A study of subclinical hypothyroidism treated with alternate day fixed dose thyroxine therapy


  • Dharmendra Jhavar Department of Medicine, M. G. M. Medical College and M. Y. Hospital, Indore, Madhya Pradesh, India
  • Mohit Naredi Department of Medicine, M. G. M. Medical College and M. Y. Hospital, Indore, Madhya Pradesh, India




Background: Subclinical hypothyroidism (SCH) is a biochemical diagnosis wherein free T4 is within normal range while serum TSH value >5mIU/L. We aimed to study effects of alternate day fixed dose thyroxine therapy on this subset of patients with a 3month follow up of various clinical and biochemical parameters.

Methods: It was an interventional trial. Fifty consecutive consenting participants with SCH aged 18-45 years were started on alternate day 50µg thyroxine and were observed for 3 months for changes in body mass index, blood pressure, serum cholesterol, serum triglyceride, serum TSH, T3 and T4 levels.

Results: Forty four out of fifty participants had initial TSH levels between 5-10 µU/mL and at the end of 3 months, 58% of these (n=29/44) shown improved thyroid profile as their TSH fell to the target 2-4 µU/mL. Seven participants’ (n=7,14%) turned into iatrogenic hyperthyroidism as their T3 and T4 levels rose above normal and TSH levels fell to below 1 µU/mL. Another 7 participants (n=7,14%) showed increased T3 and T4 levels (n=3, n=4 respectively) above normal range with TSH still within normal range. One patient (n=1,2%) had persistently raised TSH levels. Out of 6 participants (n=6,12%) who had initial TSH>10 µU/mL, 3 participants achieved normal TSH with alternate day therapy (n=3,6%) while 3 participants did not achieve euthyroid status (n=3,6%). Authors observed decrease in cholesterol levels (initial=183.18±52.96 mg/dL, final=170.04±42.13 mg/dL, p<0.05). It lead to reduction in weight (initial BMI=24.11±5.69, final=23.33±5.30, p<0.05).

Conclusions: Authors found that treatment of SCH with alternative day thyroxine therapy is effective in normalizing TSH values. Its dose needs to be titrated according to TSH levels to avoid side effects. It decreased cost of therapy resulting in good compliance in noncompliant patients and reduced pill burden helped the patients in adhering to the therapy.


Kalra S, Unnikrishnan AG, Talwar V. The rule of two-thirds in thyroid epidemiology. Ind J Endocrinol Metab. 2016;20(6):744-745.

Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RGJ, Mooijaart SP et al: Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. N Engl J Med, 4/3/2017.

Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:526.

Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA et al. 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; 87:489.

Unnikrishnan AG, Kalra S, Sahay RK, Bantwal G, John M and Tewari N. Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India. Ind J Endocrinol Metab. 2013;17(4):647-52.

Pearce SHS, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J. 2013;2(4):215-28.

Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS et al. Guidelines for the treatment of hypothyroidism: prepared by the American thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670-1751.

Biondi B, Cooper DS; The clinical significance of subclinical thyroid dysfunction. Endocrine Rev. 2008 29:76-131.

Dayal D, Saini L, Attri SV, Singh B, Bhalla AK; Daily versus alternate day thyroxine therapy to maintain euthyroidism in children with congenital hypothyroidism. Int J Endocrinol Metab. 2013 Oct; 11(4):e9499.

Rangan S, Tahrani AA, Macleod AF, Moulik AF. Once weekly thyroxine treatment as a strategy to treat noncompliance. Postgrad Med J. 2007 Oct 1;83(984):e3.

Bornschein A, Paz-Filho G, Graf H, Carvalho GA. Treating primary hypothyroidism with weekly doses of levothyroxine: a randomized, single-blind, crossover study. Arq Bras Endocrinol Metabol. 2012;56(4):250-8.

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.

Knudsen N, Laurberg P, Rasmussen LB, Bülow I, Perrild H, Ovesen L et al. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab. 2005;90:4019.

Monzani F, Caraccio N, Kozàkowà M, Dardano A, Vittone F, Virdis A et al. Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study. J Clin Endocrinol Metab. 2004;89:2099.

Meier C, Staub JJ, Roth CB, Guglielmetti M, Kunz M, Miserez AR et al. TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study). J Clin Endocrinol Metab. 2001;86:4860.

Iqbal A, Jorde R, Figenschau Y. Serum lipid levels in relation to serum thyroid-stimulating 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, Mansour M, Khalil NA. Increased atherogenic low-density lipoprotein cholesterol in untreated subclinical hypothyroidism. Endocr Pract. 2008;14:570.

Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Jolanta U et al. 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.






Original Research Articles