Exp Clin Endocrinol Diabetes 2022; 130(04): 223-228
DOI: 10.1055/a-1543-8826
Article

Patients with Central Hypothyroidism are Less Sufficiently Treated with Levothyroxine than Patients with Primary Hypothyroidism

Barbara Samec
1   Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
,
Gaja Setnikar
1   Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
,
Simona Gaberscek
1   Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
2   Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
,
Tomaz Kocjan
1   Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
3   Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
› Author Affiliations

Abstract

Background Contrary to patients with hypothyroidism after radioiodine (HRI) or after thyroidectomy (HTh), patients with central hypothyroidism (CH) cannot rely on thyrotropin (TSH) level to guide their treatment with L-thyroxine (L-T4). Consequently, they are at constant risk of under- or overtreatment. We aimed to establish the adequacy of L-T4 treatment in patients with CH in our cohort.

Methods Consecutive patients with CH on L-T4 treatment were compared with patients adequately treated for HRI or HTh. Levels of free thyroxine (fT4) and free triiodothyronine (fT3) were evaluated and the fT4/fT3 ratio was calculated.

Results Forty patients with CH, 136 patients with HRI and 43 patients with HTh were included in this study. Patients with HRI were significantly younger than patients with HTh and CH (p<0.001 for both). Levels of fT4 were significantly lower in CH than in adequately treated patients with HRI and HTh (median (range), 15.6 (12.7–21.3), 18.4 (12.2–28.8), and 18.7 (13.8–25.5) pmol/L, respectively, p<0.001 for both comparisons). Levels of fT3 did not differ significantly (p=0.521) between CH, HRI and HTh (median (range), 4.5 (2.7–5.9), 4.3 (3.2–6.2), and 4.4 (2.9–5.5) pmol/L, respectively). Accordingly, the fT4/fT3 ratio was significantly lower in the CH group than in HRI and HTh groups (median (range), 3.7 (2.5–5.2), 4.2 (1.2–7.7), and 4.4 (2.5–6.1), respectively, p<0.001 for both comparisons).

Conclusions Patients with CH have lower fT4 levels and lower fT4/fT3 ratios than patients adequately treated for HRI or HTh. The cause for this difference may be the unreliable TSH levels in patients with CH.



