims to refine surgical 
protocols and inform updates to existing guidelines, thereby advancing the 
management of thyroidectomy for Graves' disease and AIT. 
 
2. Objectives 
The aim of this study is to explore potential differences in the morbidity of thyroidectomy 
for Graves' disease and AIT based on thyroid metabolic status prior to or during the 
procedure. Our hypothesis suggests that there will be no significant differences in 
relevant complication rates, such as transient and permanent nerve palsy, transient and 
permanent hypoparathyroidism, reoperation, severe adverse intraoperative cardiac 
events, or the onset of a "thyroid storm" [13-15].  
If this hypothesis is confirmed, patients with Graves' disease and AIT who are 
scheduled for thyroidectomy would no longer need to wait to reach a state of 
euthyroidism. This would streamline preoperative assessments and expedite surgical 
planning, leading to reduced costs and shorter waiting times, and minimizing exposure 
to dangerous and excessive levels of thyroxine. 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 13/19 
The primary endpoint is the relevant complication rate in both groups: transient and 
permanent nerve palsy, transient and permanent hypoparathyroidism, reoperation for 
postoperative haemorrhage, and occurrence of a “thyroid storm". 
Our secondary endpoints are results of other complications, duration of surgery, 
estimated blood loss, intraoperative tachycardia, length of hospital stay, ICU monitoring, 
preoperative medications, use of autofluorescence, angiofluorescence, and 
neuromonitoring, preoperative calcium and/or vitamin D supplementation, clinic volume. 
 
3. Design 
We are planning a prospective, observational, multicenter, multinational study based on 
the EUROCRINE® registry. Eurocrine® is an international endocrine surgical quality 
registry based in the EU. The project will be a Swiss national and multinational 
multicenter study. 
Several other in Eurocrine® participating, international clinics have agreed to participate 
in the study. It is planned that a total of around 25 clinics in various European countries 
will take part in the study. In a first step, the participating centers in Switzerland will be 
opened. 
The data will be prospectively entered into the registry online in encrypted form, as is 
usual with the Eurocrine® registry. For the EUORCRINE registry itself a declaration of 
no objection has been issued in May 2017 (2017-00683). The clinics participating in our 
study do this part of the data entry as before. The participant can then be enrolled in the 
study via a my-Eurocrine add-on module and additional study-specific routine data can 
be collected directly in the Registry online platform. All variables, along with the study-
specific variables, are systematically collected in the centers as a component of patient 
care, since these parameters are essential for treatment. The operation itself, the 
preoperative or postoperative treatments are not altered in any way. Information about 
postoperative complications will be registered at the Eurocrine database as previously 
implemented. 
 
Patients with Graves' disease or AIT can be included in this study and will be assigned 
to two groups. We rely on free triiodothyronine (fT3) and free thyroxine (fT4) levels to 
assess functional status since the TSH level may not accurately reflect the patient's true 
functional status. Patients will be classified as uncontrolled if their levels of fT3 or fT4 
are elevated, or as controlled (normal fT3 and fT4) immediately prior to surgery (normal 
ranges for all ages: fT4 12.0 - 22.0 pmol/l; fT3 3.1 - 6.8 pmol/l). The fT3 and fT4 tests 
will be conducted no more than one week before surgery. Consecutive patient 
enrolment is necessary to accurately reflect real clinical conditions. The standard 
variables are recorded as usual, with the addition of the study-specific variables (see 
CRF). All complications will be documented to evaluate the risk of surgery in both 
controlled and uncontrolled metabolic states.  
For diagnosing patients with "thyroid storm", we opted to utilize the established 
Japanese Association classification [13], which is deemed more suitable for clinical 
settings compared to the "Burch and Wartofsky" scale [14].  
 
4. Origin of the data/biological material 
 
We want to analyze data routinely collected in the clinical practice for adult, non-
pregnant patients who underwent surgical management of Graves ' disease and AIT in 
different functional states. The variables are summarized in the CRF (refer to CRF).  
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 14/19 
All data will be collected in the Eurocrine database with the standard module and an 
add-on specific variable my-Eurocrine module for study specific routine data. All 
participating sites will use the Eurocrine database and collect their data prospectively 
online and in a coded form. In the Eurocrine data register, data is routinely recorded up 
to six months postoperatively in the event of complications occurring during treatment. 
This period also corresponds to that of our study project. 
 
We plan to run the study for 2 years and will start as soon as a positive ethical decision 
has been made. If enough patients have been enrolled before the end of the 2 years, 
the study will be stopped early. 
 
5. Inclusion criteria 
- Adult patients (≥ 18 years of age) undergoing surgical treatment for Graves' 
disease or Amiodarone-induced thyrotoxicosis (AIT) with biochemically confirmed 
hyperthyroidism or on specific medication for the treatment of Graves' disease or 
AIT. 
- Patients providing signed informed consent. 
 
