Wechselseitige Beziehung zwischen Schilddrüsenerkrankungen und Diabetes

Zusammenfassung

Aktuell sind etwa 8,9 Millionen Menschen in Deutschland von Diabetes betroffen, und jedes Jahr kommt mehr als eine halbe Millionen Menschen hinzu. In der Mehrzahl der Fälle handelt es sich um einen Typ-2-Diabetes, ein Typ-1-Diabetes ist hingegen sehr viel seltener. Auch Schilddrüsenerkrankungen weisen eine hohe Prävalenz auf und nehmen mit dem Alter zu. Im mittleren Lebensalter weist bereits jeder Zweite morphologische Schilddrüsenveränderungen auf. Die Rate an Schilddrüsenfunktionsstörungen liegt bei nahezu 10% der Allgemeinbevölkerung. Zahlreiche epidemiologische Untersuchungen weisen darauf hin, dass Diabetes und Schilddrüsenerkrankungen häufig miteinander vergesellschaftet sind. Die vorliegende Arbeite möchte einen Überblick geben über den Zusammenhang zwischen den verschiedenen Diabetestypen und funktionellen und morphologischen Schilddrüsenauffälligkeiten. Auch sollen mögliche zugrundeliegenden Mechanismen diskutiert werden.

Diabetes mellitus und Schilddrüsenerkrankungen weisen – unabhängig voneinander – eine hohe Prävalenz auf und nehmen mit dem Alter zu. Beide sind häufig miteinander vergesellschaftet. Im Fokus der Forschung steht dabei der Zusammenhang zwischen den verschiedenen Diabetestypen sowie funktionellen und morphologischen Schilddrüsenauffälligkeiten. Auch werden mögliche zugrundeliegenden Mechanismen untersucht.

Abstract

Currently, around 8.9 million people in Germany are affected by diabetes and more than half a million people are diagnosed every year. The majority of cases are type 2 diabetes, whereas type 1 diabetes is much rarer. Thyroid disorders also have a high prevalence and increase with age. In middle age, every second person already has morphological thyroid changes. The rate of thyroid dysfunction is almost 10% of the general population. Numerous epidemiological studies indicate that diabetes and thyroid disorders are often associated with each other. This paper aims to provide an overview of the relationship between the different types of diabetes and functional and morphological thyroid abnormalities. Possible underlying mechanisms will also be discussed.

Kernaussagen

• Bei hypothyreoten Patienten mit Typ-1-Diabetes sind die renale Insulin-Clearance und die Glukoneogenese vermindert.

• Aufgrund des verminderten Insulinbedarfs und der erhöhten Gefahr einer Hypoglykämie muss die Insulindosis entsprechend angepasst werden.

• Nach der Initiierung einer Substitutionstherapie mit L-Thyroxin steigt der Insulinbedarf an.

• Morbus Basedow ist eine häufige Ursache für eine Hyperthyreose bei Patienten mit Typ-1-Diabetes, hingegen liegen bei Patienten mit Typ-2-Diabetes eher Schilddrüsenautonomien vor.

• Die bei der Hyperthyreose vermehrte hepatische Glukoseproduktion gemeinsam mit der gesteigerten Glykogenolyse begünstigen die Entstehung einer Hyperinsulinämie, einer gestörten Glukosetoleranz und einer Insulinresistenz.

• Infolge dieser Veränderungen kann ein Prädiabetes zu einem manifesten Typ-2-Diabetes fortschreiten, sich die Stoffwechseleinstellung eines bereits bestehenden Diabetes verschlechtern und sich eine diabetische Ketoazidose entwickeln.

• Schwerwiegende Erkrankungen, wie eine unzureichende Blutglukosekontrolle, können erheblichen Einfluss auf die Schilddrüsenfunktion haben und so eine die Beurteilung der Schilddrüsenhormone erschweren.

• Während internationale Fachgesellschaften bei Typ-1-Diabetes regelmäßige Kontrolluntersuchungen der Schilddrüsenfunktion empfehlen, ist dies für Typ-2-Diabetes nicht der Fall.

