Cardiac and Plasma Catecholamine Responses to Exercise in Patients with Hyperthyroidism T. Kinugawa, K. Ogino, H. Kitamura, H. Miyakoda, M. Saitoh, J. Hasegawa, H. Kotake, C. Shigemasa and H. Mashiba
Introduction Because numerous clinical features of hyperthyroidism are common in the increased adrenergic activity (Harrison 1964), the relation between hyperthyroidism and the function of the sympathoadrenal system has been investigated for many years. However, the precise nature of this inter-relationship has not been fully elucidated despite the intensive studies of the possible interactions between thyroid hormones and the sympathetic nervous system (Waldstein 1966; Levy 1971; Landsberg 1977; Werner 1978; Klein and Levy 1984). There have been some reports concerning the resting plasma catecholamine levels in hyperthyroid patients (Christensen 1973; Staffer, Jiang, Gorman and Pikler 1973; Coulombe, Dussault and Walker 1976). However, to our knowledge, no data has been available concerning the serial plasma catecholamine response to dynamic exercise test. In this study, we measured the serial plasma norepinephrine (NE) and epinephrine (E) concentrations during multistage treadmill exercise test in patients with hyperthyroidism before therapy and after the clinical control of the disease by antithyroid treatments. Patients and Methods 24 patients (9 M, 15 F) with hyperthyroidism, aged 19—71 (mean 42 ± 16 yrs) and age-sex matched control subjects (9 M, 15 F), aged 16—69 (mean 42 + 16) were studied. All patients had diffuse goiter with clinical symptoms of hyperthyroidism and elevated thyroid hormone levels (serum free T3; 13.4 ± 6 . 9 pg/ml, normal values: 2.2-5.2 pg/ml, serum free T4; 5.6 ± 3 . 3 ng/dl, 0.70-1.96 ng/dl). Thyroid hormone levels were measured by RIA with Amerlex kit (Radiochemical Center, Amersham, United Kingdom). The patients showed no signs or symptoms of heart failure. Electrocardiography showed the presence of sinus rhythm in all patients except atrial fibrillation in one female. Each subject gave informed consent. The first exercise test was performed before the therapy was initiated. None of the patients was administered beta-blocking agents. Patients with hyperthyroidism and normal subjects exercised by treadmill exercise under the modified Bruce protocol (Sotohata, Shino, Kondo and Tsuzuki 1979). Electrocardiograms were continuously monitored and systolic blood pressure (SBP) was measured at one minute intervals. The criteria for stopping exercise were marked shortness of breath, leg fatigue, achievement of the 85% of calculated maximal predicted heart rate (HR) and finish stage 5 (exercise time: 15 minutes). 11 patients (4 M, 11 F, mean 40 ± 14) were re-examined after they were made euthyroid by the administration of Thiamazole or Propylthiouracil. One female was treated by the combination therapy of antithyroid drug and subtotal thyroidectomy.
Horm.metab.Res.23 (1991)295-297 © Georg Thieme Verlag Stuttgart -New York
Venous blood samples were drawn for plasma NE and E determinations from an antecubital venous cannula after at least 15 minutes bed rest, in the last minute of each exercise stage, immediately and 5 minutes after exercise. They were analyzed using a highperformance liquid chromatography combined with the trihydroxyindole fluorometric procedure. The normal ranges of plasma N E and E levels at rest are 60—450 pg/ml, and less than 120 pg/ml, respectively. Replicate measurements of plasma N E and E have coefficients of variation of 3.0% and 3.8% (intraassay), and 4.2% and 4.8 % (interassay). Statistical analysis was performed using an unpaired Student's West. A probability value of 0.05 or less was considered significant.
Results Exercise time and reasons for termination Reasons for termination of 24 hyperthyroid patients were achievement of target HR for 21, symptoms for 3; in 24 normal subjects, target HR for 17, finish stage 5 for 5 and symptoms for 2. In 24 hyperthyroid patients, 1 stopped exercise at stage I, 10 at stage II, 7 at stage III and 6 at stage IV. In 24 normal subjects, 2 stopped exercise at stage II, 6 at stage III, 3 at stage IV and 13 at stage V. The average exercise time of the hyperthyroid patients and normal subjects was 6.8 ± 2.7, 11.9 ± 2.9 minutes, respectively.
