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Abstract
Background and Objectives
Abnormal thyroid function influences the cardiovascular system. In particular, brief thyroid functional change due to levothyroxine (LT4) suppression therapy and withdrawal in papillary thyroid cancer (PTC) patients can affect cardiovascular system and other biochemical markers. However, the effect of brief thyroid functional change on arterial stiffness has not been evaluated. Therefore, we evaluated the changes in arterial stiffness according to short-term thyroid hormone levels in patients who underwent total thyroidectomy and radioactive iodine (RAI) therapy for PTC.
Materials and Methods
Patients with PTC (n=17; 15 females, mean age 52 years) who underwent total thyroidectomy and RAI therapy were enrolled in this study. The arterial stiffness was evaluated using the corrected augmentation index for heart rate (AI@75) and brachial-ankle pulse wave velocity (BaPWV). Serum thyroid hormone levels and arterial stiffness parameters were checked three times consecutively: the day before thyroidectomy (Visit 1; baseline euthyroid state), after LT4 withdrawal (Visit 2; pre-RAI hypothyroid state) and 4 weeks after RAI (Visit 3; post-RAI thyrotoxic state). Biochemical markers, which can influence the arterial stiffness, were also measured.
Results
The heart rate, AI@75 and serum thyroid hormone levels changed significantly at each visit. BaPWV was not significantly changed. Changes in AI@75 correlated with systolic blood pressure (SBP), serum thyroid hormone levels, total cholesterol and high density lipoprotein cholesterol in univariate analysis. In multivariate analysis, SBP was the independent factor for AI@75 changes.
References
1. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007; 116(15):1725–35.
2. Nagasaki T, Inaba M, Yamada S, Shirakawa K, Nagata Y, Kumeda Y, et al. Decrease of brachial-ankle pulse wave velocity in female subclinical hypothyroid patients during normalization of thyroid function: a double-blind, placebocontrolled study. Eur J Endocrinol. 2009; 160(3):409–15.
3. Volzke H, Robinson DM, Schminke U, Ludemann J, Rettig R, Felix SB, et al. Thyroid function and carotid wall thickness. J Clin Endocrinol Metab. 2004; 89(5):2145–9.
4. Napoli R, Biondi B, Guardasole V, Matarazzo M, Pardo F, Angelini V, et al. Impact of hyperthyroidism and its correction on vascular reactivity in humans. Circulation. 2001; 104(25):3076–80.
5. Bodlaj G, Pichler R, Brandstatter W, Hatzl-Griesenhofer M, Maschek W, Biesenbach G, et al. Hyperthyroidism affects arterial stiffness, plasma NT-pro-B-type natriuretic peptide levels, and subendocardial perfusion in patients with Graves' disease. Ann Med. 2007; 39(8):608–16.
6. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006; 16(2):109–42.
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. Botella-Carretero JI, Gomez-Bueno M, Barrios V, Caballero C, Garcia-Robles R, Sancho J, et al. Chronic thyrotropinsuppressive 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.
9. 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.
10. Wieshammer S, Keck FS, Waitzinger J, Henze E, Loos U, Hombach V, et al. Acute hypothyroidism slows the rate of left ventricular diastolic relaxation. Can J Physiol Pharmacol. 1989; 67(9):1007–10.
11. 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.
12. Hoftijzer HC, Bax JJ, Heemstra KA, Bleeker GB, Delgado V, van der Klaauw AA, et al. Short-term overt hypothyroidism induces discrete diastolic dysfunction in patients treated for differentiated thyroid carcinoma. Eur J Clin Invest. 2009; 39(3):204–10.
13. Matsui Y, Kario K, Ishikawa J, Eguchi K, Hoshide S, Shimada K. Reproducibility of arterial stiffness indices (pulse wave velocity and augmentation index) simultaneously assessed by automated pulse wave analysis and their associated risk factors in essential hypertensive patients. Hypertens Res. 2004; 27(11):851–7.
14. Waddell TK, Dart AM, Medley TL, Cameron JD, Kingwell BA. Carotid pressure is a better predictor of coronary artery disease severity than brachial pressure. Hypertension. 2001; 38(4):927–31.
15. Chirinos JA, Zambrano JP, Chakko S, Veerani A, Schob A, Willens HJ, et al. Aortic pressure augmentation predicts adverse cardiovascular events in patients with established coronary artery disease. Hypertension. 2005; 45(5):980–5.
16. Richardson CJ, Maki-Petaja KM, McDonnell BJ, Hickson SS, Wilkinson IB, McEniery CM. Comparison of estimates of central systolic blood pressure and peripheral augmentation index obtained from the Omron HEM-9000AI and SphygmoCor systems. Artery Res. 2009; 3(1):24–31.
17. Hickson SS, Butlin M, Mir FA, Graggaber J, Cheriyan J, Khan F, et al. The accuracy of central SBP determined from the second systolic peak of the peripheral pressure waveform. J Hypertens. 2009; 27(9):1784–8.
