Hyperthyroidism may be associated with hypoleptinemia in spite of

Öz

Aim: Influences of thyroid hormones on leptin levels are controversial. We aimed to evaluate serum leptin levels in women with hyperthyroidism before and after treatment.

Material and Methods: Newly diagnosed 27 hyperthyroid women (age 35±10 years, body mass index (BMI) 26.21±5.44 kg/m²) and 30 healthy women were included the study. BMI, body fat mass (FM) and fat percent (F%) were determined. Standard oral glucose tolerance test (OGTT) was performed and area under the curve (AUCglu120) of glucose for determined insulin resistance was measured in all subjects. Serum leptin levels were determined with radioimmunoassay before and after treatment.

Results: Serum leptin levels in hyperthyroid patients were lower than control subjects (19.95±19.81 and 35.90±22.73 ng/dl, p<0.01). Leptin levels in hyperthyroid state were also lower than in euthyroid state (19.95±19.81 and 24.54±19.99 ng/dl, p=0.028) in the hyperthyroid group. With the treatment of hyperthyroidism serum leptin levels showed significant increase and it became indifferent from control subjects. However antropometric parameters did not show any significant difference with the treatment. AUCglu120 values in hyperthyroid women were higher than control subjects (165704±3276 and 12567±2102 mg.min/dl, respectively and p<0.001). After the treatment, AUCglu120 values decreased and it became indifferent from control subjects in hyperthyroid women.

Conclusions: Serum leptin levels were low in women with hyperthyroidism and hypoleptinemia can be corrected with tretament of hyperthyroidism. Low serum leptin levels in hyperthyroidism can not be explained with differences in body fat and BMI. More importantly, glucose disposal may impair in hyperthyroidism and it may recover with euthyroidism independent from serum leptin levels.

Key Words: Hyperthyroidism, leptin, insulin resistance, BMI

Anahtar Kelimeler

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Hipertiroidizm insulin rezistansına rağmen hipoleptinemi ile ilişkili olabilir

Öz

Amaç: Tiroid hormonlarının leptin üzerine etkisi tartışmalıdır. Biz hipertiroidili kadınlarda tedavi öncesi ve tedavi sonrası serum leptin düzeylerini değerlendirmeyi amaçladık.

 Gereç ve Yöntemler: Yeni tanı konulan 27 hipertiroidili kadın (yaş 35±10 yıl, vücut kitle indeksi (BMI) 26,21±5,44 kg/m²) ve yaş ve BMI’I benzer 30 sağlıklı kadın (yaş 36±10 yıl, BMI 25,48±6,97 kg/m²) çalışmaya alındı. BMI, vücut yağ kitlesi (FM) ve yağ yüzdesi (%F) belirlendi. Standart oral glukoz tolerans testi yapıldı ve insulin direncini belirlemek için glukozun eğri altında kalan alanı (AUCglu120) her kişi için hesaplandı. Serum leptin düzeyleri tedavi öncesi ve tedavi sonrası radioimmunoassay ile belirlendi.

 Bulgular: Hipertiroidili hastalarda serum leptin düzeyleri kontrol grubundan düşüktü (19,95±19,81 ve 35,90±22,73 ng/dl, p<0,01). Hipertiroidi grubunda hipertiroid koşullarda leptin düzeyleri de ötiroid durumdan daha düşüktü (19,95±19,81 ve 24,54±19,99 ng/dl, p=0,028). Hipertiroidi tedavisi ile serum leptin düzeyleri belirgin olarak artış gösterdi ve kontrol grubundan farksız hale geldi. Fakat antropometrik parametreler tedavi ile belirgin farklılık göstermedi. Hipertiroidili kadınlarda AUCglu120 değerleri kontrol grubundan yüksekti (165704±3276 ve 12567±2102 mg.dk/dl, p<0,001). Tedavi sonrasında hipertiroidili kadınlarda AUCglu120 değerleri azaldı ve kontrolden farksız hale geldi.

