Use of lithium carbonate for the treatment of amiodarone-induced thyrotoxicosis

Among the amiodarone-induced thyroid dysfunctions, thyrotoxicosis is the most troublesome and with the highest rate of morbidity and mortality. Treatment consists in the use of a high dose of anti-thyroid drugs and steroids in an isolated form or in combination. Association of several other drugs have been proposed for the treatment of refractory cases. In this study we report the case of a 40 y.o. patient, with a history of idiopatic dilated miocardiopathy, who developed severe amioradone-induced thyrotoxicosis after heart transplantation. Since the patient did not respond to an initial treatment consisting of a high dose of anti-thyroid drugs combined with steroids, a low dose of lithium carbonate was added for a short period of time, which resulted in normalization of the thyroid function. In this case, the addition of lithium carbonate to the two other drugs resulted in a successful and safety therapy in controlling amiodarone-induced thyrotoxicosis.     

Reversible sinus dysfunction during treatment with lithium carbonate]

The case reported concerns a symptomatic transitory sinus node abnormality in a 75 years old woman treated with Lithium Carbonate (750 mg/d) for a manic-depressive psychosis. This patient, admitted to the hospital for bradycardia and repeated episodes of syncope was shown to present sinus pauses greater than 3 seconds. Lithium therapy was discontinued. 72 hours later electrophysiologic studies, performed to evaluate sinus node function, were normal. It is therefore the author's opinion that in patients receiving Lithium therapy who present syncope, dizziness, or bradycardia a sinus node abnormality of iatrogenic origin must be considered. The importance of this diagnosis is in the rapid reversibility of the sinus node dysfunction with discontinuation of therapy.     

Association between lithium use and thyrotoxicosis caused by silent thyroiditis

OBJECTIVE: To determine the incidence of silent thyroiditis in lithium users and characterize lithium-associated thyrotoxicosis. DESIGN: Retrospective record review. PATIENTS: 400 consecutive patients (300 with Graves' disease and 100 with silent thyroiditis) who underwent radioiodine scanning of the thyroid. MEASUREMENTS: Odds of lithium exposure. RESULTS: The odds of lithium exposure were increased 4.7-fold in patients with silent thyroiditis compared with those with Graves' disease (95% CI: 1.3, 17). Lithium-associated silent thyroiditis occurred with an incidence rate of approximately 1.3 cases per 1000 person-years, and lithium-associated thyrotoxicosis occurred with an incidence rate of approximately 2.7 cases per 1000 person-years, higher than the reported incidence rates of silent thyroiditis (< 0.03-0.28 cases per 1000 person-years) and of thyrotoxicosis (0.8-1.2 cases per 1000 person-years) in the general population. CONCLUSION: Thyrotoxicosis caused by silent thyroiditis might be associated with lithium use.     

Hyperaldosteronism in thyrotoxicosis]

In 30 patients with a moderately severe and severe form of thyrotoxicosis a study was made of urinary aldosterone excretion following acid hydrolysis, by thin-layer chromatography. During decompensation the majority of the patients displayed an increased aldosterone excretion. Medicinal compesation of the disease did no lead to normalization of the mineralocorticoid function of the adrenal glands, whereas aldosterone excretion remained high in many of the patients. To ascertain the mechanisms of increase of aldosterone excretion in thyrotoxicosis a correlative analysis was carried out of associations between the aldosterone excretion and the circulating blood and plasma volume, potassium blood plasma content, catecholamine and 17-oxycorticoid excretion. On the basis of the results obtained and literature data it was supposed that intensified beta-adrenergic activity of the nervous system and increased catecholamine production participated in increase in the mineralocorticoid function of the adrenal glands during thyrotoxicosis.     

State of the renin-angiotensin system in thyrotoxicosis]

A study was made of the blood plasma renin activity in 63 patients suffering from thyrotoxicosis before the treatment and in 42 healthy individuals. In comparison with the healthy, renin activity was increased in patients with thyrotoxicosis and displayed a positive correlation with the severity of the disease the level of protein-bound iodine, tachycardia and the degree of loss of weight. Stimulation of the renin-angiotensin system by the salt-free diet, hydrochlorthiazide and by placing the body into orthostatic position caused a relatively weaker increase in the renin activity in comparison with such in healthy individuals. Following successful treatment and the occurrence of an euthyroidal state renin activity proved to fall to the normal level. An increased renin activity was combined with increased urinary aldosterone excretion with a normal serum electrolyte level. Such combination pointed to the secondary character of aldosteronism. Block of the alpha- and beta-adrenergic receptors led to reduction in the level of renin activity. Despite the frequent affection of hepatic function there was revealed no correlation between the increase in the renin activity and the pathological results of hepatic tests. Plasma renin activity was reduced in 8 patients with myxedema. It is supposed that the principal factors causing activation of the renin-angiotensin system in thyrotoxicosis were the loss of water and electrolytes by the organism and the appearance of oversensitivity to adrenergic receptors.     

