Journal List > J Korean Thyroid Assoc > v.7(2) > 1056561

Yeo, Jo, Lee, Yi, Kang, and Son: Effect of Short-Term Hypothyroid State on Lipid Profile and Cardiovascular Risk Markers in Subjects Preparing Radioactive Iodine Therapy


Background and Objectives

The relationship between short-term hypothyroidism due to levothyroxine (LT4) withdrawal for radioactive iodine (RI) therapy in patients with differentiated thyroid cancer (DTC) and risk of cardiovascular disease is not clear. In this study, we evaluated the impact of short-term overt hypothyroidism on lipid profiles and cardiovascular parameters in patients with DTC.

Materials and Methods

We recruited 195 patients with DTC who were preparing RI therapy from March 2008 to February 2012. We analyzed the effect of thyroid stimulating hormone (TSH) level on the clinical, biochemical, and cardiovascular risk markers at the end of LT4 withdrawal protocol (P2).


After LT4 withdrawal (P2), TSH and total cholesterol (TC) levels were significantly increased (p<0.005). After adjustment for multiple factors such as age, sex, body mass index (BMI), hypertension and diabetes mellitus (DM), the positive relationship between TSH and TC remained significant (p=0.04). Mean levels of homocysteine, low density lipoprotein-cholesterol, triglyceride were increased. However, levels of high density lipoprotein-cholesterol, cystatin C, C-reactive protein, apolipoprotein B (ApoB), apolipoprotein A1 (Apo A1), lipoprotein (a) (Lp[a]), aspartate transaminase, alanine aminotransferase, total bilirubin, uric acid remained within normal range. Splitting the whole cohort into the three different age groups, serum Apo B, Lp(a) levels and BMI increased with increasing age (p< 0.05). And splitting into three different TSH level groups (1st group; <79 μIU/mL, 2nd group; 79-121 μIU/mL, 3rd group; > 121 μIU/mL), all values did not have a statistical significant meaning except Apo A1.


Short-term hypothyroidism induced worsening of lipid metabolic parameters, but not enough to induce the cardiovascular risk in patients with thyroid cancer.