Schlüsselwörter

Schilddrüsenfunktionsstörung - Schilddrüsenkrebs - Schilddrüsenautoimmunität - Typ-1-Diabetes - Typ-2-Diabetes

Keywords

Thyroid dysfunction - thyroid cancer - thyroid autoimmunity - type 1 diabetes - type 2 diabetes

Publication History

Article published online:
10 June 2024

• Literatur

• 1 DDG Fact Sheet (Gesundheitsbericht Diabetes 2024, Kirchheim Verlag). https://www.ddg.info/ddg-factsheet
• 2 Reiners C, Wegscheider K, Schicha H. et al. Prevalence of thyroid disorders in the working population of Germany: Ultrasonography screening in 96,278 unselected employes. Thyroid 2004; 14: 926-932
• 3 Khattak RM, Ittermann T, Nauck M. et al. Monitoring the prevalence of thyroid disorders in the adult population of Northeast Germany. Popul Health Metr 2016; 14: 39 DOI: 10.1186/s12963-016-0111-3. (PMID: 27833458)
• 4 Robert Koch-Institut, Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (Hrsg). Krebs in Deutschland für 2019/2020. 14. Ausgabe. Berlin. 2023
• 5 Güney E, Efe B, Akalin A. et al. Thyroid Disease in Diabetes Mellitus. Turk J Endocrinol Metab 1999; 3: 119-122
• 6 Díez JJ, Sánchez P, Iglesias P. et al. Prevalence of thyroid dysfunction in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 2011; 119: 201-207
• 7 Díez JJ, Iglesias P. An analysis of the relative risk for goitre in euthyroid patients with type 2 diabetes. Clin Endocrinol (Oxf) 2014; 80: 356-361 DOI: 10.1111/cen.12169. (PMID: 23414115)
• 8 Tseng CH. Metformin reduces risk of benign nodular goiter in patients with type 2 diabetes mellitus. Eur J Endocrinol 2019; 180: 365-372 DOI: 10.1530/EJE-19-0133. (PMID: 30986765)
• 9 Meng X, Xu S, Chen G. et al. Metformin and thyroid disease. J Endocrinol 2017; 233: R43-R51 DOI: 10.1530/JOE-16-0450. (PMID: 28196954)
• 10 Dos Santos PB, Gertrudes LN, Conceição FL. et al. Effects of Metformin on TSH Levels and Benign Nodular Goiter Volume in Patients Without Insulin Resistance or Iodine Insufficiency. Front Endocrinol (Lausanne) 2019; 10: 465 DOI: 10.3389/fendo.2019.00457. (PMID: 31379737)
• 11 Barmpari ME, Kokorou M, Micheli A. et al. Thyroid Dysfunction among Greek Patients with Type 1 and Type 2 Diabetes Mellitus as a Disregarded Comorbidity. J Diabetes Res 2017; 2017: 6505814
• 12 Pimenta WP, Mazeto CF, Shibata SA. et al. Associação de tireopatias em uma população de pacientes com diabetes. Arq Bras Endocrinol Metab 2005; 49: 234-240
• 13 Al-Attas OS, Al-Daghri NM, Alkharfy KM. et al. Urinary iodine is associated with insulin resistance in subjects with diabetes mellitus type 2. Exp Clin Endocrinol Diabetes 2012; 120: 618-622
• 14 Karakaya RE, Saka M, Ozdemir D. Determining the relationship between dietary iodine intake, urinary iodine excretion and thyroid functions in people with type 2 diabetes mellitus. Arch Endocrinol Metab 2020; 64: 383-389 DOI: 10.20945/2359-3997000000233. (PMID: 32267361)
• 15 Steiß JO, Otten A, Graef V. et al. Schilddrüsensonographie und Harnjodidausscheidung bei Kindern und Jugendlichen mit Diabetes mellitus Typ I. Klin Padiatr 1996; 208: 327-333
• 16 Karaköse M, Hepsen S, Çakal E. et al. Frequency of nodular goiter and autoimmune thyroid disease and association of these disorders with insulin resistance in polycystic ovary syndrome. J Turk Ger Gynecol Assoc 2017; 18: 85-89
• 17 Miranda-Filho A, Lortet-Tieulent J, bray F. et al. Thyroid cancer incidence trends by histology in 25 countries: a population-based study. Lancet Diabetes Endocrinol 2021; 9: 225-234 DOI: 10.1016/S2213-8587(21)00027-9. (PMID: 33662333)
