Thyroid Function and Ultrasonography Abnormalities in Lithium-Treated Bipolar Patients: A Cross-sectional Study with Healthy Controls

Abstract

Introduction: Lithium has many effects on thyroid physiology. Although these side effects have been known for a long time, large sample studies of lithium-treated patients using ultrasonography are lacking. The aim of this study is to investigate the detailed thyroid morphologies, hormone levels, and antibodies of lithium-treated patients compared with healthy controls.Methods: This cross-sectional study involved 84 lithium-treated patients with bipolar disorder and 65 gender and age similar controls who had never been exposed to lithium. Subjects between 18 and 65 years of age were eligible for the study. Venous blood samples were acquired to determine the levels of free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid antibodies; also, ultrasonographic examinations of the patients' thyroid glands were performed.Results: There were no statistically significant differences in smoking habits, known thyroid disease, thyroid medication use, familial thyroid disease, fT4 level, autoimmunity, thyroid nodule presence, or Hashimoto' s thyroiditis between the lithium and control groups. The median TSH level and thyroid volume were significantly higher in the lithium group. In the lithium group, 14 cases (16.7%) of hypothyroidism, seven cases (8.3%) of subclinical hypothyroidism, and one case (1.2%) of subclinical hyperthyroidism were defined; in the control group, seven cases (10.8%) of hypothyroidism and two cases (3.1%) of subclinical hyperthyroidism were defined. Thyroid dysfunction, goiter, parenchymal abnormality, ultrasonographically defined thyroid abnormality, and thyroid disorder were found to be more prevalent in the lithium group. 90% of patients with goiter and 74.3% of patients with ultrasonographic pathologies were euthyroid. Conclusion:It is important to note that 90% of the patients with goiter were euthyroid. This indicates that monitoring by blood test alone is insufficient. The prevalence rates of 47.6% for goiter and 83.3% for ultrasonographic pathology demonstrate that ultasonographic follow-up may be useful in lithium-treated patients. To determine whether routine ultrasonographic examination is necessary, large sample prospective studies are necessary due to the limitations of this study.

Thyroid structure and function in long‐term lithium‐treated and lithium‐naïve bipolar patients

“…In our study, patients receiving lithium had significantly higher thyroid volume, the higher number of focal changes >1 cm, and more frequent goiter, compared with lithium-naïve subjects. The percentage of goiter (40%) concurs with the results of studies by other investigators (Bauer et al, 2007;Bocchetta et al, 1991;Kuman Tunçel et al, 2017;Ozpoyraz et al, 2002).…”

“…Such a relationship between thyroid hormones and goiter has not been specifically investigated so far. It is of note that in the paper of Kuman Tunçel et al (), most of the patients with goiter were found to be euthyroid. Our results may suggest a significant contribution to higher thyroid volume and goiter in lithium‐treated patients was made by a proliferation of thyrocytes, due to the stimulation by lithium of Wnt/beta‐catenin signaling (Rao et al, ).…”

“…However, after 10 years of follow up, the same group of researchers found an increase in the occurrence of goiter with the duration of lithium treatment, on the average of 2.1% of patients per year (Bocchetta et al, ). The frequency of goiter in lithium‐treated patients found in studies performed in the 21st century ranged between 30% and 59% (Bauer et al, ; Kuman Tunçel, Akdeniz, Özbek, Kavukçu, & Ünal Kocabaş, ; Ozpoyraz, Tamam, & Kulan, ). The mechanisms of lithium‐induced goiter can include the inhibition of thyroid hormone release resulting in an increase of TSH that leads to the increment of the volume and the activation by lithium of tyrosine kinase and the influence on intracellular signaling by cyclic AMP and Wnt/beta‐catenin thus inducing the proliferation of thyrocytes (Lazarus, ).…”

Lithium can cause hyperthyroidism as well as hypothyroidism: A systematic review of an under-recognised association

“…By contrast, a retrospective analysis of laboratory data (Shine et al, 2015) and a cross-sectional comparison of those exposed to lithium therapy and controls did not find any association between that lithium therapy in general and hyperthyroidism (Kuman Tuncel et al, 2017). However, the former study did report an association in patients with higher than median lithium concentrations (Shine et al, 2015).…”

Lithium-associated hypothyroidism and potential for reversibility after lithium discontinuation: Findings from the LiSIE retrospective cohort study

“…An even earlier report of Schou et al (1968) pertained to lithium-associated euthyroid goitre, which was reversible once lithium was discontinued. A later study, however, did not show any correlation between goitre and thyroid function in lithium-treated patients with BPAD (Kuman Tunçel et al, 2017). Soon, further cases of thyroid dysfunction associated with lithium were published, leading to speculations that myxoedema was a possible side effect of lithium treatment (Vestergaard and Poulsen, 1972).…”