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Daylong pituitary hormones in morbid obesity: effects of bariatric surgery

International Journal of Obesity volume 33, pages 166–172 (2009)Cite this article

Abstract

Moderate obesity is known to be associated with multiple endocrine abnormalities. Less information is available on the hormonal status of patients with morbid obesity and on the effects of major weight loss. We studied 16 severely obese (BMI 40.6–69.9 kg/m2) nondiabetic patients and 7 nonobese (BMI range 24.6–27.7 kg/m2), sex- and age-matched healthy volunteers. During 24 h in a metabolic ward, four meals were administered and hourly blood samples were drawn from a central venous catheter for the measurement of glucose, insulin, leptin, thyrotropic hormone (TSH), growth hormone (GH) and prolactin. Insulin sensitivity was measured by a euglycaemic hyperinsulinaemic clamp. Studies were repeated 6 months after biliopancreatic diversion, a mainly malabsorptive surgical approach, which caused an average weight loss of 35±4 kg (or 26±2% of initial weight). Compared with controls, patients were hyperinsulinaemic (290±31 vs 88±4 pmol l−1, P=0.0002), insulin resistant (23.5±2.8 vs 52.9±4.9 μmol min−1 kgFFM−1, P=0.0006) and hyperleptinaemic (52.5±5.8 vs 10.9±3 ng ml−1, P=0.0002). Plasma TSH levels were increased throughout the day–night cycle (averaging 2.02±0.18 vs 1.09±0.19 μU ml−1 of controls, P=0.01), whereas serum GH levels were suppressed (0.46±0.10 vs 3.01±1.15, P=0.002). Following surgery, the hyperinsulinaemia and insulin resistance were fully normalized; in concomitance with a major drop in leptin levels (to 14.4±2.7 ng ml−1, P=0.02), TSH decreased and GH increased to near-normal levels. In the whole dataset, mean 24-h leptin levels were directly related to mean 24-h TSH levels after controlling for confounders this relationship was lost only after adjusting for fat mass. We conclude that in morbid obesity leptin is a determinant of changes in pituitary function.

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References

  1. Kokkoris P, Pi-Sunyer FX . Obesity and endocrine disease. Endocrinol Metab Clin North Am 2003; 32: 895–914.

    Article  CAS  PubMed  Google Scholar 

  2. Veldhuis JD, Iranmanesh A, Ho KK, Waters MJ, Johnson ML, Lizarralde G . Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. J Clin Endocrinol Metab 1991; 72: 51–59.

    Article  CAS  PubMed  Google Scholar 

  3. Williams T, Berelowitz M, Joffe SN, Thorner MO, Rivier J, Vale W et al. Impaired growth hormone responses to growth hormone-releasing factor in obesity. A pituitary defect reversed with weight reduction. N Engl J Med 1984; 311: 1403–1407.

    Article  CAS  PubMed  Google Scholar 

  4. Wauters M, Considine RV, Van Gaal LF . Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol 2000; 143: 293–311.

    Article  CAS  PubMed  Google Scholar 

  5. Mantzoros CS . The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med 1999; 130: 671–680.

    Article  CAS  PubMed  Google Scholar 

  6. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New Engl J Med 1996; 334: 292–295.

    Article  CAS  PubMed  Google Scholar 

  7. Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 1996; 348: 159–161.

    Article  CAS  PubMed  Google Scholar 

  8. Wing RR, Sinha MK, Considine RV, Lang W, Caro JF . Relationship between weight-loss maintenance and changes in plasma serum leptin levels. Horm Metab Res 1996; 28: 698–703.

    Article  CAS  PubMed  Google Scholar 

  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: 1632–1634.

    CAS  PubMed  Google Scholar 

  10. Sreenan S, Caro JF, Refetoff S . Thyroid dysfunction is not associated with alterations in serum leptin levels. Thyroid 1997; 7: 407–409.

    Article  CAS  PubMed  Google Scholar 

  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: 497–499.

    CAS  PubMed  Google Scholar 

  12. Yoshida T, Monkawa T, Hayashi M, Saruta T . Regulation of expression of leptin mRNA and secretion of leptin by thyroid hormone in 3T3-L1 adipocytes. Biochem Biophys Res Commun 1997; 232: 822–826.

