Attention deficit-hyperactivity disorder in people with generalized resistance to thyroid hormone


Hauser P, Zametkin AJ




N Engl J Med


BACKGROUND. Attention deficit-hyperactivity disorder is a well-recognized psychiatric disorder of childhood. Its cause is unknown, but there is evidence of a familial predisposition. Symptoms suggestive of this disorder have been reported in subjects with generalized resistance to thyroid hormone, a disease caused by mutations in the thyroid receptor-beta gene and characterized by reduced responsiveness of peripheral and pituitary tissues to the actions of thyroid hormone. We systematically evaluated the presence and severity of attention deficit-hyperactivity disorder in 18 families with a history of generalized resistance to thyroid hormone. METHODS. We studied 49 affected and 55 unaffected family members; 52 were adults, and 52 were children. All subjects were evaluated with structured psychiatric questionnaires by interviewers who were unaware of the medical diagnosis. The number of symptoms of attention deficit-hyperactivity disorder was calculated for each subject. RESULTS. Among the adults, 11 of 22 subjects with generalized resistance to thyroid hormone (50 percent) and 2 of 30 unaffected subjects (7 percent) had met the criteria for attention deficit-hyperactivity disorder as children (P < 0.001). Among the children, 19 of 27 subjects resistant to thyroid hormone (70 percent) and 5 of 25 unaffected subjects (20 percent) met the criteria for the disorder (P < 0.001). The odds of having attention deficit-hyperactivity disorder were 3.2 times higher for affected male subjects than for affected female subjects and were 2.7 times higher for unaffected male subjects than for unaffected female subjects. The mean symptom score was 2.5 times higher in the affected group than in the unaffected group (7.0 vs. 2.8, P < 0.001). The frequency of other psychiatric diagnoses was similar in the two groups. CONCLUSIONS. In our study sample, attention deficit-hyperactivity disorder is strongly associated with generalized resistance to thyroid hormone.