 Sonuçlar: Serum leptin düzeyleri hipertiroidili kadınlarda düşüktür ve hipertiroidinin tedavisi ile hipoleptinemi düzeltilebilir. Hipertiroidide düşük serum leptin düzeyleri vücut yağı ve BMI ile açıklanamaz. Daha da önemlisi hipertiroidide glukoz dağılımı bozulabilir ve serum leptin düzeylerinden bağımsız olarak ötiroidizm ile iyileşebilir.

 Anahtar Kelimeler: Hipertroidizm, leptin, insulin rezistansı, vücut kitle indeksi

Anahtar Kelimeler

• Hipertroidizm, leptin, insulin rezistansı, vücut kitle indeksi

Kaynakça

1. Leonhardt U, Gerdes E, Ritzel U, Schafer G, Becker W, Ramadori G. Immunoreactive leptin and leptin mRNA expression are increased in rat hypo- but not hyperthyroidism. J Endocrinol 1999;163:115-21.
2. Kautzky-Willer A, Ludwig C, Nowotny P, Roden A, et al Elevation of plasma leptin concentrationsin obese hyperinsulinaemic hypothyroidism before and after treatment. Eur J Clin Inves1999;29:395-403.
3. Jap TS, Hoand JGSW. Insulin secretion and sensitivity in hyperthyroidism. Horm Metabol Res 1989;21:261-6.
4. Bech K, Damsbo P, Eldrup E, et al ß-cell function and glucose and lipid oxidation in Graves’ disease” Clin Endocrinol 1996;4:59-66.
5. Dimitriadis G, Mitrou P, Lambadiari V, Boutati E, Maratou E, Koukkou E, Tzanella M, Thalassinos N, Raptis SA. Glucose and lipid fluxes in the adipose tissue after meal ingestion in hyperthyroidism. J Clin Endocrinol Metab. 2005:29 [Epub ahead of print].
6. Fukuchi M, Shimabukuro M, Shimajiri Y, Oshiro Y, Higa M, Akamine H, Komiya I, Takasu N. Evidence for a deficient pancreatic beta-cell response in a rat model of hyperthyroidism. Life Sci 2002:19;71:1059-70.
7. Chu CH, Lam HC, Lee JK, Lu CC, Sun CC, Wang MC, Chuang MJ. Hyperthyroidism-associated insulin resistance is not mediated by adiponectin levels. J Thyroid Res 2011:18;2011:194721.
8. Yoshida T, Momotani N, Hayashi M, Monkawa T, Ito K, Saruta T. Serum leptin concentrations in patients with thyroid disorders. Clin Endocrinol (Oxf) 1998;48:299-302.

