AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Lithium is used for treatment of bipolar manic-depressive disorder. Like iodide, lithium inhibits thyroid hormone (TH) release. In supratherapeutic doses in rodents, as well as in vitro, lithium also inhibits thyroglobulin (Tg) iodination and coupling reactions. Lithium treatment has been associated with the development of goiter. The prevalence of this condition ranges from 20% in patients residing in iodine-replete areas to 87% in patients residing in or emigrating from iodine-deficient areas or who are on long-term lithium therapy. The latter statistic highlights the importance of susceptible individuals' iodine status, especially in view of the downward trends in iodine sufficiency of the US population over the last decade, as reported in recent data analyses from the National Health and Nutrition Examination Survey (NHANES) III study.

Goiter has been described within several weeks of initiation of lithium therapy; although, in most cases, months to several years elapse before goiter develops. The latter point is pertinent because lithium therapy is usually prescribed long-term for the control of bipolar illness. Lithium-induced goiter is usually characterized by small, smooth, and nontender nodules; in some cases, nodules may regress over time. A smaller percentage of patients treated with lithium (5-20%) may actually develop hypothyroidism with or without goiter development. In most of these cases, the hypothyroidism is subclinical. Thyrotoxicosis can also be observed in lithium-treated patients, but it is rare, with a prevalence of 0.7%.

Pathophysiology

Lithium is highly concentrated in the thyroid gland against a concentration gradient, probably by active transport. In clinically useful doses, lithium induces a marked decrease in the release of preformed TH from the thyroid. Its primary effect seems to be the blockade of colloid droplet formation in the apical pole of the thyrocyte and, hence, inhibition of TH release, a process stimulated by thyrotropin and mediated by cyclic adenosine monophosphate (cAMP) within the thyrocyte.

The exact mechanism of action of lithium at the molecular level remains unknown. While earlier reports suggested either (1) lack of lithium effects on cAMP synthesis or (2) lithium-induced inhibition of cAMP synthesis, more recent work in a strain of rat thyroid follicular cells (FRTL-5) and a cell line of Chinese hamster ovary fibroblasts stably transfected with the human thyrotropin receptor (CHO-R) showed significant potentiation of the cAMP response to exogenous thyrotropin by lithium.

With regard to the effects of lithium on thyrocyte growth, in the FRTL-5 cell system lithium was found to stimulate cell proliferation in the absence of thyrotropin stimulation, yet, surprisingly, under thyrotropin stimulation, lithium diminished thyrocyte proliferation, especially when used at higher concentrations. Whether the above in vitro data gathered from nonhuman thyroid cell lines and using acute exposure to lithium reflect the situation in patients typically treated long-term with lithium remains speculative.

In a pathophysiologic context, exposure to lithium causes a mild initial elevation of thyrotropin levels as a compensatory pituitary response to the initial lithium-induced decline in TH release. Hormone stores eventually increase, thus leading, in most cases, to normal TH output despite a reduced fractional TH secretion capability. The tendency of the thyroid gland to "escape" the inhibitory effects of lithium is similar to that observed with iodine therapy, although it is less marked.

The above sequence may be the mechanism for the development of euthyroid goiter observed in these patients. Concomitant hypothyroidism probably occurs in individuals predisposed to thyroid failure, because most persons in this subgroup already have positive antithyroidal antibodies. Additionally, lithium-induced hypothyroidism is observed more frequently in patients with a prior history of a damaged thyroid gland (eg, following external radiation or iodine I 131 therapy administered to treat previously diagnosed hyperthyroidism).

Although the cause of the rarely encountered condition of lithium-induced thyrotoxicosis is not clear, some authorities have speculated that lithium may directly stimulate autoimmune reactions. On the other hand, thyroid autoimmunity, per se, reportedly is highly prevalent in patients with bipolar disorder, probably more so than in normothymic control subjects.

Frequency

United States

The prevalence of goiter in patients receiving lithium therapy is approximately 15-20%. Up to a third of patients on lithium therapy who develop goiter (ie, 5% of all patients on lithium therapy) also may develop hypothyroidism, which usually remains subclinical. The development of clinically evident thyrotoxicosis is rare.