18. Diekman MJ, Harms MP, Endert E, Wieling W, Wiersinga WM. Endocrine factors related to changes in total peripheral vascular resistance after treatment of thyrotoxic and hypothyroid patients. Eur J Endocrinol. 2001; 144(4):339–46.
19. Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine. 2004; 24(1):1–13.
20. Duntas LH. Thyroid disease and lipids. Thyroid. 2002; 12(4):287–93.
21. Obuobie K, Smith J, Evans LM, John R, Davies JS, Lazarus JH. Increased central arterial stiffness in hypothyroidism. J Clin Endocrinol Metab. 2002; 87(10):4662–6.
22. Obuobie K, Smith J, John R, Davies JS, Lazarus JH. The effects of thyrotoxicosis and its treatment on central arterial stiffness. Eur J Endocrinol. 2002; 147(1):35–40.
23. Osman F, Franklyn JA, Holder RL, Sheppard MC, Gammage MD. Cardiovascular manifestations of hyperthyroidism before and after antithyroid therapy: a matched case-control study. J Am Coll Cardiol. 2007; 49(1):71–81.
24. Nagasaki T, Inaba M, Kumeda Y, Hiura Y, Shirakawa K, Yamada S, et al. Increased pulse wave velocity in subclinical hypothyroidism. J Clin Endocrinol Metab. 2006; 91(1):154–8.
25. Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab. 2007; 92(5):1715–23.
26. Napoli R, Guardasole V, Angelini V, Zarra E, Terracciano D, D'Anna C, et al. Acute effects of triiodothyronine on endothelial function in human subjects. J Clin Endocrinol Metab. 2007; 92(1):250–4.
27. Dagre AG, Lekakis JP, Papaioannou TG, Papamichael CM, Koutras DA, Stamatelopoulos SF, et al. Arterial stiffness is increased in subjects with hypothyroidism. Int J Cardiol. 2005; 103(1):1–6.
28. Oliviero U, Cittadini A, Bosso G, Cerbone M, Valvano A, Capalbo D, et al. Effects of longterm L-thyroxine treatment on endothelial function and arterial distensibility in young adults with congenital hypothyroidism. Eur J Endocrinol. 2010; 162(2):289–94.
29. Yavuz DG, Yazici D, Toprak A, Deyneli O, Aydin H, Yuksel M, et al. Exogenous subclinical hyperthyroidism impairs endothelial function in nodular goiter patients. Thyroid. 2008; 18(4):395–400.
30. Park KS, Rue JI, Kim SK, Kim IJ, Lim SW, Park SW, et al. Comparison of common carotid artery intima-media thickness between subclinical hypothyroidism and euthyroidism. J Korean Endocr Soc. 2006; 21(6):490–6.
31. 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.
Fig. 1.
The changes in AI@75 levels and correlated factors at each visit. Baseline was the euthyroid state, pre-RAI was the hypothyroid state and post-RAI was the mild thyrotoxic state. Statistical significance was evaluated using univariate analysis with the generalized estimating equation. AI@75: correction of augmentation index for heart rate, fT4: free thyroxine, HDL-C: high-density lipoprotein cholesterol, RAI: radioactive iodine therapy, SBP: systolic blood pres-sure, TC: total cholesterol, TSH: thyroid stimulating hor-mone.
Table 1.
Change of biochemical results and hemodynamic parameters (n=17)
| Variables | Visit 1 | Visit 2 | Visit 3 | ∗p value | † p value | ‡ p value |
|---|---|---|---|---|---|---|
| TSH (mIU/L) | 2.1±0.9 | 76.1±23.0 | 0.5±0.9 | ＜0.001 | 0.002 | ＜0.001 |
| T3 (ng/dL) | 108.0±17.4 | 21.5±3.8 | 147.3±42.0 | ＜0.001 | 0.006 | 0.001 |
| fT4 (ng/dL) | 1.2±0.2 | 0.1±0.1 | 2.4±0.9 | ＜0.001 | ＜0.001 | ＜0.001 |
| SBP (mmHg) | 128.7±16.8 | 121.4±17.7 | 132.5±18.5 | 0.097 | 0.286 | 0.297 |
| DBP (mmHg) | 78.9±11.7 | 77.6±10.7 | 78.2±12.7 | 0.736 | 0.831 | 0.811 |
| HR (bpm) | 72.7±10.3 | 69.8±10.3 | 82.1±11.3 | 0.155 | 0.001 | ＜0.001 |
| CBP (mmHg) | 134.2±20.4 | 125.7±19.9 | 137.1±19.8 | 0.109 | 0.722 | 0.517 |
| AI (%) | 81.2±13.3 | 75.5±12.3 | 83.4±12.4 | 0.070 | 0.622 | 0.054 |