Responses of HR, SBP, NE and E At rest, HR (hyperthyroid vs normal; 96 ± 4 vs 69 ± 2 bpm, P < 0.01) and SBP (137 ± 3 vs 126 ± 3 mmHg, P < 0.01) were higher in patients with hyperthyroidism. During early stage of exercise, HR and SBP were significantly higher in patient group, especially SBP response at first stage of exercise was exaggerated. Both peak HR (156 + 5 vs 147 + 3 bpm, n. s.) and peak SBP ( 1 6 9 ± 5 vs 164 + 4 mmHg, n. s.) were not different betweent the two groups (Fig. 1A and B). Resting N E (80 ± 7 vs 124 ± 1 0 pg/ml, P < 0.05) was significantly lower in patients with hyperthyroidism. NE increased gradually in both groups during exercise, however, plasma N E concentrations at peak exercise (310 + 38 vs 475 ± 3 8 pg/ml, P < 0.01), immediately and 5 minutes after exercise were significantly lower in patient group (Fig. 1C). The increment of N E to resting values (231 + 37 vs 351 ± 3 5 pg/ml, P < 0.05) at peak exercise was also lower in hyperthyroid patients. There was no difference in E levels at rest (22 ± 2 vs 29 ± 4 pg/ml n. s.). Plasma E response to exercise was rather exaggerated during exercise, and the value at first stage of exercise (69 ± 12
Received: 6 July 1990
Accepted: 4 Febr. 1991 after revision
Downloaded by: National University of Singapore. Copyrighted material.
First Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan
Horm. metab. Res. 23 (1991)
T. Kinugawa, K. Ogino, H. Kitamura, H. Miyakoda, M. Saitoh, J. Hasegawa et al. Fig. 1 Responses of heart rate, systolic blood pressure, plasma norepinephrine and epinephrine to exercise in patients with hyperthyroidism ( • ) and normal subjects (O). Values were expressed by mean±SEM *P
Introduction Because numerous clinical features of hyperthyroidism are common in the increased adrenergic activity (Harrison 1964), the relation between hyperthyroidism and the function of the sympathoadrenal system has been investigated for many years. However, the precise nature of this inter-relationship has not been fully elucidated despite the intensive studies of the possible interactions between thyroid hormones and the sympathetic nervous system (Waldstein 1966; Levy 1971; Landsberg 1977; Werner 1978; Klein and Levy 1984). There have been some reports concerning the resting plasma catecholamine levels in hyperthyroid patients (Christensen 1973; Staffer, Jiang, Gorman and Pikler 1973; Coulombe, Dussault and Walker 1976). However, to our knowledge, no data has been available concerning the serial plasma catecholamine response to dynamic exercise test. In this study, we measured the serial plasma norepinephrine (NE) and epinephrine (E) concentrations during multistage treadmill exercise test in patients with hyperthyroidism before therapy and after the clinical control of the disease by antithyroid treatments. Patients and Methods 24 patients (9 M, 15 F) with hyperthyroidism, aged 19—71 (mean 42 ± 16 yrs) and age-sex matched control subjects (9 M, 15 F), aged 16—69 (mean 42 + 16) were studied. All patients had diffuse goiter with clinical symptoms of hyperthyroidism and elevated thyroid hormone levels (serum free T3; 13.4 ± 6 . 9 pg/ml, normal values: 2.2-5.2 pg/ml, serum free T4; 5.6 ± 3 . 3 ng/dl, 0.70-1.96 ng/dl). Thyroid hormone levels were measured by RIA with Amerlex kit (Radiochemical Center, Amersham, United Kingdom). The patients showed no signs or symptoms of heart failure. Electrocardiography showed the presence of sinus rhythm in all patients except atrial fibrillation in one female. Each subject gave informed consent. The first exercise test was performed before the therapy was initiated. None of the patients was administered beta-blocking agents. Patients with hyperthyroidism and normal subjects exercised by treadmill exercise under the modified Bruce protocol (Sotohata, Shino, Kondo and Tsuzuki 1979). Electrocardiograms were continuously monitored and systolic blood pressure (SBP) was measured at one minute intervals. The criteria for stopping exercise were marked shortness of breath, leg fatigue, achievement of the 85% of calculated maximal predicted heart rate (HR) and finish stage 5 (exercise time: 15 minutes). 11 patients (4 M, 11 F, mean 40 ± 14) were re-examined after they were made euthyroid by the administration of Thiamazole or Propylthiouracil. One female was treated by the combination therapy of antithyroid drug and subtotal thyroidectomy.
