Comparing the effects of alternate day and daily thyroxine replacement therapy in subclinical hypothyroidism

Sanjay Mishra; Arjit Gupta

doi:10.18203/2320-6012.ijrms20221178

Authors

Sanjay Mishra Department of Pathology, King George’s Medical University, Lucknow, Uttar Pradesh, India
Arjit Gupta Department of Medicine, Vivekanand Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

DOI:

https://doi.org/10.18203/2320-6012.ijrms20221178

Keywords:

Subclinical hypothyroidism, TSH, T4, Thyroxine

Abstract

Background: Subclinical hypothyroidism (SCH) is defined as serum thyroid-stimulating hormone (TSH) level above upper limit of normal despite normal levels of serum free thyroxine. According to recommendations, L-thyroxine treatment for hormone replacement therapy should be continued on daily basis. However, some trials have challenged daily regimen for management of hypothyroidism and have suggested dosage scheduling at weekly, twice-a-week or alternate day as possible alternatives having similar effect as for daily regimen.

Methods: Study was prospective randomized cross-over intervention design. Thyroid functions (T3, T4 and TSH) were measured using third generation non-isotopic immunochemiluminescence method using standard protocol. 120 patients with clinically established hypothyroidism were enrolled in study.

Results: Difference in mean TSH levels of group I and group II were not found to be statistically significant at baseline (8.247±2.288 mIU/ml versus 8.210±2.650; p=0.935), at 6 weeks (2.337±1.792 mIU/ml versus 2.843±2.410 mIU/ml; p=0.195) and at 12 weeks (2.508±1.180 mIU/ml versus 2.831±1.200 mIU/ml; p=0.191). Difference in mean T3 levels of group I and group II were not found to be statistically significant at baseline (1.118±0.199 ng/dl versus 1.184±0.187 ng/dl; p=0.061), at 6 weeks (1.266±0.295 ng/dl versus 1.196±0.289 ng/dl; p=0.192) and at 12 weeks (1.121±0.211 ng/dl versus 1.179±0.203 ng/dl; p=0.174). Difference in mean T4 levels group I and group II were not found to be statistically significant at baseline (8.422±2.054 µg/dl versus 7.899±2.333 µg/dl; p=0.196), at 6 weeks (8.852±2.836 µg/dl versus 8.533±2.672 µg/dl; p=0.527) and at 12 weeks (8.159±2.235 µg/dl versus 7.990±2.463 µg/dl; p=0.728).

Conclusions: The findings of present study show that alternate day L-thyroxine is a viable solution for the management of SCH.

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References

Cooper DS. Subclinical hypothyroidism. N Engl J Med. 2001;345(4):260-5.

Hollowell JG, Staehling NW, Flanders WD. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87(2):489-99.

Karmisholt J, Andersen S, Laurberg P. Variation in thyroid function tests in patients with stable untreated subclinical hypothyroidism. Thyroid. 2008;18(3):303-8.

Fatourechi V. Subclinical Hypothyroidism: An Update for Primary Care Physicians. Mayo Clinic Proceedings. 2009;84(1):65-71.

Biondi B, Fazio S, Palmieri EA, Carella C, Panza N, Cittadini A et al. Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism. The Journal of Clinical Endocrinology & Metabolism. 1999;84(6):2064-7.

Monzani F, Di Bello V, Caraccio N, Bertini A, Giorgi D, Giusti C et al. Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol Metab. 2001;86(3):1110-5.

Virtanen VK, Saha HH, Groundstroem KW, Salmi J, Pasternack AI. Thyroid hormone substitution therapy rapidly enhances left-ventricular diastolic function in hypothyroid patients. Cardiol. 2001;96(2):59-64.

Brenta G, Mutti LA, Schnitman M, Fretes O, Perrone A, Matute ML. Assessment of left ventricular diastolic function by radionuclide ventriculography at rest and exercise in subclinical hypothyroidism, and its response to L-thyroxine therapy. The American journal of cardiology. 2003;91(11):1327-30.

Yazici M, Gorgulu S, Sertbas Y, Erbilen E, Albayrak S, Yildiz O et al. Effects of thyroxin therapy on cardiac function in patients with subclinical hypothyroidism: index of myocardial performance in the evaluation of left ventricular function. International journal of cardiology. 2004;95(2):135-43.

