Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Day–night variations in thyroid stimulating hormone and its relation with clinical status and metabolic parameters in patients with cirrhosis of the liver

  • 205 Accesses

  • 3 Citations


To investigate day–night variations in thyroid stimulating hormone (TSH) and its relation with clinical status and metabolic parameters in patients with cirrhosis. Forty-one patients with negative thyroid antibodies and normal thyroid function tests who were diagnosed with cirrhosis were included. Thirty-five age- and gender-matched healthy subjects were included in control group.TSH, fT3, and fT4 levels, which were measured both in the morning and late evening. The difference between nocturnal TSH and morning TSH (ΔTSH) were compared between groups. Relation between Child-Turcotte-Pugh, model for End-Stage Liver Disease (MELD) and MELD-Na scores and levels of thyroid hormones, ΔTSH and serum sodium (Na) levels was investigated. Relation between ΔTSH and clinical status and metabolic parameters was also evaluated. The mean morning fT3, nocturnal fT3, nocturnal TSH, and ΔTSH levels were significantly lower, morning and nocturnal fT4 levels were higher in patients with cirrhosis (p < 0.001, p < 0.001, p = 0.004, p < 0.001, and p < 0.001).As the ROC analysis, day–night variation was detected to be impaired in the event that difference between nocturnal TSH level and morning TSH level was lower than 1 uIU/mL in patients with cirrhosis with a sensitivity of 92.7 % and specificity of 71.4 % (p < 0.001).A significant positive correlation was found between serum Na levels and fT3 in patients with cirrhosis (r = 0.479, p = 0.001), and a significant negative correlation was found between the severity of clinical status and low levels of fT3 in patients with cirrhosis (p < 0.001).Nocturnal TSH increase does not occur in cases of cirrhosis without known thyroid disease and with normal thyroid function tests, which may be an early finding of impaired thyroid functions in patients with cirrhosis.

This is a preview of subscription content, log in to check access.

Fig. 1


  1. 1.

    S.M. Adler, L. Wartofsky, The nonthyroidal illness syndrome. Endocrinol. Metab. Clin. N. Am. 36, 657–672 (2007)

  2. 2.

    C. Lucke, R. Hehrmann, K. von Mayersbach, A. von zur Muhlen, Studies on circadian variation of plasma TSH, thyroxine and triiodothyronine in man. Acta Endocrinol. 86, 81–88 (1977)

  3. 3.

    D.C. Parker, A.E. Pekary, J.M. Hersman, Effect of normal and reversed sleep-wake upon nyctohumural rhythmicity of plasma thyrotropin: evidence suggestive of an inhibitory influence in sleep. J. Clin. Endocrinol. Metab. 43, 318–329 (1976)

  4. 4.

    G. Brabant, U. Ranft, K. Ocran, R.D. Hesch, A. von zur Muhlen, Thyrotropin: an episodically secreted hormone. Acta Endocrinol. 112, 315–322 (1986)

  5. 5.

    G. Brabant, U. Rranft, K. Ocran, R.D. Hesch, A. von Zur Mühlen, Pulsatile pattern of thyrotropin release in normal men. Clin. Chim. Acta 155, 159–162 (1986)

  6. 6.

    S.L. Greenspan, A. Klibanski, D. Schoenfeld, E.C. Ridgway, Pulsatile secretion of thyrotropin in men. J. Clin. Endocrinol. Metab. 63, 661–668 (1986)

  7. 7.

    L. Bartalena, G.F. Placidi, E. Martino, M. Falcone, L. Pellegrini, L. Dell’Osso, A. Pacchiarotti, A. Pinchera, Nocturnal serum thyrotropin (TSH) surge and the TSH response to TSH-releasing hormone: dissociated behavior in untreated depressives. J. Clin. Endocrinol. Metab. 71, 650–655 (1990)

  8. 8.

    J. Bechrends, K. Prank, E. Dogu, G. Brabant, Central nervous system control of thyrotropin secretion during sleep and wakefulness. Horm. Res. 49, 173–178 (1998)

  9. 9.

    D.A. Fisher, Physiological variations in thyroid hormones; physiological and pathophysiological considerations. Clin. Chem. 42, 135–139 (1996)

  10. 10.

    A.T. Blei, P. Zee, Abnormalities of circadian rhythmicity in liver disease. J. Hepatol. 29, 832–835 (1998)

  11. 11.

