Ludzkie koronawirusy - autor: Krzysztof Pyrć z Zakładu Mikrobiologii, Wydział Biochemii, Biofizyki i Biotechnologii, Uniwersytet Jagielloński, Kraków

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© Borgis - Postępy Nauk Medycznych 12/2017, s. 694-698 | DOI: 10.25121/PNM.2017.30.12.694
*Helena Jastrzębska
Lithium therapy and thyroid disorders
Lit a zaburzenia tarczycowe
Department of Endocrinology, Centre of Postgraduate Medical Education, Bielański Hospital, Warsaw
Head of Department: Professor Wojciech Zgliczyński, MD, PhD
Streszczenie
Lit jest rekomendowany do leczenia ostrej manii i choroby afektywnej dwubiegunowej, a także jako długotrwała profilaktyka zaburzeń dwubiegunowych. Lit gromadzi się w gruczole tarczowym wbrew gradientowi stężeń i działa wielokierunkowo, powodując hamowanie proteolizy, czyli uwalniania hormonów z gruczołu tarczowego, zwiększenie zawartości jodu w tarczycy, hamowanie sprzęgania reszt tyrozynowych do tyroksyny i trijodotyroniny. Może powodować wole i niedoczynność tarczycy, a także autoimmunizacyjną chorobę tarczycy. Wole stwierdza się u około 40-50% leczonych, niedoczynność tarczycy u 20-30%, nadczynność tarczycy 2-3-krotnie częściej niż w ogólnej populacji. Przed podaniem litu chorzy powinni odbyć badanie fizykalne tarczycy i oznaczenie stężenia TSH oraz przeciwciał przeciw peroksydazie tarczycowej i ultrasonografię tarczycy. W czasie leczenia zalecana jest ponowna ocena co 6-12 miesięcy. Zaburzenia czynności tarczycy wymagają leczenia zwykle bez konieczności odstawiania litu. Z uwagi na zdolność do hamowania wydzielania hormonów tarczycy lit może być zastosowany w leczeniu chorób tarczycy, w tym nadczynności. Nie jest stosowany jako leczenie pierwszego wyboru ze względu na działania niepożądane i dostępność innych silnie działających leków przeciwtarczycowych. Zdolność do zwiększenia retencji jodu w tarczycy może być wykorzystana celem zwiększenia skuteczności leczenia radiojodem.
Summary
Lithium is approved for the treatment of acute mania and bipolar disorder and also as long-term prophylaxis of bipolar disorders. Lithium highly concentrates in the thyroid gland against a concentration gradient, probably by active transport. It acts in multiple directions, in particular, inhibiting the thyroid hormone release from thyroid gland, increasing the iodine content in the thyroid gland, inhibiting the coupling the iodotyrosine residues to form iodothyronines tyroxine and triiodothyronine. Lithium may cause goiter and hypothyroidism, as well as autoimmune thyroid disease. Goiter is noted in about 40-50%, hypothyroidism in 20-30% of patients. The incidence of hyperthyroidism is less frequent in lithium-treated patients but is still 2-3 time higher than in the general population. Prior to lithium administration, patients should undergo a physical examination of the thyroid gland and estimation of TSH and antithyroid peroxidase antibodies and/or ultrasound of the thyroid gland. Re-evaluation is recommended every 6 to 12 months. Thyroid dysfunction usually requires treatment without the need to discontinue lithium. Because of its ability to inhibit thyroid hormone secretion, lithium can be used to treat thyroid diseases including hyperthyroidism. It is not used as a first-line treatment because of the side effects and the availability of other potent antithyroid agents. The ability to increase thyroid iodine retention may be used to augment the efficacy of radioiodine treatment.
Introduction
Lithium, an element in the alkali metal group, is approved for the treatment of acute mania and bipolar disorder and also as a long-term prophylaxis of bipolar disorders (1). Lithium act by substituting potassium ions, which affects the ratio of these ions inside and outside the cell. These changes may affect the release of certain neurotransmitters and their uptake. Lithium plays a neuroprotective role, increasing gray matter volume in several brain areas including the amygdalea, hippocampus and prefrontal cortex. At the cellular level lithium decreases excitatory and increases inhibitory neurotransmission. Lithium is available only for oral administration as lithium carbonate salt. It is almost completely absorbed from the gastrointestinal tract. Peak levels occur in 2-4 hours. The plasma elimination half-life of a single dose of lithium takes from 12 to 27 hours. Lithium is almost exclusively excreted by the kidneys and dosing must be adjusted to the renal function. Most filtered lithium is reabsorbed in the proximal tubule. Reabsorption of lithium is increased in patients who are hyponatremic or volume depleted, both of which are possible consequences of diuretic therapy. The therapeutic dose to obtain the desired therapeutic serum levels of 0.6-1.2 mEq/L is 300-2700 mg/d (2).
Lithium side effects and toxicity
