Endocrinol Metab.  2024 Aug;39(4):615-621. 10.3803/EnM.2023.1896.

Adequate Dose of Levothyroxine for Thyroid-Stimulating Hormone Suppression after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer

• Ryu HJ
• Choi MS
• Park H
• Kim TH
• Chung JH
• Park SY
• Kim SW

• KMID: 2558945
• DOI: http://doi.org/10.3803/EnM.2023.1896

Abstract

Background
The adequate dose of levothyroxine (LT4) for patients who have undergone total thyroidectomy (TT) for differentiated thyroid cancer (DTC) is uncertain. We evaluated the LT4 dose required to achieve mild thyroid-stimulating hormone (TSH) suppression in DTC patients after TT.
Methods
The electronic medical records of patients who underwent TT for DTC and received mild TSH suppression therapy were reviewed. Linear regression analysis was performed to evaluate the association between LT4 dose (μg/kg) and an ordinal group divided by body mass index (BMI). We also evaluated the trend in LT4 doses among groups divided by BMI and age.
Results
In total, 123 patients achieved mild TSH suppression (0.1 to 0.5 mIU/L). The BMI variable was divided into three categories: <23 kg/m² (n=46), ≥23 and <25 kg/m² (n=30), and ≥25 kg/m² (n=47). In the linear regression analysis, BMI was negatively associated with the LT4 dose after adjusting for age and sex (P<0.001). The LT4 doses required to achieve mild TSH suppression based on the BMI categories were 1.86, 1.71, and 1.71 μg/kg, respectively (P for trend <0.001). Further analysis with groups divided by age and BMI revealed that a higher BMI was related to a lower LT4 dose, especially in younger patients aged 20 to 39 (P for trend=0.011).
Conclusion
The study results suggest an appropriate LT4 dose for mild TSH suppression after TT based on body weight in patients with DTC. Considering body weight, BMI, and age in estimating LT4 doses might help to achieve the target TSH level promptly.

Keyword

Levothyroxine; Body mass index; Thyroid-stimulating hormone suppression; Thyroid neoplasms

Figure

• 

  Fig. 1. Flowchart for the inclusion and exclusion of study subjects. EMR, electronic medical record; BMI, body mass index; TSH, thyroid-stimulating hormone.

• 

  Fig. 2. Scatter plots and Pearson correlation coefficients (r) for body mass index (BMI) and levothyroxine (LT4) dose in differentiated thyroid cancer patients after total thyroidectomy. (A) Correlation between BMI and daily LT4 dose (µg/day). (B) Correlation between BMI and body weight-based LT4 dose (µg/kg/day).

• 

Reference

1. Sherman SI. Thyroid carcinoma. Lancet. 2003; 361:501–11.

2. Carayon P, Thomas-Morvan C, Castanas E, Tubiana M. Human thyroid cancer: membrane thyrotropin binding and adenylate cyclase activity. J Clin Endocrinol Metab. 1980; 51:915–20.

3. Cooper DS, Specker B, Ho M, Sperling M, Ladenson PW, Ross DS, et al. Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative Registry. Thyroid. 1998; 8:737–44.

4. Fish LH, Schwartz HL, Cavanaugh J, Steffes MW, Bantle JP, Oppenheimer JH. Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism: role of triiodothyronine in pituitary feedback in humans. N Engl J Med. 1987; 316:764–70.

5. Burmeister LA, Goumaz MO, Mariash CN, Oppenheimer JH. Levothyroxine dose requirements for thyrotropin suppression in the treatment of differentiated thyroid cancer. J Clin Endocrinol Metab. 1992; 75:344–50.

6. Biondi B, Cooper DS. Benefits of thyrotropin suppression versus the risks of adverse effects in differentiated thyroid cancer. Thyroid. 2010; 20:135–46.

7. Wang LY, Smith AW, Palmer FL, Tuttle RM, Mahrous A, Nixon IJ, et al. Thyrotropin suppression increases the risk of osteoporosis without decreasing recurrence in ATA low- and intermediate-risk patients with differentiated thyroid carcinoma. Thyroid. 2015; 25:300–7.

8. Grani G, Ramundo V, Verrienti A, Sponziello M, Durante C. Thyroid hormone therapy in differentiated thyroid cancer. Endocrine. 2019; 66:43–50.

9. Ozdemir S, Ozis ES, Gulpinar K, Aydin TH, Suzen B, Korkmaz A. The effects of levothyroxine substitution on body composition and body mass after total thyroidectomy for benign nodular goiter. Endocr Regul. 2010; 44:147–53.

10. Mistry D, Atkin S, Atkinson H, Gunasekaran S, Sylvester D, Rigby AS, et al. Predicting thyroxine requirements following total thyroidectomy. Clin Endocrinol (Oxf). 2011; 74:384–7.

11. Ojomo KA, Schneider DF, Reiher AE, Lai N, Schaefer S, Chen H, et al. Using body mass index to predict optimal thyroid dosing after thyroidectomy. J Am Coll Surg. 2013; 216:454–60.

12. Papoian V, Ylli D, Felger EA, Wartofsky L, Rosen JE. Evaluation of thyroid hormone replacement dosing in overweight and obese patients after a thyroidectomy. Thyroid. 2019; 29:1558–62.

13. Seo MH, Lee WY, Kim SS, Kang JH, Kang JH, Kim KK, et al. 2018 Korean Society for the Study of Obesity guideline for the management of obesity in Korea. J Obes Metab Syndr. 2019; 28:40–5.

14. Roos A, Linn-Rasker SP, van Domburg RT, Tijssen JP, Berghout A. The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, doubleblind trial. Arch Intern Med. 2005; 165:1714–20.

15. Di Donna V, Santoro MG, de Waure C, Ricciato MP, Paragliola RM, Pontecorvi A, et al. A new strategy to estimate levothyroxine requirement after total thyroidectomy for benign thyroid disease. Thyroid. 2014; 24:1759–64.

16. Al-Dhahri SF, Al-Angari SS, Alharbi J, AlEssa M. Optimal levothyroxine dose in post-total thyroidectomy patients: a prediction model for initial dose titration. Eur Arch Otorhinolaryngol. 2019; 276:2559–64.

17. Jin J, Allemang MT, McHenry CR. Levothyroxine replacement dosage determination after thyroidectomy. Am J Surg. 2013; 205:360–4.

18. Jonklaas J. Sex and age differences in levothyroxine dosage requirement. Endocr Pract. 2010; 16:71–9.

19. Devdhar M, Drooger R, Pehlivanova M, Singh G, Jonklaas J. Levothyroxine replacement doses are affected by gender and weight, but not age. Thyroid. 2011; 21:821–7.

20. Santini F, Pinchera A, Marsili A, Ceccarini G, Castagna MG, Valeriano R, et al. Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases. J Clin Endocrinol Metab. 2005; 90:124–7.

21. Zurlo F, Larson K, Bogardus C, Ravussin E. Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest. 1990; 86:1423–7.

22. Piers LS, Soares MJ, McCormack LM, O’Dea K. Is there evidence for an age-related reduction in metabolic rate? J Appl Physiol (1985). 1998; 85:2196–204.

23. Tzankoff SP, Norris AH. Effect of muscle mass decrease on age-related BMR changes. J Appl Physiol Respir Environ Exerc Physiol. 1977; 43:1001–6.