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Affective Disorder and Hyperthyroidism
CITATION:  Thomas, A.F., Kvist, T.K., et al.  (2005).  Increased risk of affective disorder following hospitalisation with hyperthyroidism – a register-based study.  European Journal of Endocrinology, Vol 152, Issue 4, 535-543.


Objective: The pattern of comorbidity between thyroid disorders and affective disorder is not fully known. We assessed whether hospitalisation with hyperthyroidism was a risk factor for hospitalisation with affective disorder and evaluated the temporal relationship between these events. 

Design: A historical prospective cohort study comparing patients with hyperthyroidism with patients with non-toxic goitre or osteoarthritis, using existing data from Danish registers. The observational period was from 1 January 1977 to 31 December 1999. 

Methods: Three study cohorts were identified by their International Classification of Diseases (ICD) diagnoses at discharge from hospital and consisted of all patients with a first hospital admission with the index diagnoses of hyperthyroidism, osteoarthritis, or non-toxic goitre. Later admissions to psychiatric hospital wards with discharge ICD diagnoses of affective disorder were used as events of interest. Rates of re-admission were estimated using competing risks models in survival analyses. Age, sex, substance abuse, and calendar time were included as co-variables. 

Results: A study sample of 183 647 patients discharged with an index diagnosis was identified. In total 1374 events occurred in the observational period. An index diagnosis of hyperthyroidism was associated with an increased risk of hospitalisation with affective disorder for both sexes and for all age-bands investigated, compared with the other index diagnoses. The risk was greatest in the first six months after index hospitalisation (rate ratio, 95% confidence interval: 3.60 (2.58–5.04)). 

Conclusions: Patients hospitalised with hyperthyroidism are at greater risk of re-admission with depressive disorder or bipolar disorder than control patients. This suggests that hyperthyroidism is associated with long-term mood disturbances.


1. Lazarus JH. Hyperthyroidism. Lancet 1997 349 339–343.[CrossRef][ISI][Medline] 

2. Whybrow PC & Bauer M. Behavioral and psychiatric aspects of thyrotoxicosis. In Werner and Ingbar’s The Thyroid, edn 8, ch. 48, pp 837–842. Eds LE Braverman & RD Utiger. Philadelphia: Lippencott-Raven Publishers, 2000. 

3. Henley WN & Koehnle TJ. Thyroid hormones and the treatment of depression: an examination of basic hormonal actions in the mature mammalian brain. Synapse 1997 27 36–44.[CrossRef][ISI][Medline] 

4. Marangell LB, Ketter TA, George MS, Pazzaglia PJ, Callahan AM, Parekh P, Andreason PJ, Horwitz B, Herscovitch P & Post RM. Inverse relationship of peripheral thyrotropin-stimulating hormone levels to brain activity in mood disorders. American Journal of Psychiatry 1997 154 224–230.[Abstract] 

5. Kirkegaard C & Faber J. The role of thyroid hormones in depression. European Journal of Endocrinology 1998 138 1–9.[Free Full Text] 

6. Bauer M, Heinz A & Whybrow PC. Thyroid hormones, serotonin and mood: of synergy and significance in the adult brain. Molecular Psychiatry 2002 7 140–156.[CrossRef][ISI][Medline] 

7. Placidi GPA, Boldrini M, Patronelli A, Fiore E, Chiovato L, Perugi G & Marazziti D. Prevalence of psychiatric disorders in thyroid diseased patients. Neuropsychobiology 1998 38 222–225.[CrossRef][ISI][Medline] 

8. Kathol RG, Turner R & Delahunt J. Depression and anxiety associated with hyperthyroidism: response to antithyroid therapy. Psychosomatics 1986 27 501–505.[ISI][Medline] 

9. Maes M, Meltzer HY, Cosyns P, Suy E & Schotte C. An evaluation of basal hypothalamic–pituitary–thyroid axis function in depression: results of a large-scale and controlled study. Psychoneuroendocrinology 1993 18 607–620.[CrossRef][ISI][Medline] 