International

The prevalence of goiter in patients receiving lithium therapy is higher in patients from iodine-deficient areas and in patients receiving long-term therapy (20-87%). Up to 20% of patients receiving lithium therapy who develop goiter (ie, a fourth to a half of all patients on lithium therapy) have concomitant hypothyroidism.

Mortality/Morbidity

Neither lithium-induced goiter nor hypothyroidism cause mortality directly. Morbidity is mostly related to concomitant hypothyroidism and local compressive symptoms from thyroid enlargement (eg, dysphonia, dysphagia, voice-quality changes, neck discomfort). Lithium is potentially toxic and can cause arrhythmias, atrioventricular block, nephrogenic diabetes insipidus, agranulocytosis, confusion, seizures, mental status changes, and coma. Lithium-induced heart atrioventricular block can be exacerbated by the hypothyroid state. However, these adverse effects occur at supratherapeutic serum lithium levels, which are avoided by serial monitoring of these levels, especially in the setting of renal impairment (creatinine clearance, <40 mL/min).

Race

No well-described racial differences are reported.

Sex

No differences in the incidence or prevalence of goiter formation have been reported between men and women, although lithium-induced hypothyroidism is more common in women. Further, because males generally have larger thyroid gland volume than females, lithium-induced global thyroid enlargement theoretically may lead to more compressive symptomatology in males than in females, although this has not been reported to date.

Age

Older patients are more prone to the development of goiter.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients are usually asymptomatic. Documenting the duration of lithium therapy is important. Symptoms of hypothyroidism or thyrotoxicosis do not differ from those observed in states of thyroid deficiency or excess due to other causes; however, because patients either have bipolar affective disorder or mania, symptoms of thyroid dysfunction may be misinterpreted or missed altogether because these 2 classes of conditions share several similarities with regard to clinical presentation.

Physical

The thyroid gland enlargement is smooth, symmetrical, and nontender. Because goiter nodules are usually small, dyspnea due to laryngotracheal pressure is usually absent. The physical signs of hypothyroidism or thyrotoxicosis do not differ from those observed in states of thyroid deficiency or excess, respectively, attributable to other causes.

Causes

Lithium carbonate is the direct cause.

• The following are contributing factors for goiter formation:
• • Iodide deficiency

  • Prior or subclinical autoimmune thyroid disease

  • Prior ¹³¹I-induced or external radiation–induced thyroid gland damage

  • Possible concomitant exposure to environmental and dietary goitrogens other than lithium (eg, polychlorinated biphenyls [PCBs], thiocyanate, naturally occurring thioglycosides and glucosinolates found in vegetables in the Brassica species such as Brussels sprouts).

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Thyrotoxicosis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Confirmation of the diagnosis of lithium-induced goiter is mostly derived from a positive history of prolonged lithium intake and a positive physical examination finding. Determining whether the patient originates from an iodine-deficient area and whether he or she has a positive family history of goiter or other thyroid disorders is important. Laboratory studies are indicated to exclude concomitant hypothyroidism and the existence of a thyroid-specific autoimmune process.
• Serum thyrotropin
• • This is a first-level test.

  • Levels higher than normal indicate concomitant hypothyroidism.

• Circulating antithyroid peroxidase (anti-TPO) and anti-Tg antibodies
• • These are first-level tests.

  • These antibodies indicate the presence of a thyroid-specific autoimmune process and a higher likelihood of hypothyroidism in the future in cases in which thyroid function test findings are normal. The frequency of positivity of antithyroidal antibodies is higher in lithium-treated patients with either overt or subclinical hypothyroidism versus control subjects with comparable thyrotropin levels.

• Serum free thyroxine (T4) and total triiodothyronine (T3) tests
• • These are second-level tests.

  • Low levels indicate hypothyroidism, although T3 (or even free T3) testing alone is usually insensitive for a diagnosis of hypothyroidism. Furthermore, serum thyrotropin testing is more sensitive for a diagnosis of hypothyroidism than free T4 testing.

• Exaggerated response of thyrotropin to thyrotropin-releasing hormone (TRH) stimulation test
• • This is a third-level test.

  • This test is usually unnecessary and is mostly reserved for research purposes. Findings are positive in patients with hypothyroidism (clinical or subclinical). Of note, TRH is no longer commercially available as a diagnostic agent in the United States, although it can be manufactured in pharmacies of certain academic centers engaged in clinical endocrinology research.