    D. Velissaris, M. Karanikolas, A. Kalogeropoulos, E. Solomou, P. Polychronopoulos, K. Thomopoulos, C. Labropoulou-Karatza, Pituitary hormone circadian rhythm alterations in cirrhosis patients with subclinical hepatic encephalopathy. World J. Gastroenterol. 14, 4190–4195 (2008)

  12. 12.

    P. Pasqualetti, D. Colantonio, R. Casale, G. Natali, Endocrine changes of the liver in the cirrhotic alcoholic: analysis of circadian rhythms of anteriopituitary, adrenocortical, and gonadal hormones. Riv. Eur. Sci. Med. Farmacol. 11, 227–235 (1989)

  13. 13.

    G. Gursoy, B. Cakir, M.K. Ozturk, S. Guler, K. Gul, O. Topaloğlu, D. Yucel, Diurnal variation in ultrasonographic dimensions of thyroid gland. Biol Rhythm Res. 36, 361–367 (2005)

  14. 14.

    R. Ersoy, K. Gül, M. Gümüş, A. İpek, O. Topaloglu, C. Aydin, A. Dirikoc, B. Cakir, The relationship between diurnal variation of TSH and thyroid blood flow with doppler ultrasonography in healthy adults”. Biol. Rhythm Res. 39, 85–91 (2007)

  15. 15.

    D. Schuppan, N.H. Afdhal, Liver cirrhosis. Lancet 371, 838–851 (2008)

  16. 16.

    H. Chen, X. Qi, C. He, Z. Yin, D. Fan, G. Han, Coagulation imbalance may not contribute to the development of portal vein thrombosis in patients with cirrhosis. Thromb. Res. 131, 173–177 (2013)

  17. 17.

    R.S. Brown Jr, K.S. Kumar, M.W. Russo, M. Kinkhabwala, D.L. Rudow, P. Harren, S. Lobritto, J.C. Emond, Model for end-stage liver disease and child-turcotte-pugh score as predictors of pre-transplantation disease severity, post-transplantation outcome, and resource utilization in united network for organ sharing status 2A patients. Liver Transpl. 8, 278–284 (2002)

  18. 18.

    G. D’Amico, G. Garcia-Tsao, L. Pagliaro, Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J. Hepatol. 44, 217–231 (2006)

  19. 19.

    R.N.H. Pugh, I.M. Murray-Lyon, J.L. Dawson, M.C. Pietroni, R. Williams, Transection of the esophagus for bleeding oesophageal varices. Br. J. Surg. 60, 646–649 (1973)

  20. 20.

    M. Malinchoc, P.S. Kamath, F.D. Gordon, C.J. Peine, J. Rank, P.C. ter Borg, A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 31, 864–871 (2000)

  21. 21.

    S.W. Biggins, W.R. Kim, N.A. Terrault, S. Saab, V. Balan, T. Schiano, J. Benson, T. Therneau, W. Kremers, R. Wiesner, P. Kamath, G. Klintmalm, Evidence-based incorporation of serum sodium concentration into MELD. Gastroenterology 130, 1652–1660 (2006)

  22. 22.

    K.H. Zou, A.J. O’Malley, L. Mauri, Receiver-operating characteristic analysis for evaluating diagnostic tests and predictive models. Circulation 115, 654–657 (2007)

  23. 23.

    K. Guven, F. Keletimur, M. Yucesoy, Thyroid function tests in non-alcoholic cirrhotic patients with hepatic encephalopathy. Eur. J. Med. 2, 83–85 (1993)

  24. 24.

    R. Malik, H. Hodgson, The relationship between the thyroid gland and the liver. Q. J. Med. 95, 559–569 (2002)

  25. 25.

    M. Borzio, R. Caldara, F. Borzio, V. Piepoli, P. Rampini, C. Ferrari, Thyroid function tests in chronic liver disease: evidence for multiple abnormalities despite clinical euthyroidism. Gut 24, 631–636 (1983)

  26. 26.

    P.G. Walfish, H. Orrego, Y. Israel, J. Blake, H. Kalant, Serum triiodothyronine and other clinical and laboratory indices of alcoholic liver disease. Ann. Intern. Med. 91, 13–16 (1979)

  27. 27.

    D.M. Klachko, E.R. Johnson, The liver and circulating thyroid hormones. J. Clin. Gastroenterol. 5, 465–471 (1983)

  28. 28.

    J.A. Romijn, W.M. Wiersinga, Decreased nocturnal surge of thyrotropin in nonthyroidal illness. J. Clin. Endocrinol. Metab. 70, 35–42 (1990)

  29. 29.