9. Valcavi R, Zini M, Peino R, Casanueva FF, Dieguez C. Influence of thyroid status on serum immunoreactive leptin levels. J Clin Endocrinol Metab.1997;82:1632-4.
10. Considine RV, Sinha MK, Heiman ML, et al Serum immunoreactive leptin concentrations in normal weight and obese human. N Engl J Med. 1996; 334:292-5.
11. Mantzoros CS, Rosen HN, Greenspan SL, Flier JS, Moses AC. Short-term hyperthyroidism has no effect on leptin levels in man. J Clin Endocrinol Metab 1997;82:497-9.
12. Zimmermann-Belsing T, Dreyer M, Holst JJ, Feldt-Rasmussen U. The relationship between the serum leptin concentrations of thyrotoxic patients during treatment and their total fat mass is different from that of normal subjects. Clin Endocrinol (Oxf) 1998;49:589-95.
13. Escobar-Morreale HF, Escobar del Rey F, Morreale de Escobar G. Thyroid hormones influence serum leptin concentrations in the rat. Endocrinology. 1997;138:4485-8.
14. Barr VA, Malide D, Zarnowski MJ, Taylor SI, Cushman SW. Insulin stimulates both leptin secretion and production by rat white adiposetissue. Endocrinology 1997;138:4463-72.
15. Santini F, Galli G, Maffei M, Fierabracci P, Pelosini C, Marsili A, Giannetti M, Castagna MG, Checchi S, Molinaro E, Piaggi P, Pacini F, Elisei R, Vitti P,Pinchera A. Acute exogenous TSH administration stimulates leptin secretion in vivo. Eur J Endocrinol. 2010;163:63-7.
16. Siemińska L, Wojciechowska C, Kos-Kudła B, Marek B, Kajdaniuk D, Nowak M, Głogowska-Szelag J, Foltyn W, Strzelczyk J. Serum concentrations of leptin,adiponectin, and interleukin-6 in postmenopausal women with Hashimoto’s thyroiditis. Endokrynol Pol 2010;61:112-6.
17. Modan M, Harris MI, Halkin H. Evaluation of WHO and NDDG criteria for impaired glucose tolerance. Results from two national samples. Diabetes 1989;38:1630 –5.
18. Matsuda M, Defronzo R. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp Diabetes Care 1999;22:1462-1470.
19. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2005;28 Suppl 1:S37-42.
20. Korbonits M. Leptin and the thyroid--a puzzle with missing pieces. Clin Endocrinol (Oxf) 1998;49:569-72.
21. Hsieh CJ, Wang PW, Wang ST, Liu RT, Tung SC, Chien WY, Lu YC, Chen JF, Chen CH, Kuo MC. Serum leptin concentrations of patients with sequential thyroid function changes. Clin Endocrinol (Oxf) 2002;57:29-34.
22. Oge A, Bayraktar F, Saygili F, Guney E, Demir S. TSH influences serum leptin levels ndependent of thyroid hormones in hypothyroid and hyperthyroid patients. Endocr J 2005;52:213-7.
23. Sesmilo G, Casamitjana R, Halperin I, Gomis R, Vilardell E. Role of thyroid hormones on serum leptin levels. Eur J Endocrinol 1998;139:428-30.
24. Leonhardt U, Ritzel U, Schafer G, Becker W, Ramadori G. Serum leptin levels in hypo- and hyperthyroidism. J Endocrinol 1998;157:75-9.
25. Yaturu S, Prado S, Grimes SR. Changes in adipocyte hormones leptin, resistin, and adiponectin in thyroid dysfunction. J Cell Biochem 2004:15;93:491-6.
26. Blevins JE, Schwartz MW, Baskin DG. Peptide signals regulating food intake and energy homeostasis. Can J Physiol Pharmacol 2002;80:396-406.
27. Seppel T, Kosel A, Schlaghecke R.bBioelectrical impedance assessment of body composition in thyroid disease. Eur J Endocrinol 1997;136:493-498.
28. Sjöström L. 1996 The metabolic syndrome of human obesity. In: Bouchard C, Bray GA eds. Regulation of body weight: biological and behavioral mechanisms. New York: Wiley and Sons; 61–83.
29. Lönn L, Stenlöf K, Ottosson M, et al Body weight and body composition changes after treatment of hyperthyroidism. J Clin Endocrinol Metab 1998;83:4269–73.
30. Pelleymounter MA, Cullen MJ, Baker BM, et al Effect of the obese gen product on body weight regulation in ob/ob mice. Science 1995;269:540-43.
