, Volume 59, Issue 1, pp 137–142 | Cite as

Hyperthyroid patients without Graves' orbitopathy are not at increased risk of developing glaucoma: a nationwide Danish register-based case-control study

  • F. Brandt
  • M. Thvilum
  • L. Hegedüs
  • T. H. Brix
Original Article



Graves' disease (GD) and toxic nodular goiter (TNG) are associated with various comorbidities. However, it is unclarified whether TNG and GD without orbitopathy are associated with glaucoma.


This was a case-control study using record-linkage data from nationwide Danish health registers. 28,461 patients with GD and 17,283 with TNG were included. Each case was age and sex matched with four non-hyperthyroid controls and followed over a mean period of 8 years. Data on glaucoma was obtained by record linkage within the National Danish Patient Register and/or the Danish National Prescription Registry. Logistic and Cox regression models were used to assess the risk of glaucoma before and after the diagnosis of GD and TNG.


Compared to controls, there was a significantly increased frequency of glaucoma in patients with GD (4.6 vs. 4.2%, P = 0.006) and in patients with TNG (6.2 vs. 5.7%, P = 0.003). Prior to the diagnosis of hyperthyroidism, the odds ratio (OR) for glaucoma was non-significant in GD (1.09, 95% CI: 1.00–1.18) but slightly increased in TNG (1.13, 95% CI: 1.02–1.24). However, in TNG the OR attenuated completely when only including patients without co-morbidity in the analysis (1.03, 95% CI: 0.93–1.14). After adjustment for pre-existing co-morbidity, the hazard ratio (HR) for glaucoma following GD and TNG was not significantly increased (HR 1.08, 95% CI: 0.98–1.18 and HR 1.10, 95% CI: 0.99–1.21, respectively).


Neither prior to nor following the diagnosis of GD and TNG had any significant association with glaucoma.


