Abstract
Background and objective: Lithium, widely used in the prophylaxis of psychiatric patients with bipolar affective disorders, is well known to induce thyroid alterations. However, a possible metabolic linkage between blood thyroxine levels and its regulatory function on erythrocyte glutathione concentration has not yet been evaluated in lithium-treated patients. The aim of this study was to assess the antioxidative capacity of erythrocytes in lithium-induced hypothyroidism before and after thyroxine replacement.
Patients and methods: Thyroid ultrasound with clinical and laboratory evaluation of thyroid function and thyroid-stimulating hormone assay were performed prior to and at 6-month intervals during lithium prophylaxis in 76 patients with bipolar affective disorders. The daily lithium dosage was adjusted to 600–1200mg and the mean duration of treatment was 2.2 ± 0.4 years. Final assessment revealed that 12 patients had evidence of primary hypothyroidism, and these were assigned as the test group. Lithium prophylaxis was supplemented with thyroxine at a dosage of 100 mg/day within 6 months after thyroid dysfunction was diagnosed. Red blood cell superoxide dismutase activities and the glutathione contents were measured before and after thyroxine replacement. In order to assess the effect of long-term lithium administration on red blood cell glutathione and superoxide dismutase levels, 12 patients who had not developed hypothyroidism during the follow-up period were selected for the lithium-treated euthyroid group. Mann Whitney U-test and Wilcoxon rank sum W-test were used for comparison of data.
Results: A comparison of the lithium-treated test group with healthy volunteers and their own values after thyroxine replacement revealed a significant decrease in red blood cell glutathione concentrations (p = 0.000) in the hypothyroid state. However, no clinically significant changes were observed in red blood cell superoxide dismutase activities of the test group. A statistical survey also demonstrated that there was no significant difference in the thyroid-stimulating hormone values as well as the red blood cell glutathione contents or superoxide dismutase activities between healthy controls and lithium-treated euthyroid subjects.
Conclusions: It is most likely that lithium primarily inhibited hormone production in the thyroid and that this led to a compensatory increase in thyroid-stimulating hormone secretion with a significant decrease in the red blood cell glutathione content. While the red blood cell glutathione content of hypothyroid patients was reduced to 40% of the post-thyroxine level, unchanged superoxide dismutase activity might render the erythrocytes vulnerable to oxidative stress and ultimately haemolysis. Thyroxine replacement during lithium prophylaxis of psychiatric patients is advisable in order to prevent subclinical hypothyroidism and related defects of erythrocyte antioxidant capacity.
Similar content being viewed by others
Notes
The use of trade names is for product identification purposes only and does not imply endorsement.
References
Johnston AM, Eagles JM. Lithium-associated clinical hypothyroidism: prevalence and risk factors. Br J Psychiatry 1999 Oct; 175: 336–9
Perrild H, Hegedus L, Baastrup PC, et al. Thyroid function and ultrasonically determined thyroid size in patients receiving long-term lithium treatment. Am J Psychiatry 1990 Nov; 147 (11): 1518–21
Kleiner J, Altshuler L, Hendrick V, et al. Lithium-induced hypothyroidism: review of the literature and guidelines for treatment. J Clin Psychiatry 1999 Apr; 60 (4): 249–55
Lombardi G, Panza N, Biondi B, et al. Effects of lithium treatment on hypothalamic-pituitary-thyroid axis: a longitudinal study. J Endocrinol Invest 1993 Apr; 16 (4): 259–63
Temple R, Berman M, Robbins J, et al. The use of lithium in the treatment of thyrotoxicosis. J Clin Invest 1972 Oct; 51: 2746–56
