Post-thyroidectomy Vocal Cord Paralysis Along With Hypocalcemia: STROBE - Guided Prospective Cohort

Post-thyroidectomy Vocal Cord Paralysis Along With Hypocalcemia: Prospective, Matched-randomized Observational Cohort Compatible With STROBE Guidelines

In the present study, the severity of recurrent laryngeal nerve injury (RLNI) and hypocalcemia (H) will be followed-up and the probable interrelation between them will be proposed considering the clinical situation of patients, e.g. improvement in hypocalcemia also make a positive effect on voice? (any objective sign? Ca? PTH?), return of voice is parallel with the improvement in hypocalcemia? Postoperative calcium (Ca), parathyroid hormone (PTH), regular vocal cord evaluations by ear-nose-throat (ENT) exams, deterioration-stability-improvement of clinical symptoms regarding both Ca metabolism and vocal cord function will be noted at regular intervals (postoperative day 1-3-first, weekly control/first month, monthly/first 6-month, 3-monthly/6-12 months) at outpatient controls. Serum Ca, PTH, ENT evaluation of vocal cords-noted.

Study Overview

• Status: Unknown
• Conditions: Thyroid Neoplasms; Thyroid Cancer, Papillary; Vocal Cord Paralysis; Thyroid Cancer; Thyroid Nodule; Vocal Cord Paresis; Multinodular Goiter; Iatrogenic Hypocalcemia; Calcium Deficiency; Iatrogenic Hypoparathyroidism; Vocal Cord; Injury, Superficial; PTH
• Intervention / Treatment: Procedure: Total thyroidectomy

Detailed Description

Total thyroidectomy is currently the preferred surgical treatment modality for both thyroid carcinomas and benign disorders such as multinodular goitre, since it minimizes the risk of recurrence and eliminates the complication risks of repeat or completion surgery. Vocal cord paralysis due to injury to recurrent laryngeal nerve (RLN) is the most dreaded complication of total thyroidectomy. The reported incidence of temporary RLN injury (RLNI) varies between 0 and 12 %, while the incidence of permanent RLNI has been reported to be much lower (0-3.5 %). In case of bilateral RLNI, respiratory distress and aspiration can develop rapidly and may result in mortality. Therefore, all precautions including close monitoring and tracheostomy should be undertaken without any delay. The best known technique to avoid injury to RLN is meticulous dissection of the nerve throughout its anatomic pathway. However, functional impairment of RLN is not visible macroscopically and intraoperative nerve monitoring (IONM) has been developed to monitor the nerve to avoid unnecessary dissection. Meticulous hemostasis can be achieved with harmonic sealing instrument, since improper hemostasis is known to increase the risk of RLNI. Despite the lack of evidence to support an advantage of IONM over the standard anatomic dissection of RLN, surgeons have adopted it in increasing ratios. The second most feared compliation of thyroidectomy is iatrogenic hypocalcemia. Transient symptomatic hypocalcemia after total thyroidectomy occurs in approximately 7% to 25% of cases, but permanent hypocalcemia is less common (0.4% to 13.8%). Size and invasion of tumor, operative trauma and vascular compromise determines the severity of symptoms.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34764
    • Recruiting
    • Umraniye Education and Research Hospital, Health Sciences University
    • Contact: Ethem UNAL, MD, PhD, USMLE & IFSO- Certified Board CSS; Phone Number: 1951 0090(216)6321818; Email: drethemunal@gmail.com
    • Contact: Kadir M YILDIRAK, MD; Phone Number: 1951 0090(216)6321818; Email: kadiryildira@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with benign or malign thyroid diseases, eligable for total thyroidectomy

Description

Inclusion Criteria:

• Patients with total thyroidectomy indication, for either benign (e.g. multinodular goitre) or malign (e.g. thyroid carcinoma) thyroid disease
• >17 year-old
• Available for close follow-ups at outpatient clinic
• Available for close vocal cord exams

Exclusion Criteria:

• Patients with recurrent thyroid disease (benign/malign), prepared for a second operation
• Preferance of thyroid surgery other than total thyroidectomy

