Journal of Endocrinological Investigation

, Volume 41, Issue 4, pp 389–393 | Cite as

TSH oscillations in young patients with type 1 diabetes may be due to glycemic variability

  • G. Bellastella
  • M. I. Maiorino
  • L. Scappaticcio
  • O. Casciano
  • M. Petrizzo
  • M. Caputo
  • V. A. Paglionico
  • D. Giugliano
  • K. Esposito
Original Article



A relationship between thyroid dysfunction and diabetes mellitus has been described by several authors but the role of glycemic variability is still unclear. We planned the present study to evaluate the influence of glycemic variability on thyroid hormones and TSH concentrations in patients with type 1 diabetes mellitus (T1DM).


Seventy-seven young patients with T1DM were enrolled and evaluated for basal glucose concentrations, HbA1c, thyroid hormones and TSH concentrations. Glucose variability was investigated by considering the standard deviation of blood glucose readings and by calculating the mean amplitude of glycemic excursions and continuous overlapping net glycemic action (CONGA). The low (LBGI) and high (HBGI) blood glucose indices were also calculated. The correlations between TSH, thyroid hormones, glycemia and HbA1c were studied in patients and in controls, whereas those between TSH, thyroid hormones and indices of glucose variability only in patients.


No correlations were observed in T1DM patients between free thyroid hormones and glycemic values, HbA1c and indices of glucose variability, while an inverse correlation was observed between TSH levels and glycemic values (r = −0.27; p = 0.01), CONGA index (r = −0.35; p = 0.001) and HBGI (r = −0.28; p = 0.01) but not with HbA1c (r = −0.1; p = 0.47).


Our results suggest a direct action of glycemic excursions on TSH secretion, regardless of variations of thyroid hormone concentrations. Thus, the evaluation of thyroid function through the assay of TSH concentrations in these patients should be made, if possible, by multiple samples on patients in euglycemic state to avoid underestimation or overestimation of thyroid dysfunction due to a wrong diagnosis of euthyroidism or dysthyroidism with consequent inappropriate choice of therapeutic options.