• 18 Dorak MT, Karpuzoglu E. Gender differences in cancer susceptibility: an inadequately addressed issue. Front Genet 2012; 3: 268 DOI: 10.3389/fgene.2012.00268. (PMID: 23226157)
• 19 Siegel RL, Miller KD, Fedewa SA. et al. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67: 7-30 DOI: 10.3322/caac.21395. (PMID: 28248415)
• 20 Lim H, Devesa SD, Sosa JA. et al. Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974–2013. JAMA 2017; 317: 1338-1348 DOI: 10.1001/jama.2017.2719. (PMID: 28362912)
• 21 Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 2006; 295: 2164-2167 DOI: 10.1001/jama.295.18.2164. (PMID: 16684987)
• 22 Haymart MR, Banerjee M, Reyes-Gastelum D. et al. Thyroid Ultrasound and the Increase in Diagnosis of Low-Risk Thyroid Cancer. J Clin Endocrinol Metab 2019; 104: 785-792 DOI: 10.1210/jc.2018-01933. (PMID: 30329071)
• 23 Vaccarella S, Franceschi S, Bray F. et al. Worldwide Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis. N Engl J Med 2016; 375: 614-617 DOI: 10.1056/NEJMp1604412. (PMID: 27532827)
• 24 Enewold L, Zhu K, Ron E. et al. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005. Cancer Epidemiol Biomarkers Prev 2009; 18: 784-791 DOI: 10.1158/1055-9965.EPI-08-0960. (PMID: 19240234)
• 25 Fiore M, Conti GO, Caltabiano R. et al. Role of Emerging Environmental Risk Factors in Thyroid Cancer: A Brief Review. Int J Environ Res Public Health 2019; 16: 1185
• 26 Aschebrook-Kilfoy B, Sabra MM, Brenner A. et al. Diabetes and thyroid cancer risk in the National Institutes of Health-AARP Diet and Health Study. Thyroid 2011; 21: 957-963 DOI: 10.1089/thy.2010.0396. (PMID: 21767143)
• 27 Dong WW, Zhang DL, Wang ZH. et al. Different types of diabetes mellitus and risk of thyroid cancer: A meta-analysis of cohort studies. Front Endocrinol (Lausanne) 2022; 13: 971213 DOI: 10.3389/fendo.2022.971213. (PMID: 36213272)
• 28 Yeo Y, Ma SH, Hwang Y. et al. Diabetes mellitus and risk of thyroid cancer: a meta-analysis. PLoS One 2014; 9: e98135 DOI: 10.1371/journal.pone.0098135. (PMID: 24927125)
• 29 Li H, Qian J. Association of diabetes mellitus with thyroid cancer risk: A meta-analysis of cohort studies. Medicine (Baltimore) 2017; 96: e8230
• 30 Müssig K, Häring HU. Insulin signal transduction in normal cells and its role in carcinogenesis. Exp Clin Endocrinol Diabetes 2010; 118: 356-359 DOI: 10.1055/s-0029-1243603. (PMID: 20140848)
• 31 Müssig K, Staiger H, Kantartzis K. et al. Diabetes, Insulin, Insulinanaloga und Krebs. Dtsch Med Wochenschr 2010; 135: 924-929
• 32 Lammers R, Gray A, Schlessinger J. et al. Differential signalling potential of insulin- and IGF-1-receptor cytoplasmic domains. EMBO J 1989; 8: 1369-1375 DOI: 10.1002/j.1460-2075.1989.tb03517.x. (PMID: 2548842)
• 33 Kellerer M, von Eye CH, Mühlhöfer A. et al. Insulin- and insulin-like growth factor-I receptor tyrosine-kinase activities in human renal carcinoma. Int J Cancer 1995; 62: 501-507 DOI: 10.1002/ijc.2910620502. (PMID: 7665217)
• 34 Moller DE, Yokota A, Caro JF. et al. Tissue-specific expression of two alternatively spliced insulin receptor mRNAs in man. Mol Endocrinol 1989; 3: 1263-1269 DOI: 10.1210/mend-3-8-1263. (PMID: 2779582)
• 35 Tamez-Pérez HE, Martìnez E, Quintanilla-Flores DL. et al. The rate of primary hypothyroidism in diabetic patients is greater than in the non-diabetic population. An observational study. Med Clin (Barc) 2012; 138: 475-477
• 36 Haymart MR, Repplinger DJ, leverson GE. et al. Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. J Clin Endocrinol Metab 2008; 93: 809-814
