Correspondence

Attention Deficit-Hyperactivity Disorder

N Engl J Med 1993; 329:966-967September 23, 1993

Article

To the Editor:

The report by Hauser et al. (April 8 issue)1 suggests that “attention deficit-hyperactivity disorder is strongly associated with generalized resistance to thyroid hormone.” In this study, the diagnoses of attention deficit-hyperactivity disorder were based on interviews, parental reports, or retrospective evaluations. At first glance (or retrospectively), other psychiatric or medical disorders may seem to mimic this disorder. Indeed, the presence of other psychiatric disorders or cognitive dysfunction (e.g., pervasive developmental disorders, mental retardation, and learning disabilities) has been reported in patients with generalized resistance to thyroid hormone2. Unfortunately, diagnoses based only on parental reports or questionnaires focused solely on criteria from the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised,3 may fail to detect these other disorders and could easily lead to the misdiagnosis of attention deficit-hyperactivity disorder.

An additional problem is the retrospective diagnosis of attention deficit-hyperactivity disorder. There are no validated measures for the retrospective diagnosis of this disorder in childhood. Therefore, extreme caution should be used before any relation can be assumed between generalized resistance to thyroid hormone and the presumptive childhood diagnosis of attention deficit-hyperactivity disorder.

Mark A. Stein, Ph.D.
Bennett L. Leventhal, M.D.
University of Chicago, Chicago, IL 60637

3 References

1. 1

   Hauser P, Zametkin AJ, Martinez P, et al. Attention deficit-hyperactivity disorder in people with generalized resistance to thyroid hormone. N Engl J Med 1993;328:997-1001
   Full Text | Web of Science | Medline

2. 2

   Refetoff S, Weiss RE, Usala SJ. The syndromes of resistance to thyroid hormone. Endocr Rev 1993;14:348-399
   Web of Science | Medline

3. 3

   Diagnostic and statistical manual of mental disorders, 3rd ed. rev.: DSM-III-R. Washington, D.C.: American Psychiatric Association, 1987.
   

To the Editor:

Generalized resistance to thyroid hormone is a rare disorder, whereas attention deficit-hyperactivity disorder occurs in about 5 percent of children. If 50 to 70 percent of the patients with a rare thyroid malady also have attention deficit-hyperactivity disorder, then the most compelling conclusion one can draw is that other patients with generalized resistance to thyroid hormone should be screened for this disorder. We are concerned that the considerable lay audience for research in this area will falsely conclude that all children with attention deficit-hyperactivity disorder should have thyroid-function tests at substantial cost, and that children who have had a less than optimal response to psychomotor stimulant drugs should be treated with triiodothyronine. We trust that this was not the authors' intent.

Randall Rowlett, M.D.
Linda Zetley, M.D.
250 W. Coventry Ct., Milwaukee, WI 53217

To the Editor:

I take exception to the editorial comment by Dr. Ciaranello (April 8 issue)1 that “a comprehensive evaluation of a child suspected of having [attention deficit-hyperactivity] disorder must include pediatric, neurologic, and psychiatric assessments.” There are instances in which such consultations are necessary, but they are not appropriate for every child with attention deficit-hyperactivity disorder. The pediatrician who receives training in developmental pediatrics is now well prepared to handle many of these children with only an occasional consultation.

Anthony P. DeSpirito, M.D.
Jersey Shore Medical Center, Neptune, NJ 07754

1 References

1. 1

   Ciaranello RD. Attention deficit-hyperactivity disorder and resistance to thyroid hormone -- a new idea? N Engl J Med 1993;328:1038-1039
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Stein and Leventhal question the validity of the diagnosis of attention deficit-hyperactivity disorder in patients with generalized resistance to thyroid hormone. The psychiatric diagnoses in our study were obtained with validated and structured psychiatric interviews. Because the disorder, by definition, presents in childhood, its diagnosis in adults can only be retrospective. In our study, however, the majority of adults given a diagnosis of attention deficit-hyperactivity disorder as children continued to have symptoms of the disorder as adults. In addition, most children had enough symptoms at the time of the interview to meet the criteria for the disorder. None of the patients had a history of pervasive developmental disorders. Neuropsychological tests showed that only three patients had a full-scale IQ of less than 70, the definition of mild mental retardation1. Although specific developmental disorders (commonly called learning disabilities), particularly language disorders, have been noted in some patients with generalized resistance to thyroid hormone,2 their presence does not preclude the diagnosis of attention deficit-hyperactivity disorder. It is not uncommon to find both disorders in the same person3.