Pathogenesis of cardiac insufficiency in thyrotoxicosis]

The purpose of the work was to study some problems relating to the pathogenesis of cardiac insufficiency in patients with thyrotoxicosis. To do this a total of 108 patients suffering from thyrotoxicosis with varying degree of severity and aged from 17 to 59 were examined. In addition to the general clinical examination vectoro-, poly- and mechanocardiography was employed. The resulting findings ascertained two possible ways for the development of cardiac insufficiency in patients under consideration. One of them is cardiac hyperfunction that comes to the forefront. In this case the myocardial changes are of a stage-wise nature. The myocardial contractility at the onset of the affection is up, a slight hypertrophy is developing, chiefly, of the outflow passages. As the disease progresses further hypertrophy gains in intensity and dilation of the heart comes in as an intercurrent factor. At this time the contractile function of the myocardium is still unaffected and the patients are at a stage of compensation. With progressing dystrophy and wearing away of the myocardium its contractility is declining and signs of cardiac incompetence appear. Such a development is characteristic of patients with severe course of thyrotoxicosis, long-standing disease and frequent relapses. Of the other way is typical cardiac hyperfunction of low intensity. To the forefront come dystrophic alterations in the myocardium unaccompanied by hypertrophy, and in this case cardiac insufficiency is of latent nature. Such alterations are seen to occur with a milder course of thyrotoxicosis, with the disease of short duration. Dynamic observations bear proof to a reversible nature of hypertrophy and dystrophy of the myocardium.     

Use of lithium carbonate in the therapy of diffuse toxic goiter

Altogether 22 patients with diffuse toxic goiter and 14 with neurocirculatory dystonia, treated with lithium carbonate, were examined. Radioimmunoassay of the blood serum triiodothyronine (T3), thyroxine (T4), and thyrotropic hormone (TTH) was used to evaluate the clinical and functional effect of the drug. Lithium carbonate in a dose of 900-1800 mg daily during 4-6 weeks produced a significant reduction in T3 level; the level of T4 was less reduced, and the TTH concentration increased. The pulse rate of patient diminished. Antithyroid effect of the drug is more expressed in patients with medium severity thyrotoxicosis. No side effects were recorded.     

Focal segmental glomerulosclerosis in patients receiving lithium carbonate

Lithium carbonate is a commonly used psychiatric medication with a number of toxic renal effects, which include nephrotic-range proteinuria. A review of the literature concerning lithium-induced proteinuria is presented and three cases of nephrotic-range proteinuria are described in association with lithium therapy. The pathology in these three cases was focal segmental glomerulosclerosis, a finding not previously described.     

Haematological effects of lithium and its use in treatment of neutropenia

Conclusion Lithium is a safe drug to use and results so far fully justify continued experimentation with this agent in a variety of haematological disorders. The major haematological effect of lithium in man is stimulation of granulopoiesis, the most likely mode of action being an enhancement of CSA production. Consistent with this view is the observation that neutropenic states most likely to benefit from lithium treatment are those where impaired CSA activity is demonstrable. While the physiological importance of CSA is still not completely understood experience with lithium would support a major role for CSA in the regulation of granulopoiesis. Colony-stimulating factors are produced by monocyte-macrophages, lymphocytes, and endothelial cells. Further work will be required to define the physiological significance and effect of lithium on CSA production by each of these cell types.The success of lithium in protecting granulopoiesis following cancer chemotherapy suggests that CSA production is suboptimal in this situation. Defective CSA production may be an important and hitherto unrecognised effect of cancer chemotherapeutic agents and further studies are indicated.There is little evidence that lithium directly affects pluripotent stem cells in man, and it is clearly without effect in most cases of severe aplastic anaemia where stem-cell failure is almost total. However, the inhibitory action of lithium on suppressor lymphocytes might be put to therapeutic use in pure red cell aplasia or in cases of aplastic anaemia where inhibition of erythroid or granulocyte precursor cells can be unequivocally demonstrated in co-culture.