• 37 Fiore E, Rago T, Provenzale MA. et al. Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role. Endocr Relat Cancer 2009; 16: 1251-1260
• 38 Almquist M, Johansen D, Björge T. et al. Metabolic factors and risk of thyroid cancer in the Metabolic syndrome and Cancer project (Me-Can). Cancer Causes Control 2011; 22: 743-751 DOI: 10.1007/s10552-011-9747-2. (PMID: 21380729)
• 39 Rapp K, Schroeder J, Klenk J. et al. Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia 2006; 49: 945-952
• 40 Stocks T, Rapp K, Bjørge T. et al. Blood glucose and risk of incident and fatal cancer in the metabolic syndrome and cancer project (me-can): analysis of six prospective cohorts. PLoS Med 2009; 6: e1000201 DOI: 10.1371/journal.pmed.1000201. (PMID: 20027213)
• 41 Lopez R, Arumugam A, Joseph R. et al. Hyperglycemia enhances the proliferation of non-tumorigenic and malignant mammary epithelial cells through increased leptin/IGF1R signaling and activation of AKT/mTOR. PLoS One 2013; 8: e79708
• 42 Moreno-Sánchez R, Rodríguez-Enríquez S, Marín-Hernández A. et al. Energy metabolism in tumor cells. FEBS J 2007; 274: 1393-1418 DOI: 10.1111/j.1742-4658.2007.05686.x. (PMID: 17302740)
• 43 Díez JJ, Iglesias P. An analysis of the relative risk for hypothyroidism in patients with Type 2 diabetes. Diabet Med 2012; 29: 1510-1514 DOI: 10.1111/j.1464-5491.2012.03687.x. (PMID: 22507223)
• 44 Han C, He X, Xia X. et al. Subclinical hypothyroidism and type 2 diabetes: a systematic review and meta-analysis. PLoS One 2015; 10: e0135233 DOI: 10.1371/journal.pone.0135233. (PMID: 26270348)
• 45 Chaker L, Ligthart S, Korevaar TIM. et al. Thyroid function and risk of type 2 diabetes: a population-based prospective cohort study. BMC Med 2016; 14: 150 DOI: 10.1186/s12916-016-0693-4. (PMID: 27686165)
• 46 Roa Dueñas OH, Van der Burgh AC, Ittermann T. et al. Thyroid Function and the Risk of Prediabetes and Type 2 Diabetes. J Clin Endocrinol Metab 2022; 107: 1789-1798
• 47 Rong F, Dai H, Wu Y. et al. Association between thyroid dysfunction and type 2 diabetes: a meta-analysis of prospective observational studies. BMC Med 2021; 19: 257
• 48 Chang CH, Yeh YC, Shih SR. et al. Association between thyroid dysfunction and dysglycaemia: a prospective cohort study. Diabet Med 2017; 34: 1584-1590
• 49 Fleiner HF, Bjøro T, Midthjell K. et al. Prevalence of thyroid dysfunction in autoimmune and type 2 diabetes: the population-based HUNT study in Norway. J Clin Endocrinol Metab 2016; 101: 669-677 DOI: 10.1210/jc.2015-3235. (PMID: 26583583)
• 50 Alwan H, Villoz F, Feller M. et al. Subclinical thyroid dysfunction and incident diabetes: a systematic review and an individual participant data analysis of prospective cohort studies. Eur J Endocrinol 2022; 187: S35-S46 DOI: 10.1530/EJE-22-0523. (PMID: 36070417)
• 51 Toulis KA, Stagnaro-Green A, Negro R. et al. Maternal subclinical hypothyroidsm and gestational diabetes mellitus: a meta-analysis. Endocr Pract 2014; 20: 703-714 DOI: 10.4158/EP13440.RA. (PMID: 24449677)
• 52 Kent NL, Young SL, Akison LK. et al. Is the link between elevated TSH and gestational diabetes mellitus dependant on diagnostic criteria and thyroid antibody status: a systematic review and meta-analysis. Endocrine 2021; 74: 38-49
• 53 Luo J, Wang X, Yuan L. et al. Association of thyroid disorders with gestational diabetes mellitus: a meta-analysis. Endocrine 2021; 73: 550-560
• 54 Yang Y, Li Q, Wang Q. et al. Thyroid antibodies and gestational diabetes mellitus: a meta-analysis. Fertil Steril 2015; 104: 665-671.e3
