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Central nervous system (CNS) leukemia is a frequent diagnosis in pediatric acute myeloblastic leukemia (AML) and includes neural symptoms. However, CNS leukemia is rarely associated with central hypsothyroidism.A 2-year-old female with AML with MLL rearrangement presented with CNS infiltration. Laboratory tests suggested the presence of central hypothyroidism (thyroid-stimulating hormone [TSH]: 0.48 mIU/ml, normal range 0.7–6.4 mIU/ml; serum free thyroxine [FT4]: 0.62 ng/dl, normal range 0.8–2.2 ng/dl; free triiodothyronine: 1.57 pg/ml, normal range 2.7–5.6 pg/ml). Magnetic resonance imaging detected no lesions in the hypothalamus, pituitary, or thyroid.Levothyroxine (2.5 mg/kg/day) was administered together with chemotherapy and intrathecal injection of methotrexate, cytarabine, and hydrocortisone into the cerebrospinal fluid. The FT4 concentration increased after levothyroxine treatment, but later decreased after relapse of CNS leukemia. The TSH concentrations remained low. After remission of CNS leukemia, the TSH and FT4 concentrations quickly recovered to their normal ranges.We believe that the CNS leukemia directly affected TSH and thyroid hormone secretion in our patient.