This page contains a Flash digital edition of a book.
Beck-Peccoz_US Endocrinology 22/12/2009 12:00 Page 120
Thyroid Disorders
resistance index was higher in our RTH patients, according to recent was significantly reduced, and triglycerides were slightly elevated. This
data from Owen et al.
42
These authors found an increased arterial finding could be consistent with increased sympathetic activity and
stiffness in RTH compared with sex- and age-matched normal controls. adipose tissue lipolisys. Remarkably, the strong correlation between
This vascular pattern is more similar to that observed in hypothyroid fasting plasma FFA concentrations and insulin resistance is well-known.
than hyperthyroid subjects, in which a lower arterial stiffness has been The mechanism for this is unclear: one hypothesis is that skeletal muscle
reported. In addition, the TRβ knock-in mouse model of RTH displays an metabolism of fatty acid is impaired, leading to muscle lipotoxicity
impaired endothelial vascular function and hypercholesterolemia and impaired insulin action; alternatively, RTH subjects exhibit hepatic
compared with wt controls.
43
In the vascular endothelial cell the RTH action that may also be associated with reduced hepatic sensitivity
predominant TR isoform is TRα. Equally, these data suggest that TRβ to insulin action.
may have a certain role in endothelial function. However, a number of
the rapid effects of thyroid hormone on the vascular wall are mediated Conclusion
via a non-genomic mechanism. Furthermore, the elevated arterial In addition to reduced vascular compliance and echocardiographic
stiffness may lead to increased cardiovascular risk in RTH. abnormalities, RTH subjects exhibit some features of metabolic syndrome,
such as insulin resistance together with elevated circulating triglycerides
Ciulla and co-workers
44
found that the echoreflectivity (dCVF%) of and reduced HDL cholesterol levels, which suggests that overall cardio-
interventricular septum was slightly higher in the RTH patients metabolic risk in this disorder may be increased. n
compared with controls and hyperthyroid subjects, but lower than in
hypothyroid patients. The echoreflectivity is a marker of fibrous
Irene Campi, MD, is a Clinical Fellow in the Endocrinology
myocardial remodeling related to increased myocardial collagen
and Diabetology Unit at the Fondazione Policlinico–Istituto
deposition. This parameter represents a risk factor for the performance di Ricovero e Cura a Carattere Scientifico (IRCCS) at the
of coronary circulation, systodiastolic function, and electric stability of
University of Milan. She is member of the European
Thyroid Association (ETA) and the European Society of
the heart. As suggested by animal models of hypothyroidism,
45,46
the lack
Endocrinology (ESE). She has had five papers published in
of TH induces a significant increase in myocardial echoreflectivity. The peer-reviewed journals and her major scientific interest is
authors speculate that while myocytes mainly express the TRα isoform,
the pathophysiology of thyroid diseases.
which could explain the hyperkinetic pattern seen in some of RTH, other
non-myocyte cells may present a prevalence of TRβ with a phenotype
Deborah Mannavola, PhD, is a Research Assistant in the Endocrine Unit at the University
of Milan. Her major scientific interest is the pathophysiology of the
that mimics a situation of mild hypothyroidism. In terms of the lipid
hypothalamic–pituitary–thyroid axis and rare thyroid diseases. Dr Mannavola completed
profile, Owen observed significantly elevated low-density lipoprotein
a fellowship in endocrinology and thyroid research in the Endocrinology and Thyroid Unit
(LDL) cholesterol levels in RTH subjects compared with controls.
42
in the Division of Biological Sciences at the University of Chicago, and received her PhD
in molecular medicine from the University of Milan.
Furthermore, dyslipidemia is associated with reduced nitric oxide
bioavailability and impairment of smooth-muscle relaxation that could
Paolo Beck-Peccoz, MD, is a Full Professor of Endocrinology
also increase arterial stiffness.
and Director of the School of Specialization in Endocrinology
and Metabolic Diseases at the University of Milan, and Chief
Mitchell and co-workers (personal communication) observed that the
of the Endocrinology and Diabetology Unit at the
Fondazione Ospedale Maggiore Istituto di Ricovero e Cura a
insulin sensitivity index (ISI) and homeostasis model assessment–insulin
Carattere Scientifico (IRCCS) in Milan. His major research
resistance (HOMA-IR) was strikingly elevated in a group of RTH subjects
interest is the pathophysiology of the hypothalamic–
compared with controls. Moreover, plasma free fatty acid (FFA)
pituitary–thyroid axis.
concentrations were ~30%, high-density lipoprotein (HDL) cholesterol
1. Kinugawa K, et al., Circ Res, 2001;89:591–8. 15. Chatterjee VK, et al., Oxford Textbook of Endocrinology, London: 31. Parrilla RA, et al., J Clin Invest, 1991;88:2123–30.