1. Jung KW, Won YJ, Kong HJ, Oh CM, Seo HG, Lee JS. Cancer statistics in Korea: incidence, mortality, survival and prevalence in 2010. Cancer Res Treat. 2013; 45(1):1–14.
2. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL. et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009; 19(11):1167–214.
3. Hilts SV, Hellman D, Anderson J, Woolfenden J, Van Antwerp J, Patton D. Serial TSH determination after T3 withdrawal or thyroidectomy in the therapy of thyroid carcinoma. J Nucl Med. 1979; 20(9):928–32.
4. Peppa M, Betsi G, Dimitriadis G. Lipid abnormalities and cardiometabolic risk in patients with overt and subclinical thyroid disease. J Lipids. 2011; 2011:575840.
5. Kutluturk F, Yuce S, Tasliyurt T, Yelken BM, Aytan P, Ozturk B. et al. Changes in metabolic and cardiovascular risk factors before and after treatment in overt hypothyroidism. Med Glas (Zenica). 2013; 10(2):348–53.
6. Regalbuto C, Alagona C, Maiorana R, Di Paola R, Cianci M, Alagona G. et al. Acute changes in clinical parameters and thyroid function peripheral markers following L-T4 withdrawal in patients totally thyroidectomized for thyroid cancer. J Endocrinol Invest. 2006; 29(1):32–40.
7. Duntas LH, Biondi B. Short-term hypothyroidism after Levothyroxine-withdrawal in patients with differentiated thyroid cancer: clinical and quality of life consequences. Eur J Endocrinol. 2007; 156(1):13–9.
8. Lien EA, Nedrebo BG, Varhaug JE, Nygard O, Aakvaag A, Ueland PM. Plasma total homocysteine levels during short-term iatrogenic hypothyroidism. J Clin Endocrinol Metab. 2000; 85(3):1049–53.
9. Bicikova M, Hampl R, Hill M, Stanicka S, Tallova J, Vondra K. Steroids, sex hormone-binding globulin, homocysteine, selected hormones and markers of lipid and carbohydrate metabolism in patients with severe hypothyroidism and their changes following thyroid hormone supplementation. Clin Chem Lab Med. 2003; 41(3):284–92.
10. Chrisoulidou A, Pazaitou-Panayiotou K, Kaprara A, Platoyiannis D, Lafaras C, Boudina M. et al. Effects of thyroxine withdrawal in biochemical parameters and cardiac function and structure in patients with differentiated thyroid cancer. Minerva Endocrinol. 2006; 31(2):173–8.
11. Erbil Y, Ozbey N, Giris M, Salmaslioglu A, Ozarmagan S, Tezelman S. Effects of thyroxine replacement on lipid profile and endothelial function after thyroidectomy. Br J Surg. 2007; 94(12):1485–90.
12. Chang HJ, Kim KW, Choi SH, Lim S, Park KU, Park do J. et al. Endothelial function is not changed during short-term withdrawal of thyroxine in patients with differentiated thyroid cancer and low cardiovascular risk. Yonsei Med J. 2010; 51(4):492–8.
13. Botella-Carretero JI, Alvarez-Blasco F, Sancho J, Escobar-Morreale HF. Effects of thyroid hormones on serum levels of adipokines as studied in patients with differentiated thyroid carcinoma during thyroxine withdrawal. Thyroid. 2006; 16(4):397–402.
14. Mazzaferri EL, Massoll N. Management of papillary and follicular (differentiated) thyroid cancer: new paradigms using recombinant human thyrotropin. Endocr Relat Cancer. 2002; 9(4):227–47.
15. Botella-Carretero JI, Gomez-Bueno M, Barrios V, Caballero C, Garcia-Robles R, Sancho J. et al. Chronic thyrotropin-suppressive therapy with levothyroxine and short-term overt hypothyroidism after thyroxine withdrawal are associated with undesirable cardiovascular effects in patients with differentiated thyroid carcinoma. Endocr Relat Cancer. 2004; 11(2):345–56.
16. Di Paola R, Alagona C, Pezzino V, Mangiameli S, Regalbuto C. Left ventricular function in acute hypothyroidism: a Doppler echocardiography study. Ital Heart J. 2004; 5(11):857–63.
17. Fommei E, Iervasi G. The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans. J Clin Endocrinol Metab. 2002; 87(5):1996–2000.
18. Catargi B, Parrot-Roulaud F, Cochet C, Ducassou D, Roger P, Tabarin A. Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. Thyroid. 1999; 9(12):1163–6.
19. Shong YK, Ryu JS, Lee KU, Kim GS, Lee M. Serum lipids and apolipoproteins in subclinical and overt hypothyroidism and their changes with thyroxine therapy. J Korean Soc Endocrinol. 1992; 7(1):31–8.
20. Engler H, Riesen WF. Effect of thyroid hormones on Lp(a) and lipid metabolism. Clin Chem Lab Med. 1998; 36(9):731–5.
21. Sharma AK, Arya R, Mehta R, Sharma R, Sharma AK. Hypothyroidism and cardiovascular disease: factors, mechanism and future perspectives. Curr Med Chem. 2013; 20(35):4411–8.
22. Miller VM, Redfield MM, McConnell JP. Use of BNP and CRP as biomarkers in assessing cardiovascular disease: diagnosis versus risk. Curr Vasc Pharmacol. 2007; 5(1):15–25.
23. Christ-Crain M, Meier C, Guglielmetti M, Huber PR, Riesen W, Staub JJ. et al. Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A crosssectional and a double-blind, placebo-controlled trial. Atherosclerosis. 2003; 166(2):379–86.
24. Jublanc C, Bruckert E, Giral P, Chapman MJ, Leenhardt L, Carreau V. et al. Relationship of circulating C-reactive protein levels to thyroid status and cardiovascular risk in hyperlipidemic euthyroid subjects: low free thyroxine is associated with elevated hsCRP. Atherosclerosis. 2004; 172(1):7–11.
25. Nagasaki T, Inaba M, Shirakawa K, Hiura Y, Tahara H, Kumeda Y. et al. Increased levels of C-reactive protein in hypothyroid patients and its correlation with arterial stiffness in the common carotid artery. Biomed Pharmacother. 2007; 61(2-3):167–72.
26. Lee WY, Suh JY, Rhee EJ, Park JS, Sung KC, Kim SW. Plasma CRP, apolipoprotein A-1, apolipoprotein B and Lpa levels according to thyroid function status. Arch Med Res. 2004; 35(6):540–5.
27. Bayraktar M, Van Thiel DH. Abnormalities in measures of liver function and injury in thyroid disorders. Hepatogastroenterology. 1997; 44(18):1614–8.
28. Jeong HJ, Kim CG, Lee KM, Jeong SJ, Song HC, Bom HS. Reversible changes of clinical chemical tests in severe hypothyroid patients with differentiated thyroid cancer who were admitted for radioiodine therapy. J Korean Surg Soc. 2004; 66(1):10–3.

