Thyroid Enlargement (Goiter) from Lithium Use

Definition

Lithium-induced goiter is a condition where the thyroid gland enlarges in patients using lithium. Due to the location of the thyroid gland, it causes a swelling in the neck. The condition is caused by the use of lithium in the treatment of bipolar disorder. However, there are other more common causes of goiter that are not associated with lithium. Although patients who are more likely to experience this condution have a history of iodine deficiency or existing thyroid disease, a goiter can occur even with adequate iodine intake and normal thyroid function and structure.

Underactivity of the thyroid gland (hypothyroidism) may be seen in a minority of patients with lithium-induced goiter and an even smaller percentage of patients may experience high thyroid hormone levels (thyrotoxicosis) associated with an overactive thyroid gland (hyperthyroidism). Lithium is known to be toxic to humans and is present in very small quantities in the human body. The function of naturally occurring lithium remains unknown. One of the other consequence of therapeutic use of this metal is lithium induced kidney disease (nephropathy).

Incidence

About 1 in 5 patients using lithium may experience a goiter. The risk increases substantially with long term lithium use. People from regions with endemic iodine deficiency are also at a greater risk. Hypothyroidism occurs in about 1 out of 3 patients with lithium-induced goiter but hyperthyroidism is rare. Females and older patients on lithium are also at a higher risk of goiter.

Pathophysiology

Overview thyroid gland

The thyroid gland is located in the neck and extends to the upper part of the thoracic (chest) cavity. It is responsible for the production of two hormone – thyroxine (T4) and triiodothyronine (T4). The thyroid hormones have a range of effects in the human body but the most widely known is its ability to increase metabolic activity. Regulation of the the thyroid hormone levels in the blood is through a negative feedback mechanism involving the hypothalamus and pituitary gland. Hypothalamic secretion of thyrotropin-releasing hormone (TRH) acts on the pituitary which then secretes thyroid-stimulating hormone (TSH)

Enlarged thyroid gland

Excessive stimulation of the thyroid gland by TSH increases thyroid hormone production. In order to compensate the thyroid gland enlarges. Sometimes other factors, other than TSH, can increase proliferation of the thyroid cells and subsequently increase thyroid hormone production and secretion. Enlargement of the thyroid gland is known as a goiter. The entire gland may be enlarged but sometime there may only be lumps known as thyroid nodules. Enlargement of the thyroid gland and nodules may not mean overactivity. In fact, the thyroid hormone levels can be lower than normal in these cases.

Picture of goiter from Wikimedia Commons

Lithium use and the thyroid

Lithium accumulates in the thyroid gland. It increases the growth of thyroid cells (thyrocytes) but decreases the release of thyroid hormones from the gland. The feedback mechanism initially attempts to compensate for this by increasing TSH secretion. This compensatory mechanism leads to normal thyroid hormone levels. Therefore most patients with lithium-induced goiter have normal thyroid hormone levels in the blood stream (euthyroid). Enlargement of the thyroid gland may be present but the compensatory mechanism means that there is no disturbance in the thyroid hormone levels.

Hypo- and Hyperthyroidism with Lithim

However, some patients may experience hypothyroidism with lithium-induced goiter. It appears that in these cases there is some underlying mechanism that contributes to thyroid underactivity. These patients often have an iodine deficiency, previous damage to the thyroid gland or autoimmune mechanisms that causes thyroid inflammation. Hypothyroidism may therefore have occurred even without lithium use. Conversely, there is a small percentage of patients who experience hyperthyroidism (overactive thyroid). The reason why a minority of cases leads to thyrotoxicosis (high thyroid hormone levels) is unclear.

Symptoms

Most patients with lithium-induced goiter do not exhibit any symptoms. A visible neck swelling is rarely present. However, the enlargement may be felt during a physical examination. In most cases, lithium-induced goiter does not present with any significant increase or decrease in thyroid hormone levels. Therefore the symptoms of hypothyroidism and hyperthyroidism are not present. When it does occur, the symptoms are essentially the same to hypo- and hyperthyroidism in patients who do not use lithium.

Often the symptoms of hypo- and hyperthyroidism are missed in patients with lithium-induced goiter, as the focus is on the underlying bipolar depression. Some of the symptoms may actually be a part of the manic depressive disorder itself. However, it is important to take note of the symptoms of thyroid disturbances, which are often subtle in the initial stages.

Hypothyroidism

• Increased sensitivity to cold.
• Tiredness.
• Moderate weight gain.
• Thinning hair.
• Dry skin.
• Constipation.
• Poor memory.

Hyperthyroidism

• Intolerance to heat.
• Hyperactive.
• Rapid weight loss.
• Brittle hair.
• Sweating.
• Diarrhea.
• Tremor.

Causes

Lithium used in the treatment of bipolar disorder is in the form of lithium carbonate. Sometimes lithium citrate may be used. It is the lithium that induces goiter by causing proliferation of epithelial cells in the thyroid gland known as thyrocytes. It affects about 1 in 5 patients on lithium therapy but those at the greatest risk of goiter may have or more of the following contributing factors :

• Endemic iodine deficiency.
• Previous history of thyroid problems.
• Concomitant thyroid disease unrelated to lithium use (may be undiagnosed or asymptomatic).
• Radiation therapy to the neck or prior use of radioactive iodine.
• Substances and foods that disturb iodine uptake and cause glandular enlargement (goitrogen).

Diagnosis

Even though there is no visible swelling of the gland, the enlargement can be felt during palpation. This is conducted by a doctor during a physical examination. The gland is smooth and the enlargement is symmetrical. It is usually painless. Small smooth nodules are not easily palpable. The final diagnosis is made on the findings of an enlarged thyroid gland in a patient using lithium.

There are no specific investigations required for the diagnosis of lithium-induced goiter. Many of the same tests and scans that would be done for any cause of goiter or thyroid hormone disturbance would also be done in lithium-induced goiter. This includes  :

• Thyroid panel – T4, T3, TSH.
• Thyroid antibodies.
• Thyroid ultrasound.
• Radioactive iodine uptake (RAIU) test.

Treatment

Lithium therapy is not usually discontinued immediately once a goiter is diagnosed. The patient needs to be carefully assessed and the decision to discontinue lithium therapy is undertaken after careful consideration of the patient’s mental health. Lithium-induced goiter can be managed with the use of medication if stopping lithium intake is not feasible. Sometimes surgery is necessary in rare cases.

Levothyroxine (LT4) is the drug of choice. It is mainly used to treat hypothyroidism but may also be considered for goiter with normal thyroid hormone levels. Patients with a history of risk factors for the condition, apart from just lithium use, may be treated prophylactically with levothyroxine.

Surgical removal of the thyroid gland (thyroidectomy) may be considered in patients with hyperthyroidism where discontinuing lithium use is not advisable. There are other thyroid disorders where a thyroidectomy is considered and if present, the surgery should be undertaken irrespective of lithium use.

References :

www.uptodate.com/contents/lithium-and-the-thyroid

emedicine.medscape.com/article/120243-overview