Clinical and Surgical Outcomes of Total Thyroidectomy in Basedow's Disease: the Effect of Lugol Solution

NCT ID: NCT05784792

Last Updated: 2024-03-20

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-01
• Study Completion Date: 2024-04-26

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.

Conditions

Basedow Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Lugol -

No pre-operative Lugol Solution preparation

Group Type: NO_INTERVENTION

No interventions assigned to this group

Lugol +

Pre-operative Lugol preparation (10 drops per day orally three times a day for 7 days for an amount of 10,5 ml of Lugol solution that contains 1,68 gr of Iodine).

Group Type: ACTIVE_COMPARATOR

Lugol -

Intervention Type: OTHER

Patients that undergo total thyroidectomy without Lugol solution pretreatment

Interventions

Lugol -

Patients that undergo total thyroidectomy without Lugol solution pretreatment

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Padova

OTHER

Sponsor Role: lead

Responsible Party

Maurizio Iacobone

MD, FEBS (Endocrine Surgery), Associate Professor, Head in Chief of Endocrine Surgery Unit of Padua University Hospital, Italy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maurizio Iacobone, Prof

Role: STUDY_DIRECTOR

University of Padova

Locations

Azienda Università di Padova, Endocrine Surgery Unit

Padua, PD, Italy

Countries

Italy

References

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Reference Type: RESULT

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Reference Type: RESULT

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Schiavone D, Crimi F, Cabrelle G, Pennelli G, Sacchi D, Mian C, Torresan F, Iacobone M. Role of Lugol solution before total thyroidectomy for Graves' disease: randomized clinical trial. Br J Surg. 2024 Aug 2;111(8):znae196. doi: 10.1093/bjs/znae196.

Reference Type: DERIVED

PMID: 39129619 (View on PubMed)

Other Identifiers

UPd39962

Identifier Type: -

Identifier Source: org_study_id