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Seo, Chung, Kang, Kim, Cheon, Paeng, Lee, Park, Park, and Choe: High Serum Levels of Thyroid-Stimulating Hormone and Sustained Weight Gain in Patients with Thyroid Cancer Undergoing Radioiodine Therapy
Original Article

Int J Thyroidol 2016;9(1):19-28.

Published online: 20 May 2016

DOI: https://doi.org/10.11106/ijt.2016.9.1.19

High Serum Levels of Thyroid-Stimulating Hormone and Sustained Weight Gain in Patients with Thyroid Cancer Undergoing Radioiodine Therapy

Hyo Jung Seo1, June-Key Chung2, , Keon Wook Kang2, E. Edmund Kim2, 5, Gi Jeong Cheon2, Jin Chul Paeng2, Dong Soo Lee2, 4, Young Joo Park3, Do Joon Park3, Jae Gol Choe1

1Department of Nuclear Medicine, Korea University College of Medicine, Seoul, Korea

2Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea

3Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

4Department of Molecular Medicine and Biopharmaceutical Sciences, WCU Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea

5University of California, Irvine, California, USA

Correspondence: June-Key Chung, MD, Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: 82-2-2072-3376, Fax: 82-2-745-7690, E-mail: jkchung@snu.ac.kr

Received 6 August 2015       Revised 21 April 2016       Accepted 25 April 2016

Copyright © 2016 Korean Thyroid Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background and Objectives

The extent of weight gain and its association with clinical factors in patients undergoing radioiodine therapy for differentiated thyroid cancer remain unclear. We analyzed clinical factors related to sustained weight gain after serum thyroid-stimulating hormone (TSH) stimulation for radioiodine (I-131) therapy.

Materials and Methods

The study population included 301 adult patients who underwent total thyroidectomy followed by radioiodine therapy and visited the thyroid clinic regularly. Group 1 received a single radioiodine therapy treatment, while group 2 received multiple radioiodine treatment. Data on transient weight gain, defined as weight gain that resolved (±5%) within 1 year after radioiodine therapy, were collected from medical records. Sustained weight gain was defined as body mass index after treatment (BMI post) – BMI before treatment (BMI pre) ≥2 kg/m2 more than 1 year following radioiodine therapy. Subjective symptoms were scored by questionnaire. Logistic regression analysis was performed using various clinical and laboratory factors to identify risk factors associated with sustained weight gain.

Results

Two hundred and fifty-nine (86%) patients showed transient weight gain and 23 (8%) patients showed sustained weight gain. TSH at therapy and T4-on TSH differed significantly in all patients and in the patients in group 1 with sustained weight gain. The proportion of patients with basal BMI≥25 kg/m2 in group 1 with sustained weight gain also differed significantly. Univariate analysis revealed that high serum levels of TSH at therapy (≥100 μ IU/mL) and hypercholesterolemia were associated with sustained weight gain in group 1. Multivariate analysis showed that TSH at therapy levels ≥100 μ IU/mL was associated with sustained weight gain in group 1. Of 283 patients remaining after excluding those with insufficient TSH suppression during follow-up, T4-on TSH levels were lower in the sustained weight gain group compared to those without sustained weight gain. TSH at therapy levels ≥100 μ IU/mL were significantly associated with sustained weight gain in multivariate analysis.

Conclusion

Most patients (86%) had transient weight gain after TSH at therapy, while 8% of patients showed sustained weight gain. Univariate and multivariate analysis revealed relatively high TSH levels (≥100 μ IU/mL) to be a risk factor for patients that received a single dose of radioiodine therapy. Insufficient T4 dose was not associated with sustained weight gain.

Keywords: Radioiodine therapy, I-131, Weight gains, TSH at therapy, Hypercholesterolemia

