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Horm Metab Res 2021; 53(04): 264-271
DOI: 10.1055/a-1336-3502
Endocrine Care

Development and Prospective Validation of the Levothyroxine Dose Prediction Model in Primary Hypothyroidism

Rekha Singh 
1   Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, Bhopal, India
2   Nizam’s Institute of Medical Sciences, Hyderabad, India
,
Ashwani Tandon
2   Nizam’s Institute of Medical Sciences, Hyderabad, India
3   Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Bhopal India
,
Ashish Awasthi
4   Indian Institute of Public Health, Gandhinagar, India
5   Centre for Chronic Conditions and Injuries, Public Health Foundation of India, Gurugram, India
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Abstract

Multiple visits are needed to achieve euthyroidism on levothyroxine in newly detected primary hypothyroidism. We aimed to develop a levothyroxine dose estimation algorithm for primary hypothyroidism. Adults with newly diagnosed hypothyroidism were enrolled prospectively, first in the training cohort, followed by the validation cohort separated by time and person. We developed a predictive algorithm from Training Cohort and validated the model in Validation Cohort. Training Cohort: In this cohort, 358 subjects (259 women and 99 men) were enrolled. The median duration needed to achieve euthyroidism was 4±0.5 months. The mean levothyroxine daily dose was 60.5±34.1 μg. Data of euthyroid subjects within 6 months of treatment initiation and age range 18–65 years were used for algorithm development. In the multivariable linear regression algorithm, pretreatment serum thyrotropin level, and sex formed the best-fit predictive model (adjusted R2 0.73, p-value <0.001). Validation Cohort: Eighty-four subjects (61 women and 23 men) were enrolled and started on an estimated levothyroxine dose derived from the developed prediction model. On the first follow-up on treatment, 34/50 participants achieved euthyroidism (68%) at 1.5 months. In conclusion, the proposed prediction model for levothyroxine dose estimation effectively achieves early euthyroidism in two-third subjects in the age range of 18–65 years.

