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ARTICLES: N. A. Aziz, J.M.M. van der Burg, G. B. Landwehrmeyer, P. Brundin, T. Stijnen, EHDI Study Group, and R. A.C. Roos Weight loss in Huntington disease increases with higher CAG repeat number Neurology 2008; 71: 1506-1513 [Abstract] [Full text] [PDF]

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Weight loss in Huntington disease increases with higher CAG repeat number

Gordon J. Gilbert   (29 January 2009)

Reply from the authors

N. Ahmad Aziz, Jorien M.M. van der Burg, G. Bernhard Landwehrmeyer, Patrik Brundin, Theo Stijnen, and Raymund A.C. Roos   (29 January 2009)

Weight loss in Huntington disease increases with higher CAG repeat number 29 January 2009
Gordon J. Gilbert 500 Pasadena Avenue South, St. Petersburg, FL 33707 Send Correspondence to journal: Re: Weight loss in Huntington disease increases with higher CAG repeat number drgg22{at}tampabay.rr.com Gordon J. Gilbert	I read the article by Aziz et al. with interest. [1] The authors present a strong case for a hyper-metabolic link between expanding CAG repeat number and the characteristic weight loss in Huntington disease (HD). It is notable that such recognized hyper-metabolic disorders as thyrotoxicosis may also cause chorea. Perhaps therapeutic efforts to lower the metabolic rate by suppressing thyroid function should be investigated in patients with HD. Reference 1. Aziz NA, van der Burg GB, Landwehrmeyer GB et al. Weight loss in Huntington disease increases with higher CAG repeat number. Neurology 2008;71:1506-1513. Disclosure: The author reports no disclosures.
Reply from the authors 29 January 2009
N. Ahmad Aziz, Leiden University Medical Center, Department of Neurology K-05-Q 110, P.O. Box 9600, Albinusdreef 2, 2300 RC Leiden, the Netherlands, Jorien M.M. van der Burg, G. Bernhard Landwehrmeyer, Patrik Brundin, Theo Stijnen, and Raymund A.C. Roos Send Correspondence to journal: Re: Reply from the authors N.A.Aziz{at}lumc.nl N. Ahmad Aziz, et al.	We appreciate Dr. Gilbert’s interest in our findings. [1] The concept of suppressing thyroid function in HD in order to counteract weight loss is intriguing. In addition, as Dr. Gilbert also points out, thyroid hormone excess has been associated with chorea so altering thyroid function might also influence the choreactic movements in HD. [2] However, a number of caveats should be considered. First, although we found an increased rate of weight loss in HD patients with higher CAG repeat number, the precise mechanisms underlying this association are still unclear. [1] A higher metabolic rate due to mitochondrial dysfunction may be involved, but whether mitochondrial dysfunction in HD would respond to changes in thyroid hormone levels has yet to be investigated. [1] Second, the hypothalamic-pituitary-thyroid axis function has been rarely studied in HD patients. [3] Although normal basal levels of thyroxine, triiodothyronine and thyroid-stimulating hormone (TSH) have been reported in HD patients, others have found an impaired TSH response to thyrotropin-releasing hormone stimulation. [3] Therefore, more detailed studies of thyroid function in HD are needed. Third, besides regulating bodies metabolic rate, thyroid hormones have also a myriad of other effects, including the regulation of normal brain function, heart rate and myocardial contractility, gastrointestinal motility and renal water clearance. Moreover, as thyroid hormones affect protein synthesis and degradation, they can also alter the production, responsiveness and metabolic clearance of other hormones. Therefore, iatrogenically induced changes in thyroid function are likely to entail complex alterations in systemic physiology. However, the concept of direct modulation of the metabolic rate in HD remains intriguing and should be tested in the transgenic disease models now available. It is interesting that caloric restriction, which is known to lower basal metabolic rate, has been shown to slow disease progression, ameliorate weight loss, and increase survival in an HD transgenic mouse model.[4] References 2. Sudo K, Tashiro K. Hyperthyroidism-associated chorea. Lancet 1998;352:239. 3. Aziz NA, Swaab DF, Pijl H, Roos RA. Hypothalamic dysfunction and neuroendocrine and metabolic alterations in Huntington's disease: clinical consequences and therapeutic implications. Rev Neurosci 2007;18:223-251. 4. Duan W, Guo Z, Jiang H, Ware M, Li XJ, Mattson MP. Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc Natl Acad Sci USA 2003; 100:2911-2916. Disclosure: The authors report no disclosures.