Lithium Linked to Thyroid Dysfunction, but Only in Women

Daniel M. Keller, PhD

April 13, 2015

VIENNA — Almost 1 in 6 women with bipolar disorder (BPD) develop hypothyroidism while being treated with lithium, new research shows. There was no significant correlation with the duration of the illness or with age. Male patients did not show signs of hypothyroidism.

Lithium therapy of BPD has been associated with deterioration of kidney function that was dependent on duration of treatment and patient age, with significant deterioration after 10 years. Most hypothyroidism occurs during the initial years of lithium administration, but the dynamics of thyroid function after 10 years of lithium treatment had not been known.

Researchers from the Poznan University of Medical Sciences, in Poland, therefore performed a cross-sectional assessment of thyroid hormones and antithyroid antibodies among patients with BPD who had received lithium for a period of 10 to 19 years or for 20 years or more. They reported their findings here at the European Psychiatric Association (EPA) 23rd Congress.

Patients (n = 66; 21 men/45 women) ranged in age from 24 to 85 years (mean, 62 ± 13 years) and had been treated with lithium for 10 to 44 years (mean, 21 ± 9 years).

"We found clinical hypothyroidism only in seven female patients, and in three of them, this hypothyroidism occurred within the first year of lithium therapy," researcher Jerzy Sowiński, MD, PhD, said.

Excluding these seven patients, whose treatment was supplemented with thyroxine, there was no difference between male and female patients regarding hormone levels, including free thyroxine (T4), free triiodothyronine (T3), or thyroid stimulating hormone (TSH) levels. There was no difference in the levels of these hormones for patients who received lithium for less than 20 years vs those who received lithium for 20 years or longer.

Table. Thyroid Hormone Levels and Antithyroid Antibodies With Lithium Treatment (mean ± SD)

Hormone Lithium 10 - 19 Years (n = 32) Lithium ≥20 Years (n = 27)
Thyroid stimulating hormone (mIU/L) 2.18 ± 1.81 2.22 ± 3.98
Free thyroxine (ng/dL) 1.04 ± 0.34 0.98 ± 0.17
Triiodothyronine (nmol/L) 2.49 ± 0.45 2.14 ± 0.34
Antibody Lithium 10 - 19 Years (n = 38) Lithium ≥20 Years (n = 28)
Antithyroid peroxidase 45% 32%
Antithyroglobulin 68% 61%
Anti-TSH receptor 8% 4%


There was also no significant correlation with age or duration of illness and no differences among the 38 patients with and the 28 patients without a family history of a mood disorder.

A large proportion of patients had antibodies to thyroid peroxidase and to thyroglobulin. Dr Sowiński reported that the presence of these antibodies had a positive correlation with TSH levels and a negative correlation with free T3 levels. Again, there was no difference in the occurrence of antibodies with respect to sex, age, duration of illness, or family history of a mood disorder.

Dr Sowiński noted that the lack of an effect of duration of lithium treatment on thyroid function is in contrast to diminishing kidney function with ongoing lithium therapy.

Because all patients in the study had received lithium, it was not possible to correlate hormone levels with the BPD itself as opposed to being an effect of the lithium, although Dr Sowiński mentioned that autoimmune thyroiditis is an endophenotype for BPD.

He also cited a published analysis of 77 studies showing that long-term lithium treatment was associated with a sixfold increased risk for clinical hypothyroidism in patients receiving the drug for a mean of 70 months. After a mean of 18 months, there was a fourfold increased risk for elevations in TSH levels.

Previous studies have shown that subclinical hypothyroidism accompanies BPD, with a blunted TSH response to thyrotropin-releasing hormone, as well as an increased incidence of antithyroid peroxidase antibodies.

Lithium accumulates in the thyroid gland in a three- to fourfold higher concentration than in plasma and leads to decreased production and release of thyroid hormones, Dr Sowiński noted. Lithium has also been associated with hyperthyroidism as well as hypothyroidism. Goiter, immunologic disturbances, and structural changes in the thyroid gland have also been seen.

Session moderator Birgit Völlm, MD, PhD, professor of forensic psychiatry at the University of Nottingham, in the United Kingdom, commented to Medscape Medical News, "It's good news that we're not causing any more damage by giving [lithium] for longer, at least not to the thyroid. And it's useful to look at that because, as he said, we don't really know what happens after 10 or 20 years."

Lack of knowledge of long-term outcomes affects both older and newer drugs. "Some of the pharmacological studies...they're 6 months if you're lucky, and nobody looks at what happens later," she said. "So I think it's very, very important that people look at that long-term course."

There was no commercial funding for the study. Dr Sowiński and Dr Völlm report no relevant financial relationships.

European Psychiatric Association (EPA) 23rd Congress. Abstract 0182. Presented March 29, 2015.


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