eMedicine Specialties > Endocrinology > Thyroid

Goiter, Lithium-Induced: Treatment & Medication

Author: Nicholas J Sarlis, MBBS, MD, PhD, FACP, Medical Director, Department of Oncology-US Medical Affairs Department, Sanofi-Aventis Pharmaceuticals
Coauthor(s): Boaz Hirshberg, MD, Associate Director, CVMD, Pfizer
Contributor Information and Disclosures

Updated: Dec 18, 2008

Treatment

Medical Care

Because as many as one fourth to one third of patients on long-term lithium therapy develop hypothyroidism, provide regular follow-up care on 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 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 dietary 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

Levothyroxine (LT4) is the drug of choice 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 pharmacologic preparation of thyroid hormone 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.

Thyroid hormone replacements

A normally functioning thyroid gland produces and secretes the major thyroid hormones (THs) levothyroxine (LT4) and L-triiodothyronine. Complex feedback mechanisms of the hypothalamic-pituitary-thyroid axis regulate the rate of production and secretion.13,14 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 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 the suppression of endogenous TH secretion.


Levothyroxine (Synthroid, Levoxyl)

In active form, influences growth and maturation of tissues. LT4 is involved in normal growth, metabolism, and development. LT4 preparations contain synthetic crystalline L-3,3',5,5'-tetraiodothyronine sodium salt. Synthetic LT4 is identical to that produced in the human thyroid gland.
The mechanism of action is complex and only partially understood. Following absorption from the GI tract, a large proportion of circulating T4 is converted into T3, and both are transported into cells. T3, the proposed active form (from cell cytoplasm), and T3 and T4 (generated in situ) diffuse into the nucleus and bind to specific thyroid receptor proteins, which appear to be attached primarily to DNA. Receptor binding leads to the activation or repression of DNA transcription, altering the amounts of mRNA and resultant proteins. Changes in the concentration of proteins in various tissues and organs are responsible for metabolic changes.
THs enhance oxygen consumption of most body tissues and increase the basal metabolic rate and metabolism of carbohydrates, lipids, and proteins, thus exerting a profound influence on every organ system.

Adult

1.6-1.8 mcg/kg/d PO

Pediatric

1-12 months: 7-15 mcg/kg/d PO
1-5 years: 5-7 mcg/kg/d PO
5-10 years: 3-5 mcg/kg/d PO
10-18 years: 2-4 mcg/kg/d PO

Cholestyramine, iron sulfate, calcium salts, and soy products may decrease absorption; estrogens may decrease response to TH therapy in patients with nonfunctioning thyroid glands; effect of anticoagulants increased when administered with LT4; activity of some beta blockers may decrease when hypothyroid patient is converted to a euthyroid state.

Documented hypersensitivity, uncorrected adrenal insufficiency

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Caution with suspected or documented ischemic heart disease or heart failure and in elderly patients; place patients with untreated or suboptimally treated adrenal failure on TH replacement therapy gradually while their other nonthyroidal diseases are addressed fully; periodically monitor thyroid status
In pregnant patients on TH replacement therapy, check thyroid function tests at least every trimester to avoid underreplacement with TH, which could have deleterious effects on fetal development due to relative deprivation of an adequate transplacental TH supply

More on Goiter, Lithium-Induced

Overview: Goiter, Lithium-Induced
Differential Diagnoses & Workup: Goiter, Lithium-Induced
Treatment & Medication: Goiter, Lithium-Induced
Follow-up: Goiter, Lithium-Induced
References
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Further Reading

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Keywords

lithium-induced goiter, thyroid, bipolar, TSH, lithium, hypothyroidism, bipolar disorder, thyroid symptoms, goiter, hypothyroid, thyroid problems, thyroid nodules, thyroid gland, thyroid hormone, manic depression, hypothyroidism symptoms, mood disorders, mood disorder, manic depressive, bipolar treatment, lithium effects, lithium side effects, goiter lithium therapy, lithium treatment, thyroid-stimulating hormone, lithium toxicity, lithium-induced thyromegaly, thyrotropin, thyroglobulin, Tg, cyclic adenosine monophosphate, cAMP, euthyroid goiter, thyrotoxicosis, iodine, iodine deficiency, thyrocytes, bipolar manic-depressive disorder,

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Contributor Information and Disclosures

Author

Nicholas J Sarlis, MBBS, MD, PhD, FACP, Medical Director, Department of Oncology-US Medical Affairs Department, Sanofi-Aventis Pharmaceuticals
Nicholas J Sarlis, MBBS, MD, PhD, FACP is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American Federation for Medical Research, American Head and Neck Society, American Medical Association, American Society for Therapeutic Radiology and Oncology, American Society of Clinical Oncology, American Thyroid Association, Association for Psychological Science, Endocrine Society, European Society for Medical Oncology, New York Academy of Sciences, and Royal Society of Medicine
Disclosure: Sanofi-Aventis Salary Employment

Coauthor(s)

Boaz Hirshberg, MD, Associate Director, CVMD, Pfizer
Boaz Hirshberg, MD is a member of the following medical societies: American Dietetic Association
Disclosure: Nothing to disclose.

Medical Editor

Steven R Gambert, MD, MACP, Chairman, Department of Medicine, Physician-in-Chief, Sinai Hospital of Baltimore; Professor of Medicine, Program Director, Internal Medicine Program, Johns Hopkins University School of Medicine
Steven R Gambert, MD, MACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American Geriatrics Society, Association of Professors of Medicine, Endocrine Society, and Gerontological Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Don S Schalch, MD, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics
Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical Research, and Endocrine Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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