Lithium goiter

Lithium. In the lithium carbonate treatment of certain psychotic states, a low incidence (3.6%) of hypothyroidism and goiter production have been observed as side effects (6,36) (see Psychopharmacologicalagents). It has been proposed that the mechanism of this action is the inhibition of adenyl cyclase. Lithium salts have not found general acceptance in the treatment of hyperthyroidism (see Lithiumand lithium compounds). 

Lithium is concentrated in the thyroid gland and can impair thyroid hormone synthesis. Although goiter is uncommon, as many as 30% of patients develop at least transiently elevated thyroid-stimulating hormone values. Lithium-induced hypothyroidism is not usually an indication to discontinue the drug. Patients can be supplemented with levothyroxine if continuation of lithium is desired.30... 

When lithium is to be used during pregnancy, it should be used at the lowest effective dose in order to avoid floppy infant syndrome, hypothyroidism, and nontoxic goiter in the infant. 

Up to 30% of patients on maintenance lithium therapy develop transiently elevated serum concentrations of thyroid-stimulating hormone, and 5% to 35% of patients develop a goiter and/or hypothyroidism, which is dose-related and more likely to occur in women. This is managed by adding levothyroxine to the regimen. 

Biosynthetic defects in thyroid hormonogenesis may also result in an inability of the thyroid gland to produce sufficient hormone and may be due to inherited enzymatic deficiencies or the ingestion of natural or therapeutically administered antithyroid agents. An example in the latter category is lithium, widely used to treat psychiatric disorders and associated with the development of hypothyroidism and goiter. It is concentrated by the thyroid, where it inhibits thyroidal I uptake, incorpora-... 

The many effects of lithium on thyroid physiology and on the hypothalamic-pituitary axis and their clinical impact (goiter, hypothyroidism, and hyperthyroidism) have been reviewed (620). Lithium has a variety of effects on the hypothalamic-pituitary-thyroid axis, but it predominantly inhibits the release of thyroid hormone. It can also block the action of thyroid stimulating hormone (TSH) and enhance the peripheral degradation of thyroxine (620). Most patients have enough thyroid reserve to remain euthyroid during treatment, although some initially have modest rises in serum TSH that normalize over time. 

Both goiter and hypothyroidism continue to be reported as complications of lithium therapy (621,622,623). 

In 1989, in 150 patients at different stages of lithium therapy, thyroid function was assessed and subsequently 118 were reassessed at least once and 54 completed a 10-year follow-up (625). The annual rates of new cases of thyroid dysfunction were subclinical hypothyroidism 1.7%, goiter 2.1%, and autoimmunity 1.4%. While these figures were little different from those found in the general population, the authors acknowledged that lithium was a potential cause of thyroid dysfunction. 

Of 42 bipolar patients who had taken lithium for 4-156 months, three had subclinical hypothyroidism, three had subclinical hyperthyroidism, and one was overtly hyperthyroid (623). Ultrasonography showed that goiter was present in 38% and mild thyroid dysfunction was suggested in 48% because of an apparent increased conversion of free T4 to free T3. There was no correlation between the duration of lithium therapy and thyroid abnormalities. 

When 22 men and 38 women who had taken lithium for at least a year (mean 6.9 years) for bipolar disorder were evaluated for adverse effects, hypothyroidism requiring thyroid supplementation was found in 16 (14 women and 2 men) 9 had a goiter (637). The area from which some of the patients came was known to have a high background incidence of thyroid dysfunction. 

Despite the predominantly antithyroid effects of lithium, thyrotoxicosis continues to be described during treatment and after withdrawal (642-644). In a retrospective review of 201 patients taking lithium (mean duration 6.4 years), hypothyroidism requiring supplemental thyroxine developed in 10% (3.4% of men, 15% of women) after a mean duration of 56 months. Women over 50 years of age tended to have an earlier onset. Two patients developed goiter requiring surgery and two others developed thyrotoxicosis (631). 

Euthyroid or hypothyroid goiter can also complicate lithium therapy, although the goiter is seldom of clinical importance and tends to resolve on withdrawal or with thyroxine treatment. In one ultrasound study, there was a... 

After several months of continuous therapy with lithium, diabetes insipidus and goiter may develop. The kidney tubules then become insensitive to the action of antidiuretic hormone, and its administration is ineffective. Either a dose reduction or discontinuation of the lithium corrects this side effect without leaving any residual pathology. In the... 

Of 42 bipolar patients who had taken lithium for 4—156 months, three had subclinical hypothyroidism, three had subclinical hyperthyroidism, and one was overtly hyperthyroid (256). Ultrasonography showed that goiter... 

Reports of fetal goiter and a variety of other lithium-related adverse events in newborns have been reviewed (488). 

Neonates born to mothers taking lithium included a boy with a goiter and chemical hypothyroidism who required temporary treatment with oral thyroxine for 11 weeks... 

Frassetto F, Tourneur Martel F, Barjhoux CE, Villier C, Bot BL, Vincent F. Goiter in a newborn exposed to lithium in utero. Ann Pharmacother 2002 36(ll) 1745-8. 

Despite this variety of clinical findings, frank hypothyroidism and clinical goiter actually are rare sequelae of lithium therapy. However, it is difficult to predict lithium-induced thyroid dysfunction, and regular TRH determinations should be carried out to identify any late-developing disorder (43). 

As lithium is a very potent drug, longterm therapy and prophylaxis (normally 140-280 mg per day, resulting in serum lithium levels of 0.5-1.0 mmol L ) may be associated with unpleasant side effects, including tremor of the hands, goiter, hypo-... 

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