Attention Deficit-Hyperactivity Disorder in People with Generalized Resistance to Thyroid Hormone

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-β 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 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., Attention deficit-hyperactivity disorder is one of a group of disruptive behavior disorders that also includes conduct and oppositional disorders¹. The major symptoms are motor restlessness, impulsiveness, inattention, and distractibility. Persons with this disorder have little evidence of neuroanatomical abnormalities or abnormalities of neurotransmitter function,² and the few studies of neuroendocrine function have largely been confined to the effects of treatment with sympathomimetic medications³. Studies of families suggest that relatives of children with attention deficit-hyperactivity disorder have a much higher risk of this disorder as well as of antisocial personality disorder and depression than do relatives of children without…