While it is effective drug for the treatment of bipolar disorders, lithium therapy is associated with risk of toxicity even when blood level is in narrow therapeutic window (2). Elderly patients may exhibit signs of toxicity at serum levels ordinarily tolerated by other patients. The central nervous system is the major system affected, although the renal, gastrointestinal, endocrine, and cardiovascular systems also may be involved (3). Lithium toxicity may be of an acute or chronic nature. Acute intoxication manifestations are predominantly gastrointestinal, but progression to neuromuscular signs may occur, acute-on-chronic both gastrointestinal and neurologic manifestations may be also present, whatever chronic manifestations are primarily neurologic. Acute toxicity occurs typically in the setting of accidental or intentional overdose. Diarrhea, vomiting, somnolence, muscular weakness and lack of coordination may be early signs of lithium toxicity, and can occur at lithium concentrations below 2.0 mEq/L. At higher concentrations, dizziness, ataxia, blurred vision, tinnitus and a large output of dilute urine may be seen. Serum lithium concentrations above 3.0 mEq/L may cause a complex clinical picture involving multiple organs and organ systems with coma, and eventually death. Chronic toxicity often manifests as gradual development of neurological symptoms similar to those of late phase of acute toxicity. Chronic lithium treatment may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. Lithium can cause hyponatremia by decreasing sodium reabsorption by the renal tubules, leading to sodium depletion. It can also cause chronic tubulointerstitial nephropathy. An encephalopathic syndrome, characterized by weakness, lethargy, fever, tremulousness and confusion and extrapyramidal symptoms has occurred in patients treated with lithium and an antipsychotic. Lithium can precipitate serotonin syndrome, a potentially life-threatening condition. Long-term lithium treatment is associated with persistent hyperparathyroidism and hypercalcemia. There have been reports of a possible association between treatment with lithium and the unmasking of Brugada syndrome. Brugada syndrome is a disorder characterized by abnormal electrocardiographic findings and a risk of sudden death. Pseudotumor cerebri characterized by increased intracranial pressure and papilledema have been reported with lithium use. The risk of lithium toxicity is especially high in patients with significant renal or cardiovascular disease, severe dehydration or sodium depletion, and in patients receiving medications that may affect kidney function, such as angiotensin converting enzyme inhibitors, diuretics loops and thiazides and nonsteroidal anti-inflammatory drugs (indomethacin, piroxicam, selective cyclooxygenase-2 (COX-2) inhibitors). Accurate lithium treated patient's evaluation requires both clinical and laboratory analysis. Before initiating treatment with lithium, renal function, serum electrolytes and thyroid function should be evaluated. There have been no adequate studies conducted to evaluate the mutagenic potential of lithium. Due to potential risk to the featus and neonate, lithium can not be recommended during pregnancy and breast-feeding (1). Lithium is contraindicated in patients with known hypersensitivity to any ingredient in the lithium carbonate tablet. No specific antidote for lithium poisoning is known. Early symptoms of toxicity can usually be treated by reduction or cessation of lithium. Treatment of lithium intoxication depends on the degree of toxicity. In cases of mild toxicity lithium discontinuation may be sufficient. Moderate toxic episodes require fluid infusion with saline diuresis. The most severe cases defined by extraordinarily high lithium levels above 4 mmol/l or marked clinical symptoms may require hemodialysis (4).
Lithium and thyroid
Lithium highly concentrates in the thyroid gland against a concentration gradient, probably by active transport. In clinically useful doses, lithium, like iodine decreases the release of preformed thyroid hormones from the thyroid. Its primary effect seems to be the blockade of colloid droplet formation in the apical pole of the thyrocyte and hence, inhibition of thyroid hormone release, a process stimulated by thyrotropin and mediated by cyclic adenosine monophosphate (cAMP) within the thyrocyte. Lithium alters the structure of thyroglobulin, thereby affecting protein conformation and function and resulting in a clinical picture of a mild iodotyrosine coupling defect. Finally, lithium reduces hepatic deiodination and clearance of free thyroxine (T4) (5, 6). The latter induces a decrease in the activity of type I 5’-deiodinase enzyme. The inhibition of thyroid hormone secretion results in decreased serum T4 and T3 concentrations, a compensatory increase in pituitary secretion of thyrotropin (TSH) and secretion of a normal amount of thyroid hormone by an enlarged thyroid gland. Thyroid enlargement may also occur as a result of lithium induced alterations in the function of insulin-like growth factor, tyrosine kinase, and/or Wnt/beta-catenin signaling (7). The tendency of the thyroid gland to “escape” the inhibitory effects of lithium is similar to that observed with iodine, although it is less marked. Because of a risk of the thyroid dysfunction in lithium treated patients thyroid parameters should be checked before lithium is instituted and then monitored after 6-12 months. All patients should undergo physical examination and a laboratory evaluation, including serum TSH and antithyroid antibodies (TPO), ultrasound of the thyroid gland is also recommended. If thyroid function is abnormal at the initial evaluation, lithium can still be given if necessary but the thyroid dysfunction should be treated.
Goiter

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Piśmiennictwo
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otrzymano: 2017-11-10
zaakceptowano do druku: 2017-11-30

Adres do korespondencji:
*Helena Jastrzębska
Klinika Endokrynologii Centrum Medyczne Kształcenia Podyplomowego Szpital Bielański
ul. Cegłowska 80, 01-809 Warszawa
tel. +48 (22) 834-31-31
hjastrzebska@cmkp.edu.pl

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