Imaging Studies

• Thyroid ultrasonography
• • This is a first-level test.

  • Thyroid ultrasonography can be used to quantitate thyroid size and may show a small volumetric increase in persons with lithium-induced goiter.

• Iodine I 123 uptake test
• • This is a second-level test.

  • ¹²³I uptake may be slightly increased in some patients with euthyroid goiter because of compensation of the gland for decreased coupling and/or iodination despite normal serum thyrotropin levels. ¹²³I uptake is definitely increased in the small percentage of patients who develop lithium-induced thyrotoxicosis.

• Perchlorate discharge test
• • This is a third-level test.

  • Results are usually normal (negative), and the test is rarely performed outside an academic setting.

• Iodide-perchlorate discharge test
• • This is a third-level test.

  • This test is seldom indicated. Results are positive in almost all patients on long-term lithium therapy.

Histologic Findings

Biopsy of the thyroid gland is unnecessary in the vast majority of patients with lithium-induced goiter, although the histological changes that occur in lithium-induced goiter have been studied in a research setting.

Studies of the effects of lithium administration on normal thyroid gland histology in rodents suggest that hyperplasia and colloid depletion occur early in the course of therapy. Eventually, cellular hyperplasia and accumulation of colloid and Tg in supranormal amounts occur. Because lithium inhibits both colloid endocytosis (pinocytosis) and iodine efflux from the thyroid, nodules associated with colloid goiter observed in patients on lithium therapy tend to be rich in Tg. In patients with underlying thyroid pathology (eg, multinodular goiter, postthyroiditis changes), histological features of the underlying pathology are evident.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Because as many as a fourth to a third of patients on long-term lithium therapy develop hypothyroidism, provide regular follow-up care on both a clinical and biochemical basis for symptoms and signs of hypothyroidism and increased serum thyrotropin levels, respectively.

Before the initiation of lithium therapy, identify patients at increased risk for the development of hypothyroidism (eg, patients originating from iodine-deficient areas, those with a strong family history of thyroid disorders, women, elderly patients, patients exposed to other goitrogens). Suspicion of goiter upon physical examination may prompt the physician to order ultrasonography to record the baseline dimensions of the thyroid gland and to exclude underlying structural thyroid disease. Baseline thyroid function tests, including thyrotropin, free T4, total T3, anti-TPO, and anti-Tg antibodies, also are important.

Whether all patients being treated with lithium for a long period require prophylactic therapy with levothyroxine (LT4) is debatable. Such prophylactic treatment is probably not indicated if both goiter and hypothyroidism have been excluded prior to initiation of lithium therapy. Provide regular follow-up care for patients on long-term lithium therapy by regularly assessing their history, physical examination findings, and serum thyrotropin levels. Rising levels of thyrotropin should prompt the physician to repeat a full evaluation, including serum measurements of free T4, total T3, anti-TPO, and anti-Tg antibodies.

If the diagnosis of hypothyroidism is established, early initiation of LT4 therapy is indicated, especially when discontinuation of lithium is inadvisable because of the patient's psychiatric status.

For patients who develop goiter over time, even in the absence of hypothyroidism (clinical or subclinical), also consider LT4 therapy aimed at restoring normal serum thyrotropin levels.

Diagnose and treat rare cases of lithium-induced thyrotoxicosis as indicated for similar cases attributable to other causes of hyperthyroidism; discontinuing lithium therapy is not necessary, and it can also be dangerous (in the context of exacerbation of manic-depressive illness).

Surgical Care

Although specific surgical treatment is not usually necessary, in rare cases, long-term lithium administration may induce hyperthyroidism that is difficult to control, necessitating thyroidectomy. Similarly, the underlying or concomitant thyroid disorder (eg, multinodular goiter, nontoxic endemic goiter) may dictate the need for surgical intervention.

A more expanded discussion of the indications, techniques, and complications of thyroid surgery in each of the above contingencies can be found in respective eMedicine articles (eg, Goiter, Nontoxic, Hyperthyroidism).

Consultations

In most cases, the primary care physician may opt to consult with an endocrinology specialist, especially in cases of lithium-induced thyrotoxicosis. The development of compressive local symptoms requires an evaluation by a surgical or ear, nose, and throat specialist.