10. Brownlie BE, Rae AM, Walshe JW & Wells JE. Psychoses associated with thyrotoxicosis – ‘thyrotoxic psychosis’. A report of 18 cases, with statistical analysis of incidence. European Journal of Endocrinology 2000 142 438–444.[Abstract/Free Full Text] 

11. Nath J & Sagar R. Late-onset bipolar disorder due to hyperthyroidism. Acta Psychiatrica Scandinavica 2001 104 72–73.[ISI][Medline] 

12. Fava M, Labbate LA, Abraham ME & Rosenbaum JF. Hypothyroidism and hyperthyroidism in major depression revisited. Journal of Clinical Psychiatry 1995 56 186–192.[ISI][Medline] 

13. Engum A, Bjoro T, Mykletun A & Dahl AA. An association between depression, anxiety and thyroid function – a clinical fact or an artefact? Acta Psychiatrica Scandinavica 2002 106 27–34.[ISI][Medline] 

14. Stern RA, Robinson B, Thorner AR, Arruda JE, Prohaska ML & Prange AJ Jr. A survey study of neuropsychiatric complaints in patients with Graves’ disease. Journal of Neuropsychiatry and Clinical Neuroscience 1996 8 181–185.[Abstract/Free Full Text] 

15. Perrild H, Hansen JM, Arnung K, Olsen PZ & Danielsen U. Intellectual impairment after hyperthyroidism. Acta Endocrinologica 1986 112 185–191.[Medline] 

16. Fahrenfort JJ, Wilterdink AM & van der Veen EA. Long-term residual complaints and psychosocial sequelae after remission of hyperthyroidism. Psychoneuroendocrinology 2000 25 201–211.[CrossRef][ISI][Medline] 

17. Wallace JE, MacCrimmon DJ & Goldberg WM. Acute hyperthyroidism: cognitive and emotional correlates. Journal of Abnormal Psychology 1980 89 519–527.[ISI][Medline] 

18. MacCrimmon DJ, Wallace JE, Goldberg WM & Streiner DL. Emotional disturbance and cognitive deficits in hyperthyroidism. Psychosomatic Medicine 1979 41 331–340.[Abstract] 

19. Paschke R, Harsch I, Schlote B, Vardarli I, Schaaf L, Kaumeier S, Teuber J & Usadel KH. Sequential psychological testing during the course of autoimmune hyperthyroidism. Klinishe Wochenschrift 1990 68 942–950. 

20. Trzepacz PT, McCue M, Klein I, Greenhouse J & Levey GS. Psychiatric and neuropsychological response to propranolol in Graves’ disease. Biological Psychiatry 1988 23 678–688.[ISI][Medline] 

21. Zeitlhofer J, Saletu B, Stary J & Ahmadi R. Cerebral function in hyperthyroid patients. Psychopathology, psychometric variables, central arousal and time perception before and after thyreostatic therapy. Neuropsychobiology 1984 11 89–93.[ISI][Medline] 

22. Kahaly GJ, Hardt J, Petrak F & Egle UT. Psychosocial factors in subjects with thyroid-associated ophthalmopathy. Thyroid 2002 12 237–239.[CrossRef][ISI][Medline] 

23. Scheffer C, Heckmann C, Mijic T & Rudorff KH. Chronic distress syndrome in patients with Graves’ disease. Medizinische Klinik 2004 99 578–584.[ISI][Medline] 

24. Berkson J. Limitations of the application of fourfold table analysis to hospital data. Biometric Bulletin 1946 2 126–135. 

25. Munk-Jorgensen P & Mortensen PB. The Danish Psychiatric Central Register. Danish Medical Bulletin 1997 44 82–84.[ISI][Medline] 

26. WHO. Klassifikation af sygdomme. Systematisk del. International Classification of Diseases. Eight revison, Danish edition. Sundhedsstyrelsen, 1971. 

27. WHO. Klassifikation af sygdomme. Systematisk del. International Statistical Classification of Diseases and Health Related Problems. Tenth revision, Danish edition. Sundhedsstyrelsen og Munksgaard, 1993. 