Surks MI, Ortiz E, Daniels GH. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;29:228-38.

Razvi S, Ingoe L, Keeka G. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab. 2007;92:1715.

Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebocontrolled study. J Clin Endocrinol Metab. 2002;87:1533.

Iqbal A, Jorde R, Figenschau Y. Serum lipid levels in relation to serum thyroidstimulating hormone and the effect of thyroxine treatment on serum lipid levels in subjects with subclinical hypothyroidism: the Tromsø Study. J Intern Med. 2006;260:53.

Mikhail GS, Alshammari SM, Alenezi MY. Increased atherogenic lowdensity lipoprotein cholesterol in untreated subclinical hypothyroidism. Endocr Pract. 2008;14:570.

Pearce SHS, Brabant G, Duntas LH. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thy J. 2013;2(4):215-28.

Taylor J, Williams BO, Frater J, Stott DJ, Connell J. Twice-weekly dosing for thyroxine replacement in elderly patients with primary hypothyroidism. J Int Med Res. 1994;22(5):273-7.

Grebe SKG, Cooke RR, Ford HC. Treatment of Hypothyroidism with Once Weekly Thyroxin. J Clin Endocrinol Metab. 1997;82:870-5.

Dayal D, Saini L, Attri SV. Daily Versus Alternate Day Thyroxine Therapy to Maintain Euthyroidism in Children With Congenital Hypothyroidism. Int J Endocrinol Metab. 2013;11(4):e9499:1-5.

Vermeire E, Hearnshaw H, Van Royen P, Denekens J. Patient adherence to treatment: three decades of research. A comprehensive review. J Clin Pharm Ther. 2001;26(5):331-42.

Snedecor GW, Cochran WG. Statistical Methods. 8th edn, 1989.

Unnikrishnan AG, Menon UV. Thyroid disorders in India: An epidemiological perspective. Ind J Endocrinol Metab. 2011;15(2):S78-81.

Roberts CG, Ladenson PW. Hypothyroidism. Lancet. 2004;363:793-803.

Bondi B, Klein IW. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine. 2004;24:1-13.

Bhimte B, Vamne A, Agrawal BK, Thanna RC. A Cross-Sectional Study of Prevalence of Hypothyroidism in Adult Population of Bhopal. Int J Health Sc Res. 2015;5(9):268-72.

Dhadhal R, Mulchandani V, Parakh R, Joshee A, Mangukiya K, Bathwar N. A cross sectional study of prevalence of hypothyroidism in adult population of Udaipur district. GJBB. 2015;4(1):103-6.

Vaishnav R, Alam MF. Prevalence and pattern of Hypothyroidism in patients attending the Outpatient department of a tertiary care teaching hospital. Int Arch BioMed Clin Res. 2015;1(1):10-12.

Ichiki T. Thyroid hormone and atherosclerosis. Vascul Pharmacol. 2010;52:151-6.

Steinberg AD. Myxedema and coronary artery disease–a comparative autopsy study. Ann Intern Med. 1968;68:338-444.

Benetti-Pinto CL, Piccolo BVR, Garmes HM, Juliato TCR. Subclinical hypothyroidism in young women with polycystic ovary syndrome: an analysis of clinical, hormonal, and metabolic parameters. Fertil Steril. 2013;99(2):588-92.

Joffe RT, Pearce EN, Hennessey JV, Ryan JJ, Stern RA. Subclinical Hypothyroidism, Mood, and Cognition in the Elderly: A Review. Int J Ger Psych. 2013;28(2):111-8.

Seshadri KG. Subclinical hypothyroidism in children. Indian Journal of Endocrinology and Metabolism. 2012;16(2):S156-8.

Cerbone M, Bravaccio C, Capalbo D. Linear growth and intellectual outcome in children with long-term idiopathic subclinical hypothyroidism. Eur J Endocrinol. 2011;164(4):591-7.

Deshmukh V, Behl A, Iyer V, Joshi H, Dholye JP, Varthakavi PK. Prevalence, clinical and biochemical profile of subclinical hypothyroidism in normal population in Mumbai. Ind J Endocrinol Metab. 2013;17(3):454-9.