Higher Post-operative Levothyroxine Substitution Dose Needed in Right Compared to Left Lobe Hemithyroidectomy - a Retrospective Cohort Study
Conditions: Hemithyroidectomy, Hypothyroidism
Sponsor: Medical University of Vienna

 
Differences in Levothyroxine requirements after hemithyroidectomy 
 
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Differences in incidence of hypothyroidism and 
levothyroxine dosages in relation to right or left lobe 
hemithyroidectomy 
 
- An exploratory retrospective study  
 
 
 
 
Version 1.1 
February 20th 2020 
 
 
Applicant: 
Dr.med.univ. Carola Deischinger1 
Carola.deischinger@meduniwien.ac.at 
 
Principal investigator: 
Dr. Lana Kosi-Trebotic1 
Phone: +43 (1) 40400 20690  
E-mail: lana.kosi-trebotic@meduniwien.ac.at 
 
Subinvestigators: 
Dr.med.univ. Carola Deischinger1 
Univ. Prof. Dr. Christian Scheuba² 
 
1Med. Univ of Vienna, Dep. of Internal Medicine III, Division of Endocrinology and 
Metabolism, Gender Medicine Unit 
² Med. Univ of Vienna, Dep. of General Surgery, Division of Endocrine Surgery 

 
Differences in Levothyroxine requirements after hemithyroidectomy 
 
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Table of contents 
 
1 
Background ......................................................................................................... 3 
2 
Research questions and aims ............................................................................. 4 
3 
Study design ........................................................................................................ 4 
4 
Patients ............................................................................................................... 4 
4.1 
Inclusion criteria............................................................................................. 4 
4.2 
Exclusion criteria ........................................................................................... 4 
5 
Primary and secondary parameters..................................................................... 5 
6 
Methodology ........................................................................................................ 5 
6.1 
Statistical analysis ......................................................................................... 5 
6.1.1 
Null hypothesis ........................................................................................ 6 
6.1.2 
Secondary hypotheses ........................................................................... 6 
6.1.3 
Number of patients .................................................................................. 6 
7 
Data protection .................................................................................................... 6 
8 
Benefit-risk assessment ...................................................................................... 6 
9 
References .......................................................................................................... 7 
10 Appendix ............................................................................................................. 7 
10.1 
Abbreviations and acronyms: ..................................................................... 7 
 

 
Differences in Levothyroxine requirements after hemithyroidectomy 
 
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1 
Background 
Thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are produced in the 
follicular cells of the thyroid gland and can impact nearly every cell in the human 
body. They are essential to the human metabolism, influence the basal metabolic 
rate, bone growth, neural maturation, the body's sensitivity to catecholamines, cell 
development and differentiation as well as protein, fat and carbohydrate metabolism. 
With about 5000 µg, the thyroid is the largest storage of T4.1(p303) Therefore, the 
maintenance of adequate thyroid hormones levels is crucial for the patient’s quality of 
life after a hemithyroidectomy. The thyroid is constituted of a right and a left lobe as 
well as a connecting isthmus. In most patients, the right lobe is significantly larger 
than left lobe.2 In a 2009 study by Ying and Yung, the right lobe was 6.8ml as 
opposed to the left lobe with a volume of 5.66ml.3 Although the remaining lobe 
adapts and continues to grow up to 30% from its original size to compensate for the 
loss,4, thyroid hormone supplementation is required in approximately 22% of all 
patients after thyroid lobectomy.5,6 In order to predict the necessity of thyroid 
hormone replacement therapy after hemithyroidectomy, risk factors such as a higher 
TSH before surgery, but also the resected thyroid volume have been identified in the 
past. Surprisingly, the resected thyroid volume showed significant negative 
correlation with postoperative TSH levels in a 2015 study by Lee et al.5 Previous 
studies aiming at optimizing post-surgery levothyroxine dosages incorporated sex, 
age, body surface area (BSA) and body mass index (BMI) but not if the right of left 
thyroid gland was resected into their calculations.7,8 Therefore, the study at hand 
aims at investigating a possible difference in levothyroxine requirements depending 
on the side of the resection to ensure adequate treatment. 

 
Differences in Levothyroxine requirements after hemithyroidectomy 
 
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2 
Research questions and aims 
- 
Research Questions: We hypothesize a possible influence of right vs left 
hemithyroidectomy on developing postoperative hypothyroidism as well as 
treatment dosage. 
 
- 
The aim of this study is to be able to better predict the necessity, dosage and 
starting point of levothyroxine treatment after a hemithyroidectomy.  
 
3 
Study design 
The study at hand is an exploratory retrospective study conducted on approximately 
1250 patients who received a hemithyroidectomy at the Medical University of Vienna, 
Department of General Surgery, Division of Endocrine Surgery. A possible 
confounding factor is that the underlying conditions such as goiter or nodules which 
lead to the surgery might differ in the patients.  
 
4 
Patients 
All patients who received a hemithyroidectomy at the Department of General 
Surgery, Division of Endocrine Surgery between 1994 and 2018 will be included in 
the study which are around 50 per year totalling around 1250 patients. Due to the 
study design, no power calculations have been conducted beforehand. However, 
considering similar studies5,6, this sample size was deemed sufficient in order to 
achieve valid results and a statistical power of 0.8.  
4.1 Inclusion criteria 
➢ 18 years 
➢ Males and females 
➢ St.p. hemithyroidectomy 
4.2 Exclusion criteria 
➢ Radiation therapy 
➢ Pregnancy 
➢ Previous thyroid surgery (e.g. nodule removal surgery) 

 
Differences in Levothyroxine requirements after hemithyroidectomy 
 
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5 
Primary and secondary parameters 
The occurrence of post-surgery hypothyroidism and levothyroxine dosage is the 
primary outcome parameter. The secondary outcome parameter is the timespan 
between hemithyroidectomy and the need for levothyroxine treatment.  
 