6. Exclusion criteria 
- Children and minors (<18 years). 
- Pregnant women. 
- Patients unable or unwilling to provide informed consent due to language 
barriers or intellectual limitations. 
- Patients undergoing concurrent parathyroidectomy for primary or secondary 
hyperparathyroidism, lymph node clearance, or redo surgery. 
- Surgical procedures performed for other reasons than Graves' disease or AIT  
 
7. Information and consent of participants 
 
We will collect and analyze data routinely collected in clinical practice. The consent 
procedure at all Swiss sites are as followed:   
 Patients are informed through our documents entitled <General consent for the re-
use of health-related data and samples for research purposes.> (refer to the 
attached documents for all Swiss clinics except for hospital Männedorf). All study 
patients provide approved informed consent for the further use of their medical 
records and tissue samples using the general document from the Hospital 
 For clinics that do not have general consent for their clinics (e.g. Hospital of 
Männedorf and clinics abroad), the Eurocrine consent form is used as standard 
(German and English versions available, refer to attached documents). 
 If a patient does not agree to the General Consent of the Swiss sites using the 
General Consent, but agrees to the use of data related to the thyroid disease and 
treatment, the patient can be enrolled in the study by signing the Eurocrine Consent. 
 
8. Scientific methods and sample size 
 
As of March 2024, the European registry for endocrine surgery, EUROCRINE®, has 
documented 114,000 thyroid resections conducted across 141 centers in Europe. 
Among these, an estimated 1,800 cases per year underwent surgery for either Graves' 
disease or Amiodarone-induced thyrotoxicosis (AIT). 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 15/19 
Sample Size Calculation: 
 
The sample size for this non-inferiority study was determined based on the desired 
power (1-β), non-inferiority margin (δ), and expected complication rate (p). A 
significance level (α) of 0.05 was chosen for hypothesis testing. For this study, a desired 
power of 0.8 and a non-inferiority margin of 0.1 were selected. A different group 
distribution was calculated from the known group sizes of the retrospective studies [8-
10], assuming a distribution of 60% for the euthyroid, controlled group and 40% for the 
uncontrolled group, with an error margin of 10%. With an expected complication rate of 
0.25, the calculated total sample size was approximately 405 participants. The following 
formula for the sample size (n) for an unbalanced, two-sample non-inferiority test of 
proportions was used. 
 
𝑛 =
2 ∙൬𝑍ଵିఈ
ଶ+ 𝑍ఉ൰
ଶ
∙𝑝∙(1 −𝑝)
𝛿ଶ
 
 
 
  
To compare patient outcomes in controlled versus uncontrolled functional states, a 
sample size of 405 patients is necessary based on the given assumptions. To adjust for 
center variability and missing data, a correction factor of 1.2 will be applied, resulting in 
a final sample size of 486 patients. Data collection will continue for two years or until 
486 patients are included, with interim analysis after six months to confirm preliminary 
findings. Since slightly more European clinics are participating in the study than Swiss 
clinics, we assume a sample size of 230 patients for Switzerland. It must be 
acknowledged that this is merely an estimation, as the percentage of operations for 
Graves' disease and Amiodarone-induced thyrotoxicosis in relation to other thyroid 
operations in European clinics is not currently known. 
Statistical analyses will be performed using R version 4.2.1. The descriptive analyses 
will comprise measures of central tendency, dispersion, and location for quantitative 
variables, as well as frequency distributions for qualitative variables. Logistic regression 
will be used to compare the complication rate (primary endpoint) between preoperative 
thyroid function states (controlled versus uncontrolled) and determine if it is not 
significantly worse than the predefined margin, while adjusting for covariates such as 
age, gender, comorbidities such as congestive heart disease, BMI and ASA, and clinic 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 16/19 
volume. In addition, we will investigate a possible correlation between the occurrence of 
tachycardia and thyroid storm and free T3 and T4 levels. The level of statistical 
significance will be set at p < 0.05. 
The basis for our sample size calculation is based on retrospective data, as no 
comparable studies have been published to date. Wherever possible, we based our 
calculations on real-world values, such as complication rates, which we calculated from 
the EUROCRINE database. However, there is a potential for selection bias as we will 
be collecting data prospectively and have no control over the actual group sizes or 
differences. However, with the commitment of multiple centers across Europe, we are 
confident that we will achieve a balanced cohort and minimize the risk of selection bias. 
 
9. Reporting obligations 
The ethics committee must be notified of any change of project leader in advance. The 
completion or discontinuation of the research project must be reported to the ethics 
committee within 90 days. 
 
