Clinical trial NCT05784792: Clinical and Surgical Outcomes of Total Thyroidectomy in Basedow's Disease: the Effect of Lugol Solution
Official title: Clinical and Surgical Outcomes of Total Thyroidectomy in Basedow's Disease: the Effect of Lugol Solution
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Basedow Disease
Keywords: Lugol Solution
Total Thyroidectomy
Lead sponsor: University of Padova
Sponsor class: OTHER
First posted: 2023-03-27
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Case-Control study
Primary purpose: TREATMENT

Brief summary: Preoperative preparation of patient with Basedow's disease is crucial to avoid severe thyrotoxicosis resulting from leakage of thyroid hormone into the circulation at the time of surgery. Moreover, hyperthyroidism-related hypervascularization and tissue fragility caused by Basedow's disease thyroiditis may cause intraoperative bleeding that can reduce the visualization and preservation of parathyroid glands and laryngeal nerves with subsequent higher risk of related morbidity including neck hematoma, hypoparathyroidism and vocal cords paresis. Although some endocrine surgeons administer before surgery Lugol solution to decrease thyroid gland vascularity in Basedow's disease, there is still not an agreement on its effectiveness.

The aims of the present trial are to evaluate the impact of pre-operative short-term Lugol solution treatment (7 days) on surgical outcomes through modification of thyroid vascularity and surgical related morbidity, in patients with Basedow's disease.

Detailed description: The study will investigate the effects of Lugol solution treatment before surgery on thyroid vascularity and tissue fragility in patients with Basedow's disease, and if these changes are associated or not with different surgical outcomes.

Hyperthyroidism is associated with hemodynamic changes, decreasing peripheral resistance that are related to both direct cardio-stimulatory effects of thyroid hormone. Preoperative preparation of the patient is crucial to avoid intra-operative or postoperative thyroid storms and to decrease the vascularity of the gland.

Inorganic iodide (Lugol solution) decreases the synthesis of thyroid hormone and release of hormone from the thyroid in the short term. Iodine also seems to reduce thyroid cellularity and vascularity and therefore is used in the preparation of patients for thyroidectomy. This effect transiently blocks thyroid hormone generation, with thyroid hormone synthesis recovering in few days.

On this matter doppler techniques seem to be the best method to evaluate blood flow in the thyroid gland.

Thyroid vascularity in Basedow's disease patients can be evaluated by monitoring CD-34 and CD-31 expression using immunohistochemistry. The vascular density of different tissues has been assessed by counting vessels labeled using immunohistochemistry with antibodies against different endothelial markers on paraffin-embedded sections. Antibodies that are most commonly used are directed against the endothelial antigens factor eight-related antigen, CD-31 (platelet endothelial cell adhesion molecule), CD-34. CD-34 is the most sensitive and specific marker currently available for the detection of angiogenesis. The use of these markers reflects total vascular density.

Moreover some authors showed that iodide inhibits vascular endothelial growth factor (VEGF) expression in cultured human thyroid follicles, and, consequently, they suggest that pro-angiogenic and anti-angiogenic factors may at least partly account for the iodide-induced decrease in thyroid blood flow. Cross-talk between angiogenesis and inflammation has also been reported. T cells can deliver VEGF to inflammatory sites and VEGF can augment pro-inflammatory T cell differentiation and promote angiogenesis.

So the detection of VEGF could be useful in the demonstration of Lugol effect on pretreated patients.

Investigators hypothesize that Lugol solution might act through different mechanisms. It probably decreases both angiogenic stimuli and blood flow in Basedow's disease. Decreased angiogenesis and blood flow resulted in a significantly decreased number of visible vessels. Therefore, it is reasonable to think that increased vascular density could reflect increased angiogenic input to this disease. Lugol solution could also act directly to vessels wall, changing arteries and veins lumen.

These modifications could cause a reduction of intra-operative bleeding that could allow better visualization and preservation of the surrounding nerves, vasculature, and parathyroid glands and so better surgical and clinical outcomes.

Eligibility criteria: Inclusion Criteria:

* diagnosis of Basedow disease candidate to total thyroidectomy
* age\>18 years

Exclusion Criteria:

* age\<18 years;
* presence of solitary toxic nodule
* fine-needle aspiration biopsy result indicating cancer or suspicious cytology
* anticoagulant usage or coagulation disorders
* a previous thyroid operation
* pregnancy

Primary outcomes:
measure: Intra and post-operative blood loss (mL).
timeFrame: Intra and post-operative bleeding (1st and 2nd day after surgery)
Secondary outcomes:
measure: Post-operative laryngeal nerves palsy.
timeFrame: Laryngeal ultrasound on 1st and 2nd day and indirect laryngoscopy in case of dysphonia
measure: Intra and post-operative thyrotoxicosis.
timeFrame: During surgery and on 1st and 2nd day after surgery
measure: Post-operative hypocalcemia (hypoparathyroidism, hungry bone syndrome).
timeFrame: Blood sample on 1st and 2nd day after surgery.
Other outcomes:
measure: Change of ultrasound thyroid vascularization: blood flow velocity (v) variation (mm/sec).
timeFrame: Thyroid US doppler data: 7 days before surgery and the day before surgery (after 1 week).
measure: Change of ultrasound thyroid vascularization: resistance index (RI) variation.
timeFrame: Thyroid US doppler data: 7 days before surgery and the day before surgery (after 1 week).
measure: Change of ultrasound thyroid vascularization: pulsatility index (PI) variation
timeFrame: Thyroid US doppler data: 7 days before surgery and the day before surgery (after 1 week).
measure: Change of US thyroid volume (mL).
timeFrame: Thyroid US doppler data: 7 days before surgery and the day before surgery (after 1 week). Intra-operative thyroid volume detection (the day of surgery).
measure: Change of thyroid tissue: immunohistochemical evaluation of thyroid tissue mean vessels density.
timeFrame: Post-operative pathological and immunoistochemical data recorded (in 30 days after surgery).
measure: Change of thyroid vascularization stimuli: VEGF levels variation (pg/mL).
timeFrame: Blood samples: 7 days before surgery and the day before surgery (after 1 week).
measure: Change of thyroid function and biochemical data: FT3 and FT4 variation (pmol/L).
timeFrame: Blood samples: 7 days before surgery and the day before surgery (after 1 week).
measure: Change of thyroid function and biochemical data: TSH variation (mIU/L).
timeFrame: Blood samples: 7 days before surgery and the day before surgery (after 1 week).
measure: Change of thyroid function and biochemical data: Ab anti TG, Ab anti TPO, Ab anti TSH variation (U/L).
timeFrame: Blood samples: 7 days before surgery and the day before surgery (after 1 week).
Locations:
city: Padova
country: Italy
facility: Azienda Università di Padova, Endocrine Surgery Unit
state: PD
Study officials:
affiliation: University of Padova
name: Maurizio Iacobone, Prof
role: STUDY_DIRECTOR
References:
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