Background Attention deficit-hyperactivity disorder is a well-recognizedpsychiatric disorder of childhood. Its cause is unknown, butthere is evidence of a familial predisposition. Symptoms suggestiveof this disorder have been reported in subjects with generalizedresistance to thyroid hormone, a disease caused by mutationsin the thyroid receptor- gene and characterized by reduced responsivenessof peripheral and pituitary tissues to the actions of thyroidhormone. We systematically evaluated the presence and severityof attention deficit-hyperactivity disorder in 18 families witha 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 evaluatedwith structured psychiatric questionnaires by interviewers whowere unaware of the medical diagnosis. The number of symptomsof attention deficit-hyperactivity disorder was calculated foreach subject.
Results Among the adults, 11 of 22 subjects with generalizedresistance to thyroid hormone (50 percent) and 2 of 30 unaffectedsubjects (7 percent) had met the criteria for attention deficit-hyperactivitydisorder as children (P<0.001). Among the children, 19 of27 subjects resistant to thyroid hormone (70 percent) and 5of 25 unaffected subjects (20 percent) met the criteria forthe disorder (P<0.001). The odds of having attention deficit-hyperactivitydisorder were 3.2 times higher for affected male subjects thanfor affected female subjects and 2.7 times higher for unaffectedmale subjects than for unaffected female subjects. The meansymptom score was 2.5 times higher in the affected group thanin the unaffected group (7.0 vs. 2.8, P<0.001). The frequencyof other psychiatric diagnoses was similar in the two groups.
Conclusions In our study sample, attention deficit-hyperactivitydisorder is strongly associated with generalized resistanceto thyroid hormone.
Source Information
From the Molecular and Cellular Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases (P.H., A.J.M., B.D.W.); and the Section on Clinical Brain Imaging, Laboratory of Cerebral Metabolism (A.J.Z., J.A.M.), the Laboratory of Developmental Psychology (P.M.), and the Division of Basic Brain and Behavioral Sciences (B.V.), National Institute of Mental Health -- both at the National Institutes of Health, Bethesda, Md.
Address reprint requests to Dr. Hauser at the Molecular and Cellular Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bldg. 10, Rm. 8D-14, 9000 Rockville Pike, Bethesda, MD 20892.
Attention Deficit-Hyperactivity Disorder
Stein M. A., Leventhal B. L., Rowlett R., DeSpirito A. P., Hauser P., Zametkin A. J., Weintraub B., Ciaranello R. D.
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N Engl J Med 1993;
329:966-967, Sep 23, 1993.
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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. 
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