    Article  CAS  PubMed  Google Scholar 

  13. Escobar-Morreale HF, Escobar del Rey F, Morreale de Escobar G . Thyroid hormones influence serum leptin concentrations in the rat. Endocrinology 1997; 138: 4485–4488.

    Article  CAS  PubMed  Google Scholar 

  14. Sesmilo G, Casamitjana R, Halperin I, Gomis R, Vilardell E . Role of thyroid hormones on serum leptin levels. Eur J Endocrinol 1998; 139: 428–430.

    Article  CAS  PubMed  Google Scholar 

  15. Corbetta S, Englaro P, Giambona S, Persani L, Blum WF . Beck-Peccoz P Lack of effects of circulating thyroid hormone levels on serum leptin concentrations. Eur J Endocrinol 1997; 137: 659–663.

    Article  CAS  PubMed  Google Scholar 

  16. Nakamura T, Nagasaka S, Ishikawa S, Hayashi H, Saito T, Kusaka I et al. Association of hyperthyroidism with serum leptin levels. Metabolism 2000; 49: 1285–1288.

    Article  CAS  PubMed  Google Scholar 

  17. Kok P, Roelfsema F, Frölich M, Meinders AE, Pijl H . Spontaneous diurnal thyrotropin secretion is enhanced in proportion to circulating leptin in obese premenopausal women. J Clin Endocrinol Metab 2005; 90: 6185–6191.

    Article  CAS  PubMed  Google Scholar 

  18. Alagna S, Cossu ML, Gallo P, Tilocca PL, Pileri P, Alagna G et al. Biliopancreatic diversion:long-term effects on gonadal function in severely obese men. Surg Ob Relat Dis 2006; 2: 82–86.

    Article  Google Scholar 

  19. Alagna S, Cossu ML, Masala A, Atzeni MM, Ruggiu M, Satta FM et al. Evaluation of serum leptin levels and thyroid function in morbidly obese patients treated with bariatric surgery. Eat Weight Disord 2003; 8: 95–99.

    Article  CAS  PubMed  Google Scholar 

  20. De Marinis L, Bianchi A, Mancini A, Gentilella R, Perrelli M, Giampietro A et al. Growth hormone secretion and leptin in morbid obesity before and after biliopancreatic diversion: relationship with insulin and body composition. J Clin Endocrinol Metab 2004; 89: 174–180.

    Article  CAS  PubMed  Google Scholar 

  21. Scopinaro N, Gianetta E, Civalleri D, Bonalumi U, Bachi V . Biliopancreatic bypass for obesity.II. Initial experience in man. Br J Surg 1979; 66: 619–620.

    Google Scholar 

  22. Siri WE . Body composition from fluid spaces and density: analysis of methods. In: Brozek J, Henschel A (eds). Techniques of measuring body composition. Natl Acad Sci, Natl Res Counc 1961. Washington DC, pp 107–141.

    Google Scholar 

  23. Culebras JM, Moore FD . Total body water and the exchangeable hydrogen. I. Theoretical calculation of nonaqueous exchangeable hydrogen in men. Am J Physiol 1977; 232: R54–R59.

    CAS  PubMed  Google Scholar 

  24. DeFronzo RA, Tobin JD, Andres R . Glucose clamp techique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214–E223.

    CAS  PubMed  Google Scholar 

  25. Sheng HP, Huggins RA . A review of body composition studies with emphasis on total body water and fat. Am J Clin Nutr 1979; 32: 630–647.

    Article  CAS  PubMed  Google Scholar 

  26. Van Cauter EV, Polonsky KS, Blackman JD, Roland D, Sturis J, Byrne MM et al. Temporal patterns of glucose tolerance in obesity: relationship to sleep-related growth hormone secretion and circadian cortisol rhythmicity. J Clin Endocrinol Metab 1994; 79: 1797–1805.

    CAS  PubMed  Google Scholar 

  27. Heptulla R, Smitten A, Teague B, Tamborlane WV, Ma YZ, Caprio S . Temporal patterns of circulating leptin levels in lean and obese adolescents: relationships to insulin, growth hormone, and free fatty acids rhythmicity. J Clin Endocrinol Metab 2001; 86: 90–96.