Publication History

Received: 26 March 2021
Received: 03 June 2021

Accepted: 29 June 2021

Article published online:
30 July 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Díez JJ.. Hypothyroidism in patients older than 55 years: an analysis of the etiology and assessment of the effectiveness of therapy. J Gerontol A Biol Sci Med Sci 2002; 57: 315-320 doi:10.1093/gerona/57.5.m315
  • 2 Almandoz JP, Gharib H.. Hypothyroidism: etiology, diagnosis and management. Med Clin North Am 2012; 96: 203-221 doi:10.1016/j.mcna.2012.01.005
  • 3 Lania A, Persani L, Beck-Peccoz P.. Central hypothyroidism. Pituitary 2008; 11: 181-186 doi:10.1007/s11102-008-0122-6
  • 4 Yamada M, Mori M.. Mechanisms related to the pathophysiology and management of central hypothyroidism. Nat Clin Pract Endocrinol Metab 2008; 4: 683-694 doi:10.1038/ncpendmet0995
  • 5 Persani L, Ferretti E, Borgato S. et al. Circulating thyrotropin bioactivity in sporadic central hypothyroidism. J Clin Endocrinol Metab 2000; 85: 3631-3635 doi:10.1210/jcem.85.10.6895
  • 6 Jonklaas J, Bianco AC, Bauer AJ. et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid 2014; 24: 1670-1751 doi:10.1089/thy.2014.0028
  • 7 Gordon MB, Gordon MS.. Variations in adequate levothyroxine replacement therapy in patients with different causes of hypothyroidism. Endocr Pract 1999; 5: 233-238 doi:10.4158/EP.5.5.233
  • 8 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 doi:10.1210/jc.2004-1306
  • 9 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 doi:10.1089/thy.2011.0029
  • 10 Shimon I, Cohen O, Lubetsky A. et al. Thyrotropin suppression by thyroid hormone replacement is correlated with thyroxine level normalization in central hypothyroidism. Thyroid 2002; 12: 823-827 doi:10.1089/105072502760339406
  • 11 Ferretti E, Persani L, Jaffrain-Rea ML. et al. Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism. J Clin Endocrinol Metab 1999; 84: 924-929 doi:10.1210/jcem.84.3.5553
  • 12 Slawik M, Klawitter B, Meiser E. et al. Thyroid hormone replacement for central hypothyroidism: a randomized controlled trial comparing two doses of thyroxine (T4) with a combination of T4 and triiodothyronine. J Clin Endocrinol Metab 2007; 92: 4115-4122 doi:10.1210/jc.2007-0297
  • 13 Iverson JF, Mariash CN.. Optimal free thyroxine levels for thyroid hormone replacement in hypothyroidism. Endocr Pract 2008; 14: 550-555 doi:10.4158/EP.14.5.550
  • 14 Persani L, Cangiano B, Bonomi M.. The diagnosis and management of central hypothyroidism in 2018. Endocr Connect 2019; 8: R44-R54 doi:10.1530/EC-18-0515
  • 15 Panicker V, Cluett C, Shields B. et al. A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine. J Clin Endocrinol Metab 2008; 93: 3075-3081 doi:10.1210/jc.2008-0397
  • 16 Grmek J, Gaberšček S, Biček A. at al. Usefulness of free thyroxine to free triiodothyronine ratio for diagnostics of various types of hyperthyroidism. Zdrav Vestn 2015; 84: 366-372
  • 17 Sesmilo G, Simó O, Choque L. et al. Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism. Endocrinol Nutr 2011; 58: 9-15 doi:10.1016/j.endonu.2010.09.006
  • 18 Klose M, Marina D, Hartoft-Nielsen ML. et al. Central hypothyroidism and its replacement have a significant influence on cardiovascular risk factors in adult hypopituitary patients. J Clin Endocrinol Metab 2013; 98: 3802-3810 doi:10.1210/jc.2013-1610
  • 19 Carrozza V, Csako G, Yanovski JA. et al. Levothyroxine replacement therapy in central hypothyroidism: a practice report. Pharmacotherapy 1999; 19: 349-355 doi:10.1592/phco.19.4.349.30940
  • 20 Koulouri O, Auldin MA, Agarwal R. et al. Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine. Clin Endocrinol (Oxf) 2011; 74: 744-749 doi:10.1111/j.1365-2265.2011.03984.x
  • 21 Agha A, Walker D, Perry L. et al. Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitary patients. Clin Endocrinol (Oxf) 2007; 66: 72-77 doi:10.1111/j.1365-2265.2006.02688.x
  • 22 Alexopoulou O, Beguin C, Nayer PD. et al. Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients. Eur J Endocrinol 2004; 150: 1-8 doi:10.1530/eje.0.1500001
  • 23 Persani L, Brabant G, Dattani M. et al. 2018 European Thyroid Association (ETA) guidelines on the diagnosis and management of central hypothyroidism. Eur Thyroid J 2018; 7: 225-237 doi:10.1159/000491388
  • 24 Maia AL, Kim BW, Huang SA. et al. Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. J Clin Invest 2005; 115: 2524-2533 doi:10.1172/JCI25083
  • 25 Samuels MH.. Effects of variation in physiological cortisol levels on thyrotropin secretion in subjects with adrenal insufficiency: a clinical research center study. J Clin Endocrinol Metab 2000; 85: 1388-1393 doi:10.1210/jcem.85.4.6540
  • 26 Kirchengast S.. Gender differences in body composition from childhood to old age: an evolutionary point of view. J Life Sci 2010; 2: 1-10 doi:10.1080/09751270.2010.11885146