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letter
. 1982 Dec;74(12):1195–1210.

Endocrine Metabolic Relationships in Patients with Leprechaunism

M Joycelyn Elders, HK Schedewie, J Olefsky, B Givens, F Char, DM Bier, D Baldwin, RH Fiser, S Seyedabadi, Arthur Rubenstein
PMCID: PMC2561419  PMID: 7154104

Abstract

Leprechaunism is a rare, heritable syndrome, associated with multiple dysmorphic and pathologic features, suggestive of an endocrine dysfunction. Few endocrine and metabolic studies have been obtained because of the rarity of the syndrome, and the small size and early demise of these infants. The authors present here the clinical, anatomic, and endocrine-metabolic studies of three patients, with a view toward careful delineation of the syndrome and further characterization of the metabolic defect.

The most striking and consistent metabolic derangements present in all of these patients were fasting hypoglycemia (less than 20 mg/dL), postprandial hyperglycemia (more than 250 mg/dL), marked hyperinsulinemia (more than 2000 μU/mL), and severe insulin resistance (less than a 20 percent decrease in blood sugar with 0.3 to 1.0 U/kg of regular insulin IV). Hyperinsulinemia was observed in response to oral feedings and glucose infusion, and after tolbutamide. Insulin secretion was less marked with amino acid infusions. Normal increments in blood glucose occurred following alanine, galactose, and glycerol. Glucagon caused a rise in glucose 4 hours after a meal, but no response was seen after a 12-hour fast. Pituitary, gonadal, and adrenal hormone levels were normal, and there was a normal response pattern to GnRH and TRH. Hyperinsulinemia would appear to be the biochemical hallmark of this disease. Our previous studies were suggestive of a postreceptor defect in insulin action. The present endocrine-metabolic studies are compatible with this hypothesis. Interaction of supraphysiologic concentrations of plasma insulin with growth factor receptors, this may provide a partial explanation for some of the dysmorphic features seen in the disorder.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Archer J. A., Gorden P., Roth J. Defect in insulin binding to receptors in obese man. Amelioration with calorie restriction. J Clin Invest. 1975 Jan;55(1):166–174. doi: 10.1172/JCI107907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aynsley-Green A., Williamson D. H., Gitzelmann R. Hepatic glycogen synthetase deficiency. Definition of syndrome from metabolic and enzyme studies on a 9-year-old girl. Arch Dis Child. 1977 Jul;52(7):573–579. doi: 10.1136/adc.52.7.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bar R. S., Gorden P., Roth J., Kahn C. R., De Meyts P. Fluctuations in the affinity and concentration of insulin receptors on circulating monocytes of obese patients: effects of starvation, refeeding, and dieting. J Clin Invest. 1976 Nov;58(5):1123–1135. doi: 10.1172/JCI108565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. COONS A. H., LEDUC E. H., CONNOLLY J. M. Studies on antibody production. I. A method for the histochemical demonstration of specific antibody and its application to a study of the hyperimmune rabbit. J Exp Med. 1955 Jul 1;102(1):49–60. doi: 10.1084/jem.102.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. D'Ercole A. J., Underwood L. E., Groelke J., Plet A. Leprechaunism: studies of the relationship among hyperinsulinism, insulin resistance, and growth retardation. J Clin Endocrinol Metab. 1979 Mar;48(3):495–502. doi: 10.1210/jcem-48-3-495. [DOI] [PubMed] [Google Scholar]
  6. DONOHUE W. L., UCHIDA I. Leprechaunism: a euphemism for a rare familial disorder. J Pediatr. 1954 Nov;45(5):505–519. doi: 10.1016/s0022-3476(54)80113-2. [DOI] [PubMed] [Google Scholar]
