, Volume 2, Issue 1, pp 17–22 | Cite as

Hormone studies in patients with Huntington’s disease

  • Stephen Podolsky


Huntington’s disease (HD), characterized by progressive dementia and movement disabilities, is dominantly inherited and begins before age 40. Premature aging like neuronal degeneration and lipofuscin accumulation occur in parts of the cerebral cortex, caudate nucleus and hypothalamus. Post mortem analysis of the basal ganglia indicates a variety of neurotransmitter abnormalities occur.

Eighteen patients with Huntington’s disease were studied by oral and L-dopa modified glucose tolerance tests (GTT) and intravenous arginine tolerance tests, performed under standardized metabolic conditions. The GTT was repeated in 14 patients after three days of L-dopa administered 0.5 g three times daily plus 0.5 g given 30 minutes prior to the repeat test. Seven patients had an initial diabetic type GTT. Mean peak plasma insulin level in the nondiabetic group occurred at 1/2 hour and was 60.2 ± 10.1 μU/ml, but in the diabetic group the peak insulin level occurred at 2 hours and was 155.9 ± 33.8 μU/ml. There was failure of suppression of growth hormone (GH) during the GTT, with a rise to abnormally high levels at 5 hours (18.6 ± 5.6 ng/ml). L-dopa abolished the glucose-induced GH suppression in control subjects and instead caused a sharp rise in GH. Patients with HD had elevated pretest GH levels (17.9 ± 2.3 ng/ml) with a prompt fall after L-dopa plus glucose. Arginine infusion resulted in elevated insulin levels in HD patients with impaired glucose tolerance, compared to the nondiabetic patients (91.9 ± 17.4 μU/ml vs 45.2 ± 5.7 μU/ml). Peak GH response to arginine occurred at one hour (28.3 ± 3.7 ng/ml) and was significantly higher in the series of patients with HD than in controls.

It is uncertain whether the neurotransmitter and endocrine abnormalities in HD are secondary to hypothalamic cell death or the initial cause of cellular dysfunction in the brain.