Horm.metab.Res.23 (1991)295-297 © Georg Thieme Verlag Stuttgart -New York
Venous blood samples were drawn for plasma NE and E determinations from an antecubital venous cannula after at least 15 minutes bed rest, in the last minute of each exercise stage, immediately and 5 minutes after exercise. They were analyzed using a highperformance liquid chromatography combined with the trihydroxyindole fluorometric procedure. The normal ranges of plasma N E and E levels at rest are 60—450 pg/ml, and less than 120 pg/ml, respectively. Replicate measurements of plasma N E and E have coefficients of variation of 3.0% and 3.8% (intraassay), and 4.2% and 4.8 % (interassay). Statistical analysis was performed using an unpaired Student's West. A probability value of 0.05 or less was considered significant.
Results Exercise time and reasons for termination Reasons for termination of 24 hyperthyroid patients were achievement of target HR for 21, symptoms for 3; in 24 normal subjects, target HR for 17, finish stage 5 for 5 and symptoms for 2. In 24 hyperthyroid patients, 1 stopped exercise at stage I, 10 at stage II, 7 at stage III and 6 at stage IV. In 24 normal subjects, 2 stopped exercise at stage II, 6 at stage III, 3 at stage IV and 13 at stage V. The average exercise time of the hyperthyroid patients and normal subjects was 6.8 ± 2.7, 11.9 ± 2.9 minutes, respectively.
Responses of HR, SBP, NE and E At rest, HR (hyperthyroid vs normal; 96 ± 4 vs 69 ± 2 bpm, P < 0.01) and SBP (137 ± 3 vs 126 ± 3 mmHg, P < 0.01) were higher in patients with hyperthyroidism. During early stage of exercise, HR and SBP were significantly higher in patient group, especially SBP response at first stage of exercise was exaggerated. Both peak HR (156 + 5 vs 147 + 3 bpm, n. s.) and peak SBP ( 1 6 9 ± 5 vs 164 + 4 mmHg, n. s.) were not different betweent the two groups (Fig. 1A and B). Resting N E (80 ± 7 vs 124 ± 1 0 pg/ml, P < 0.05) was significantly lower in patients with hyperthyroidism. NE increased gradually in both groups during exercise, however, plasma N E concentrations at peak exercise (310 + 38 vs 475 ± 3 8 pg/ml, P < 0.01), immediately and 5 minutes after exercise were significantly lower in patient group (Fig. 1C). The increment of N E to resting values (231 + 37 vs 351 ± 3 5 pg/ml, P < 0.05) at peak exercise was also lower in hyperthyroid patients. There was no difference in E levels at rest (22 ± 2 vs 29 ± 4 pg/ml n. s.). Plasma E response to exercise was rather exaggerated during exercise, and the value at first stage of exercise (69 ± 12
Received: 6 July 1990
Accepted: 4 Febr. 1991 after revision
Downloaded by: National University of Singapore. Copyrighted material.
First Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan
Horm. metab. Res. 23 (1991)
T. Kinugawa, K. Ogino, H. Kitamura, H. Miyakoda, M. Saitoh, J. Hasegawa et al. Fig. 1 Responses of heart rate, systolic blood pressure, plasma norepinephrine and epinephrine to exercise in patients with hyperthyroidism ( • ) and normal subjects (O). Values were expressed by mean±SEM *P