Fig. 1.
Study protocols for evaluation of effect of short–term hypothyroid state on lipid and cardiovascular risk markers in subjects with thyroid cancer preparing radioiodine therapy.
Table 1.
Basal characteristics of subjects
Age, years 47.6± 12.4
Female, % 85.1 (n=166)
BMI, kg/m2 24.7±3.7
SBP, mmHg 118.7± 14.8
DBP, mmHg 75.9± 11.3
Hypertension, % 23.1 (n=45)
Diabetes, % 7.1 (n=14)
FBS, mg/dL 90.8± 18.2

BMI: body mass index, DBP: diastolic blood pressure, FBS: fasting blood sugar, SBP: systolic blood pressure

Table 2.
Changes in parameters during follow-up
P1 P2 p value
TSH, μIU/mL 3.9±14.1 102.8±47.6 <0.001
T3, ng/mL 1.3±0.2 0.4±0.2 <0.001
FT4, ng/dL 1.2±0.3 0.5±0.2 <0.001
TC, mg/dL 198.8±43.4 262.1±56.7 <0.001
LDLc, mg/dL 152±53.6 169.7±50.3 0.059
HDLc, mg/dL 59.6±15.6 63.4±20.9 0.090
TG, mg/dL 205.9±108.6 212.0±128.1 0.068
SBP, mmHg 118.7±14.8 115.7± 16.9 0.017
DBP, mmHg 75.9±11.3 77.5±10.2 0.015
BMI, kg/m2 24.7±3.7 24.8±3.8 0.312

BMI: body mass index, DBP: diastolic blood pressure, P1: the last day on levothyroxine (LT4) at their usual TSH-suppressive doses, P2: 4 weeks after withdrawal of LT4, SBP: systolic blood pressure

Table 3.
Delta correlation of total cholesterol associated with variables
R Total cholesterol p value
Mean BP 0.131 0.276
Body mass index 0.019 0.687
T3 –0.257 0.054
FT4 –0.292 0.067
TSH 0.305 0.029

BP: blood pressure, FT4: free T4, TSH: thyroid stimulating hormone

Table 4.
Biochemical findings during hypothyroid states (P2)
Mean±SD Reference ranges
TG, mg/dL 212.0±128.1 0–200
LDLc, mg/dL 169.7±50.3 0–160
HDLc, mg/dL 63.4±20.9 45–65
Homocysteine, μmol/L 15.4±7.1 5–15
Cystatin C, mg/L 0.7±0.2 0.51–1.0
hsCRP, mg/dL 0.1±0.2 0–0.5
ApoB, mg/dL 125.5±38.3 50–130
Apo A1, mg/dL 143.3±23.0 120–220
Lipoprotein(a), mg/dL 36.4±27.7 0–40
AST, IU/L 38.0±17.4 10–40
ALT, IU/L 35.1±23.1 6–40
Total Bilirubin, mg/dL 1.2±7.8 0.3–1.3
Uric Acid, mg/dL 4.79±1.42 2.5–8.0

Apo A1: apolipoprotein A1, Apo B: apolipoprotein B, ALT: alanine aminotransferase, AST: aspartate aminotransferase, HDLc: high-density lipoprotein cholesterol, hsCRP: C-reactive protein, LDLc: low-density lipoprotein cholesterol, TG: triglycerides

Table 5.
Clinical and biochemical parameters (P2) in the three different age groups
1st group
2nd group
3rd group
p value Post hoc Scheffe
Sex, % female 87.0% 77.9% 90.4% 0.103
BMI, kg/m2 23.4±3.5 24.9±4.1 25.4±3.3 0.009 1:3
DM, % 1.9% 1.5% 16.4% 0.001 1:3, 2:3
Tg Ab, % 13.0% 5.9% 13.7% 0.271
SBP, mm/Hg 114.0± 12.3 117.4±14.3 123.4±15.9 0.001 1:3
DBP, mm/Hg 73.2± 10.5 75.4±11.5 78.3±11.3 0.015 1:3
LDLc, mg/dL 162.5±41.6 172.6±49.5 172.3±56.7 0.466
HDLc, mg/dL 66.3± 15.6 60.44±13.8 64.0±28.4 0.296
TG, mg/dL 185.8± 114.6 213.1±132.6 230.3±131.7 0.154
Homocysteine, μmol/L 17.2±9.7 14.3±6.7 14.9±4.5 0.073
Cystatin C, mg/L 0.6±0.1 0.6±0.1 0.8±0.1 <0.001 1:3, 2:3
hsCRP, mg/dL 0.1±0.9 0.1±0.3 0.1±0.2 0.125
Apo B, mg/dL 113.6±34.0 126.2±37.2 133.6±40.2 0.013 1:3
Apo A1, mg/dL 146.8±21.5 141.1±20.3 142.9±26.2 0.386
Lipoprotein(a), mg/dL 25.5±14.7 34.9±23.7 45.7±34.8 < 0.001 1:3
Thyroglobulin, mg/dL 8.9±40.7 3.7±6.4 8.8±24.0 0.420
Total bilirubin, mg/dL 0.7±0.3 2.2±13.2 0.5±0.2 0.381
AST, IU/L 36.2±19.4 38.0±14.4 39.4±18.5 0.576
ALT, IU/L 33.8±28.1 37.9±22.0 33.4±19.8 0.455
Uric acid, mg/dL 4.6±1.3 5.0±1.6 4.8±1.3 0.347

