CH.A.D.D. FACT SHEET ATTENTION DEFICIT DISORDER AND GENERALIZED RESISTANCE TO THYROID HORMONE (GRTH) Summary: Scientists at the National Institutes for Health (NIH) have discovered a link between Generalized Resistance to Thyroid Hormone (GRTH), a rare genetic disorder in which the body is unable to appropriately use thyroid hormone, and Attention Deficit Disorders (ADD). GRTH is believed to be relatively uncommon; it is highly unlikely that a substantial percentage of people with ADD have GRTH. The importance of this study is that it provides further evidence that ADD is a neurobiological disorder. Discussion: NIH researchers have documented a link between ADD and GRTH, a disorder caused by a gene coding for a defective thyroid hormone receptor in a selected group of patients. Persons with GRTH are unable to appropriately use thyroid hormone. Thyroid hormone is one of the most important hormones in the body, as it controls the rate of metabolism. It is essential for normal brain development. The interplay between the thyroid hormone and thyroid receptor may influence neurotransmitter systems thought to be involved in the "organic operation" of ADD. While scientists do not know the incidence of GRTH in the population, it is believed to be very rare. Researchers at NIH studied 104 members of 18 families. Forty-nine person in the sample had GRTH; 55 did not. Of the adults who had GRTH, 50% had ADD as a child. Only 7% of the adults who did not have GRTH had ADD as a child. Of the children who had GRTH, 70% were diagnosed as having ADD. Of the children who did not have GRTH, 20% were diagnosed as having ADD. The findings were published in The New England Journal of Medicine on April 8, 1993. For the vast majority of children and adults with ADD, the study will have little immediate impact. It is highly unlikely that a substantial percentage of person with ADD also have GRTH. CH.A.D.D. does not recommend, nor does the study conclude, that children with ADD be screened for GRTH as a routine measure. This study represents an invaluable addition to our knowledge of ADD. Evidence that, in a small group of person, ADD is associated with a specific gene defect lends credence to the growing understanding that AD is a neurobiologically based disorder. When discussing the importance of this research, study co-author Dr. Alan Zametkin of NIH says, "It's not bad parenting, overcrowded schools, or unmotivated kids. ADHD is a neuropsychiatric problem based on brain physiology." A document link between GRTH and ADD in some cases may prove to be a crucial clue as scientist s search for exact cause or causes of ADD. The authors recommend other studies examining a possible link between ADD and other, less obvious thyroid-related causes of ADD. Questions and Answers: Q. What does this study mean for parents of children with ADD? A. It is one more piece of evidence that ADD is a neurobiological disorder. Previous NIH research used advanced brain imaging techniques to document that adults with ADD have less than normal brain metabolism rates. This body of research, combined with other data including family studies and drug response studies, should help lay to rest non-scientific "theories" that ADD is caused by such variables as a chaotic home environment, excessive television viewing, or poor diet. In the immediate future, this study will not affect the treatment and management of the vast majority of children with ADD. Q. What is GRTH? A. GRTH is a disorder caused by a gene coding for a defective thyroid hormone receptor. According to Black's Medical Dictionary, thyroid hormone "is one of the most important in the body and controls the rat of metabolism." Thyroid hormone affects how strong our heart beats, how we concentrate and think, and the rate at which we burn calories. Thyroid hormone s produced in a small gland, called the thyroid, located under the Adam's apple in the neck. Once produced, thyroid is transmitted throughout the body via the blood stream. In order for thyroid hormone to exert its effect, it interacts with a specific receptor or "sensor' located in the nucleus of cells in the body. When there is too little thyroid hormone in the body, a person may complain of tiredness, feeling cold all the time, depression, an increase in weight or an inability to loose weight, and leg cramps. Children with too little thyroid hormone in the body may also experience abnormally slow growth. When there is too much thyroid in the body, the person may complain of heart palpitations, feeling hot all the time, weight loss despite and increase in appetite, nervousness, hair loss, and trembling hands. In some people, there is plenty of thyroid hormone, but due to a genetic defect the thyroid receptor is prevented from binding with the thyroid hormone. This leads t a situation in which the person has high levels of thyroid hormone in the blood, but has symptoms similar to someone with too little thyroid hormone. Such a condition, first identified in 1972, is called generalized resistance to thyroid hormone or GRTH. GRTH can be treated. Q. How many people have GRTH? A. The exact incidence of GRTH is not known. However, we do know that GRTH is a very rare genetic disorder whereas ADD occurs in about 3-5% ofthe population. This means that if a person has GRTH, it is likely that he or she will also have ADD symptoms. But the reverse is not true. If a person has ADD, it is not likely that he or she will also have GRTH. To better determine the incidence of GRTH, NIH researchers are collaborating with the Newborn Screening Program of the Wadsworth Center for Laboratories and Research of the New York Sate Department of Health to identify infants with GRTH. Q. Should children with ADD be routinely tested for GRTH? A. CH.A.D.D. considers this an important study, adding much to our knowledge about ADD. However, given that GRTH is such a rare disorder, CH.A.D.D. believes that it wold be premature to conclude that because of this study all children with ADD should be test for GRTH. You may want to consult with your psysician as to whether to have your child (or yourself if you are an adult with ADD) tested for GRTH. Conversely, if your child has GRTH, you may want to have him or her assessed for the presence of ADD symptoms as well s specific learning disabilities. Q. Will treatment for GRTH result in improvement in the symptoms of ADD? A. It is not yet known whether treatment for GRTH will also result in improvement in the symptoms of ADD. Please consult with your physician should you have further questions about the connection between GRTH and ADD. This fact sheet is based upon the article entitled, "Attention Deficit-Hyperactivity Disorder in People with Generalized Resistance to Thyroid Hormone" published in the April 8, 1993 issue of The New England Journal of Medicine by Peter Hauser, M.D., et al.