In cases of lithium-induced thyrotoxicosis, consultation with a cardiologist may be necessary, especially in elderly patients who have a high prevalence of coronary artery disease, arrhythmias, and congestive heart failure.

Diet

No specific diet restrictions are needed.

Activity

No restrictions in exercise or activity patterns are advisable or necessary, with the exception of patients who have severe lithium-induced thyrotoxicosis with cardiovascular symptoms, in which case any strenuous activity should be avoided (as in all cases of severe thyrotoxicosis).

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

LT4 is the DOC for patients who develop lithium-induced hypothyroidism or goiter (when discontinuance of lithium therapy is not feasible). Slightly higher doses (enough to keep the thyrotropin level in the range of 0.4 mIU/L) may be necessary if the patient has rapidly growing or large nodules from goiter, especially in the presence of local compressive symptoms. LT4 is the most commonly used pharmacological preparation of TH for treating goiter and other hypothyroid states. The rationale for thyrotropin suppression therapy in persons with goiter is that a reduction in thyrotropin secretion may decrease the growth and function of abnormal thyroid tissue.

Drug Category: Thyroid hormone replacements

A normally functioning thyroid gland produces and secretes major THs LT4 and L-triiodothyronine. Complex feedback mechanisms of the hypothalamic-pituitary-thyroid axis regulate the rate of production and secretion. The action of thyrotropin, which is produced in the anterior pituitary gland, stimulates the thyroid gland to secrete THs.

Thyrotropin secretion is mainly controlled by TRH produced in the hypothalamus and by circulating THs that act as feedback inhibitors of both thyrotropin and TRH. When concentrations of T4 and T3 are decreased, secretion of thyrotropin and TRH is increased and vice versa. When the thyroid gland fails to function, hypothyroidism develops, and therapy with TH is absolutely indicated. Additionally, exogenous administration of TH to euthyroid individuals results in suppression of endogenous TH secretion.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• No further inpatient care is usually required.

Further Outpatient Care

• A review of patient history, a physical examination, and an evaluation of thyrotropin levels are indicated within 6 months immediately after the initiation of lithium therapy and annually thereafter.
• The treating physician must be aware that rare cases of thyrotoxicosis have been reported following discontinuation of lithium therapy.

In/Out Patient Meds

• LT4 sodium

Transfer

• All care is typically performed in an ambulatory clinic setting; thus, no specific transfer requirements are applicable.

Deterrence/Prevention

• Regular follow-up with an endocrinologist is indicated within 6 months immediately after the initiation of lithium therapy and annually thereafter (with thyrotropin levels and neck palpation) for all patients on long-term lithium therapy.

Complications

• Hypothyroidism
• Hyperthyroidism (rare)
• Compressive symptoms from goiter progression
• Lithium toxicity

Prognosis

• Long-term prognosis ranges from very good to excellent.