Rowlett and Zetley are concerned about the public's interpretation of our findings and ask for clarification of our intent. As we stated, it is unlikely that a substantial percentage of people with attention deficit-hyperactivity disorder also have generalized resistance to thyroid hormone. This condition is relatively uncommon, but in many cases it either is misdiagnosed as hyperthyroidism or is not diagnosed until adulthood. In a recent screening study of newborns, thyroid hormone abnormalities suggestive of generalized resistance to thyroid hormone occurred as frequently as once in 10,000 to 30,000 live births4. Prospective studies should be undertaken to determine the prevalence of generalized resistance to thyroid hormone and other less obvious thyroid hormone abnormalities in people with attention deficit-hyperactivity disorder. We do not currently recommend routine thyroid hormone screening of children and adults with the disorder, but instead advise a more selective approach, screening only those with symptoms suggestive of thyroid disease or a family history of it. Finally, we do not recommend thyroid hormone treatment for children with attention deficit-hyperactivity disorder.

Peter Hauser, M.D.
Alan J. Zametkin, M.D.
Bruce Weintraub, M.D.
National Institutes of Health, Bethesda, MD 20892

4 References

1. 1

   Hauser P, Wiggs E, Leonard C, Mixson AJ, An S, Weintraub BD. Neurobiologic correlates of generalized resistance to thyroid hormone. Presented at the American Federation of Clinical Research Annual Meeting, Washington, D.C., 1993. abstract.
   

2. 2

   Mixson AJ, Parrilla R, Ransom SC, et al. Correlations of language abnormalities with localization of mutations in the beta-thyroid receptor in 13 kindreds with generalized resistance to thyroid hormone: identification of four new mutations. J Clin Endocrinol Metab 1992;75:1039-1045
   CrossRef | Web of Science | Medline

3. 3

   Shaywitz BA, Shaywitz SE. Comorbidity: a critical issue in attention deficit disorder. Child Neurol 1991;6:Suppl:S13-S22
   

4. 4

   Pass KA, Hedden MB, Morris JE, Mizejewski GJ. Newborn screening for thyroid resistance: implications for attention deficit-hyperactivity disorder. Presented at the Second Annual Meeting of the International Society for Neonatal Screening, Lille, France, 1993. abstract.
   

Author/Editor Response

In response to Dr. DeSpirito, perhaps my experience has been skewed, but I have always found attention deficit-hyperactivity disorder to be a difficult diagnostic and treatment problem. In addition to all the psychosocial problems that must be considered, there are neurologic and metabolic disorders that share features with the disorder and sometimes mimic it entirely. I have wanted the help of my colleagues in pediatrics and neurology to rule out treatable metabolic and neurologic disorders before deciding to initiate stimulant medication or some other treatment.

My experience has been that my colleagues in pediatric medicine need my help as well, and I am flattered that they have not hesitated to ask for it. In particular, the busy pediatrician may lack the time to follow a patient taking stimulant medication as closely as most studies suggest is necessary. A good deal of dose adjustment is necessary, with frequent follow-up visits and discussions with the child and family; it is difficult to do this in a brief office visit. I would not quarrel with Dr. DeSpirito if he believes he can do this himself, although I would if he said it did not need to be done.

Roland D. Ciaranello, M.D.
Stanford University School of Medicine, Stanford, CA 94305

Citing Articles (1)

Citing Articles

1. 1

   P. Ucls, S. Lorente, F. Rosa. (1996) Neurophysiological methods testing the psychoneural basis of attention deficit hyperactivity disorder. Child's Nervous System 12:4, 215-217
   CrossRef