Schou M, Amdisen A, Jensen SE, et al. Occurrence of goitre during lithium treatment, BMJ 1968 Sep; 3: 710–3
Lee S, Chow CC, Wing YK, et al. Thyroid function and psychiatric morbidity in patients with manic disorder receiving lithium therapy. J Clin Psychopharmacol 2000 Apr; 20 (2): 204–9
Tellian FF, Rueda-Vasquez E. Effect of serum lithium levels on thyrotropin levels, South Med J 1993 Oct; 86 (10): 1182–3
Terao T, Oga T, Nozaki S, et al. Possible inhibitory effect of lithium on peripheral conversion of thyroxine to triiodothyronine: a prospective study. Int Clin Psychopharmacol 1995 Jan; 10 (2): 103–5
Smigan L, Wahlin A, Jacobsson L, et al. Lithium therapy and thyroid function tests: a prospective study. Neuropsychobiology 1984; 11 (1): 39–43
Bschor T, Bauer M. Thyroid gland function in lithium treatment. Nervenarzt 1998 Mar; 69 (3): 189–95
Nehal M, Baquer NZ. Changes in hexokinase and glucose-6-phosphate dehydrogenase in red cells during hypo and hyperthyroidism. Biochem Int 1989 Jul; 19 (1): 193–9
Dada OA, Abugo O, Ogunmola GB. Thyroid hormones and reactivities of genetic variants of human erythrocytic glucose-6-phosphate dehydrogenase Enzyme 1983; 30 (4): 217–22
Jacob HS, Jandl JH. Effects of sulfhydryl inhibition on red blood cells. III: Glutathione in the regulation of the hexose monophosphate pathway. J Biol Chem 1966 Sep; 241 (18): 4243–50
Nassi P, Liguri G, Nediani C, et al. Increased acylphosphatase levels in erythrocytes from hyperthyroid patients. Clin Chim Acta 1989 Aug; 183 (3): 351–8
Vuopio P, Viherkoski M, Nikkila E, et al. The content of reduced glutathione (GSH) in the red blood cells in hypo- and hyperthyroidism. Ann Clin Res 1970; 2: 184–6
Peterson S, Sanga A, Eklof H, et al. Classification of thyroid size by palpation and ultrasonography in field surveys. Lancet 2000 Jan; 355 (9198): 106–10
Knudsen N, Bols B, Bulow I, et al. Validation of ultrasonography of the thyroid gland for epidemiological purposes. Thyroid 1999 Nov; 9 (11): 1069–74
Berghout A, Wiersinga WM, Smits NJ, et al. The value of thyroid volume measured by ultrasonography in the diagnosis of goiter. Clin Endocrinol 1988 Apr; 28 (4): 409–14
Heikkila RE, Cabbat FS. A sensitive assay for superoxide dismutase based on the autooxidation of 6-hydroxy dopamine. Anal Biochem 1976; 75: 356–62
Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963 May; 61 (5): 882–8
Woober KA. Subclinical thyroid dysfunction. Arch Intern Med 1997 May; 157 (10): 1065–8
Smith TJ, Davis FB, Davis PJ. Stereochemical requirements for the modulation by retinoic acid of thyroid hormone activation of Ca (2+)-ATPase and binding at the human erythrocyte membrane. Biochem J 1992 Jun; 284 (Pt 2): 583–7
Hennemann G, Docter R, Friesema EC, et al. Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability. Endocr Rev 2001 Aug; 22 (4): 451–76
Aliciguzel Y, Ozdem SN, Ozdem SS, et al. Erythrocyte, plasma and serum antioxidant activities in untreated toxic multinodular goiter patients. Free Radic Biol Med 2001 Mar, 70
Asayama K, Dobashi K, Hayashibe H, et al. Lipid peroxidation and free radical scavengers in thyroid dysfunction in the rat: a possible mechanism of injury to heart and skeletal muscle in hyperthyroidism. Endocrinology 1987 Dec; 121 (6): 2112–8
Chattopadhyay S, Zaidi G, Das K, et al. Effects of hypothyroidism induced by 6-n-propylthiouracil and its reversal by T3 on rat heart superoxide dismutase, catalase and lipid peroxidation. Indian J Exp Biol 2003 Aug; 41 (8): 846–9
Acknowledgements
This study was supported by grant from the Gazi University Research Project Fund. The authors have no potential conflicts of interest that are directly relevant to the contents of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Engin, A., Altan, N. & Isik, E. Erythrocyte Glutathione Levels in Lithium-Induced Hypothyroidism. Drugs in R D 6, 35–40 (2005). https://doi.org/10.2165/00126839-200506010-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00126839-200506010-00004