6 
Methodology 
The list of patients who underwent a hemithyroidectomy will be provided by the 
IT4Science department via a data extraction from the RDA database. Further 
information necessary for the analysis (side of hemithyroidectomy, type and dosage 
of treatment) will be extracted from the AKH-Informationsmanagement (AKIM) at the 
General Hospital of Vienna (AKH), analyzed and pseudonymized by Dr. Carola 
Deischinger 
and, 
then, 
safely 
secured 
on 
a 
server 
at 
the 
Chiari 
Stoffwechselambulanz. 
6.1 Statistical analysis 
The collected data will be analyzed by descriptive statistics and illustrated in SPSS 
(Version 22) by using graphs, tables and boxplots. All data is password protected and 
anonymized to ensure adequate privacy protection.  
Normally distributed data will be described by calculating median, mean and standard 
deviation. Patient baseline characteristics will be described as percentages and 
frequencies for categorical variables or mean and median values and standard 
deviation for normally distributed continual variables. In order to ensure 
comparability, a Levene’s Test for Equal Variances will be performed. Differences of 
characteristics between the groups will be analyzed by unpaired T- tests for 
continuous variables. Possible confounding factors such as age, sex, underlying 
disease and BMI will be identified and adjusted for in a multiple logistic regression 
model. 
In order to compare the levothyroxine dosages, a parametrical test (t-test) with a 
significance level of p<0.05 will be performed. Adequate transformations such as the 
Levene’s Test for Equal Variances will be applied to deal with not normally distributed 
residues and, thus, ensure comparable variances. For illustrational purposes, bar 
charts, histograms and boxplots will be used. 
 

 
Differences in Levothyroxine requirements after hemithyroidectomy 
 
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6.1.1 
Null hypothesis 
H0: The side of the resected thyroid lobe in a hemithyroidectomy does not influence 
the hypothyroidism occurrence and levothyroxine dosage requirements after surgery. 
6.1.2 
Secondary hypothesis 
H0: There are no sex differences between men and women depending on the side of 
the resected thyroid lobe in the occurrence of hypothyroidism and the needed 
levothyroxine dosage after a hemithyroidectomy. 
 
6.1.3 
Number of patients 
Approximately 1250 patients 
 
7 
Data protection  
 
Various measures will be implemented to ensure data protection and avoid 
unauthorized use and loss of data. Data will be stored on a secure server at the 
Medical University of Vienna, Chiari Stoffwechselambulanz which is password 
protected and kept in a locked room. Only authorized personnel have access to the 
Chiari Stoffwechselambulanz and the server. A full description of the technical and 
organizational measures can be provided on request. Data protection for this study is 
the responsibility of Dr. Carola Deischinger. 
 
8 
Benefit-risk assessment 
Although there is no direct benefit for the patients due to the retrospective character 
of the study, negative side effects are not to be expected as well. Besides a possible 
data breach, which is minimized by pseudonymization and data protection, the 
patients are not at risk in any way. The results obtained in this study can be used to 
optimize patient care. 

 
Differences in Levothyroxine requirements after hemithyroidectomy 
 
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9 
References 
1.  
Kronenberg HM, Melmed S, Polonsky KS, Reed Larsen P. Williams Textbook 
of Endocrinology. Edition 11. Philadelphia: Elsevier Inc.; 2008. 
2.  
Ying M, Sin M, Pang S. Sonographic measurement of thyroid gland volume: A 
comparison of 2D and 3D ultrasound. Radiography. 2005;11(4):242-248. 
doi:10.1016/j.radi.2005.03.010 
3.  
Ying M, Yung DMC. Asymmetry of thyroid lobe volume in normal Chinese 
subjects: Association with handedness and position of esophagus. Anat Rec. 
2009;292(2):169-174. doi:10.1002/ar.20803 
4.  
Pustelnik FS, Gronbek C, Døssing H, et al. The compensatory enlargement of 
the remaining thyroid lobe following hemithyroidectomy is small and without 
impact on symptom relief. Eur Arch Oto-Rhino-Laryngology. 2018;275(1):161-
167. doi:10.1007/s00405-017-4777-3 
5.  
Lee DY, Seok J, Jeong WJ, Ahn SH. Prediction of thyroid hormone 
supplementation after thyroid lobectomy. J Surg Res. 2015. 
doi:10.1016/j.jss.2014.07.003 
6.  
Verloop H, Louwerens M, Schoones JW, Kievit J, Smit JWA, Dekkers OM. Risk 
of Hypothyroidism following Hemithyroidectomy: Systematic Review and Meta-
Analysis of Prognostic Studies. J Clin Endocrinol Metab. 2012;97(7):2243-
2255. doi:10.1210/jc.2012-1063 
7.  
Jin J, Allemang MT, McHenry CR. Levothyroxine replacement dosage 
determination after thyroidectomy. Am J Surg. 2013;205(3):360-364. 
doi:10.1016/j.amjsurg.2012.10.015 
8.  
Mistry D, Atkin S, Atkinson H, et al. Predicting thyroxine requirements following 
total thyroidectomy. Clin Endocrinol (Oxf). 2011;74(3):384-387. 
doi:10.1111/j.1365-2265.2010.03940.x 
 
10 Appendix 
10.1 Abbreviations and acronyms:  
BMI – Body mass index 
BSA – Body surface area 
SPSS - Statistical Package for the Social Sciences