31. Matsubara M, Yoshizawa T, Morioka T, Katayose S. Serum leptin and lipids in patients with thyroid dysfunction. J Atheroscler Thromb 2000;7:50-4.
32. Iglesias P, Alvarez Fidalgo P, Codoceo R, Diez JJ. Serum concentrationsof adipocytokines in patients with hyperthyroidism and hypothyroidism before and after control of thyroid function. Clin Endocrinol (Oxf) 2003;59:621-9.
33. Fain LN, Coronel EC, Beauchamp MJ, Bahouth SW. Expression of leptin and beta 3-adrenerjic receptors in rat adipose tissue in altered thyroid status. Biochemical journal 1997;322:145-50.
34. Teixeira PF, Cabral MD, Silva NA, Soares DV, Braulio VB, Couto AP, Henriques JL, Costa AJ, Buescu A, Vaisman M. Serum leptin in overt and subclinical hypothyroidism: effect of levothyroxine treatment and relationship to menopausal status and body composition. Thyroid 2009;19:443-50.
35. Pinkney JH, Goodrick SJ, Katz J, Johnson AB, Lightman SL, Coppack SW, Mohamed-Ali V. Leptin and the pituitary-thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects.Clin Endocrinol (Oxf) 1998;49:583-8. ARIKAN DURMAZ et al
36. Hyperthyroidism may be associated with hypoleptinemia in spite of ınsulin resistance
37. Leonhardt U, Gerdes E, Ritzel U, Schafer G, Becker W, Ramadori G. Immunoreactive leptin and leptin mRNA expression are increased in rat hypo- but not hyperthyroidism. J Endocrinol 1999;163:115-21.
38. Kautzky-Willer A, Ludwig C, Nowotny P, Roden A, et al Elevation of plasma leptin concentrationsin obese hyperinsulinaemic hypothyroidism before and after treatment. Eur J Clin Inves1999;29:395-403.
39. Jap TS, Hoand JGSW. Insulin secretion and sensitivity in hyperthyroidism. Horm Metabol Res 1989;21:261-6.
40. Bech K, Damsbo P, Eldrup E, et al ß-cell function and glucose and lipid oxidation in Graves’ disease” Clin Endocrinol 1996;4:59-66.
41. Dimitriadis G, Mitrou P, Lambadiari V, Boutati E, Maratou E, Koukkou E, Tzanella M, Thalassinos N, Raptis SA. Glucose and lipid fluxes in the adipose tissue after meal ingestion in hyperthyroidism. J Clin Endocrinol Metab. 2005:29 [Epub ahead of print].
42. Fukuchi M, Shimabukuro M, Shimajiri Y, Oshiro Y, Higa M, Akamine H, Komiya I, Takasu N. Evidence for a deficient pancreatic beta-cell response in a rat model of hyperthyroidism. Life Sci 2002:19;71:1059-70.
43. Chu CH, Lam HC, Lee JK, Lu CC, Sun CC, Wang MC, Chuang MJ. Hyperthyroidism-associated insulin resistance is not mediated by adiponectin levels. J Thyroid Res 2011:18;2011:194721.
44. Yoshida T, Momotani N, Hayashi M, Monkawa T, Ito K, Saruta T. Serum leptin concentrations in patients with thyroid disorders. Clin Endocrinol (Oxf) 1998;48:299-302.
45. Valcavi R, Zini M, Peino R, Casanueva FF, Dieguez C. Influence of thyroid status on serum immunoreactive leptin levels. J Clin Endocrinol Metab.1997;82:1632-4.
46. Considine RV, Sinha MK, Heiman ML, et al Serum immunoreactive leptin concentrations in normal weight and obese human. N Engl J Med. 1996; 334:292-5.
47. Mantzoros CS, Rosen HN, Greenspan SL, Flier JS, Moses AC. Short-term hyperthyroidism has no effect on leptin levels in man. J Clin Endocrinol Metab 1997;82:497-9.
48. Zimmermann-Belsing T, Dreyer M, Holst JJ, Feldt-Rasmussen U. The relationship between the serum leptin concentrations of thyrotoxic patients during treatment and their total fat mass is different from that of normal subjects. Clin Endocrinol (Oxf) 1998;49:589-95.
49. Escobar-Morreale HF, Escobar del Rey F, Morreale de Escobar G. Thyroid hormones influence serum leptin concentrations in the rat. Endocrinology. 1997;138:4485-8.
50. Barr VA, Malide D, Zarnowski MJ, Taylor SI, Cushman SW. Insulin stimulates both leptin secretion and production by rat white adiposetissue. Endocrinology 1997;138:4463-72.