2. Klein I, et al., N Engl J Med, 2001;344(7):501–9. Oxford University Press, 2002;339–49. 32. Swanson EA, et al., Endocrinology, 2003;144:4820–25.
3. Dillmann WH, Thyroid, 2002;12,(6):447–52. 16. Beck–Peccoz P, et al., Thyroid, 1994;4(2):225–32. 33. Gloss B, et al., Endocrinology, 1999;140:897–902.
4. Kahaly GJ, et al., Endocr Rev, 2005;26(5):704–28. 17. Beck–Peccoz P, et al., J Clin Endocrinol Metab, 1990;71:19–25. 34. Pazos-Moura C, et al., Circ Res, 2000;86; 700–706.
5. Danzi S, et al., Thyroid, 2002;12(6): 467–72. 18. Tolulope O, et al., Ann Clin Biochem, 2006;43:431–40. 35. Miller LD, et al., Genome Biol, 2004;5(5):R31.
6. Ojamaa K, et al., Endocrinology, 1993;132:1002–6. 19. Ortiga-Carvalho TM, et al., Endocrinology, 2004;145(4):1625–33. 36. Belke DD, 8th International Workshop on RTH, in abstract
7. Ojamaa K, et al., Endocrinology, 1996; 137:802–8. 20. Zhang XY, et al., Mol Endocrinol, 2002;16:2077–92. book OP#8.
8. Kreuzberg U, et al., Am J Physiol Heart Circ Physiol, 21. O’Shea PJ, et al., J Clin Endocrinol, 2002;175:553–70. 37. Belke DD, et al., Endocrinology, 2007;148(6):2870–77.
2000;278:H723–H730. 22. Wikström L, et al.,EMBO J, 1998;17(2):455–61. 38. Makino A, et al., Endocrinology, 2009;150:2008–15.
9. Jiang M, Xu A, Am J Physiol Heart Circ Physiol, 23. Johansson C, et al., Am J Physiol, 1999;276:H 2006–12. 39. Brucker-Davis F, et al., Ann Intern Med, 1995;123(8):572–83.
2000;278:H1429–H1438. 24. Weiss RE, et al., Endocrinology, 1998;139: 4945–52. 40. Pulcrano M, et al., J Clin Endocrinol Metab, 2009;94(8):2812–16.
10. Pachucki J, et al., Circ Res, 1999;85:498–503. 25. Macchia PE, et al., Proc Natl Acad Sci U S A, 2001;98:349–54. 41. Weiss RE, et al., Am J Physiol Endocrinol Metab,
11. Klein I, et al., Circulation, 2007;116:1725–35. 26. Ludwig A, et al., EMBO J, 1999;18(9):2323–9. 2002;283:E428–35.
12. Kahaly GG, et al., JCEM, 2002; 87(1):204–12. 27. Gloss B, et al., Endocrinology, 2001;142(2):544–50. 42. Owen PJ, et al., Clin Endocrinol, 2009;70(4):650–54.
13. Pohlenz J, et al., J Clin Endocrinol Metab, 1999;84:3919–28. 28. Esaki T, et al., Am J Physiol Endocrinol Metab, 43. Owen PJ, et al., Eur J Clin Invest, 2007;37:390–95.
14. Refetoff S, Werner and Ingbars’s The Thyroid: A Fundamental and 2004;287:E1149–E1153. 44. Ciulla MM, et al., Thyroid, 2001;11(7):613–19.
Clinical Text (ninth edition), Philadelphia, PA: Lippincott, Williams 29. Kaneshige M, et al., Proc Natl Acad Sci U S A, 2000;97:13209–14. 45. Yao J, et al., Cardiovasc Res, 1992;26:603–7.
and Wilkins, 2005;1109–29. 30. Kaneshige M, et al., Proc Natl Acad Sci U S A, 2001;98:15095–100. 46. Grover-McKay M, et al., Invest Radiol, 1984;26:227–32.
120 US ENDOCRINOLOGY
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100  |  Page 101  |  Page 102  |  Page 103  |  Page 104  |  Page 105  |  Page 106  |  Page 107  |  Page 108  |  Page 109  |  Page 110  |  Page 111  |  Page 112  |  Page 113  |  Page 114  |  Page 115  |  Page 116  |  Page 117  |  Page 118  |  Page 119  |  Page 120  |  Page 121  |  Page 122  |  Page 123  |  Page 124
Produced with Yudu - www.yudu.com