Lithium and the thyroid
- Martin I Surks, MD
Martin I Surks, MD
- Professor of Medicine and Pathology
- Albert Einstein College of Medicine
The antithyroid actions of lithium were first investigated in detail when it was noted that patients with psychiatric disease treated with lithium carbonate developed hypothyroidism and goiter. Animal and human studies subsequently revealed that lithium increases intrathyroidal iodine content, inhibits the coupling of iodotyrosine residues to form iodothyronines (thyroxine [T4] and triiodothyronine [T3]) [1-3], and inhibits release of T4 and T3 [2-4].
The mechanism by which lithium inhibits thyroid hormone release is not well understood. In vitro, lithium decreases colloid droplet formation within thyroid follicular cells, a reflection of decreased pinocytosis of colloid from the follicular lumen . The efficiency of proteolytic digestion of thyroglobulin within phagolysosomes also may be impaired.
This topic will review the clinical effects of lithium on thyroid function. In addition to inducing hypothyroidism, the magnitude of the lithium-induced inhibition of thyroid hormone secretion is sufficient to make lithium useful in the treatment of some patients with hyperthyroidism or thyroid cancer.
THYROID DISEASE IN LITHIUM-TREATED PATIENTS
Lithium can cause goiter and hypothyroidism, and its use has been associated with both thyroid autoimmunity and hyperthyroidism [6,7]. Because of the high incidence of thyroid dysfunction that occurs during lithium treatment, patients should have a careful thyroid physical examination and determination of serum thyroid-stimulating hormone (TSH) and antithyroid peroxidase antibody titers before lithium treatment is begun. Patients with normal thyroid function initially should be reevaluated every 6 to 12 months for several years, and thyroid dysfunction should be treated if diagnosed. The development of thyroid dysfunction does not typically require discontinuation of lithium. If thyroid function is abnormal at the initial evaluation, lithium can still be given, if necessary, but the thyroid dysfunction should be treated.
Goiter — Goiter is the most common thyroid abnormality in lithium-treated patients, occurring in approximately 40 to 50 percent [8-11]. The inhibition of thyroid hormone secretion that occurs during lithium treatment results in decreased serum T4 and T3 concentrations, a compensatory increase in pituitary secretion of TSH and, in a new steady state, secretion of a normal amount of thyroid hormone by an enlarged thyroid gland . Thyroid enlargement may also occur as a result of lithium-induced alterations in the function of insulin-like growth factor, tyrosine kinase, and/or Wnt/beta-catenin signalling [11,12]. In affected patients, the thyroid is enlarged to approximately twice the normal size, and the goiter is usually diffuse, although nodular goiter has also been reported . The goiters usually occur within the first two years of treatment.
- Bagchi N, Brown TR, Mack RE. Studies on the mechanism of inhibition of thyroid function by lithium. Biochim Biophys Acta 1978; 542:163.
- Berens SC, Bernstein RS, Robbins J, Wolff J. Antithyroid effects of lithium. J Clin Invest 1970; 49:1357.
- Burrow GN, Burke WR, Himmelhoch JM, et al. Effect of lithium on thyroid function. J Clin Endocrinol Metab 1971; 32:647.
- Spaulding SW, Burrow GN, Bermudez F, Himmelhoch JM. The inhibitory effect of lithium on thyroid hormone release in both euthyroid and thyrotoxic patients. J Clin Endocrinol Metab 1972; 35:905.
- Williams JA, Berens SC, Wolff J. Thyroid secretion in vitro: inhibition of TSH and dibutyryl cyclic-AMP stimulated 131-I release by Li+1. Endocrinology 1971; 88:1385.
- Barbesino G. Drugs affecting thyroid function. Thyroid 2010; 20:763.
- McDermott MT, Burman KD, Hofeldt FD, Kidd GS. Lithium-associated thyrotoxicosis. Am J Med 1986; 80:1245.
- Perrild H, Hegedüs L, Baastrup PC, et al. Thyroid function and ultrasonically determined thyroid size in patients receiving long-term lithium treatment. Am J Psychiatry 1990; 147:1518.
- Bocchetta A, Bernardi F, Pedditzi M, et al. Thyroid abnormalities during lithium treatment. Acta Psychiatr Scand 1991; 83:193.