10. Data protection 
Uncoded data, coding and storage of the key 
 
The data is available in coded form from the Eurocrine registry. Every patient is coded 
under a unique participant number.This coded number is transmitted to the participating 
clinic and is stored in a secured file together with the clinic's patient identification 
number for internal identification of authorized personnel only. It should be noted that 
the intrahospital patient identification number is not transmitted to the Eurocrine 
Register.  
  
For all participating Swiss and International centers:  
The key to the code is kept in a secured file, available to the local study team only, as 
all members of this study are active in patient care in their Department of Thoracic, 
Visceral- and/or Endocrine Surgery. After completion of the study, the key list is stored 
in a secure, access-protected location at the respective hospital independently of the 
study team. 
Project data will be handled with uttermost discretion and will only be accessible to 
authorized personnel who require the data to fulfil their duties within the scope of the 
research project.  
 
The evaluation of all coded data will take place in Winterthur and the study team only 
has access to the coded data from the Eurocrine registry. No physical data of the 
included patients of all other clinics will leave their clinic.  
 
11. Information on the storage of data and samples 
 
Data generation, transmission, storage, and analysis of health-related personal data 
within this project will strictly follow the current Swiss and European legal requirements 
for data protection. This research project will be conducted in accordance with the 
protocol, the Declaration of Helsinki (3), the principles of Good Clinical Practice, the 
Human Research Act (HRA) (2) as well as other locally relevant regulations. Coding will 
safeguard participants’ confidentiality. 
  

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 17/19 
In order to facilitate the secure transfer of data extracted from Eurocrine, an invitation to 
transfer data is transmitted from Cantonal Hospital of Winterthur to Eurocrine via the 
secure data transfer portal, WebTransfer ZH (https://webtransfer.zh.ch/de/transfer). 
The original file with coded data received from the Eurocrine Registry will be duplicated 
to avoid any alteration or deletion. This list will be stored by the project leader (Andrea 
Goldmann, MD, Visceral- and Thoracic Surgery, Winterthur Cantonal Hospital). A 
backup copy is saved in a separate, secure folder on a second access-protected drive 
on the KSW server.  
All data will be recorded in a secure, password-protected Excel file. To be able to track 
all changes, the track change mode will be activated in Excel. Regularly updated and 
dated PDF copies of the data will be generated, each signed by the project leader. 
These copies will be safely store in a secured restricted location available exclusively to 
authorized personnel (study participants). To ensure confidentiality, data will be coded 
using the Eurocrine-based system.  
Only surgeons directly involved in patient care, will have access to Eurocrine, secured 
by 2-step personal identification, will have the key. This means that the study team of 
one center will only have access to the code and Eurocrine patient information of their  
respective center.   
 
12. Retention period 
 
Once the study is finished, coded data will be conserved 5 years in Winterthur Cantonal 
Hospital. 
 
13. Ethical and regulatory requirements 
 
Risk-benefit assessment:   
Given the purely observational nature of this project, the study does not expose patients 
to any harm. The study uses an already established data registry (Eurocrine®), the 
participating clinics are trained in the handling of patient data and security aspects and 
have been using the data registry for years. The study-specific additional variables 
module can be completed easily and with little additional effort, so we can expect a high 
and complete level of data entry. 
 
The primary advantages lie in this study’s potential to optimize pre-operative 
management of surgically treated patients with Graves' disease or AIT.  
The ability of the Eurocrine registry to achieve high case numbers with good quality 
data means that there is an opportunity to conduct multicenter studies to strengthen the 
evidence base for patient management. Until now, no prospective study has been 
conducted on this topic due to the large number of cases required. This is now possible 
and a great enrichment for our patients. We hope that the results of our study will allow 
us to optimize the treatment of our patients.   
 
This project complies with the regulatory requirements of the HRA and the HRO. The 
prerequisite for carrying out the research project is the approval of the competent ethics 
committee. 
 
 
 
 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 18/19 
14.  Results / transparency / publication 
 
The results can be generalized on a particular cohort: patients with surgically treated 
Graves' disease and Amiodarone-induced Thyrotoxicosis in a controlled or uncontrolled 
functional status.  
  
The results will be published in a peer- reviewed journal in an anonymized form (under 
the form of tables and results of statistical analysis) and available on PubMed.   
 
15. Funding / Data sharing / Declaration of interest 
 
No funding sources are currently available. There is no conflict of interest. The project 
sponsor from Winterthur (Dr. Andrea Goldmann) has planned to make a publication with 
the results. All involved clinics will be listed as co-authors. 
   
