Lithium-Induced Goiter - Diagnosis and Treatment

Introduction

The antithyroid actions of lithium were first investigated and studied in detail when it was noticed that the patients with psychiatric diseases treated with lithium medications developed goiter, hypothyroidism, and in rare cases, hyperthyroidism. Apart from having direct toxic effects on the thyroid gland, lithium also reduces or stops the production and release of thyroid hormones. This leads to hypothyroidism. In response to this, thyroid-stimulating hormone (TSH) production is increased, and the thyroid gland enlarges. The diagnosis of lithium-induced goiter mainly consists of medical history, physical examination, and thyroid ultrasound. The treatment includes thyroid hormone replacement therapy.

What Is Lithium and What Are Its Uses?

Lithium is a chemical element, also known as lithium salt, used in medicine to treat conditions like bipolar disorder, depression, mania (feeling highly excited and overactive), hyper-mania (a less severe form of mania), and so on. It is available in the form of lithium carbonate as tablets and lithium citrate as liquids and is given only on prescription (not an over-the-counter drug). Lithium is classified as a mood stabilizer in medicine.

What Are the Various Side Effects of Lithium When Used in Medication?

Lithium also has multiple side effects associated with long-term use of the drug. The most common side effects include nausea, vomiting, diarrhea, parageusia (metallic taste in mouth), increased urination, shakiness of the hands, and other such symptoms. More severe side effects of lithium, when used for a long time, are hypothyroidism (underactive thyroid gland), lithium toxicity, diabetes insipidus (a condition characterized by increased urination and excessive thirst), and lithium-induced goiter. Lithium also harms the growing fetus when the mother consumes it during pregnancy, especially during the first trimester. In addition, it can lead to congenital heart defects in the child.

What Is a Goiter?

A swelling or lump in the neck resulting from an enlargement of the thyroid gland is referred to as a goiter. Generally, the thyroid gland is not prominent, but in the case of goiter, the gland enlarges and forms a lump that can be easily seen and palpated. The most common cause of goiter is iodine deficiency, prevalent in developing countries and individuals of low socioeconomic status. Most goiters are noncancerous, and in very rare cases, they become cancerous.

What Is Lithium-Induced Goiter?

• Goiters developing as a result of side-effects of lithium therapy in patients with bipolar disorder, depression, and mania are known as lithium-induced goiter.

• The influence of lithium on the thyroid gland is one of the acute side effects of long-term drug use. Goiter is the most common thyroid problem in patients treated with lithium.

• In the case of patients affected by lithium-induced goiter, the size of the thyroid gland increases almost twice the standard size.

• Lithium-induced goiters are generally diffused (with no nodules), but in rare cases, they may become nodular.

• Lithium-induced goiter can develop within a few weeks of the use of the drug but usually develops within the first two years of lithium treatment.

• Lithium is accumulated in the thyroid gland three to four times more than in the blood (plasma).

• Prolonged use of lithium causes reduced production and inhibition of the release of the thyroid hormone. This leads to increased thyroid-stimulating hormone concentration in the body, leading to thyroid enlargement.

How Common Is Lithium-Induced Goiter?

Lithium-induced goiter is the most prevalent form of thyroid disorder in patients under lithium treatment, occurring in approximately 40 to 50 percent of the patients. However, the frequency of occurrence also depends on the availability of iodine in that region.

How Does Lithium Cause Goiter?

The exact process of goiter formation in lithium-treated patients is unknown. However, the following mechanisms have been proposed:

• Lithium reduces the production and inhibits the release of thyroid hormones. To compensate for this lack of thyroid hormones in the body, secretion of the thyroid-stimulating hormone is increased. This leads to stimulation and subsequent thyroid gland enlargement, eventually forming a goiter.

• Another possible theory of the mechanism of goiter formation in lithium-treated patients suggests that lithium causes increased division of thyroid hormone-producing cells (thyrocytes) and activates tyrosine kinase enzyme and beta-catenin signaling pathways.

What Are the Other Thyroid Disorders Caused by Lithium Use?

• Lithium-induced goiter is the most common thyroid disorder caused by long-term lithium use. However, it can also lead to subclinical and clinical hypothyroidism and, in rare cases, hyperthyroidism and thyroid toxicity.

• Hypothyroidism occurs in about 52 percent of lithium-treated patients.

• Hypothyroidism induced by lithium can occur during the first few weeks to 18 months of the treatment with the drug.

• The cause of lithium-induced hypothyroidism and subclinical hypothyroidism is the inhibition of the thyroid gland's production and release of thyroid hormones.

• Lithium-induced hypothyroidism is more common in females over the age of 50 years with a family history of thyroid disorders.

• Lithium-induced hyperthyroidism is fairly less common as compared to goiter and hypothyroidism.

• Lithium-induced hyperthyroidism is characterized by temporary and painless thyroiditis (inflammation of the thyroid gland) and occurs due to the direct toxic effect of lithium on the thyroid gland.

How Is Lithium-Induced Goiter Diagnosed?

• The diagnosis of lithium-induced goiter requires obtaining a detailed medical history of the patient. The prolonged use of lithium for bipolar or other psychiatric disorders will suggest an association with some sort of thyroid condition.

• Lithium-induced goiters are usually diagnosed with the help of thyroid ultrasonography, which is a simple, cost-effective, and accurate method for determining goiter and other thyroid gland abnormalities among patients on lithium medication. A thyroid ultrasound will help evaluate the size of the goiter and check for any nodules in it.

• A thyroid scan may also be done to confirm the diagnosis of lithium-induced goiter. In this test, radioactive material is injected into the thyroid gland to produce an image of the thyroid on a computer screen. This test is done to check the functioning of the thyroid.

• In the case of the presence of nodules, a fine needle biopsy is done to take samples of fluids or tissues.

How Is Lithium-Induced Goiter Treated?

Patients with lithium-induced goiter should be treated the same way as those diagnosed with goiter. The treatment modalities for lithium-induced goiter include:

• Thyroid hormone replacement drugs are given to balance the deficiency of thyroid hormones in the body. Levothyroxine helps protect against the development of the goiter and proves the effectiveness of the treatment. Levothyroxine is, however, advised for patients with significant enlargement of the thyroid gland and in the presence of symptoms of constriction and compression (like difficulty in swallowing and difficulty in sleeping).

• The dosage of Levothyroxine should be adjusted in a way that it does not suppress the secretion of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4).

• Levothyroxine therapy may not be effective for long-duration goiters in which fibrotic changes have developed.

• If Levothyroxine therapy fails to reduce the size of goiter and there are symptoms of compression associated with it, then partial or complete thyroidectomy may be performed. Thyroidectomy is the surgical removal of the thyroid gland. Thyroidectomy is done in cases where the goiter does not respond to thyroid replacement drug or anti-thyroid drug and continues to grow. In addition, it is also done in cases where the goiter is aesthetically undesirable.

• Hypothyroidism associated with lithium use is also treated with the help of thyroid replacement drugs.

• Hyperthyroidism associated with lithium is treated with anti-thyroid drugs such as Carbimazole or a combination of Carbimazole with corticosteroids.

Conclusion

Due to the high incidence of thyroid disorders like goiter and hypothyroidism in patients undergoing lithium therapy, clinical testing of thyroid function status, thyroid size, and the presence of thyroid auto-antibodies should be performed on all patients before initiation of lithium therapy. Later, it should be done annually to see any subsequent changes occurring during the treatment. Therefore, regular assessment of thyroid function tests and thyroid ultrasonography is recommended in patients before and during lithium therapy.