One of the more consistent findings in leukemia research is the association between birth weight and childhood leukemia. Because thyroid hormones are critically involved in growth and differentiation, we speculated that hormone levels could be of significance to the development of leukemia in early life. Specifically, we hypothesized that high levels of thyroid-stimulating hormone (TSH) would be associated with a low risk of leukemia. Accordingly, high TSH (low free thyroid hormone) early after birth most likely reflects low function of the thyroid accompanied by low rate of cell turn-over and so lower risk of faulty cell divisions leading to cancer. In a matched case-control study nested from all singleton children born in Denmark between 1986 and 1998, we compared levels of TSH (as measured in a neonatal screening program for congenital hypothyroidism) in 188 cases of acute lymphoblastic leukemia (ALL) and 28 of acute myeloid leukemia (AML) with levels in 1,450 and 216 matched controls, respectively. Data were analyzed using conditional logistic regression and odds ratios (OR) were adjusted for birth weight. As hypothesized, we found a decreased risk of ALL and AML associated with high TSH (OR(ALL) = 0.7 [0.5-1.0]; OR(AML) = 0.3 [0.1-1.0]). However, both conditions were also associated with low levels of TSH (OR(ALL) = 0.4 [0.2-0.7]; OR(AML) = 0.3 [0.1-1.4]). In conclusion, extreme TSH levels a few days after birth appears to be associated with a decreased risk of acute childhood leukemia. (C) 2000 Wiley-Liss, Inc.