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. 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. Amiodarone is
a class III antiarrhythmic drug used to treat supraventricular and ventricular
arrhythmias, and to maintain sinus rhythms after cardioversion of atrial fibrillation.
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. 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.
Thyroidectomy for Graves' disease or AIT presents unique disease-specific challenges,
potentially resulting in elevated perioperative complication rates when compared to other
indications. 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. Nevertheless, data from retrospective studies show that between
21-51% of patients undergo surgery when euthyroidism is not stable or cannot be achieved.
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.
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. The study hypothesis is 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".
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.
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".
The 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.
Design:
The investigatiors 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 entered prospectively into the online registry in encrypted form, which
is the standard for the Eurocrine® registry. For the Eurocrine® registry itself a
declaration of no objection has been issued in May 2017 for Switzerland (2017-00683). The
clinics participating in the study do this part of the data entry unchanged from 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. The investigators 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", the investigators opted to utilize the
established Japanese Association classification, which is deemed more suitable for
clinical settings compared to the "Burch and Wartofsky" scale.
Origin of the data:
The investigators 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.
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 registry, data is routinely recorded up
to six months postoperatively in the event of complications occurring during treatment.
This period also corresponds to that of the study project.
It is planned to run the study for 2 years and the study 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.
Information and consent of participants:
The investigators will collect and analyze data routinely collected in clinical practice.
The consent procedure at all Swiss sites are as followed:
Patients are informed through the documents entitled <General consent for the re-use of
health-related data and samples for research purposes.>. 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, the Eurocrine consent form is used as
standard (German and English versions available).
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.