Methimazole-induced hypothyroidism paradoxically decreases homocysteine.
Clinical hypothyroidism is associated with hyperhomocysteinemia, whereas the opposite is seen in hyperthyroidism. The effects of mild thyroid dysfunction on homocysteine concentrations are not known. We performed the following study to investigate this. Total homocysteine, vitamins B6 and B12, folate, fibrinogen, plasminogen activator inhibitor type 1, and lipids were measured in 11 subjects at baseline and after methionine loading. Subjects began methimazole (MMI), 40 mg daily, and were restudied during 2 stages of hypothyroidism. Liothyronine was added and subjects were restudied once thyrotropin normalized. Methimazole was stopped and studies were repeated during 2 stages of hyperthyroidism. Data were analyzed using repeated-measures analysis of variance. Post-methionine homocysteine decreased in each hypothyroid study compared with baseline (28.8+/-10.7, 27.5+/-9.9 vs 34.4+/-9.2 micromol/L, respectively). In addition, both fasting and post-methionine homocysteine decreased in the euthyroid/MMI study arm compared with baseline despite equivalent thyrotropin values (fasting, 7.5+/-3.0 vs 8.8+/-3.5 micromol/L, P<.05; and post-methionine, 27.2+/-10.6 vs 34.4+/-9.2 micromol/L, P<.05, respectively). Fasting homocysteine decreased in the first hyperthyroidism study arm compared with baseline (6.6+/-2.3 vs 8.8+/-3.5 micromol/L, P<.05) and post-methionine homocysteine decreased in both hyperthyroid arms compared with baseline (25.2+/-8.1, 24.2+/-10 vs 34.4+/-9.2 micromol/L, P<.05 respectively). In conclusion, mild thyroid dysfunction changes homocysteine metabolism. Unexpectedly, our results suggest a homocysteine-lowering effect of MMI.
Colleran
Kathleen M
KM
Department of Internal Medicine, University of New Mexico, Albuquerque 87131, USA. kcolleran@salud.unm.edu
Romero
Leonard A
LA
Upton
Dalice A
DA
Burge
Mark R
MR
D000293:Adolescent; D000328:Adult; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007037:Hypothyroidism / Q000097:blood*; D008055:Lipids / Q000097:blood; D016015:Logistic Models; D008297:Male; D008713:Methimazole; D008715:Methionine / Q000008:administration & dosage; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood
D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1; D006710:Homocysteine; D008713:Methimazole; D025101:Vitamin B 6; D005340:Fibrinogen; D013972:Thyrotropin; D005492:Folic Acid; D008715:Methionine; D014805:Vitamin B 12