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Lithium-Induced Goiter Workup

  • Author: Nicholas J Sarlis, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
Updated: Feb 27, 2015

Laboratory 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, as follow, are indicated to exclude concomitant hypothyroidism and the existence of a thyroid-specific autoimmune process:

  • Serum thyrotropin[10, 11]
    • 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 than in control subjects with comparable thyrotropin levels.
  • Serum free thyroxine (T4) and total triiodothyronine (T3) tests[10, 11, 12]
    • 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 is free T4 testing.
  • Exaggerated response of thyrotropin to thyrotropin-releasing hormone (TRH) stimulation test[13]
    • 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

Imaging studies include the following:

  • Thyroid ultrasonography[14, 15]
    • 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.
  • 123 I uptake test
    • This is a second-level test.
    • 123 I 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.123 I 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 histologic 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 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), histologic features of the underlying pathology are evident.



There is no formal staging regarding the severity, acuity or chronicity, or seriousness of lithium-induced goiter and/or its complications.

Contributor Information and Disclosures

Nicholas J Sarlis, MD, PhD, FACP Vice President, Head of Medical Affairs, Incyte Corporation

Nicholas J Sarlis, MD, PhD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American Association of Clinical Endocrinologists, American College of Physicians, American Federation for Medical Research, American Head and Neck Society, American Medical Association, American Society for Radiation Oncology, American Thyroid Association, Endocrine Society, New York Academy of Sciences, Royal Society of Medicine, Association for Psychological Science, American College of Endocrinology, European Society for Medical Oncology, American Society of Clinical Oncology

Disclosure: Received salary from Incyte Corporation for employment; Received ownership interest from Sanofi-Aventis for previous employment; Received ownership interest/ stock & stock option (incl. rsu) holder from Incyte Corporation for employment.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

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 and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus 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, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Steven R Gambert, MD Professor of Medicine, Johns Hopkins University School of Medicine; Director of Geriatric Medicine, University of Maryland Medical Center and R Adams Cowley Shock Trauma Center

Steven R Gambert, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician Leadership, American College of Physicians, American Geriatrics Society, Endocrine Society, Gerontological Society of America, Association of Professors of Medicine

Disclosure: Nothing to disclose.


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.


The author wishes to dedicate this article to the late Jacob Robbins, MD (1922-2008), a leading figure in international thyroidology and a force majeure within the Clinical Endocrinology Branch of NIDDK, National Institutes of Health. His legacy lives on.

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