Age groups were defined as: 1st group; <39 years, 2nd group; 40–49 years, 3rd group; >50 years Apo A1: apolipoprotein A1, Apo B: apolipoprotein B, ALT: alanine aminotransferase, AST: aspartate aminotransferase, BMI: body mass index, DBP: diastolic blood pressure, HDLc: high-density lipoprotein cholesterol, hsCRP: C-reactive protein, LDLc: low-density lipoprotein cholesterol, SBP: systolic blood pressure, TG: triglycerides

Table 6.
Clinical and biochemical features of the whole cohort according to three different TSH level groups
1st group
2nd group
3rd group
p value Post hoc Scheffe
Sex, % female 80% (n=52) 84% (n=56) 90.6% (n=58) 0.239
Age, years 50.4±11.2 44.7±11.4 47.7±13.9 0.031 1:2
BMI, kg/m2 24.9±3.5 24.4±4.4 24.7±3.0 0.673
DM, % 7.6% (n=5) 7.6% (n=5) 6.3% (n=4) 0.941
Tg Ab, % 7.6% (n=5) 7.6% (n=5) 17.2% (n=11) 0.131
Systolic BP, mm/Hg 118.7±15.9 119.4±14.3 117.8±14.4 0.840
DiastolicBP, mm/Hg 75.0±11.6 76.7±11.6 75.9±10.7 0.672
LDLc, mg/dL 163.7±57.8 164.3±45.1 181.4±45.7 0.080
HDLc, mg/dL 59.1±15.7 66.4±28.3 64.7±15.5 0.114
TG, mg/Dl 212.6±143.2 195.7±114.5 228.2±125.0 0.265
Homocysteine, μmol/L 15.8±7.4 15.5±7.3 14.8±6.5 0.753
Cystatin C, mg/L 0.7±0.1 0.7±0.2 0.6±0.1 0.090
hsCRP, mg/dL 0.2±0.3 0.1±0.1 0.1±0.1 0.066
Apo B, mg/dL 127.8±40.7 118.5±31.7 130.4±41.3 0.170
Apo A1, mg/dL 138.0±24.0 149.7±21.6 142.2±22.1 0.019 1:2
Lipoprotein(a), mg/dL 36.9±31.7 35.3±24.3 37.4±26.9 0.902
Thyroglobulin, mg/dL 8.4±23.8 9.9±38.0 2.8±4.7 0.265
T3, ng/mL 0.5±0.1 0.4±0.2 0.4±0.2 0.062
FT4, mg/dL 0.7±0.2 0.5±0.2 0.5±0.2 0.059
Total bilirubin, mg/dL 0.6±0.3 2.2±13.3 0.6±0.2 0.381
AST, IU/L 37.3±18.2 35.8±17.0 41.0±16.8 0.221
ALT, IU/L 35.8±19.7 35.0±28.8 34.5±19.8 0.950
Uric acid, mg/dL 5.0±1.5 4.8±1.4 4.6±1.3 0.443

TSH groups were defined as: 1st group; <79 μIU/mL, 2nd group; 79-121 μIU/mL, 3rd group; < 121 μIU/mL Apo A1: apolipoprotein A1, Apo B: apolipoprotein B, ALT: alanine aminotransferase, AST: aspartate aminotransferase, BMI: body mass index, DBP: diastolic blood pressure, HDLc: high-density lipoprotein cholesterol, hsCRP: C-reactive protein, LDLc: low-density lipoprotein cholesterol, SBP: systolic bloodpressure, TG: triglycerides

Similar articles