  7. Dekaban A. Metabolic and chromosomal studies in leprechaunism. Arch Dis Child. 1965 Dec;40(214):632–636. doi: 10.1136/adc.40.214.632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Elders M. J., Wingfield B. S., McNatt M. L., Clarke J. S., Hughes E. R. Glucocorticoid therapy in children. Effect on somatomedin secretion. Am J Dis Child. 1975 Dec;129(12):1393–1396. doi: 10.1001/archpedi.1975.02120490011005. [DOI] [PubMed] [Google Scholar]
  9. Exton J. H. Gluconeogenesis. Metabolism. 1972 Oct;21(10):945–990. doi: 10.1016/0026-0495(72)90028-5. [DOI] [PubMed] [Google Scholar]
  10. Flier J. S., Kahn C. R., Roth J., Bar R. S. Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance. Science. 1975 Oct 3;190(4209):63–65. doi: 10.1126/science.170678. [DOI] [PubMed] [Google Scholar]
  11. GRUENWALD P., HOANG NGOC MINH Evaluation of body and organ weights in perinatal pathology. I. Normal standards derived from autopsies. Am J Clin Pathol. 1960 Sep;34:247–253. doi: 10.1093/ajcp/34.3.247. [DOI] [PubMed] [Google Scholar]
  12. Gavin J. R., 3rd, Roth J., Neville D. M., Jr, de Meyts P., Buell D. N. Insulin-dependent regulation of insulin receptor concentrations: a direct demonstration in cell culture. Proc Natl Acad Sci U S A. 1974 Jan;71(1):84–88. doi: 10.1073/pnas.71.1.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hall K. Quantative determination of the sulphation factor activity in human serum. Acta Endocrinol (Copenh) 1970 Feb;63(2):338–350. doi: 10.1530/acta.0.0630338. [DOI] [PubMed] [Google Scholar]
  14. Hamilton A. I., Blackwood H. J. Insulin deficiency and cell proliferation in oral mucosal epithelium of the rat. J Anat. 1977 Dec;124(Pt 3):757–763. [PMC free article] [PubMed] [Google Scholar]
  15. Haymond M. W., Karl I. E., Pagliara A. S. Ketotic hypoglycemia: an amino acid substrate limited disorder. J Clin Endocrinol Metab. 1974 Apr;38(4):521–530. doi: 10.1210/jcem-38-4-521. [DOI] [PubMed] [Google Scholar]
  16. Heitz P. U., Klöppel G., Häcki W. H., Polak J. M., Pearse A. G. Nesidioblastosis: the pathologic basis of persistent hyperinsulinemic hypoglycemia in infants. Morphologic and quantitative analysis of seven cases based on specific immunostaining and electron microscopy. Diabetes. 1977 Jul;26(7):632–642. doi: 10.2337/diab.26.7.632. [DOI] [PubMed] [Google Scholar]
  17. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  18. Horner J. M., Hintz R. L. Further comparisons of the [125I]somatomedin A and the [125I]somatomedin C radioreceptor assays of somatomedin peptide. J Clin Endocrinol Metab. 1979 Jun;48(6):959–963. doi: 10.1210/jcem-48-6-959. [DOI] [PubMed] [Google Scholar]
  19. KALLO A., LAKATOS I., SZIJARTO L. LEPRECHAUNISM (DONOHUE'S SYNDROME). J Pediatr. 1965 Feb;66:372–379. doi: 10.1016/s0022-3476(65)80195-0. [DOI] [PubMed] [Google Scholar]
  20. Kahn C. R., Flier J. S., Bar R. S., Archer J. A., Gorden P., Martin M. M., Roth J. The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N Engl J Med. 1976 Apr 1;294(14):739–745. doi: 10.1056/NEJM197604012941401. [DOI] [PubMed] [Google Scholar]
  21. Kobayashi M., Olefsky J. M., Elders J., Mako M. E., Given B. D., Schedwie H. K., Fiser R. H., Hintz R. L., Horner J. A., Rubenstein A. H. Insulin resistance due to a defect distal to the insulin receptor: demonstration in a patient with leprechaunism. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3469–3473. doi: 10.1073/pnas.75.7.3469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Larner J., Lawrence J. C., Walkenbach R. J., Roach P. J., Hazen R. J., Huang L. C. Insulin control of glycogen synthesis. Adv Cyclic Nucleotide Res. 1978;9:425–439. [PubMed] [Google Scholar]
  23. Marshall R. N., Underwood L. E., Voina S. J., Foushee D. B., Van Wyk J. J. Characterization of the insulin and somatomedin-C receptors in human placental cell membranes. J Clin Endocrinol Metab. 1974 Aug;39(2):283–292. doi: 10.1210/jcem-39-2-283. [DOI] [PubMed] [Google Scholar]