Growth Hormone Growth Hormone Response Peak Growth Hormone Lipofuscin Accumulation Growth Hormone Suppression 
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  1. 1.
    Bruyn, G. W.: Huntington’s chorea: historical, clinical and laboratory synopsis, in Handbook of Clinical Neurology, Vol. 6, edited by Vinken, P. J., and Bruyn, G. W., Amsterdam, North Holland Publishing Co., 1968, pp. 268–275.Google Scholar
  2. 2.
    Klintworth, G. K.: Huntington’s chorea: morphologic contributions of a century, in Advances in Neurology, Vol. 1, Huntington’s Chorea, edited by Barbeau, A., Chase, T. N., and Paulson, G. W., New York, Raven Press, 1973, pp. 353–368.Google Scholar
  3. 3.
    Andres, R., and Tobin, J. D.: Aging and the disposition of glucose, in Adv. Exp. Med. Biol., Vol. 61, Explorations in Aging, edited by Cristofalo, V. J., Roberts, J., and Adelman, R. C., New York, Plenum Press, 1974, pp. 239–249.Google Scholar
  4. 4.
    Podolsky, S., Leopold, N. A., and Sax, D. S: Increased frequency of diabetes mellitus in patients with Huntington’s chorea. Lancet, 1:1356–1359, 1972.PubMedCrossRefGoogle Scholar
  5. 5.
    Podolsky, S., and Leopold, N. A.: Growth hormone abnormalities in Huntington’s chorea effect of L-dopa administration. J. Clin. Endocrinol. Metab., 39:36–39, 1974.PubMedGoogle Scholar
  6. 6.
    Podolsky, S., and Leopold, N. A.: Abnormal glucose tolerance and arginine tolerance tests in Huntington’s disease. Gerontology, 23:55–63, 1977.PubMedGoogle Scholar
  7. 7.
    Phillipson, O. T., and Bird, E. D.: Plasma glucose, non-esterified fatty acids and amino acids in Huntington’s chorea. Clin. Science Mol. Med., 52:311–318, 1977.Google Scholar
  8. 8.
    Davidson, M. D., Green, S., and Menkes, J. H.: Normal glucose, insulin and growth hormone responses to oral glucose in Huntington’s disease. J. Lab. Clin. Med., 84:807–812, 1974.Google Scholar
  9. 9.
    Fajans, S. S., and Conn, J. W.: Early recognition of diabetes mellitus. Ann. N. Y. Acad. Sci., 82: 208–218, 1959.PubMedGoogle Scholar
  10. 10.
    Podolsky, S.: Huntington’s disease: premature brain aging with abnormalities of chemical neurotransmitters and hormonal function, in Biophysical and Biochemical Information Transfer in Recognition, edited by Vassileva-Popova, J. G., and Jensen, E. V., New York, Plenum Press, 1978, pp. 271–280.Google Scholar
  11. 11.
    Podolsky, S., and Leopold, N. A.: Growth hormone secretion in Huntington’s disease, in Growth Hormone and Related Peptides, edited by Pecile, A., and Muller, E. E., Amsterdam, Excepta Medica, 1976, pp. 252–260.Google Scholar
  12. 12.
    Caraceni, T., Paneri, A. E., Parati, E. A., Cocchi, D., and Muller, E. E.: Altered growth hormone and prolactin responses to dopaminergic stimulation in Huntington’s chorea. J. Clin. Endocrinol. Metab., 44: 870–875, 1977.PubMedGoogle Scholar
  13. 13.
    Krall, L. P., and Podolsky, S.: Long-term clinical observations of diabetic retinopathy, in Diabetes, edited by Rodriguez, R. R., and Vallence-Owen, J., Amsterdam, Excerpta Medica, 1971, pp. 268–275.Google Scholar
  14. 14.
    Podolsky, S.: Lipoatrophic diabetes and miscellaneous conditions related to diabetes mellitus, in Joslin’s Diabetes Mellitus, Eleventh Edition, edited by Marble, A., White, P., Bradley, R. F., and Krall, L. P., Philadelphia, Lea & Febiger, 1971, pp. 722–766.Google Scholar
  15. 15.
    Bolt, J. M. W., and Lewis, G. P.: Huntington’s chorea: A study of liver function and histology. Quart, J. Med., 42:151–174, 1973.Google Scholar
  16. 16.
    Oseid, S., Beck-Neilson, H., Pedersen, O., et al.: Decreased binding of insulin to its receptor in patients with congenital generalized lipodystrophy. New Engl. J. Med., 296:245–248, 1977.PubMedCrossRefGoogle Scholar
  17. 17.
    Podolsky, S., and Sheremata, W. A.: Insulin-dependent diabetes mellitus and Friedreich’s ataxia in siblings. Metabolism, 19:555–561, 1970.PubMedCrossRefGoogle Scholar
  18. 18.
    Poffenbarger, P. L., Pozefsky, T., and Soeldner, J. S.: The direct relationship of proinsulin-insulin hypersecretion to basal serum levels of cholesterol and triglyceride in myotonic dystrophy. J. Lab. Clin. Med., 87:384–396, 1976.PubMedGoogle Scholar
  19. 19.
    Schalch, D. S., Re, P. K., and Lee, L.: Diabetes mellitus and ataxia telangiectasia: Persistence of insulin hypersecretion over a six year interval. Mod. Probl. Paediat., 12:229–234, 1975.Google Scholar
  20. 20.
    Goldstein, S., and Podolsky, S.: The genetics of diabetes mellitus. Med. Clin. N. Amer., 62:639–654, 1978.PubMedGoogle Scholar