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control, s/p TT, without complication; Control (status/post-s/p total thyroidectomy-TT, without complication- demographics and BMI matched)	Procedure: Total thyroidectomy; Patients with thyroid diseases either benign (e.g. multinodular goitre) or malign (e.g. thyroid carcinoma) will be prepared for total thyroidectomy procedure and will be enrolled.
Experimental, s/p TT with only VCP; Experimental (s/p TT, with only vocal cord paralysis-VCP, uni or bilateral)	Procedure: Total thyroidectomy; Patients with thyroid diseases either benign (e.g. multinodular goitre) or malign (e.g. thyroid carcinoma) will be prepared for total thyroidectomy procedure and will be enrolled.
Experimental, s/p TT with only H; Experimental (s/p TT, with only hypocalcemia-H, transient or permanent)	Procedure: Total thyroidectomy; Patients with thyroid diseases either benign (e.g. multinodular goitre) or malign (e.g. thyroid carcinoma) will be prepared for total thyroidectomy procedure and will be enrolled.
Experimental, s/p TT with both VCP+H; Experimental (s/p TT, with both vocal cord paralysis-VCP and hypocalcemia-H); Subgroups: 4.1. VCP (Permanent) + H (Permanent) 4.2. VCP (Transient) + H (Transient) 4.3. VCP (Permanent) + H (Transient) 4.4. VCP (Transient) + H (Permanent) Please answer: Improvement in hypocalcemia also make a positive effect on voice? (any objective sign? Ca? PTH?); Return of voice is parallel with the improvement in hypocalcemia? (any objective sign? Ca? PTH?	Procedure: Total thyroidectomy; Patients with thyroid diseases either benign (e.g. multinodular goitre) or malign (e.g. thyroid carcinoma) will be prepared for total thyroidectomy procedure and will be enrolled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
s/p TT- normal (no complication)	TT: total thyroidectomy	June 01, 2020-June 01, 2021
s/p TT+VCP	VCP: vocal cord paralysis	June 01, 2020-June 01, 2021
s/p TT+H	H: hypocalcemia	June 01, 2020-June 01, 2021
s/p TT+VCP+H	Any improvement recorded? VCP? H? vice versa	June 01, 2020-June 01, 2021

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in vocal cord function /serum calcium	VCP+H	June 01, 2020-June 01, 2021

Collaborators and Investigators

• Sponsor: Umraniye Education and Research Hospital
• Investigators: Study Chair: Ethem UNAL, MD, PhD, USMLE & IFSO-Certified, Board CSS, Assoc. Professor of General Surgery and Surgical Oncology

Publications and helpful links

General Publications

• Cuschieri S. The STROBE guidelines. Saudi J Anaesth. 2019 Apr;13(Suppl 1):S31-S34. doi: 10.4103/sja.SJA_543_18.
• Giulea C, Enciu O, Toma EA, Calu V, Miron A. The Tubercle of Zuckerkandl is Associated with Increased Rates of Transient Postoperative Hypocalcemia and Recurrent Laryngeal Nerve Palsy After Total Thyroidectomy. Chirurgia (Bucur). 2019 Sept-Oct;114(5):579-585. doi: 10.21614/chirurgia.114.5.579.

Helpful Links

• STROBE guidelines
• Ethem Unal, MD, PhD (h-inde 18, i10-index 33)
• VCP
• TT complications

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 15, 2020
• Primary Completion (ANTICIPATED): June 1, 2021
• Study Completion (ANTICIPATED): June 1, 2021

Study Registration Dates

• First Submitted: May 15, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (ACTUAL): May 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 15, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Total thyroidectomy
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neurologic Manifestations; Endocrine System Diseases; Endocrine Gland Neoplasms; Parathyroid Diseases; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Cranial Nerve Diseases; Calcium Metabolism Disorders; Water-Electrolyte Imbalance; Adenocarcinoma, Papillary; Laryngeal Diseases; Vagus Nerve Diseases; Thyroid Diseases; Paralysis; Thyroid Neoplasms; Paresis; Thyroid Cancer, Papillary; Vocal Cord Paralysis; Thyroid Nodule; Hypoparathyroidism; Hypocalcemia
• Other Study ID Numbers: B.10.1TKH.4.34.H.GP0.01/1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Study is open to high-volume INTERNATIONAL endocrine surgery centers, eager to join to present STROBE compatible observational study

Available upon email requests@drethemunal@gmail.com

• IPD Sharing Time Frame: From June 01, 2020, for 6 months
• IPD Sharing Access Criteria: Contact to drethemunal@gmail.com
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No