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Fig. 1.
Number of patients with and without sustained weight gain according to subjective symptom scores. Subjective discomfort scores were categorized using a visual analog scale: 1, none; 2, mild; 3, moderate; 4, severe; and 5, extreme discomfort. The numbers of patients with and without sustained weight gain for each score were: 115 vs. 2 (1.7%) in score 1, 42 vs. 4 (8.7%) in score 2, 97 vs. 3 (3%) in score 3, 22 vs. 8 (26.7%) in score 4, and 2 vs. 6 (75%) in score 5.
ijt-9-19f1.tif
Fig. 2.
ROC curves for the evaluation TSH cutoff values. (A) The TSH at therapy cutoff value overall was 87.35 μ IU/mL (sensitivity 100 and specificity 27.17). (B) The TSH at therapy cutoff value in group 1 was 100 μIU/mL (sensitivity 100 and specificity 47.54). (C) The T4-on TSH cutoff value overall was 1.73 μIU/mL (sensitivity 30.43 and specificity 82.37). (D) The T4-on TSH cutoff value in group 1 was ＞0.90 μ IU/mL (sensitivity 100 and specificity 27.17).
ijt-9-19f2.tif
Fig. 3.
TSH at therapy levels differed significantly between patients in group 1 with (185.8±109.9 μ IU/mL) and without sustained weight gain (112.9±62.4 μIU/mL) (p=0.015). The central box in the plot represents the TSH at therapy values from the lower to upper quartiles (25 to 75 percentiles). The middle line represents the median of stimulated TSH. The horizontal line extends from the minimum to the maximum value, excluding outlier values, which are displayed as separate points.
ijt-9-19f3.tif
Fig. 4.
Proportions of sustained weight gain (BMI post− BMI pre≥2 kg/m2) were higher in TSH at therapy levels ≥100 μ IU/mL in group 1, group 2, and overall. The values for the pro-portions of patients in groups 1 and 2 with sustained weight gain for TSH at therapy levels above and below 100 μ IU/mL were 5% and 18%, and 3% and 8%, respectively, and 3% and 10% overall.
ijt-9-19f4.tif
Table 1.
Patient clinical characteristics (n=301)
Characteristics Group 1 Group 2 p
Age (years) 53.7±11.6 53.3±12.4 0.353
Sex
Male 15 54 0.283
Female 68 164  
Pathology
Papillary 82 194 0.019
Follicular 0 16  
Papillary and follicular 1 8  
Underlying disease
Diabetes mellitus 6 12 0.591
Hypertension 15 39 1.000
Hypercholesterolemia 9 12 0.128
Cardiovascular disease 2 3 0.618
Tuberculosis 2 4 0.669
Liver disease 1 1 0.207
Exercise
No 17 59 0.299
Yes 66 159  
Calorie restriction
No 64 165 0.881
Yes 19 52  
Table 2.
Patient characteristics related to weight gain
Characteristics Group 1 Group 2 Value n (%) or mean±SD
Basal BMI
BMI＜25 kg/m2 63 159 222 (74%)
BMI≥25 kg/m2 20 59 79 (26%)
Transient weight gain
Yes 73 186 259 (86%)
No 10 32 42 (14%)
Sustained weight gain
(BMI post− BMI pre≥2 kg/m2)
Yes 9 14 23 (8%)
No 74 204 278 (92%)
TSH at therapy 121.4±72.4 145.8±73.8 139.7±74.0
T4-on TSH 0.905±1.880 1.414±2.999 1.274±2.744

BMI: body mass index, BMI post: body mass index after treatment, BMI pre: body mass index before treatment, SD: standard deviation, TSH: thyroid stimulating hormone

Table 3.
Subjective discomfort scores for sustained weight gain after TSH at therapy
Subjective discomfort Sustained weight gain p
(−) (+)
No – moderate 254 9 ＜0.0001∗
Severe and extreme 24 14  

∗ p＜0.05: Chi-squared test between two groups

TSH: thyroid stimulating hormone

Table 4.
Comparisons of clinical factors according to the presence of sustained weight gain
Characteristics Sustained weight gain p Sustained weight gain p
(−) (+) (−) (+)
Overall Group 1
Sex (female) 214 18 0.888 62 6 0.210
Diabetes mellitus 18 0 0.209 6 0 0.378
Hypertension 48 6 0.290 12 3 0.210
Hypercholesterolemia 18 3 0.236      
Cardiovascular disease 5 0 0.5173 2 0 0.620
Tuberculosis 6 0 0.477 2 0 0.620
Liver disease 2 0 0.773 1 0 0.727
Exercise 207 18 0.687 58 8 0.463
Calorie restriction 2 65 6 0.769 18 1 0.376
Basal BMI≥25 kg/m2 72 7 0.635§ 16 4 0.137§
TSH at therapy (μ IU/mL) 136.2
(95% CI 127.4–144.9)		 180.1
(95% CI 136.7–223.5)		 0.022§ 112.9
(95% CI 96.9–128.9)		 185.8
(95% CI 93.9–277.8)		 0.015§
T4-on TSH (μ IU/mL) 1.20
(95% CI 0.892–1.518)		 2.10
(95% CI 0.526–3.68)		 0.021§ 0.738
(95% CI 0.449–1.027)		 2.28
(95% CI-1.124–5.692)		 ＜0.001§

