Antithyroid effects of lithium

Abstract

A B S T R A C T Lithium has been reported to be goitrogenic when used for the treatment of manic-depressive psychosis. To investigate the effects of lithium on iodine metabolism, male Sprague-Dawley rats were placed on a low iodine (LID) or normal iodine diet (NID) containing enough Li2COs to give serum lithium levels of 0.23-0.86 mEq/liter (human therapeutic range is 0.6-1.6 mEq/liter). The following effects were noted with lithium treatment: (a) thyroid weight increased concomitant with a slowing of thyroidal iodine release; (b) the ability to concentrate iodide was increased only after goiters were established; (c) on the LID, 'I uptake was elevated throughout all phases of treatment, even when the release rate was normal; (d) iodine organification was unaffected but the proportion of 'I present as iodothyronines was decreased; (e) the thyroidal 'I content was increased; (f) despite these changes, the serum PBI remained normal as did the thyroxine turnover rate; and (g) thyrotropin (TSH) levels in serum were the same as controls except for a slight elevation early in the course of treatment; TSH levels did not correlate with goitrogenesis.When LiCl was injected in large doses into intact rats (giving serum lithium levels of 3.08-3.89 mEq/liter), the iodide concentrating mechanism, 'I uptake, and 'I release rates were depressed. Similar experiments in hypophysectomized rats receiving TSH demonstrated these to be local antithyroid effects not mediated through the pituitary.The discrepancy between acute and chronic responses to lithium, and the dissociation between the inhibition of iodine release and stimulatory effects is discussed.

The Use of Lithium in the Treatment of Thyrotoxicosis

“…This is in agreement with some studies (9) but contrasts with others in which uptake was decreased (19,20) or increased (3)(4)(5). Increased iodide uptake might accompany lithium-induced goiter caused by low circulating T4 and T3 with elevated TSH (3,5,9,21,22). However, none of the present group of thyrotoxic patients became hypothyroid.…”

“…An unexpected finding, and one that differed from our rat data (5) and from studies in one thyrotoxic 2 and several euthyroid 3 T4 disappearance rates following Li' treatment that are entirely in agreement with those presented in Table II. The decrease in hormone degradation that accompanies the decreased hormone secretion induced by Li' tends to diminish the fall in serum hormone levels. In some patients (e.g., G. F.-1, Br.…”

Lithium safety and tolerability in mood disorders: a critical review

“…It is currently recognized that the treatment can inhibit the production of thyroid hormones and induce clinical signs of hypothyroidism or hyperthyroidism, and even goiter. Lithium is concentrated inside the thyroid gland and has four potentially negative effects: inhibition of iodine uptake, inhibition of iodotyrosine coupling, alteration in thyroglobulin structure, and inhibition of thyroxine secretion 30,31 . The change in thyroid stimulating hormone or thyrotropin (TSH) is commonly common observed effect 9 .…”

Lithium Therapy and Thyroid Disorders

“…In addition, lithium can increase intrathyroidal iodine content [6], which inhibits the release of T4 and T3 through a feedback mechanism. The inhibition of organic iodine formation and inhibition of thyroid hormone secretion is responsible for the initial fall in serum T4 and T3 within hours of iodide therapy [7].…”

“…When goiter formation occurs, it usually happens within the first two years of lithium treatment. Different from the direct effects on the HPA, the proposed method by which lithium induces goiter formation is thought to be through a compensatory increase in pituitary secretion of TSH from inhibition of thyroid hormone secretion by lithium, resulting in increased thyrocyte proliferation and normal thyroid hormone output [6,16]. Furthermore, other studies have demonstrated that lithium induces cellular proliferation through direct stimulation of DNA synthesis [17], activation of Wnt/β-catenin signaling [18], tyrosine kinase activation [19] and triggering a cascade of G-proteins coupled to IGF-1 receptors during the G1 phase of the cell cycle [20].…”