title: Female vulnerability for thyroid function abnormality in bipolar disorder: role of lithium treatment.
abstract: BACKGROUND
  Previous studies have provided evidence of subtle thyroid hormone metabolism abnormalities in patients with mood disorders. Although these studies are informative, the precise role of the hypothalamic-pituitary-thyroid axis in bipolar disorder, especially in women, remains unclear. We sought to further corroborate thyroid function in patients with bipolar disorder in comparison to patients with other psychiatric, as well as non-psychiatric, diagnoses.
  
  
  METHODS
  In this retrospective, cross-sectional, naturalistic study, serum thyroid-stimulating hormone (TSH) levels in a total sample of 3,204 patients were compared. The study sample included patients with bipolar disorder (n = 469), unipolar depression (n = 615), and other psychiatric diagnoses (n = 999), patients from endocrinology clinics (n = 645), and patients from dermatology clinics (n = 476). Analyses were completed using two different normal ranges for TDH: a high normal range (0.4-5.0 μIU/mL) and a low normal range (0.3-3.0 μIU/mL).
  
  
  RESULTS
  Patients with bipolar disorder showed significantly higher serum TSH levels compared to all other groups. In women, the rate of above normal range TSH was highest in patients with bipolar disorder for both high (5.0 μIU/mL; 12.1%) and low (3.0 μIU/mL; 30.4%) upper normal limits. In patients with bipolar disorder, serum TSH levels did not differ significantly between different mood states. In the lithium-treated patients (n = 240), a significantly lower percentage of women (55.9%) compared to men (71.2%) fell within the 0.3-3.0 μIU/mL normal TSH window (p = 0.016). For the high normal range (0.4-5.0 μIU/mL), serum lithium levels above 0.8 mmol/L were associated with a significantly lower proportion of female patients (59.2%) falling within the normal range than male patients (88.9%). Non-lithium treatment was not associated with a gender difference.
  
  
  CONCLUSIONS
  Our findings show a higher rate of TSH abnormality in patients with bipolar disorder, particularly those taking lithium, compared to those with other psychiatric and medical conditions. Lithium-associated thyroid dysregulation occurs more frequently in female patients. Using the low normal range TSH values at follow-up can increase sensitivity in recognizing hyperthyroidism in lithium-treated female patients, and help in preventing the development of subclinical hypothyroidism and an adverse course of illness.
authors: Department of Psychiatry, Faculty of Medicine, Izmir, Turkey; Department of Neuroscience, Health Sciences Institute, Izmir, Turkey; Brain Dynamics and Research Center, Dokuz Eylul University, Izmir, Turkey; Brain Dynamics, Cognition, and Complex Systems Research Center, Istanbul Kültür University, Istanbul, Turkey.
authors: Ayşegül
authors: A
authors: Özerdem
authors: Zeliha
authors: Z
authors: Tunca
authors: Dilek
authors: D
authors: Çımrın
authors: Ceren
authors: C
authors: Hıdıroğlu
authors: Gül
authors: G
authors: Ergör
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000097:blood / Q000150:complications / Q000188:drug therapy; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D018021:Lithium Chloride / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013959:Thyroid Diseases / Q000209:etiology*; D013972:Thyrotropin / Q000097:blood*; D055815:Young Adult
chemical_list: D018692:Antimanic Agents; D013972:Thyrotropin; D018021:Lithium Chloride
keywords: bipolar disorder; female; gender difference; lithium; thyroid function