 
16. References 
1. Blick C, Nguyen M, Jialal I. Thyrotoxicosis. [Updated 2023 Jul 4]. In: StatPearls 
[Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: 
https://www.ncbi.nlm.nih.gov/books/NBK482216/ 
2. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association 
Guidelines for Diagnosis and management of hyperthyroidism and other causes of 
thyrotoxicosis. Thyroid 2016;26(10):1343–1421. 
3. Kahaly GJ. Management of Graves Thyroidal and Extrathyroidal Disease: An 
Update. J Clin Endocrinol Metab. 2020 Dec 1;105(12):3704–20. doi: 
10.1210/clinem/dgaa646. PMID: 32929476; PMCID: PMC7543578. 
4. Goldschlager N, Epstein AE, Naccarelli GV, Olshansky B, Singh B, Collard HR, 
Murphy E; Practice Guidelines Sub-committee, North American Society of Pacing 
and Electrophysiology (HRS). A practical guide for clinicians who treat patients with 
amiodarone: 2007. Heart Rhythm. 2007 Sep;4(9):1250-9. doi: 
10.1016/j.hrthm.2007.07.020. Epub 2007 Jul 20. Erratum in: Heart Rhythm. 2007 
Dec;4(12):1590. PMID: 17765636.Bogazzi F, Bartalena L, Martino E. Approach to 
the patient with amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab. 2010 
Jun;95(6):2529-35. doi: 10.1210/jc.2010-0180. PMID: 20525904. 
5. Bartalena, L., et al. (2016). "2018 European Thyroid Association (ETA) Guidelines 
for the Management of Amiodarone-Associated Thyroid Dysfunction." European 
Thyroid Journal. [Link zur Publikation] Bartalena L, Bogazzi F, Chiovato L, 
Hubalewska-Dydejczyk A, Links TP, Vanderpump M. 2018 European Thyroid 
Association (ETA) Guidelines for the Management of Amiodarone-Associated 
Thyroid Dysfunction. Eur Thyroid J. 2018 Mar;7(2):55-66. doi: 10.1159/000486957. 
Epub 2018 Feb 14. PMID: 29594056; PMCID: PMC5869486. 
6. American Thyroid Association: Surgical management of Graves’ disease . (2023). 
Accessed: 2023: http://www.thyroid.org/surgical-management-graves-disease/. 
7. Piantanida E: Preoperative management in patients with Graves' disease. Gland 
Surg. 2017, 6:476-81.10.21037/gs.2017.05.09 
8. Burch HB, Cooper DS. Management of Graves Disease: A Review. JAMA. 2015 
Dec 15;314(23):2544-54. doi: 10.1001/jama.2015.16535. Erratum in: JAMA. 2016 
Feb 9;315(6):614. PMID: 26670972. 
9. Fazendin J, Zmijewski P, Allahwasaya A, McLeod C, Akhund R, Gillis A, Ramonell 
K, Porterfield J, Chen H, Lindeman B. Surgical Treatment of Hyperthyroidism Can 

 
GRATE Study, BASEC 2024-01766, Version 2.0; 17.11.2024  
 
Page 19/19 
Be Performed Safely Before a Euthyroid State is Achieved. Thyroid. 2023 
Jun;33(6):691-696. doi: 10.1089/thy.2022.0392. Epub 2023 May 30. PMID: 
37253173. 
10. Akram S, Elfenbein DM, Chen H, Schneider DF, Sippel RS. Assessing American 
Thyroid Association Guidelines for Total Thyroidectomy in Graves' Disease. J Surg 
Res. 2020 Jan;245:64-71. doi: 10.1016/j.jss.2019.07.029. Epub 2019 Aug 8. PMID: 
31401249; PMCID: PMC7108813.  
11. Shinall MC Jr, Broome JT, Nookala R, Shinall JB, Kiernan C, Parks L 3rd, Solórzano 
CC. Total thyroidectomy for Graves' disease: compliance with American Thyroid 
Association guidelines may not always be necessary. Surgery. 2013 
Nov;154(5):1009-15. doi: 10.1016/j.surg.2013.04.064. Epub 2013 Sep 26. PMID: 
24075271; PMCID: PMC4167905.  
12. Al Jassim A, Wallace T, Bouhabel S, et al. A retrospective cohort study: do patients 
with graves’ disease need to be euthyroid prior to surgery? J Otolaryngol Head Neck 
Surg 
2018; 47: 37 
13. Akamizu T, Satoh T, Isozaki O, et al. Diagnostic criteria, clinical features, and 
incidence of thyroid storm based on nationwide surveys. Thyroid 2012;22(7):661–
679. 
14. Burch HB, Wartofsky L. Life-threatening Thyrotoxicosis. Thyroid storm. Endocrinol 
Metab Clin North Am. 1993;22(2):263-77 
15. de Mul N, Damstra J, Nieveen van Dijkum EJM, Fischli S, Kalkman CJ, Schellekens 
WM, Immink RV. Risk of perioperative thyroid storm in hyperthyroid patients: a 
systematic review. Br J Anaesth. 2021 Dec;127(6):879-889. doi: 
10.1016/j.bja.2021.06.043. Epub 2021 Aug 11. PMID: 34389171