  21. 21.
    Colwell, J. A., and Lein, A.: Diminished insulin response to hyperglycemia in prediabetes and diabetes. Diabetes, 16:560–565, 1967.PubMedGoogle Scholar
  22. 22.
    Andres, R., and Tobin, J. D.: Endocrine systems, in Handbook of the Biology of Aging, edited by Finch, C. E., and Hayflick, L., New York, Van Nostrand-Reinhold, 1977, pp. 357–378.Google Scholar
  23. 23.
    Glick, S. M., Roth, J., Yalow, R. S., and Berson, S. A.: The regulation of growth hormone secretion. Recent Prog. Horm. Res., 21:241–283, 1965.PubMedGoogle Scholar
  24. 24.
    Hartog, M., Gaafar, M. A., Meisser, B., and Fraser, R.: Immunoassay of serum growth hormone in acromegalic patients. Brit. Med. J., 2:1229–1232, 1964.PubMedCrossRefGoogle Scholar
  25. 25.
    Reichlin, S.: Physiology of growth hormone regulation: pre-and post-immunoassay eras. Metabolism, 22: 987–993, 1973.PubMedCrossRefGoogle Scholar
  26. 26.
    Podolsky, S., Zimmerman, H. J., Burrows, B. A., Cardarelli, J. A., and Pattavina, C. G.: Potassium depletion in hepatic cirrhosis: a reversible cause of impaired growth hormone and insulin response to stimulation. New Engl. J. Med., 288:644–648, 1973.PubMedCrossRefGoogle Scholar
  27. 27.
    Podolsky, S., and Bryan, R. S.: Albright’s syndrome (polyostotic fibrous dysplasia of bone) with sexual precocity, dermoid cyst of ovary, hyperthyroidism, and insulin and growth hormone abnormalities, in Clinical Aspects of Metabolic Bone Disease, edited by Frame, B., Parfitt, A. M., and Duncan, H., Amsterdam, Excerpta Medica, 1973, pp. 484–486.Google Scholar
  28. 28.
    Boyd, A. E., III, Lebovitz, H. E., and Pfeiffer, J. B.: Stimulation of human growth hormone secretion by L-DOPA. New Engl. J. Med., 283:1425–1429, 1970.PubMedCrossRefGoogle Scholar
  29. 29.
    Eddy, R. L., Jones, A. L., Chakmakjian, Z. H., and Silverthorne, M. C.: Effect of levodopa (L-DOPA) on human hypophyseal trophic hormone release. J. Clin. Endocrinol. Metab., 33:709–712, 1971.PubMedGoogle Scholar
  30. 30.
    Hokfelt, T., and Fuxe, K.: Effects of prolactin and ergot alkaloids on the tubero-infundibular dopamine (DA) neurons. Neuroendocrinology, 9:100–122, 1972.PubMedGoogle Scholar
  31. 31.
    Fuxe, K., Hokfelt, T., Sundstedt, C.-D., Ahren, K., and Hamberger, L.: Amine turnover changes in the tubero-infundibular dopamine (DA) neurons in immature rats injected with PMS. Neuroendocrinology, 10: 282–800, 1972.PubMedGoogle Scholar
  32. 32.
    Martin, J. B.: Neural regulation of growth hormone secretion. New Engl. J. Med., 288:1384–1393, 1973.PubMedCrossRefGoogle Scholar
  33. 33.
    Leopold, N. A., and Podolsky, S.: Exaggerated growth hormone response to arginine infusion in Huntington’s disease. J. Clin. Endocrinol. Metab., 41:160–163, 1975.PubMedGoogle Scholar
  34. 34.
    Phillipson, O. T., and Bird, E. D.: Plasma growth hormone concentrations in Huntington’s chorea. Clin. Science Mol. Med., 50:551–554, 1976.Google Scholar
  35. 35.
    Keogh, H. J., Johnson, R. H., Nanda, R. N., and Sulaiman, W. R.: Altered growth hormone release in Huntington’s chorea. J. Neur., Neurosurg. and Psych., 39:244–248, 1976.CrossRefGoogle Scholar
  36. 36.
    Martin, M. M., Gaboardi, F., Podolsky, S., Raiti, S., and Calcagno, P.: Intermittent steroid therapy: Its effect on hypothalamic-pituitary-adrenal function and the response of plasma growth hormone and insulin to stimulation. New Engl. J. Med., 279:273–278, 1968.PubMedCrossRefGoogle Scholar
  37. 37.
    Podolsky, S., and Sivaprasad, R.: Assessment of growth hormone reserve: Comparison of intravenous arginine and subcutaneous glucagon stimulation tests. J. Clin. Endocrinol. Metab., 35:58–584, 1972.CrossRefGoogle Scholar
  38. 38.
    Saifer, A., and Gerstenfeld, S.: The photometric microdetermination of blood glucose with glucose oxidase. J. Lab. Clin. Med., 51:448–460, 1958.PubMedGoogle Scholar
  39. 39.
    Herbert, V., Lau, K. S., Gottlieb, C. W., and Bleicher, S. J.: Coated charcoal immunoassay of insulin. J. Clin. Endocrinol. Metab., 25:1375–1384, 1965.PubMedCrossRefGoogle Scholar
  40. 40.
    Lau, K. S., Gottlieb, C. W., and Herbert, V.: Preliminary report on coated charcoal immunoassay of human chorionic “growth hormone-prolactin” and growth hormone. Proc. Soc. Exp. Biol. Med., 123: 126–131, 1966.PubMedGoogle Scholar

Copyright information

© American Aging Association, Inc. 1979

Authors and Affiliations

  • Stephen Podolsky
    • 1
  1. 1.Endocrinology and Metabolism SectionBoston VA Outpatient ClinicBoston

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