• 55 Van den Driessche A, Eenkhoorn V, Van Gaal L. et al. Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review. Neth J Med 2009; 67: 376-387 (PMID: 20009114)
• 56 Canaris GJ, Manowitz NR, Mayor G. et al. The Colorado thyroid disease prevalence study. Arch Intern Med 2000; 160: 526-534 DOI: 10.1001/archinte.160.4.526. (PMID: 10695693)
• 57 Wu T, Flowers JW, Tudiver F. et al. Subclinical thyroid disorders and cognitive performance among adolescents in the United States. BMC Pediatr 2006; 6: 12
• 58 Warncke K, Fröhlich-Reiterer EEThon A. et al. Polyendocrinopathy in children, adolescents, and young adults with type 1 diabetes: a multicenter analysis of 28 671 patients from the German/Austrian DPV-Wiss database. Diabetes Care 2010; 33: 2010-2012
• 59 Ziegler AG, Bonifacio E. Age-related islet atoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia 2012; 55: 1937-1943 DOI: 10.1007/s00125-012-2472-x. (PMID: 22289814)
• 60 Umpierrez GE, Latif KA, Murphy MB. et al. Thyroid dysfunction in patients with type 1 diabetes: a longitudinal study. Diabetes Care 2003; 26: 1181-1185
• 61 Shun CB, Donaghue KC, Phelan H. et al. Thyroid autoimmunity in Type 1 diabetes: systematic review and meta-analysis. Diabet Med 2014; 31: 126-135 DOI: 10.1111/dme.12318. (PMID: 24103027)
• 62 Frommer L, Kahaly GJ. Type 1 Diabetes and Autoimmune Thyroid Disease-The Genetic Link. Front Endocrinol (Lausanne) 2021; 12: 618213 DOI: 10.3389/fendo.2021.618213. (PMID: 33776915)
• 63 Peppa M, Koliaki C, Nikolopoulos P. et al. Skeletal muscle insulin resistance in endocrine disease. J Biomed Biotechnol 2010; 2010: 527850 DOI: 10.1155/2010/527850. (PMID: 20300436)
• 64 Maratou E, Hadjidakis DJ, Kollias A. et al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol 2009; 160: 785-790
• 65 Pearce SH, Brabant G, Duntas LH. et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J 2013; 2: 215-228 DOI: 10.1159/000356507. (PMID: 24783053)
• 66 Garber JR, Cobin RH, Gharib H. et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid 2012; 22: 1200-1235
• 67 Peters KE, Chubb SAP, Bruce DG. et al. Prevalence and incidence of thyroid dysfunction in type 1 diabetes, type 2 diabetes and latent autoimmune diabetes of adults: The Fremantle Diabetes Study Phase II. Clin Endocrinol (Oxf) 2020; 92: 373-382 DOI: 10.1111/cen.14164. (PMID: 31984536)
• 68 Celani MF, Bonati ME, Stucci N. et al. Prevalence of abnormal thyrotropin concentrations measured by a sensitive assay in patients with type 2 diabetes mellitus. Diabetes Res 1994; 27: 15-25
• 69 Franzese A, Buono P, Mascolo M. et al. Thyroid autoimmunity starting during the course of type 1 diabetes denotes a subgroup of children with more severe diabetes. Diabetes Care 2000; 23: 1201-1202
• 70 Nederstigt C, Corssmit EPM, de Konin EJP. et al. Incidence and prevalence of thyroid dysfunction in type 1 diabetes. J Diabetes Complications 2016; 30: 420-425
• 71 Potenza M, Via MA, Yanagisawa RT. Excess thyroid hormone and carbohydrate metabolism. Endocr Pract 2009; 15: 254-262 DOI: 10.4158/EP.15.3.254. (PMID: 19364696)
• 72 American Diabetes Association Professional Practice Committee. 14. Children and Adolescents: Standards of Care in Diabetes – 2024. Diabetes Care 2024; 47 (Suppl. 01) S258-S281 DOI: 10.2337/dc24-S014. (PMID: 38078582)
• 73 Kalra S, Aggarwal S, Khandelwal D. et al. Thyroid Dysfunction and Type 2 Diabetes Mellitus: Screening Strategies and Implications for Management. Diabetes Ther 2019; 10: 2035-2044 DOI: 10.1007/s13300-019-00700-4. (PMID: 31583645)