| AI@75 (%) | 80.2±11.4 | 73.2±10.1 | 86.4±11.2 | 0.039 | 0.019 | 0.021 |
| BaPWV, Rt (m/s) | 13.8±2.9 | 13.6±2.5 | 13.7±2.4 | 0.722 | 0.906 | 0.692 |
| BaPWV, Lt (m/s) | 13.9±2.7 | 13.8±2.4 | 13.8±2.2 | 0.981 | 0.687 | 0.607 |
| TC (mg/dL) | 167.4±23.8 | 244.6±44.5 | 174.2±46.3 | 0.001 | 0.865 | 0.322 |
| HDL-C (mg/dL) | 51.2±13.6 | 63.2±15.2 | 48.0±11.7 | 0.004 | 0.878 | 0.685 |
| LDL-C (mg/dL) | 110.1±28.5 | 154.5±41.2 | 112.0±46.4 | 0.019 | 0.239 | 0.784 |
| TG (mg/dL) | 106.9±69.7 | 194.1±139.6 | 151.8±110.9 | 0.002 | 0.239 | 0.135 |
| Glu (mg/dL) | 112.2±32.7 | 107.3±36.4 | 106.6±19.0 | 0.451 | 0.593 | 0.499 |
| Hb (mg/dL) | 13.0±1.1 | 13.4±1.3 | 12.6±1.2 | 0.038 | 0.180 | 0.195 |
| Cr (mg/dL) | 0.73±0.1 | 0.69±0.1 | 0.68±0.1 | 0.348 | 0.093 | 0.041 |
| CRP (mg/dL) | 0.44±0.3 | 0.51±0.6 | 0.68±0.6 | 0.959 | 0.125 | 0.120 |
Values are means±standard deviation. Statistical significance was evaluated using generalized estimating equation analysis Visit 1 reflects baseline euthyroid state. Visit 2 reflects pre-RAI hypothyroid state. Visit 3 reflects post-RAI thyrotoxic state
AI: augmentation index, AI@75: corrected augmentation index for heart rate, BaPWV: brachial-ankle pulse wave velocity, CBP: central systolic blood pressure, Cr: creatinin, CRP: C-reactive protein, DBP: diastolic blood pressure, fT4: free thyroxine, Glu: glucose, Hb: hemoglobin, HDL-C: high density lipoprotein cholesterol, HR: heart rate, LDL-C: low density lipoprotein cholesterol, Lt: left, RAI: radioactive iodine, Rt: right, SBP: systolic blood pressure, T3: triiodothyronine, TC: total cholesterol, TG: triglyceride, TSH: thyroid stimulating hormone
Table 2.
The correlation analysis for changes of hemodynamic and biochemical parameters according to changes in AI@75, TSH, and fT4 (n=17)
| Changes in variables | Δ AI@75 | Δ TSH | Δ fT4 | |||
|---|---|---|---|---|---|---|
| 1 st phase | 2 nd phase | 1 st phase | 2 nd phase | 1 st phase | 2 nd phase | |
| Δ TSH | 0.119 | 0.442∗ | – | – | – | – |
| Δ fT4 | 0.040 | −0.092 | – | – | – | – |
| Δ T3 | −0.228 | −0.119 | – | – | – | – |
| Δ Heart rate | −0.570∗ | −0.056 | 0.021 | −0.148 | 0.102 | −0.242 |
| Δ SBP | 0.502∗ | 0.234 | 0.591∗ | 0.529∗ | −0.099 | −0.898∗ |
| Δ DBP | 0.437 | 0.219 | 0.580∗ | 0.511∗ | 0.218 | −0.115 |
| Δ CBP | 0.740∗ | 0.489∗ | 0.528∗ | 0.634∗ | 0.183 | −0.049 |
| Δ TC | −0.062 | −0.079 | 0.291 | 0.396 | 0.376 | −0.293 |
| Δ LDL-C | −0.042 | −0.049 | 0.209 | 0.236 | −0.230 | −0.422 |
| Δ HDL-C | −0.371 | −0.232 | 0.537∗ | 0.234 | 0.302 | −0.071 |
| Δ TG | 0.449 | 0.209 | −0182 | 0.022 | 0.064 | 0.193 |
| Δ Glucose | −0.100 | −0.240 | 0.118 | −0.343 | 0.118 | −0.547∗ |
| Δ Creatinin | −0.242 | −0.026 | −0.254 | −0.163 | 0.280 | −0.402 |
| Δ CRP | −0.027 | 0.163 | 0.147 | 0.299 | −0.173 | −0.047 |
All values are correlation coefficients (r) of correlation analysis. Univariate analysis was performed using Spearmanʼ s or Pearsonʼ s correlation analysis. The changes in variables were obtained by subtracting the pre-radioactive iodine (RAI) therapy values from the baseline values (1 st phase) and the post-RAI therapy values from the pre-RAI values (2 nd phase)
AI: augmentation index, AI@75: corrected augmentation index for heart rate, CBP: central systolic blood pressure, CRP: C-reactive protein, DBP: diastolic blood pressure, fT4: free thyroxine, HDL-C: high density lipoprotein cholesterol, LDL-C: Low density lipoprotein cholesterol, PWV: pulse wave velocity, SBP: systolic blood pressure, T3: triiodothyronine, TC: total cholesterol, TG: triglyceride, TSH: thyroid stimulating hormone
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