Patient Education

• Regularly educate patients with regard to the possibility of thyroid dysfunction with long-term lithium treatment.
• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to follow up with patients by monitoring thyroid anatomy and function may lead to undiagnosed hypothyroidism or hyperthyroidism as well as local symptoms from goiter progression.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Andersen BF. Iodide perchlorate discharge test in lithium-treated patients. Acta Endocrinol (Copenh). May 1973;73(1):35-42. [Medline].
• Bagchi N, Brown TR, Mack RE. Studies on the mechanism of inhibition of thyroid function by lithium. Biochim Biophys Acta. Aug 3 1978;542(1):163-9. [Medline].
• Barclay ML, Brownlie BE, Turner JG, Wells JE. Lithium associated thyrotoxicosis: a report of 14 cases, with statistical analysis of incidence. Clin Endocrinol (Oxf). Jun 1994;40(6):759-64. [Medline].
• Bartalena L, Bogazzi F, Martino E. Is thyroxine during lithium therapy necessary?. J Endocrinol Invest. Mar 1999;22(3):220-2. [Medline].
• Berens SC, Wolff J. The endocrine effects of lithium. In: Johnson FN, ed. Lithium Research and Therapy. New York, NY: Academic Press; 1975:. 443-72.
• Berens SC, Wolff J, Murphy DL. Lithium concentration by the thyroid. Endocrinology. Nov 1970;87(5):1085-7. [Medline].
• Berens SC, Bernstein RS, Robbins J, Wolff J. Antithyroid effects of lithium. J Clin Invest. Jul 1970;49(7):1357-67. [Medline].
• Bocchetta A, Mossa P, Velluzzi F, et al. Ten-year follow-up of thyroid function in lithium patients. J Clin Psychopharmacol. Dec 2001;21(6):594-8. [Medline].
• Bschor T, Baethge C, Adli M, et al. Hypothalamic-pituitary-thyroid system activity during lithium augmentation therapy in patients with unipolar major depression. J Psychiatry Neurosci. 2003;28:210-216. [Medline]. [Full Text].
• Burrow GN, Burke WR, Himmelhoch JM, et al. Effect of lithium on thyroid function. J Clin Endocrinol Metab. May 1971;32(5):647-52. [Medline].
• Calabrese JR, Gulledge AD, Hahn K, et al. Autoimmune thyroiditis in manic-depressive patients treated with lithium. Am J Psychiatry. Nov 1985;142(11):1318-21. [Medline].
• Caykoylu A, Capoglu I, Unuvar N, et al. Thyroid abnormalities in lithium-treated patients with bipolar affective disorder. J Int Med Res. Jan-Feb 2002;30(1):80-4. [Medline].
• Clower CG. Effects of lithium onthyroid function. Am J Psychiatry. Oct 1989;146(10):1357. [Medline].
• Deodhar SD, Singh B, Pathak CM, et al. Thyroid functions in lithium-treated psychiatric patients: a cross- sectional study. Biol Trace Elem Res. Feb 1999;67(2):151-63. [Medline].
• Emerson CH, Dysno WL, Utiger RD. Serum thyrotropin and thyroxine concentrations in patients receiving lithium carbonate. J Clin Endocrinol Metab. Feb 1973;36(2):338-46. [Medline].
• Fauerholdt L, Vendsborg P. Thyroid gland morphology after lithium treatment. Acta Pathol Microbiol Scand [A]. Jul 1981;89(4):339-41. [Medline].
• Gaberscek S, Kalisnik M, Pezdirc M, et al. Influence of lithium on growth and viability of thyroid follicular cells. Folia Biol (Praha). 2002;48(5):200-4. [Medline].
• Gaberscek S, Kalisnik M, Pavlin K, et al. Influence of lithium on cell function in two different cell systems. Folia Biol (Praha). 2003;49:110-114. [Medline].
• Gracious BL, Findling RL, Seman C, et al. Elevated thyrotropin in bipolar youths prescribed both lithium and divalproex sodium. J Am Acad Child Adolesc Psychiatry. Feb 2004;43(2):215-20. [Medline].
• Hollowell JG, Staehling NW, Hannon WH, et al. Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988-1994). J Clin Endocrinol Metab. Oct 1998;83(10):3401-8. [Medline].
• Hoogenberg K, Beentjes JA, Piers DA. Lithium as an adjunct to radioactive iodine in treatment-resistant Graves thyrotoxicosis. Ann Intern Med. Oct 15 1998;129(8):670. [Medline].
• Kirov G. Thyroid disorders in lithium-treated patients. J Affect Disord. Jul 1998;50(1):33-40. [Medline].
• Kupka RW, Nolen WA, Post RM, et al. High rate of autoimmune thyroiditis in bipolar disorder: lack of association with lithium exposure. Biol Psychiatry. 2002;51:305-311. [Medline].
