Hypothyroidism lithium

Treatment of Manic—Depressive Illness. Siace the 1960s, lithium carbonate [10377-37-4] and other lithium salts have represented the standard treatment of mild-to-moderate manic-depressive disorders (175). It is effective ia about 60—80% of all acute manic episodes within one to three weeks of adrninistration. Lithium ions can reduce the frequency of manic or depressive episodes ia bipolar patients providing a mood-stabilising effect. Patients ate maintained on low, stabilising doses of lithium salts indefinitely as a prophylaxis. However, the therapeutic iadex is low, thus requiring monitoring of semm concentration. Adverse effects iaclude tremor, diarrhea, problems with eyes (adaptation to darkness), hypothyroidism, and cardiac problems (bradycardia—tachycardia syndrome). 

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... 

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. 

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. 

Other causes include magnesium-containing antacids in patients with renal insufficiency, enteral or parenteral nutrition in patients with multiorgan system failure, magnesium for treatment of eclampsia, lithium therapy, hypothyroidism, and Addison s disease. 

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. 

When laboratory testing indicates that a patient with BPAD is clinically hypothyroid, even if lithium is the readily apparent cause, we recommend starting thyroid hormone replacement. Lithium should not be discontinued, particularly if it has otherwise managed the BPAD well. Thyroxine should be started at 50 ag/day. TSH levels can then be checked 6-8 weeks later. The daily dose of thyroxine can be increased in 25 g increments every 1-2 months until TSH levels have normalized. 

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. 

Lithium therapy necessitates the monitoring of thyroid function every 6-12 months in stabilised patients. Occurrence of symptoms such as lethargy, which may reflect hypothyroidism, should be monitored. 

Hypothyroidism Hypothyroidism may occur with long-term lithium administration. Patients may develop enlargement of thyroid gland and increased thyroid-stimulating hormone levels. 

Aggravation of the extrapyramidal effects of antipsychotic agents have been described and it has been reported that the use of lithium in combination with haloperidol may result in irreversible neurological toxicity. Lithium can increase the hypothyroid effects of antithyroid agents or iodides. 

A. Approximately 5% of patients taking lithium over the long term develop hypothyroidism, and thyroid status should be followed as routine care for these patients. Mr. Smith s symptoms are classic for hypothyroidism. Impairment in glucose metabolism, hepatic function, red blood cell production, and prolactin secretion are not typical complications of lithium therapy. 

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-... 

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. 

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. 

Lithium should not be administered to patients with fluctuating or unstable renal function. Because hthium may affect functioning of the cardiac sinus node, patients with sinus node dysfunction (e.g., sick sinus syndrome) should not receive hthium. Although hthium also has acute and chronic effects on the thyroid, patients with hypothyroidism may receive hthium if the thyroid disease is adequately treated and monitored. Laboratory tests that should be performed before initiation of hthium are listed in Table 5-1. 

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. 

A common mistake is to treat bipolar depression in the same manner that one treats unipolar depression, overlooking the need for a mood stabilizer. In bipolar depression, the first pharmacological intervention should be to start or optimize treatment with a mood stabilizer rather than to start administering an antidepressant medication. In addition, thyroid function should be evaluated, particularly if the patient is taking lithium. Subclinical hypothyroidism, manifested as an increased thyroid-stimulating hormone level and normal triiodothyronine and thyroxine levels, may present as depression in affectively predisposed individuals. In such cases, the addition of thyroid hormones may be beneficial, even if there is no other evidence of hypothyroidism. 

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 Neurological tremor, ataxia, seizures Endocrine hypothyroidism Cardiovascular T wave changes, sinus node dysfunction Renal polyuria, nephrogenic diabetic insipidus Dermatological hair loss, acne, psoriasis, rash Gastrointestinal nausea, diarrhea Miscellaneous fluid retention, weight gain, weakness... 

Lithium Plus Thyroid Supplementation. Treatment-resistant and rapid-cycling bipolar patients may have an increased frequency of thyroid dysfunction. Further, some patients suffer from subclinical hypothyroidism and improve with the addition of thyroid supplementation. In this context, several case reports involving this population found that high doses of the thyroid hormone levothyroxine sodium (T ) were clinically beneficial (122,123 and 124). Kusalic (1.25) found that 6 of 10 rapid cyclers had hypothyroidism, based on their thyrotropin-releasing hormone stimulation tests. Further, the average number of mood episodes per year decreased by more than 75% (i.e., from 9.7 to 2.2) after thyroxine was added to the treatment regimen. 

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

Hypothyroidism, a condition in which the circulating concentrations of thyroid hormones are too low, is the most prevalent thyroid disease. Primary hypothyroidism, the commonest form, is an autoimmune disease (Hashimoto s thyroiditis) often associated with goitre. Like other autoimmune diseases, it is more prevalent in women (4 per 1000) than in men (1 per 1000). Other causes include thyroidectomy, radioac tive ablation and, in some countries, iodine deficiency. Hypothyroidism can also be caused by several drugs, including lithium, interleukin-2 and interferon. Secondary hypothyroidism is a disease caused by decreased secretion of TSH by the pituitary. 

Because lithium affects second-messenger systems involving both activation of adenylyl cyclase and phosphoinositol turnover, it is not surprising that G proteins are also found to be affected. Several studies suggest that lithium may uncouple receptors from their G proteins indeed, two of lithium s most common side effects, polyuria and subclinical hypothyroidism, may be due to uncoupling of the vasopressin and thyroid-stimulating hormone (TSH) receptors from their G proteins. 

Lithium Mechanism of action uncertain suppresses inositol signaling and inhibits glycogen synthase kinase-3 (GSK-3), a multifunctional protein kinase No significant antagonistic actions on autonomic nervous system receptors or specific CNS receptors no sedative effects Bipolar affective disorder-prophylactic use can prevent mood swings between mania and depression Oral absorption, renal elimination half-life 20 h. narrow therapeutic window (monitor blood levels) Toxicity Tremor, edema, hypothyroidism, renal dysfunction, dysrhythmias pregnancy category D Interactions Clearance decreased by thiazides and some NSAIDs... 

Inhibition of thyroid hormone synthesis or release with the induction of hypothyroidism (or occasionally hyperthyroidism) Iodides (including amiodarone), lithium, aminoglutethimide, thioamides, ethionamide... 

Induction of autoimmune thyroid disease with hypothyroidism or hyperthyroidism Interferon-a, interleukin-2, interferon-B, lithium, amiodarone... 

Long-term side effects of lithium treatment include weight gain. The treatment is associated with development of hypothyroidism in about 10-15% of cases. There is an association with kidney disease. Birch has expressed the general view that Li may interact with magnesium-dependent processes, and theoretical chemistry supports this view. Despite the widespread clinical significance of Li, there is presently no consensus on its mode of action. One postulate for the mechanism is termed hyperpolarization . Li affects the conductivity in cell transport channels. Other explanations include modulation of neurotransmitter concentrations and inhibition of Na+/K+/Mg2+/ Ca2+ ATPases. 

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. 

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