    CAS  PubMed  Google Scholar 

  28. Rasmussen MH, Hvidberg A, Juul A, Main KM, Gotfredsen A, Skakkebaek NE et al. Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J Clin Endocrinol Metab 1995; 80: 1407–1415.

    CAS  PubMed  Google Scholar 

  29. Clasey JL, Weltman A, Patrie J, Weltman JY, Pezzoli S, Bouchard C et al. Abdominal visceral fat and fasting insulin are important predictors of 24-hour GH release independent of age, gender, and other physiological factors. J Clin Endocrinol Metab 2001; 86: 3845–3852.

    Article  CAS  PubMed  Google Scholar 

  30. Carroll PV, Christ ER, Bengtsson BA, Carlsson L, Christiansen JS, Clemmons D et al. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. J Clin Endocrinol Metab 1998; 83: 382–395.

    Article  CAS  PubMed  Google Scholar 

  31. Johannsson G, Mårin P, Lönn L, Ottosson M, Stenlöf K, Björntorp P et al. Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure. J Clin Endocrinol Metab 1997; 82: 727–734.

    CAS  PubMed  Google Scholar 

  32. Pouliot MC, Després JP, Nadeau A, Moorjani S, Prud'Homme D, Lupien PJ et al. Visceral obesity in men: association with glucose tolerance, plasma insulin, and lipoprotein levels. Diabetes 1992; 41: 826–834.

    Article  CAS  PubMed  Google Scholar 

  33. Björntorp P . ‘Portal’ adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 1990; 10: 493–496.

    Article  PubMed  Google Scholar 

  34. Sinha MK, Ohannesian JP, Heiman ML, Kriauciunas A, Stephens TW, Magosin S et al. Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest 1996; 97: 1344–1347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Florkowski CM, Collier GR, Zimmet PZ, Livesey JH, Espiner EA, Donald RA . Low-dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency. Clin Endocrinol 1996; 45: 769–773.

    Article  CAS  Google Scholar 

  36. Ahmad AM, Guzder R, Wallace AM, Thomas J, Fraser WD, Vora JP . Circadian and ultradian rhythm and leptin pulsatility in adult GH deficiency: effects of Gh replacement. J Clin Endocr Metab 2001; 86: 3499–3506.

    Article  CAS  PubMed  Google Scholar 

  37. Isokazi O, Tsushima T, Miyakawa M, Nozoe Y, Demura H, Seki H . GH directly inhibits leptin gene expression in visceral fat tissue in fatty Zucker rats. J Endocr 1999; 161: 511–516.

    Article  Google Scholar 

  38. Pinkney JH, Goodrick SJ, Katz J, Johnson AB, Lightman SL, Coppack SW et al. Leptin and the pituitary-thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects. Clin Endocrinol 1998; 49: 583–588.

    Article  CAS  Google Scholar 

  39. Reinehr T, Andler W . Thyroid hormones before and after weight loss in obesity. Arch Dis Child 2002; 87: 320–323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E et al. Role of leptin in the neuroendocrine response to fasting. Nature 1996; 382: 250–252.

    Article  CAS  PubMed  Google Scholar 

  41. Flier JS, Harri M, Hollenberg AN . Leptin, nutrition, and the thyroid: the why, the wherefore, and the wiring. J. Clin. Invest 2000; 105: 859–861.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Legradi G, Emerson CH, Ahima RS, Rand WM, Flier JS, Lechan RM . Arcuate nucleus ablation prevents fasting-induced suppression of ProTRH mRNA in the hypothalamic paraventricular nucleus. Neuroendocrinology 1998; 68: 89–97.

    Article  CAS  PubMed  Google Scholar 

  43. Jin L, Burguera BG, Couce ME, Scheithauer BW, Lamsan J, Eberhardt NL et al. Leptin and leptin receptor expression in normal and neoplastic human pituitary: evidence of a regulatory role for leptin on pituitary cell proliferation. J Clin Endocrinol Metab 1999; 84: 2903–2911.

    CAS  PubMed  Google Scholar 

  44. Jin L, Zhang S, Burguera BG, Couce ME, Osamura RY, Kulig E et al. Leptin and leptin receptor expression in rat and mouse pituitary cells. Endocrinology 2000; 141: 333–339.