Categorical data: Chi-squared test between two groups

§ p＜0.05: Independent samples t-test between two groups

BMI: body mass index, CI: confidence interval, TSH: thyroid stimulating hormone

Table 5.
Univariate analysis of risk factors associated with sustained weight gain
Factors Group 1 p Group 2 p
Odds ratio (95% CI) Odds ratio (95% CI)
TSH at therapy ≥100 μ IU/mL 3.15 (1.05–9.53) 0.041∗ 2.20 (0.22–22.20) 0.474
T4-on TSH ＞0.9 μ IU/mL 0.00 (0.00–0.00) 0.986 0.87 (0.26–2.90) 0.827
Sex (male) 2.58 (0.57–11.78) 0.241 1.12 (0.11–11.34) 0.926
Age (50–59 years) 1.02 (0.24–4.43) 0.979 0.47 (0.06–3.55) 0.471
Recurrent or metastatic thyroid cancer 0.00 (0.00–0.00) 0.329 0.00 (0.00–0.00) 0.544
Diabetes mellitus 0.00 (0.00–0.00) 0.231 0.00 (0.00–0.00) 0.356
Hypertension 2.58 (0.57–11.78) 0.241 1.05 (0.10–10.62) 0.967
Hypercholesterolemia 5.67 (1.12–28.57) 0.049∗ 0.00 (0.00–0.00) 0.496
Exercise 2.21 (0.26–18.97) 0.432 1.14 (0.11–11.53) 0.910
Calorie restriction 0.39 (0.05–3.32) 0.339 3.53 (0.47–26.72) 0.234
Basal BMI ≥25 kg/m2 2.90 (0.70–12.08) 0.154 2.78 (0.37–20.92) 0.326

∗ Statistically significant factors (p＜0.05)

BMI: body mass index, CI: confidence interval, TSH: thyroid stimulating hormone

Table 6.
Multivariate analysis of risk factors associated with sustained weight gain in group 1
Factors Odds ratio (95% CI) p
TSH at therapy ≥100 μ IU/mL 3.22 (1.06–9.79) 0.039∗
Hypercholesterolemia 1.77 (0.46–6.79) 0.404
Basal BMI ≥25 kg/m2 1.61 (0.64–4.06) 0.317

∗ Statistically significant factors (p＜0.05)

BMI: body mass index, CI: confidence interval, TSH: thyroid stimulating hormone

Table 7.
Comparisons of clinical factors according to the presence of sustained weight gain in 283 patients with well-controlled T4-on TSH levels
Characteristics Sustained weight gain p
(−) (+)
Overall
Basal BMI ≥25 kg/m2 65 5 0.869
TSH at therapy (μ IU/mL) 136.5 (95% CI 127.3–145.6) 185.8 (95% CI 136.0–235.5) 0.015§
T4-on TSH (μ IU/mL) 0.740 (95% CI 0.628–0.851) 0.605 (95% CI 0.240–0.967) 0.332
Group 1
Basal BMI ≥25 kg/m2 15 3 0.188
TSH at therapy (μ IU/mL) 113.8 (95% CI 97.3–130.2) 188.5 (95% CI 78.9–298.1) 0.010§
T4-on TSH (μ IU/mL) 0.578 (95% CI 0.391–0.765) 0.093 (95% CI −0.003–0.189) ＜0.001§

§ p＜0.05: Independent samples t-test between two groups

BMI: body mass index, CI: confidence interval, TSH: thyroid stimulating hormone

Table 8.
Univariate and multivariate analysis of risk factors associated with sustained weight gain in 78 patients in group 1 with well-controlled T4-on TSH level
Factors Odds ratio (95% CI) p
Univariate
TSH at therapy ＞100 μ IU/mL 7.50 (0.86–65.52) 0.069
T4-on TSH ＜0.303 μ IU/mL 0.00 (NA) 0.997
Hypertension 3.75 (0.74–18.95) 0.110
Hypercholesterolemia 8.25 (1.49–45.82) 0.016∗
Basal BMI ≥25 kg/m2 2.85 (0.57–14.14) 0.200
Multivariate
TSH at therapy ≥100 IU/mL 16.33 (1.21–220.26) 0.035∗
Hypercholesterolemia 2.48 (0.26–23.23) 0.426
Hypertension 5.27 (0.54–51.42) 0.153
Basal BMI ≥25 kg/m2 6.14 (0.76–49.64) 0.089

∗ Statistically significant factors (p＜0.05)

BMI: body mass index, CI: confidence interval, TSH: thyroid stimulating hormone

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