  24. Muggeo M., Bar R. S., Roth J., Kahn C. R., Gorden P. The insulin resistance of acromegaly: evidence for two alterations in the insulin receptor on circulating monocytes. J Clin Endocrinol Metab. 1979 Jan;48(1):17–25. doi: 10.1210/jcem-48-1-17. [DOI] [PubMed] [Google Scholar]
  25. Olefsky J. M. Mechanisms of the ability of insulin to activate the glucose-transport system in rat adipocytes. Biochem J. 1978 Apr 15;172(1):137–145. doi: 10.1042/bj1720137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Olefsky J. M., Reaven G. M. Decreased insulin binding to lymphocytes from diabetic subjects. J Clin Invest. 1974 Dec;54(6):1323–1328. doi: 10.1172/JCI107878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Oseid S., Beck-Nielsen H., Pedersen O., Sovik O. Decreased binding of insulin to its receptor in patients with congenital generalized lipodystrophy. N Engl J Med. 1977 Feb 3;296(5):245–248. doi: 10.1056/NEJM197702032960503. [DOI] [PubMed] [Google Scholar]
  28. PATTERSON J. H., WATKINS W. L. Leprechaunism in a male infant. J Pediatr. 1962 May;60:730–739. doi: 10.1016/s0022-3476(62)80100-0. [DOI] [PubMed] [Google Scholar]
  29. Pagliara A. S., Karl I. E., Haymond M., Kipnis D. M. Hypoglycemia in infancy and childhood. II. J Pediatr. 1973 Apr;82(4):558–577. doi: 10.1016/s0022-3476(73)80581-5. [DOI] [PubMed] [Google Scholar]
  30. Rudel L. L., Felts J. M., Morris M. D. Exogenous cholesterol transport in rabbit plasma lipoproteins. Biochem J. 1973 Jun;134(2):531–537. doi: 10.1042/bj1340531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. SCHALCH D. S., PARKER M. L. A SENSITIVE DOUBLE ANTIBODY IMMUNOASSAY FOR HUMAN GROWTH HORMONE IN PLASMA. Nature. 1964 Sep 12;203:1141–1142. doi: 10.1038/2031141a0. [DOI] [PubMed] [Google Scholar]
  32. SCHULZ D. M., GIORDANO D. A., SCHULZ D. H. Weights of organs of fetuses and infants. Arch Pathol. 1962 Sep;74:244–250. [PubMed] [Google Scholar]
  33. Sherwin R. S., Hendler R. G., Felig P. Effect of ketone infusions on amino acid and nitrogen metabolism in man. J Clin Invest. 1975 Jun;55(6):1382–1390. doi: 10.1172/JCI108057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sizonenko P. C., Paunier L., Vallotton B., Cuendet G. S., Zahnd G., Marliss E. B. Response to 2-deoxy-D-glucose and to glucagon in "ketotic hypoglycemia" of childhood: evidence for epinephrine deficiency and altered alanine availability. Pediatr Res. 1973 Dec;7(12):983–993. doi: 10.1203/00006450-197312000-00007. [DOI] [PubMed] [Google Scholar]
  35. Smals A. G., Kloppenborg P. W., Benraad T. J. Diurnal plasma testosterone rhythm and the effects of short-term ACTH administration on plasma testosterone in man. J Clin Endocrinol Metab. 1974 Apr;38(4):608–611. doi: 10.1210/jcem-38-4-608. [DOI] [PubMed] [Google Scholar]
  36. Sonowane M., Savory J., Cross R. E., Heintges M. G., Chester B. Kinetic measurement of glucose with a centrifugal analyzer; hexokinase and glucose oxidase procedures compared. Clin Chem. 1976 Jul;22(7):1100–1101. [PubMed] [Google Scholar]
  37. Tzagournis M., Chiles R., Herrold J., Skillman T. The role of endogenous insulin in different hyperlipidemic states. Diabetologia. 1972 Jul;8(3):215–220. doi: 10.1007/BF01212265. [DOI] [PubMed] [Google Scholar]
  38. UNGER R. H., EISENTRAUT A. M., McCALL M. S., MADISON L. L. Glucagon antibodies and an immunoassay for glucagon. J Clin Invest. 1961 Jul;40:1280–1289. doi: 10.1172/JCI104357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Van Wyk J. J., Underwood L. E., Hintz R. L., Clemmons D. R., Voina S. J., Weaver R. P. The somatomedins: a family of insulinlike hormones under growth hormone control. Recent Prog Horm Res. 1974;30(0):259–318. [PubMed] [Google Scholar]

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