    Article  CAS  PubMed  Google Scholar 

  45. Korbonits M, Chitnis MM, Gueorguiev M, Norman D, Rosenfelder N, Suliman M et al. The release of leptin and its effect on hormone release from human pituitary adenomas. Clin Endocrinol 2001; 54: 781–789.

    Article  CAS  Google Scholar 

  46. Kim MS, Small CJ, Stanley SA, Morgan DG, Seal LJ, Kong WM et al. The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin. J Clin Invest 2000; 105: 1005–1011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C et al. Beneficial effects of leptin on obesity, Tcell hyporesponsiveness, and neurendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002; 110: 1093–1103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L, Heymsfield S et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest 2005; 115: 3579–3586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Chan JL, Heist K, DePaoli AM, Veldhuis JD, Mantzoros CS . The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. J Clin Invest 2003; 111: 1409–1421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Schurgin S, Canavan B, Koutkia P, Depaoli AM, Grinspoon S . Endocrine and metabolic effects of physiologic r-metHuLeptin administration during acute caloric deprivation in normal-weight women. J Clin Endocrinol Metab 2004; 89: 5402–5409.

    Article  CAS  PubMed  Google Scholar 

  51. Mantzoros CS, Ozata M, Negrao AB, Suchard MA, Ziotopoulou M, Caglayan S et al. Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: evidence for possible partial TSH regulation by leptin in humans. J Clin Endocrinol Metab 2001; 86: 3284–3291.

    Article  CAS  PubMed  Google Scholar 

  52. Ortega E, Pannacciulli N, Bogardus C, Krakoff J . Plasma concentrations of free triiodothyronine predict weight change in euthyroid persons. Am J Clin Nutr 2007; 85: 440–445.

    Article  CAS  PubMed  Google Scholar 

  53. Kok P, Roelfsema F, Langendonk JG, Frölich M, Burggraaf J, Meinders AE et al. High circulating thyrotropin levels in obese women are reduced after body weight loss induced by caloric restriction. J Clin Endocrinol Metab 2005; 90: 4659–4663.

    Article  CAS  PubMed  Google Scholar 

  54. Naslund E, Andersson I, Degerblad M, Kogner P, Kral JG, Rossner S et al. Associations of leptin, insulin resistance and thyroid function with long-term weight loss in dieting obese men. J Int Med 2000; 248: 299–308.

    Article  CAS  Google Scholar 

  55. Chikunguwo S, Brethauer S, Nirujogi V, Pitt T, Udomsawaengsup S, Chand B et al. Influence of obesity and surgical weight loss on thyroid hormone levels. Surg Obes Relat Dis 2007; 3: 631–635.

    Article  PubMed  Google Scholar 

  56. Moulin de Moraes CM, Mancini MC, de Melo ME, Figueiredo DA, Villares SM, Rascovski A et al. Prevalence of subclinical hypothyroidism in a morbidly obese population and improvement after weight loss induced by Roux-en-Y gastric bypass. Obes Surg 2005; 15: 1287–1291.

    Article  PubMed  Google Scholar 

  57. Blake NG, Eckland DJ, Foster OJ, Lightman SL . Inhibition of hypothalamic thyrotropin-releasing hormone messenger ribonucleic acid during food deprivation. Endocrinology 1991; 129: 2714–2718.

    Article  CAS  PubMed  Google Scholar 

  58. Greco AV, Mingrone G, Giancaterini A, Manco M, Morroni M, Cinti S et al. Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. Diabetes 2002; 51: 144–151.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine and Metabolism Unit of the C.N.R. Institute of Clinical Physiology at the University of Pisa, Pisa, Italy

    S Camastra, S Frascerra & E Ferrannini

  2. Department of Medicine, Catholic University, Rome, Italy

    M Manco, A Iaconelli & G Mingrone

  3. Bambino Gesù Hospital, Rome, Italy

    M Manco

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Camastra, S., Manco, M., Frascerra, S. et al. Daylong pituitary hormones in morbid obesity: effects of bariatric surgery. Int J Obes 33, 166–172 (2009). https://doi.org/10.1038/ijo.2008.226

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