51. Santini F, Galli G, Maffei M, Fierabracci P, Pelosini C, Marsili A, Giannetti M, Castagna MG, Checchi S, Molinaro E, Piaggi P, Pacini F, Elisei R, Vitti P,Pinchera A. Acute exogenous TSH administration stimulates leptin secretion in vivo. Eur J Endocrinol. 2010;163:63-7.
52. Siemińska L, Wojciechowska C, Kos-Kudła B, Marek B, Kajdaniuk D, Nowak M, Głogowska-Szelag J, Foltyn W, Strzelczyk J. Serum concentrations of leptin,adiponectin, and interleukin-6 in postmenopausal women with Hashimoto’s thyroiditis. Endokrynol Pol 2010;61:112-6.
53. Modan M, Harris MI, Halkin H. Evaluation of WHO and NDDG criteria for impaired glucose tolerance. Results from two national samples. Diabetes 1989;38:1630 –5.
54. Matsuda M, Defronzo R. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp Diabetes Care 1999;22:1462-1470.
55. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2005;28 Suppl 1:S37-42.
56. Korbonits M. Leptin and the thyroid--a puzzle with missing pieces. Clin Endocrinol (Oxf) 1998;49:569-72.
57. Hsieh CJ, Wang PW, Wang ST, Liu RT, Tung SC, Chien WY, Lu YC, Chen JF, Chen CH, Kuo MC. Serum leptin concentrations of patients with sequential thyroid function changes. Clin Endocrinol (Oxf) 2002;57:29-34.
58. Oge A, Bayraktar F, Saygili F, Guney E, Demir S. TSH influences serum leptin levels ndependent of thyroid hormones in hypothyroid and hyperthyroid patients. Endocr J 2005;52:213-7.
59. Sesmilo G, Casamitjana R, Halperin I, Gomis R, Vilardell E. Role of thyroid hormones on serum leptin levels. Eur J Endocrinol 1998;139:428-30.
60. Leonhardt U, Ritzel U, Schafer G, Becker W, Ramadori G. Serum leptin levels in hypo- and hyperthyroidism. J Endocrinol 1998;157:75-9.
61. Yaturu S, Prado S, Grimes SR. Changes in adipocyte hormones leptin, resistin, and adiponectin in thyroid dysfunction. J Cell Biochem 2004:15;93:491-6.
62. Blevins JE, Schwartz MW, Baskin DG. Peptide signals regulating food intake and energy homeostasis. Can J Physiol Pharmacol 2002;80:396-406.
63. Seppel T, Kosel A, Schlaghecke R.bBioelectrical impedance assessment of body composition in thyroid disease. Eur J Endocrinol 1997;136:493-498.
64. Sjöström L. 1996 The metabolic syndrome of human obesity. In: Bouchard C, Bray GA eds. Regulation of body weight: biological and behavioral mechanisms. New York: Wiley and Sons; 61–83.
65. Lönn L, Stenlöf K, Ottosson M, et al Body weight and body composition changes after treatment of hyperthyroidism. J Clin Endocrinol Metab 1998;83:4269–73.
66. Pelleymounter MA, Cullen MJ, Baker BM, et al Effect of the obese gen product on body weight regulation in ob/ob mice. Science 1995;269:540-43.
67. Matsubara M, Yoshizawa T, Morioka T, Katayose S. Serum leptin and lipids in patients with thyroid dysfunction. J Atheroscler Thromb 2000;7:50-4.
68. Iglesias P, Alvarez Fidalgo P, Codoceo R, Diez JJ. Serum concentrationsof adipocytokines in patients with hyperthyroidism and hypothyroidism before and after control of thyroid function. Clin Endocrinol (Oxf) 2003;59:621-9.
69. Fain LN, Coronel EC, Beauchamp MJ, Bahouth SW. Expression of leptin and beta 3-adrenerjic receptors in rat adipose tissue in altered thyroid status. Biochemical journal 1997;322:145-50.
70. Teixeira PF, Cabral MD, Silva NA, Soares DV, Braulio VB, Couto AP, Henriques JL, Costa AJ, Buescu A, Vaisman M. Serum leptin in overt and subclinical hypothyroidism: effect of levothyroxine treatment and relationship to menopausal status and body composition. Thyroid 2009;19:443-50.
71. Pinkney JH, Goodrick SJ, Katz J, Johnson AB, Lightman SL, Coppack SW, Mohamed-Ali V. Leptin and the pituitary-thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects.Clin Endocrinol (Oxf) 1998;49:583-8. ARIKAN DURMAZ et al
72. Hyperthyroidism may be associated with hypoleptinemia in spite of ınsulin resistance