Hypothyroidism lithium-induced

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... 

Lithium is associated with hypothyroidism in up to 34% of patients, and hypothyroidism may occur after years of therapy. Lithium appears to inhibit thyroid hormone synthesis and secretion. Patients with underlying autoimmune thyroiditis are more likely to develop lithium-induced hypothyroidism. Patients may require LT4 replacement even if lithium is discontinued. 

Thyroid Hormone (Thyroxine, Synthroid). The most common use of thyroxine in bipolar patients is the treatment of lithium-induced hypothyroidism. Approximately 5% of patients receiving long-term lithium treatment ultimately develop hypothyroidism. When this occurs, the patient with bipolar disorder may present with symptoms of a depressive episode. Therefore, periodic thyroid axis monitoring, that is, a serum thyroid stimulating hormone (TSH) test, is required for all patients taking lithium and should always be performed when the bipolar patient experiences a depressive episode. 

The next step in the management of the depressed bipolar patient is to evaluate thyroid function. This is especially important for patients treated with lithium in order to rule out lithium-induced hypothyroidism. When this occurs, the addition of thyroid hormone replacement may relieve the depressive symptoms without any additional changes to the bipolar treatment regimen. 

Kleiner, J., Altshuler, L., Hendrick, V, and Hershman, J.M. (1999) Lithium-induced subclinical hypothyroidism review of the literature and guidelines for treatment. / Clin Psychiatry 60 249-255. 

Reversible hypothyroidism may occur in as many as 20% of the patients receiving lithium (Lindstedt et al. 1977 Myers et al. 1985). Lithium-induced hypothyroidism occurs more frequently in women. Thyroid function should be evaluated every 6-12 months during lithium treatment or if symptoms develop that might be attributable to thyroid dysfunction, including depression or rapid cycling. 

Leach MJ, Baxter MG, Critchley MA Neurochemical and behavioral aspects of lamotrigine. Epilepsia 32 (suppl 2) S4-S8, 1991 Lindstedt G, Nilsson L, Walinder J, et al On the prevalence, diagnosis and management of lithium-induced hypothyroidism in psychiatric patients. Br J Psychiatry 130 452-458, 1977... 

Lithium-induced hypothyroidism has been briefly reviewed (626). Some patients develop more persistent subclinical hypothyroidism (TSH over 5 mU/1, free thyroxine normal) and others overt hypothyroidism (higher risk in women, in those with pre-existing thyroid dysfunction, and those with a family history of hypothyroidism). Since subclinical hypothyroidism is not necessarily asymptomatic, treatment with thyroxine may be necessary in this group (627), as well as in those with more obvious hypothyroidism (628). 

The prevalence of thyroperoxidase antibodies was higher in 226 bipolar patients (28%) than in population-and psychiatric-control groups (3-18%). While there was no association with lithium exposure, the presence of antibodies increased the risk of lithium-induced hypothyroidism (632). 

In a review of lithium-induced subclinical hypothyroidism (TSH over 5 mU/1, free thyroxine normal), a prevalence of up to 23% in lithium patients was contrasted with up to 10% in the general population. It was stressed that subclinical hypothyroidism from any cause can be associated with subtle neuropsychiatric symptoms, such as depression, impaired memory and concentration, and mental slowing and lethargy, as well as with other somatic symptoms. Management guidelines were discussed (628). 

The production of thyroid disorders by lithium is common and requires constant concern throughout the treatment. Lithium-induced hypothyroidism can produce depression and other mental dysfunction, greatly confusing and complicating the patient s clinical picture. 

In a review of lithium-induced subclinical hypothyroidism (TSH over 5 mU/1, free thyroxine normal), a... 

Numata T, Abe H, Terao T, Nakashima Y. Possible involvement of hypothyroidism as a cause of lithium-induced sinus node dysfunction. Pacing Clin Electrophysiol 1999 22(6 Part l) 954-7. 

As discussed above, hthium inhibits the synthesis of thyroid hormone and its release from the thyroid, and stimulates the formahon of antithyroid anhbodies in susceptible subjects [122]. Lithium-induced hypothyroidism responds to thyroxine therapy. Lithium... 

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). 

Shopsin B, Shenkman L, Blum Hollander CS. Iodine and lithium-induced hypothyroidism. Documentationofs3mergism.yl/w JMetf(1973) 55, 695-9. 

Lithium carbonate, administered for affective and bipolar disorders, may enhance the effects of antithyroid drugs. Potassium iodide, used as an expectorant, is a major ingredient in many cough medications. Iodide derived from this source may enhance the effects of antithyroid drugs and lead to iodine-induced hypothyroidism. Iodine in topical antiseptics and radiological contrast agents may act in a similar manner. 

Jefferson JW. Lithium carbonate-induced hypothyroidism. Its many faces. JAMA 1979 242 271-272. 

In addition to the effects described above, lithium can induce diabetes insipidus and hypothyroidism in some patients, and is contraindicated in those with renal or cardiac insufficiency. 

Endocrine Thyroid A woman with thyroid carcinoma who was taking lithium for bipolar disorder discontinued her thyroid hormone replacement in preparation for radioactive iodine ( I) treatment [59" ]. Within 3 weeks she developed severe lithium toxicity, which the authors attributed to renal insuffidenqr associated with hypothyroidism [60 ]. Lithium was not withdrawn in this patient, because of an earlier suggestion that lithium can be used as an adjunct in treatment [61 ]. In an in vitro study using follicular thyroid carcinoma cell lines, lithium 10-20 nunol/1 induced expression of NR4A1 and FOSB, genes whose underexpression is associated with mahgnancy [62 ]. 

Hypothyroidism induced by iodine is well documented and it has been postulated that is is the iodide ion that is responsible, a phenomenon classically known in the Wolff-Chaikoff effect (37) This blocking effect has been shown to be enhanced by antithyroid antibodies (38,39), antipyrine (40) and lithium (41) The pathogenesis of the clinical entity known as "iodide goiter (37) in which goiter and/or hypothyroidism appears and subsides concomittantly with iodide intake and withdrawal, has been related to the Wolff-Chaikoff effect that had been demonstrated in animal In our laboratory a few cases of iodide goiters were discovered by means of XRF (see example in Fig 3) A correlation could be established between the clinical state of the patient and its TITI, demonstrating the validity of the pathogenic hypothesis Because an important part of iodine ean be washed out by perchlorate in these cases, it has been... 

---