• Kusalic M, Engelsmann F. Effect of lithium maintenance therapy on thyroid and parathyroid function. J Psychiatry Neurosci. May 1999;24(3):227-33. [Medline].
• Lakshmanan MC, Robbibs J. Thyroid hormones,thyroid stimulating hormone (TSH), thyrotropin releasing hormone (TRH), and antithyroid drugs: Lithium. In: Munson PL, ed. Principles of Pharmacology. Basic Concepts and Clinical Applications. New York, NY: Chapman & Hall;. 1995:802-7.
• Lazarus JH. Effect of lithium on the thyroid gland. In: Weetman AP, Grossman A, eds. Pharmacotherapeutics of the Thyroid Gland. Berlin, Germany: Springer-Verlag;. 1997:207-23.
• Lazarus JH. Is thyroxine during lithium therapy necessary?. J Endocrinol Invest. Dec 1998;21(11):784-6. [Medline].
• Lazarus JH. The effects of lithium therapy on thyroid and thyrotropin-releasing hormone. Thyroid. Oct 1998;8(10):909-13. [Medline].
• Lindstedt G, Nilsson LA, Walinder J, et al. On the prevalence, diagnosis and management of lithium-induced hypothyroidism in psychiatric patients. Br J Psychiatry. May 1977;130:452-8. [Medline].
• Lombardi G, Panza N, Biondi B, et al. Effects of lithium treatment on hypothalamic-pituitary-thyroid axis: a longitudinal study. J Endocrinol Invest. Apr 1993;16(4):259-63. [Medline].
• Loviselli A, Bocchetta A, Mossa P, et al. Value of thyroid echography in the long-term follow-up of lithium- treated patients. Neuropsychobiology. 1997;36(1):37-41. [Medline].
• Maes M, Song C, Lin AH, et al. In vitro immunoregulatory effects of lithium in healthy volunteers. Psychopharmacology (Berl). 1999;143:401-407. [Medline].
• Miloni E, Burgi H, Studer H, et al. Thyroglobulin-rich colloid goitres: a result of the combined action of lithium and methimazole on the rat thyroid. Acta Endocrinol (Copenh). Jun 1983;103(2):231-4. [Medline].
• 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. Feb 1985;15(1):55-61. [Medline].
• Oakley PW, Dawson AH, Whyte IM. Lithium: thyroid effects and altered renal handling. J Toxicol Clin Toxicol. 2000;38(3):333-7. [Medline].
• Ozpoyraz N, Tamam L, Kulan E. Thyroid abnormalities in lithium-treated patients. Adv Ther. Jul-Aug 2002;19(4):176-84. [Medline].
• Perrild H, Hegedus L, Baastrup PC, et al. Thyroid function and ultrasonically determined thyroid size in patients receiving long-term lithium treatment. Am J Psychiatry. Nov 1990;147(11):1518-21. [Medline].
• Persad E, Forbath N, Merskey H. Hyperthyroidism after treatment with lithium. Can J Psychiatry. Nov 1993;38(9):599-602. [Medline].
• Reus VI, Gold P, Post R. Lithium-induced thyrotoxicosis. Am J Psychiatry. May 1979;136(5):724-5. [Medline].
• Robbins J. Control of hyperthyroidism with lithium after 131-I therapy. Proceedings of the International Symposium on Graves Disease. 1978;Nagasaki, Japan:36 [Abstract].
• Rogers MP, Whybrow PC. Clinical hypothyroidism occurring during lithium treatment: two case histories and a review of thyroid function in 19 patients. Am J Psychiatry. Aug 1971;128(2):158-63. [Medline].
• Rosser R. Thyrotoxicosis and lithium. Br J Psychiatry. Jan 1976;128:61-6. [Medline].
• Schou M. Lithium prophylaxis in perspective. Pharmacopsychiatry. Jan 1992;25(1):7-9. [Medline].
• Shopsin B, Shenkman L, Blum M, Hollander CS. Iodine and lithium-induced hypothyroidism. Documentation of synergism. Am J Med. Nov 1973;55(5):695-9. [Medline].
• Smigan L, Wahlin A, Jacobsson L, von Knorring L. Lithium therapy and thyroid function tests. A prospective study. Neuropsychobiology. 1984;11(1):39-43. [Medline].
• Spaulding SW, Burrow GN, Ramey JN, Donabedian RK. Effect of increased iodide intake on thyroid function in subjects on chronic lithium therapy. Acta Endocrinol (Copenh). Feb 1977;84(2):290-6. [Medline].
• 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. Dec 1972;35(6):905-11. [Medline].
• Wharton RN. Accidental lithium carbonate treatment of thyrotoxicosis as mania. Am J Psychiatry. Jun 1980;137(6):747-8. [Medline].
• 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. Jun 1971;88(6):1385-8. [Medline].
• Wolff J. Iodide goiter and the pharmacologic effects of excess iodide. Am J Med. Jul 1969;47(1):101-24. [Medline].

Article Last Updated: May 26, 2005