28. Andersen TF, Madsen M, Jorgensen J, Mellemkjoer L & Olsen JH. The Danish National Hospital Register. A valuable source of data for modern health sciences. Danish Medical Bulletin 1999 46 263–268.[ISI][Medline] 

29. Juel K & Helweg-Larsen K. The Danish Registers of Causes of Death. Danish Medical Bulletin 1999 46 354–357.[ISI][Medline] 

30. Nilsson FM, Kessing LV, Sorensen TM, Andersen PK & Bolwig TG. Major depressive disorder in Parkinson’s disease: a register-based study. Acta Psychiatrica Scandinavica 2002 106 202–211.[CrossRef][ISI][Medline] 

31. Nilsson FM, Kessing LV, Sorensen TM, Andersen PK & Bolwig TG. Enduring increased risk of developing depression and mania in patients with dementia. Journal of Neurology, Neurosurgery and Psychiatry 2002 73 40–44.[Abstract/Free Full Text] 

32. Hermann D, Heinz A & Mann K. Dysregulation of the hypothalamic–pituitary–thyroid axis in alcoholism. Addiction 2002 97 1369–1381.[ISI][Medline] 

33. Irwin R, Ellis PM & Delahunt J. Psychosis following acute alteration of thyroid status. Australian and New Zealand Journal of Psychiatry 1997 31 762–764.[ISI][Medline] 

34. Fukao A, Takamatsu J, Murakami Y, Sakane S, Miyauchi A, Kuma K, Hayashi S & Hanafusa T. The relationship of psychological factors to the prognosis of hyperthyroidism in antithyroid drug-treated patients with Graves’ disease. Clinical Endocrinology 2003 58 550–555.[CrossRef][ISI][Medline] 

35. Sonino N, Girelli ME, Boscaro M, Fallo F, Busnardo B & Fava GA. Life events in the pathogenesis of Graves’ disease. A controlled study. Acta Endocrinologica 1993 128 293–296.[Medline] 

36. Winsa B, Adami HO, Bergstrom R, Gamstedt A, Dahlberg PA, Adamson U, Jansson R & Karlsson A. Stressful life events and Graves’ disease. Lancet 1991 338 1475–1479.[CrossRef][ISI][Medline] 

37. Bommer M, Eversmann T, Pickardt R, Leonhardt A & Naber D. Psychopathological and neuropsychological symptoms in patients with subclinical and remitted hyperthyroidism. Klinishe Wochenschrift 1990 68 552–558. 

38. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU & Kendler KS. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Archives of General Psychiatry 1994 51 8–19.[Abstract] 

39. Frost L, Vestergaard P & Mosekilde L. Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study. Archives of Internal Medicine 2004 164 1675–1678.[Abstract/Free Full Text] 

40. Kessing LV. Validity of diagnoses and other clinical register data in patients with affective disorder. European Psychiatry 1998 13 392–398.[CrossRef][ISI] 

41. Mosbech J, Jorgensen J, Madsen M, Rostgaard K, Thornberg K & Poulsen TD. [The national patient registry. Evaluation of data quality]. Ugeskrift for Laeger 1995 157 3741–3745.[Medline] 

42. Vestergaard P & Mosekilde L. Fractures in patients with hyperthyroidism and hypothyroidism: a nationwide follow-up study in 16 249 patients. Thyroid 2002 12 411–419.[CrossRef][ISI][Medline] 

43. Wells KB, Golding JM & Burnam MA. Psychiatric disorder in a sample of the general population with and without chronic medical conditions. American Journal of Psychiatry 1988 145 976–981.[Abstract] 

44. Gabriel SE, Crowson CS & O’Fallon WM. Comorbidity in arthritis. Journal of Rheumatology 1999 26 2475–2479.[ISI][Medline] 

45. Creamer P, Lethbridge-Cejku M, Costa P, Tobin JD, Herbst JH & Hochberg MC. The relationship of anxiety and depression with self-reported knee pain in the community: data from the Baltimore Longitudinal Study of Aging. Arthritis Care Research 1999 12 3–7.[ISI]