Lithium-Induced Goiter Workup

Updated: Apr 13, 2020
  • Author: Nicholas J Sarlis, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
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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 [16, 17]

    • 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 antithyroid 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 [16, 17, 18]

    • 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 [19]

    • 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 [20, 21]

    • 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.

  • 123I 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 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.