Key words

levothyroxine - hypothyroidism - thyroid stimulating hormone

Supplementary Material



Publikationsverlauf

Eingereicht: 26. September 2020

Angenommen nach Revision: 07. Dezember 2020

Artikel online veröffentlicht:
13. Januar 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Garber JR, Cobin RH, Gharib H. et al. American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012; 18: 988-1028
    CrossrefPubMedSuche in Google Scholar
  • 2 Balsa AM, Ferreira AR, Alves M. et al. Takotsubo cardiomyopathy associated with levothyroxine over-replacement. Eur Endocrinol 2017; 13: 30-32
    CrossrefPubMedSuche in Google Scholar
  • 3 Kim MK, Yun KJ, Kim MH. et al. The effects of thyrotropin-suppressing therapy on bone metabolism in patients with well-differentiated thyroid carcinoma. Bone 2015; 71: 101-105
    CrossrefPubMedSuche in Google Scholar
  • 4 Jonklaas J, Bianco AC, Bauer AJ. et al. American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism: Prepared by the American Thyroid Association Task Force on thyroid hormone replacement. Thyroid 2014; 24: 1670-16751
    CrossrefPubMedSuche in Google Scholar
  • 5 Gordon MB, Gordon MS. Variations in adequate levothyroxine replacement therapy in patients with different causes of hypothyroidism. Endocr Pract 1999; 5: 233-238
    CrossrefPubMedSuche in Google Scholar
  • 6 Loh JA, Wartofsky L, Jonklaas J. et al. The magnitude of increased levothyroxine requirements in hypothyroid pregnant women depends upon the etiology of the hypothyroidism. Thyroid 2009; 19: 269-275
    CrossrefPubMedSuche in Google Scholar
  • 7 Sawin CT, Herman T, Molitch ME. et al. Aging and the thyroid. Decreased requirement for thyroid hormone in older hypothyroid patients. Am J Med 1983; 75: 206-209
    PubMedSuche in Google Scholar
  • 8 Davis FB, LaMantia RS, Spaulding SW. et al. Estimation of a physiologic replacement dose of levothyroxine in elderly patients with hypothyroidism. Arch Intern Med 1984; 144: 1752-1754
    CrossrefPubMedSuche in Google Scholar
  • 9 Rosenbaum RL, Barzel US. Levothyroxine replacement dose for primary hypothyroidism decreases with age. Ann Intern Med 1982; 96: 53-55
    CrossrefPubMedSuche in Google Scholar
  • 10 Devdhar M, Drooger R, Pehlivanova M. et al. Levothyroxine replacement doses are affected by gender and weight, but not age. Thyroid 2011; 21: 821-827
    CrossrefPubMedSuche in Google Scholar
  • 11 Jonklaas J. Sex and age differences in levothyroxine dosage requirement. Endocr Pract 2010; 16: 71-79
    CrossrefPubMedSuche in Google Scholar
  • 12 Santini F, Pinchera A, Marsili A. et al. Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases. J Clin Endocrinol Metab 2005; 90: 124-127
    CrossrefPubMedSuche in Google Scholar
  • 13 Cunningham JJ, Barzel US. Lean body mass is a predictor of the daily requirement for thyroid hormone in older men and women. J Am Geriatr Soc 1984; 32: 204-207
    CrossrefPubMedSuche in Google Scholar
  • 14 Olubowale O, Chadwick DR. Optimization of thyroxine replacement therapy after total or near-total thyroidectomy for benign thyroid disease. Br J Surg 2006; 93: 57-60
    CrossrefPubMedSuche in Google Scholar
  • 15 Ojomo KA, Schneider DF, Reiher AE. et al. Using body mass index to predict optimal thyroid dosing after thyroidectomy. J Am Coll Surg 2013; 216: 454-460
    CrossrefPubMedSuche in Google Scholar
  • 16 Baehr KM, Lyden E, Treude K. et al. Levothyroxine dose following thyroidectomy is affected by more than just body weight. Laryngoscope 2012; 122: 834-838
    CrossrefPubMedSuche in Google Scholar
  • 17 Loh JA, Wartofsky L, Jonklaas J. et al. The magnitude of increased levothyroxine requirements in hypothyroid pregnant women depends upon the etiology of the hypothyroidism. Thyroid 2009; 19: 269-275
    CrossrefPubMedSuche in Google Scholar
  • 18 Arafah BM. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med 2001; 344: 1743-1749
    CrossrefPubMedSuche in Google Scholar
  • 19 Huber G, Staub JJ, Meier C. et al. Prospective study of the spontaneous course of subclinical hypothyroidism: Prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab 2002; 87: 3221-3226
    CrossrefPubMedSuche in Google Scholar
  • 20 Vanderpump MP, Tunbridge WM, French JM. et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995; 43: 55-68
    CrossrefPubMedSuche in Google Scholar
  • 21 Huber G, Staub JJ, Meier C. et al. Prospective study of the spontaneous course of subclinical hypothyroidism: Prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab 2002; 87: 3221-3226
    CrossrefPubMedSuche in Google Scholar
  • 22 Hollowell JG, Staehling NW, Flanders WD. 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: 489-499
    CrossrefPubMedSuche in Google Scholar
  • 23 de Vries L, Bulvik S, Phillip M. Chronic autoimmune thyroiditis in children and adolescents: At presentation and during long-term follow-up. Arch Dis Child 2009; 94: 33-37
    CrossrefPubMedSuche in Google Scholar
  • 24 Pecina J, Garrison GM, Bernard ME. Levothyroxine dosage is associated with stability of thyroid-stimulating hormone values. Am J Med 2014; 127: 240-245
    CrossrefPubMedSuche in Google Scholar
  • 25 Singh R. Does one size fit everyone? Replacement dose of levothyroxine in long-standing primary hypothyroidism in adults. Indian J Endocrinol Metab 2017; 21: 404-409
    CrossrefPubMedSuche in Google Scholar
  • 26 Kabadi UM. Optimal daily levothyroxine dose in primary hypothyroidism. Its relation to pretreatment thyroid hormone indexes. Arch Intern Med 1989; 149: 2209-2212
    CrossrefPubMedSuche in Google Scholar
  • 27 Kabadi UM, Jackson T. Serum thyrotropin in primary hypothyroidism. A possible predictor of optimal daily levothyroxine dose in primary hypothyroidism. Arch Intern Med 1995; 22: 1046-1048
    CrossrefPubMedSuche in Google Scholar
  • 28 Kabadi UM, Kabadi MM. Serum thyrotropin in primary hypothyroidism: A reliable and accurate predictor of optimal daily levothyroxine dose. Endocr Pract 2001; 7: 16-18
    CrossrefPubMedSuche in Google Scholar
  • 29 Mistry D, Atkin S, Atkinson H. et al. Predicting thyroxine requirements following total thyroidectomy. Clin Endocrinol (Oxf) 2011; 74: 384-387
    CrossrefPubMedSuche in Google Scholar
  • 30 Di Donna V, Santoro MG, de Waure C. et al. A new strategy to estimate levothyroxine requirement after total thyroidectomy for benign thyroid disease. Thyroid 2014; 24: 1759-1764
    CrossrefPubMedSuche in Google Scholar
  • 31 Del Duca SC, Santaguida MG, Brusca N. et al. Individually-tailored thyroxine requirement in the same patients before and after thyroidectomy: A longitudinal study. Eur J Endocrinol 2015; 173: 351-357
    CrossrefPubMedSuche in Google Scholar
  • 32 Teixeira PF, Reuters VS, Ferreira MM. et al. treatment of subclinical hypothyroidism reduces atherogenic lipid levels in a placebo-controlled double-blind clinical trial. Horm Metab Res 2008; 40: 50-55
    Thieme ConnectPubMedSuche in Google Scholar
  • 33 Garber JR, Cobin RH, Gharib H. et al. Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012; 18: 988-1028
    CrossrefPubMedSuche in Google Scholar
  • 34 Somwaru LL, Rariy CM, Arnold AM. et al. The natural history of subclinical hypothyroidism in the elderly: The cardiovascular health study. J Clin Endocrinol Metab 2012; 97: 1962-1969
    CrossrefPubMedSuche in Google Scholar
  • 35 Walker JN. et al. A thyroxine absorption test followed by weekly thyroxine administration: A method to assess non-adherence to treatment. Eur J Endocrinol 2013; 168: 913-917
    CrossrefPubMedSuche in Google Scholar
  • 36 Hayashi Y, Tamai H, Fukata S. et al. A long term clinical, immunological, and histological follow-up study of patients with goitrous chronic lymphocytic thyroiditis. J Clin Endocrinol Metab 1985; 61: 1172-1178
    CrossrefPubMedSuche in Google Scholar
  • 37 Duntas LH, Jonklaas J. Levothyroxine dose adjustment to optimise therapy throughout a patient’s lifetime. Adv Ther 2019; 36: 30-46
    CrossrefPubMedSuche in Google Scholar
  • 38 Unnikrishnan AG, Kalra S, Sahay RK. et al. Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India. Indian J Endocrinol Metab 2013; 17: 647-652
    CrossrefPubMedSuche in Google Scholar
  • 39 Ernst FR, Barr P, Elmor R. et al. The economic impact of levothyroxine dose adjustments: The Control HE Study. Clin Drug Investig 2017; 37: 71-83
    CrossrefPubMedSuche in Google Scholar