Cardiovascular effects of thyroxine in combination with methimazole in premenopausal female Graves' disease patients: case-control study.
OBJECTIVE
To evaluate cardiovascular consequences of combined treatment in Graves' disease patients with addition of thyroxine (LT4) to antithyroid drugs in doses sufficient to suppress serum thyrotropin (TSH) levels below normal.


METHODS
Eleven premenopausal female patients who reached subnormal TSH levels (<0.3 microIU/mL) under the combined therapy were evaluated by equilibrium radionuclide ventriculography at rest, and during the peak stage of fixed moderate exercise workload (75W) initially at diagnosis and after at least 8 months of stable euthyroidism, as judged by peripheral free thyroxine and triiodothyronine. The control group included 12 euthyroid healthy women.


RESULTS
Post-treatment resting systolic and diastolic blood pressure, heart rate, and left ventricular (LV) systolic function were similar to control values. Log-transformed TSH releasing factor-stimulated TSH response correlated with LV resting early diastolic peak filling rate (PFR) (r=0.802, p=0.003) and resting diastolic blood pressure (r=0.795, p=0.003), which, in turn, was a significant predictor of basal renin secretion (r=-0.84, p=0.001). Treated patients had increased peak exercise systolic blood pressure (median 175, interquartile range 25 vs median 156, interquartile range 29 mmHg, p=0.019), delayed recovery of post-exercise heart rate to basal levels, and reduced exercise ejection fraction (median 66, interquartile range 9 vs median 74, interquartile range 13 %, p=0.037) in comparison with controls. Exercise ejection fraction was inversely related to exercise diastolic blood pressure, (r=-0.818, p=0.002); and exercise systolic blood pressure to exercise time to peak filling rate in a heart rate-independent manner, (rpartial=0.89, p<0.001).


CONCLUSIONS
Persistent TSH suppression in LT4-treated Graves' disease patients promotes pressure dependent renin secretion, and modulates resting early LV diastolic relaxation. It is also associated with exaggerated exercise systolic blood pressure response and decreased ejection fraction response to exercise.
Karner
Ivan
I
Department of Nuclear Medicine, Osijek University Hospital, J. Huttlera 4, 31000 Osijek, Croatia.
Stefanic
Mario
M
Topuzović
Nedeljko
N
D000328:Adult; D013956:Antithyroid Agents / Q000008:administration & dosage*; D002319:Cardiovascular System / Q000000981:diagnostic imaging / Q000187:drug effects*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D015444:Exercise; D005260:Female; D015637:Gated Blood-Pool Imaging; D006111:Graves Disease / Q000188:drug therapy*; D006801:Humans; D008713:Methimazole / Q000008:administration & dosage*; D017697:Premenopause; D018709:Statistics, Nonparametric; D013972:Thyrotropin / Q000037:antagonists & inhibitors; D013974:Thyroxine / Q000008:administration & dosage*; D016277:Ventricular Function, Left / Q000187:drug effects
D013956:Antithyroid Agents; D008713:Methimazole; D013972:Thyrotropin; D013974:Thyroxine