TSH Type 1 diabetes Glycemic variability CONGA MAGE LBGI 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in the study were in accordance with the ethical standards of institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Mouradian M, Abourizk N (1983) Diabetes mellitus and thyroid disease. Diabetes Care 6:12–20CrossRefGoogle Scholar
  2. 2.
    Gray RS, Irvine WJ, Clarke BF (1979) Screening for thyroid dysfunction in diabetics. Br Med J 2:1439CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Duntas LH, Orgiazzi J, Brabant G (2011) The interface between thyroid and diabetes mellitus. Clin Endocrinol 75:1–9CrossRefGoogle Scholar
  4. 4.
    Kadiyala R, Peter R, Okosieme OE (2010) Thyroid dysfunction in patients with diabetes: clinical implications and screening strategies. Int J Clin Pract 64:1130–1139CrossRefPubMedGoogle Scholar
  5. 5.
    Huber A, Menconi F, Corathers S, Jacobson EM, Tomer Y (2008) Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms. Endocr Rev 29:697–725CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Gronich N, Deftereos SN, Lavi I, Persidis AS, Abernethy DR, Rennert G (2015) Hypothyroidism is a risk factor for new-onset diabetes: a cohort study. Diabetes Care 38:1657–1664CrossRefPubMedGoogle Scholar
  7. 7.
    Ying H, Tang YP, Bao YR, Su XJ, Cai X, Li YH, Wang DF (2016) Maternal TSH level and TPOAb status in early pregnancy and their relationship to the risk of gestational diabetes mellitus. Endocrine 54:742–750CrossRefPubMedGoogle Scholar
  8. 8.
    Korevaar TI, Nieboer D, Bisschop PH, Goddijn M, Medici M, Chaker L, de Rijke YB, Jaddoe VW, Visser TJ, Steyerberg EW, Tiemeier H, Vrijkotte TG, Peeters RP (2016) Risk factors and a clinical prediction model for low maternal thyroid function during early pregnancy: two population-based prospective cohort studies. Clin Endocrinol 85:902–909CrossRefGoogle Scholar
  9. 9.
    Jun JE, Jee JH, Bae JC, Jin SM, Hur KY, Lee MK, Kim TH, Kim SW, Kim JH (2017) Association between changes in thyroid hormones and incident type 2 diabetes: a seven-year longitudinal study. Thyroid 27:29–38CrossRefPubMedGoogle Scholar
  10. 10.
    Somers EC, Thomas SL, Smeeth L, Hall AJ (2006) Autoimmune diseases co-occurring within individuals and within families: a systematic review. Epidemiology 17:202–217CrossRefPubMedGoogle Scholar
  11. 11.
    Han C, He X, Xia X, Li Y, Shi X, Shan Z, Teng W (2015) Subclinical hypothyroidism and type 2 diabetes: a systematic review and meta-analysis. PLoS One 10:e0135233CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kabadi UM (1984) Impaired pituitary thyrotroph function in uncontrolled type II diabetes mellitus: normalization on recovery. J Clin Endocrinol Metab 59:521–525CrossRefPubMedGoogle Scholar
  13. 13.
    Bartalena L, Cossu E, Grasso L, Velluzzi F, Loviselli A, Cirillo R, Martino E (1993) Relationship between nocturnal serum thyrotropin peak and metabolic control in diabetic patients. J Clin Endocrinol Metab 76:983–987PubMedGoogle Scholar
  14. 14.
    Celani MF, Bonati ME, Stucci N (1994) Prevalence of abnormal thyrotropin concentrations measured by a sensitive assay in patients with type 2 diabetes mellitus. Diabetes Res 27:15–25PubMedGoogle Scholar
  15. 15.
    Gürsoy N, Ercan TE, Ertürk E, Imamoglu S, Annik A (1999) The relationship between the glycemic control and the hypothalamus-pituitary-thyroid axis in diabetic patients. Turk J Endocrinol Metab 4:163–168Google Scholar
  16. 16.
    Palmer SC, Mavridis D, Nicolucci A, Johnson DW, Tonelli M, Craig JC, Maggo J, Gray V, De Berardis G, Ruospo M, Natale P, Saglimbene V, Badve SV, Cho Y, Nadeau-Fredette AC, Burke M, Faruque L, Lloyd A, Ahmad N, Liu Y, Tiv S, Wiebe N, Strippoli GF (2016) Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis. JAMA 316:313–324CrossRefPubMedGoogle Scholar
  17. 17.
    Vigersky RA, Filmore-Nassar A, Glass AR (2006) Thyrotropin suppression by metformin. J Clin Endocrinol Metab 91:225–227CrossRefPubMedGoogle Scholar
  18. 18.