- Lee S, Chow CC, Wing YK, Shek CC. Thyroid abnormalities during chronic lithium treatment in Hong Kong Chinese: a controlled study. J Affect Disord 1992; 26:173.
- Lazarus JH. Lithium and thyroid. Best Pract Res Clin Endocrinol Metab 2009; 23:723.
- Rao AS, Kremenevskaja N, Resch J, Brabant G. Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/beta-catenin signalling. Eur J Endocrinol 2005; 153:929.
- Bocchetta A, Cocco F, Velluzzi F, et al. Fifteen-year follow-up of thyroid function in lithium patients. J Endocrinol Invest 2007; 30:363.
- McKnight RF, Adida M, Budge K, et al. Lithium toxicity profile: a systematic review and meta-analysis. Lancet 2012; 379:721.
- Bocchetta A, Loviselli A. Lithium treatment and thyroid abnormalities. Clin Pract Epidemiol Ment Health 2006; 2:23.
- van Melick EJ, Wilting I, Meinders AE, Egberts TC. Prevalence and determinants of thyroid disorders in elderly patients with affective disorders: lithium and nonlithium patients. Am J Geriatr Psychiatry 2010; 18:395.
- Kirov G, Tredget J, John R, et al. A cross-sectional and a prospective study of thyroid disorders in lithium-treated patients. J Affect Disord 2005; 87:313.
- Myers DH, Carter RA, Burns BH, et al. A prospective study of the effects of lithium on thyroid function and on the prevalence of antithyroid antibodies. Psychol Med 1985; 15:55.
- Wilson R, McKillop JH, Crocket GT, et al. The effect of lithium therapy on parameters thought to be involved in the development of autoimmune thyroid disease. Clin Endocrinol (Oxf) 1991; 34:357.
- Lazarus JH, McGregor AM, Ludgate M, et al. Effect of lithium carbonate therapy on thyroid immune status in manic depressive patients: a prospective study. J Affect Disord 1986; 11:155.
- Barclay ML, Brownlie BE, Turner JG, Wells JE. Lithium associated thyrotoxicosis: a report of 14 cases, with statistical analysis of incidence. Clin Endocrinol (Oxf) 1994; 40:759.
- Miller KK, Daniels GH. Association between lithium use and thyrotoxicosis caused by silent thyroiditis. Clin Endocrinol (Oxf) 2001; 55:501.
- Kristensen O, Andersen HH, Pallisgaard G. Lithium carbonate in the treatment of thyrotoxicosis. A controlled trial. Lancet 1976; 1:603.
- Ng YW, Tiu SC, Choi KL, et al. Use of lithium in the treatment of thyrotoxicosis. Hong Kong Med J 2006; 12:254.
- Bogazzi F, Giovannetti C, Fessehatsion R, et al. Impact of lithium on efficacy of radioactive iodine therapy for Graves' disease: a cohort study on cure rate, time to cure, and frequency of increased serum thyroxine after antithyroid drug withdrawal. J Clin Endocrinol Metab 2010; 95:201.
- Bal CS, Kumar A, Pandey RM. A randomized controlled trial to evaluate the adjuvant effect of lithium on radioiodine treatment of hyperthyroidism. Thyroid 2002; 12:399.
- Bogazzi F, Bartalena L, Campomori A, et al. Treatment with lithium prevents serum thyroid hormone increase after thionamide withdrawal and radioiodine therapy in patients with Graves' disease. J Clin Endocrinol Metab 2002; 87:4490.
- Takami H. Lithium in the preoperative preparation of Graves' disease. Int Surg 1994; 79:89.
- Mochinaga N, Eto T, Maekawa Y, et al. Successful preoperative preparation for thyroidectomy in Graves' disease using lithium alone: report of two cases. Surg Today 1994; 24:464.
- Koong SS, Reynolds JC, Movius EG, et al. Lithium as a potential adjuvant to 131I therapy of metastatic, well differentiated thyroid carcinoma. J Clin Endocrinol Metab 1999; 84:912.
- Liu YY, van der Pluijm G, Karperien M, et al. Lithium as adjuvant to radioiodine therapy in differentiated thyroid carcinoma: clinical and in vitro studies. Clin Endocrinol (Oxf) 2006; 64:617.
- American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19:1167.