Graves' disease Toxic nodular goiter Glaucoma Register study 



Graves' disease


Toxic nodular goiter


Graves' orbitopathy


Confidence interval


Odds ratio


Hazard ratio


Charlson score


The Danish Civil Registration System


The Danish Demographic Database


The Danish National Patient Registry


The Danish National Prescription Registry



F. Brandt has received funding from the European 392 Thyroid Association (ETA).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    J.A. Franklyn, K. Boelaert, Thyrotoxicosis. Lancet 24, 1155–1166 (2012)CrossRefGoogle Scholar
  2. 2.
    M.L. Tanda, E. Piantanida, L. Liparulo, G. Veronesi, A. Lai, L. Sassi, N. Pariani, D. Gallo, C. Azzolini, M. Ferrario, L. Bartalena, Prevalence and natural history of Graves’ orbitopathy in a large series of patients with newly diagnosed Graves’ hyperthyroidism seen at a single center. J. Clin. Endocrinol. Metab. 98, 1443–1449 (2013)CrossRefPubMedGoogle Scholar
  3. 3.
    T.J. Smith, L. Hegedüs, Graves' disease. N. Engl. J. Med. 20, 1552–1565 (2016)CrossRefGoogle Scholar
  4. 4.
    K.P. Cockerham, C. Pal, B. Jani, A. Wolter, J.S. Kennerdell, The prevalence and implications of ocular hypertension and glaucoma in thyroid-associated orbitopathy. Ophtalmology 104, 914–917 (1997)CrossRefGoogle Scholar
  5. 5.
    K. Ohtsuka, Y. Nakamure, Open-angle glaucoma associated with Graves’ disease. Am. J. Ophthalmol. 129, 613–617 (2000)CrossRefPubMedGoogle Scholar
  6. 6.
    M. Thvilum, F. Brandt, T.H. Brix, L. Hegedüs, The interrelation between hypothyroidism and glaucoma: a critical review and meta-analyses. Acta Ophtalmol. (2017)
  7. 7.
    A.J. Lee, E. Rochtchina, J.J. Wang, P.R. Healey, P. Mitchell, Open-angle glaucoma and systemic thyroid disease in an older population: the Blue Mountains Eye study. Eye 18, 600–608 (2014)CrossRefGoogle Scholar
  8. 8.
    L.C. Thygesen, C. Daasnes, I. Thaulow, H. Bronnum-Hansen, Introduction to Danish (nationwide) registers on health and social issues: structure, access, legislation, and archiving. Scand. J. Public Health 39, 12–16 (2011)CrossRefPubMedGoogle Scholar
  9. 9.
    F. Brandt, D. Almind, K. Christensen, A. Green, T.H. Brix, L. Hegedüs, Excess mortality in hyperthyroidism: the influence of preexisting comorbidity and genetic confounding. A Danish nationwide register-based cohort study of twins and singletons. J. Clin. Endocrinol. Metab. 97, 4123–4129 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    M. Thvilum, F. Brandt, D. Almind, K. Christensen, L. Hegedüs, T.H. Brix, Excess mortality in patients diagnosed with hypothyroidism: a nationwide cohort study of singletons and twins. J. Clin. Endocrinol. Metab. 98, 1069–1075 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    M.E. Charlson, P. Pompei, K.L. Ales, C.R. MacKenzie, A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J. Chronic Dis. 40, 373–383 (1987)CrossRefPubMedGoogle Scholar
  12. 12.
    P. Almagro, M. Salvadó, C. Garcia-Vidal, M. Rodríguez-Carballeira, E. Cuchi, J. Torres et al., Pseudomonas aeruginosa and mortality after hospital admission for chronic obstructive pulmonary disease. Respiration 84, 36–43 (2012)CrossRefPubMedGoogle Scholar
  13. 13.
    F. Brandt, M. Thvilum, D. Almind, K. Christensen, A. Green, L. Hegedüs, T.H. Bric, Graves' disease and toxic nodular goiter are both associated with increased mortality but differ with respect to the cause of death: a Danish population-based register study. Thyroid 23, 408–413 (2013)CrossRefPubMedGoogle Scholar
  14. 14.
    J.P. Fine, R.J. Gray, A proportional hazards model for the subdistribution of a competing risk. J. Am. Stat. Assoc. 94, 496–509 (1999)CrossRefGoogle Scholar
  15. 15.
    N. Von Thun Und Hohenstein-Blaul, K. Bell, N. Pfeiffer, F.H. Grus, Autoimmune aspects in glaucoma. Eur. J. Pharmacol. 787, 105–118 (2016)CrossRefGoogle Scholar
  16. 16.
    K. Boelaert, P.R. Newby, M.J. Simmonds, R.L. Holder, J.D. Carr-Smith, J.M. Heward et al., Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am. J. Med. 123, 183.e1–183.e9 (2010)CrossRefGoogle Scholar
  17. 17.
    A. Horwitz, B.É. Petrovski, C. Tron-Pedersen, M. Kolko, Danish nationwide data reveal a link between diabetes mellitus, diabetic, retinopathy, and glaucoma. J. Diabetes Res. 2016, 2684674 (2016)Google Scholar
  18. 18.
    S.D. Chung, H.C. Lin, S.H. Hung, Allegic rhinitis is associated with open-angle glaucoma: a population-based case-control study. Am. J. Rhinol. Allergy 28, 148–151 (2014)CrossRefGoogle Scholar
  19. 19.
    C.F. Schwensen, F. Brandt, L. Hegedüs, T.H. Brix, Mortality in Graves' orbitopathy is increased and influenced by gender, age and pre-existing morbidity: a nationwide Danish register study. Eur. J. Endocrinol. 176, 669–676 (2017)CrossRefPubMedGoogle Scholar
  20. 20.
    H.W. Bae, N. Lee, H.S. Lee, S. Hong, G.J. Seong, C.Y. Kim, Systemic hypertension as a risk factor for open-angle glaucoma: a meta-analysis of population-based studies. PLoS ONE 9, e108226 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    F. Brandt, M. Thvilum, D. Almind, K. Christensen, A. Green, L. Hegedüs, T.H. Brix, Morbidity before and after the diagnosis of hyperthyroidism: a nationwide register-based study. PLoS ONE 8, e66711 (2014)CrossRefGoogle Scholar
  22. 22.
    M. Lillevang-Johansen, B. Abrahamsen, H.L. Jørgensen, T.H. Brix, L. Hegedüs, Excess mortality in treated and untreated hyperthyroidism is related to cumulative periodes of low serum TSH. J. Clin. Endocrinol. Metab. 102, 2301–2309 (2017)CrossRefPubMedGoogle Scholar
  23. 23.
    A.F. Thomasen, T.K. Kvist, P.K. Andersen, L.V. Kessing, Increased risk of affective disorder following hospitalisation with hyperthyroidism—a register based study. Eur. J. Endocrinol. 152, 535–543 (2004)CrossRefGoogle Scholar
  24. 24.
    T.H. Brix, P.S. Hansen, K.O. Kyvik, L. Hegedüs, Cigarette smoking and risk of clinically overt thyroid disease: a population-based twin case-control study. Arch. Intern. Med. 13, 661–666 (2000)Google Scholar
  25. 25.
    Y. Zhou, W. Zhu, C. Wang, The effect of smoking on the risk of primary open-angle glaucoma: an updated meta-analyses of six observational studies. Public Health 140, 85–90 (2016)CrossRefGoogle Scholar
  26. 26.
    M.P.Y. Chan, D.C. Broadway, A.P. Khawaja, J.L.Y. Yip, D.F. Garway-Heath, J.M. Burr, R. Luben, S. Hayat, N. Dalzell, K. Khaw, P.J. Foster, Glaucoma and intraocular pressure in EPIC-Norfolk Eye study: cross sectional study. Br. Med. J. 358, j3889 (2017)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • F. Brandt
    • 1
    • 2
  • M. Thvilum
    • 2
  • L. Hegedüs
    • 2
  • T. H. Brix
    • 2
  1. 1.Department of Internal MedicineHospital of Southern JutlandSønderborgDenmark
  2. 2.Department of Endocrinology and MetabolismOdense University HospitalOdenseDenmark

Personalised recommendations