    Cappelli C, Rotondi M, Pirola I, Agosti B, Gandossi E, Valentini U, De Martino E, Cimino A, Chiovato L, Agabiti-Rosei E, Castellano M (2009) TSH-lowering effect of metformin in type 2 diabetic patients: differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients. Diabetes Care 32:1589–1590CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Rotondi M, Cappelli C, Magri F, Botta R, Dionisio R, Iacobello C, De Cata P, Nappi RE, Castellano M, Chiovato L (2011) Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome. Clin Endocrinol 75:378–381CrossRefGoogle Scholar
  20. 20.
    Cappelli C, Rotondi M, Pirola I, Agosti B, Formenti A, Zarra E, Valentini U, Leporati P, Chiovato L, Castellano M (2012) Thyreotropin levels in diabetic patients on metformin treatment. Eur J Endocrinol 167:261–265PubMedGoogle Scholar
  21. 21.
    Balsamo C, Zucchini S, Maltoni G, Rollo A, Martini AL, Mazzanti L, Pession A, Cassio A (2015) Relationships between thyroid function and autoimmunity with metabolic derangement at the onset of type 1 diabetes: a cross-sectional and longitudinal study. J Endocrinol Invest 38:701–707CrossRefPubMedGoogle Scholar
  22. 22.
    Picconi F, Di Flaviani A, Malandrucco I, Giordani I, Frontoni S (2012) Impact of glycemic variability on cardiovascular outcomes beyond glycated hemoglobin. Evidence and clinical perspectives. Nutr Metab Cardiovasc Dis 22:691–696CrossRefPubMedGoogle Scholar
  23. 23.
    Hill NR, Oliver NS, Choudhary P, Levy JC, Hindmarsh P, Matthews DR (2011) Normal reference range for mean tissue glucose and glycemic variability derived from continuous glucose monitoring for subjects without diabetes in different ethnic groups. Diabetes Technol Ther 13:921–928CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Kovatchev BP, Cox DJ, Gonder-Frederick LA, Young-Hyman D, Schlundt D, Clarke W (1998) Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index. Diabetes Care 21:1870–1875CrossRefPubMedGoogle Scholar
  25. 25.
    Perros P, McCrimmon RJ, Shaw G, Frier BM (1995) Frequency of thyroid dysfunction in diabetic patients: value of annual screening. Diabet Med 12:622–627CrossRefPubMedGoogle Scholar
  26. 26.
    Maratou E, Hadjidakis DJ, Kollias A, Tsegka K, Peppa M, Alevizaki M, Mitrou P, Lambadiari V, Boutati E, Nikzas D, Tountas N, Economopoulos T, Raptis SA, Dimitriadis G (2009) Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol 160:785–790CrossRefPubMedGoogle Scholar
  27. 27.
    Brenta G, Celi FS, Pisarev M, Schnitman M, Sinay I, Arias P (2009) Acute thyroid hormone withdrawal in athyreotic patients results in a state of insulin resistance. Thyroid 19:665–669CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Mohn A, Di Michele S, Di Luzio R, Tumini S, Chiarelli F (2002) The effect of subclinical hypothyroidism on metabolic control in children and adolescents with type 1 diabetes mellitus. Diabet Med 19:70–73CrossRefPubMedGoogle Scholar
  29. 29.
    Cavallo-Perin P, Bruno A, Boine L, Cassader M, Lenti G, Pagano G (1988) Insulin resistance in Graves’ disease: a quantitative in vivo evaluation. Eur J Clin Invest 18:607–613CrossRefPubMedGoogle Scholar
  30. 30.
    Al-Shoumer KA, Vasanthy BA, Al-Zaid MM (2006) Effects of treatment of hyperthyroidism on glucose homeostasis, insulin secretion, and markers of bone turnover. Endocr Pract 12:121–130CrossRefPubMedGoogle Scholar
  31. 31.
    Ramasamy V, Kadiyala R, Fayyaz F, Mallipedhi A, Baglioni P, Okosieme OE (2011) Value of baseline serum thyrotropin as a predictor of hypothyroidism in patients with diabetes mellitus. Endocr Pract 17:26–32CrossRefPubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2017

Authors and Affiliations

  • G. Bellastella
    • 1
  • M. I. Maiorino
    • 1
  • L. Scappaticcio
    • 1
  • O. Casciano
    • 1
  • M. Petrizzo
    • 1
  • M. Caputo
    • 1
  • V. A. Paglionico
    • 1
  • D. Giugliano
    • 1
  • K. Esposito
    • 2
  1. 1.Endocrinology and Metabolic Diseases Unit, Department of Medical, Surgical, Neurological, Metabolic, Geriatric Sciences and AgingUniversity of Campania “L. Vanvitelli”NaplesItaly
  2. 2.Diabetes Unit, Department of Medical, Surgical, Neurological, Metabolic Sciences and AgingUniversity of Campania “L. Vanvitelli”NaplesItaly

Personalised recommendations