    R. Adriaanse, J.A. Romijn, G. Brabant, E. Endert, W.M. Wiersinga, Pulsatile thyrotropin secretion in nonthyroidal illness. J. Clin. Endocrinol. Metab. 77, 1313–1317 (1993)

  30. 30.

    L. Bartalena, E. Martino, L. Petrini, F. Velluzzi, A. Loviselli, L. Grasso, C. Mammoli, A. Pinchera, The nocturnal serum thyrotropin surge is abolished in patients with adrenocorticotropin (ACTH)-dependent or ACTH-independent cushing’s SYNDROME. J. Clin. Endocrinol. Metab. 72, 1195–1199 (1991)

  31. 31.

    P.J. Caron, L.K. Nieman, S.R. Rose, B.C. Nisula, Deficient nocturnal surge of thyrotropin in central hypothyroidism. J. Clin. Endocrinol. Metab. 62, 960–964 (1986)

  32. 32.

    M.H. Samuels, K. Lillehei, B.K. Kleinschmidt-Demasters, J. Stears, E.C. Ridgway, Patterns of pulsatile pituitary glycoprotein secretion in central hypothyroidism and hypogonadism. J. Clin. Endocrinol. Metab. 70, 391–395 (1990)

  33. 33.

    P. Kok, F. Roelfsema, M. Frolich, A.E. Meinders, H. Pijl, Spontaneous diurnal thyrotropin secretion is enhanced in proportion to circulating leptin in obese premenopausal women. J. Clin. Endocrinol. Metab. 90, 6185–6191 (2005)

  34. 34.

    M.H. Samuels, P.A. McDaniel, Thyrotropin levels during hydrocortisone infusions that mimic fasting-induced cortisol elevations: a clinical research center study. J. Clin. Endocrinol. Metab. 82, 3700–3704 (1997)

  35. 35.

    L. Bartalena, E. Cossu, L. Grasso, F. Velluzzi, A. Loviselli, R. Cirillo, E. Martino, Relationship between nocturnal serum thyrotropin peak and metabolic control in diabetic patients. J. Clin. Endocrinol. Metab. 76, 983–987 (1993)

  36. 36.

    D.M. Heuman, S.G. Abou-Assi, A. Habib, L.M. Williams, R.T. Stravitz, A.J. Sanyal, R.A. Fisher, A.A. Mihas, Persistent ascites and low serum sodium identify patients with cirrhosis and low MELD scores who are at high risk for early death. Hepatology 40, 802–810 (2004)

  37. 37.

    P. Vallance, S. Moncada, Hyperdynamic circulation in cirrhosis: a role for nitric oxide? Lancet 337, 776–778 (1991)

  38. 38.

    Y.C. Chen, M.A. Cadnapaphornchai, J. Yang, S.N. Summer, S. Falk, C. Li, W. Wang, R.W. Schrier, Nonosmotic release of vasopressin and renal aquaporins in impaired urinary dilution in hypothyroidism. Am. J. Physiol. Renal. Physiol. 289, 672–678 (2005)

  39. 39.

    S.D. Marks, Nonthyroidal illness syndrome in children. Endocrine 36, 355–367 (2009)

  40. 40.

    S. Meyer, P. Schuetz, M. Wieland, C. Nusbaumer, B. Mueller, M. Christ-Crain, Low triiodothyronine syndrome: a prognostic marker for outcome in sepsis? Endocrine 39, 167–174 (2011)

  41. 41.

    G. Kostopanagiotou, K. Kalimeris, I. Mourouzis, C. Costopanagiotou, N. Arkadopoulos, D. Panagopoulos, N. Papoutsidakis, A. Chranioti, A. Pafiti, D. Spanou, V. Smyrniotis, C. Pantos, Thyroid hormones alterations during acute liver failure: possible underlying mechanisms and consequences. Endocrine 36, 198–204 (2009)

  42. 42.

    A. Tas, S. Köklü, Y. Beyazit, M. Kurt, A. Sayilir, Y. Yesil, H. Celik, Thyroid hormone levels predict mortality in intensive care patients with cirrhosis. Am. J. Med. Sci. 344, 175–179 (2012)

Download references

Conflict of interest

The authors declare no conflict of interest.

Author information

Correspondence to Reyhan Ersoy.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Atalay, R., Ersoy, R., Demirezer, A.B. et al. Day–night variations in thyroid stimulating hormone and its relation with clinical status and metabolic parameters in patients with cirrhosis of the liver. Endocrine 48, 942–948 (2015). https://doi.org/10.1007/s12020-014-0364-1

Download citation


  • Cirrhosis
  • Liver
  • Thyroid-stimulating hormone
  • Diurnal rhythm