Skip to main content
Log in

In thyroxine-replaced hypothyroid postmenopausal women under simultaneous calcium supplementation, switch to oral liquid or softgel capsule l-thyroxine ensures lower serum TSH levels and favorable effects on blood pressure, total cholesterolemia and glycemia

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

A Correction to this article was published on 28 June 2019

This article has been updated

Abstract

Purpose

In postmenopausal women under L-T4 therapy, which was subsequently accompanied by calcium carbonate (CC) supplementation taken 6–8 h after tablet L-T4, TSH levels were greater than prior to adding CC. Total cholesterolemia [CHOL], fasting glycemia [FG], systolic and diastolic blood pressure [SBP, DBP] were also greater than baseline. Our aim was to explore the effects of either liquid or softgel capsule L-T4, while maintaining CC ingestion 6–8 h, later on TSH levels, CHOL, FG, SBP, and DBP.

Methods

We proposed to 50 hypothyroid postmenopausal women under tablet L-T4 therapy, to switch to either liquid or softgel capsule L-T4 at the same daily dose while maintaining CC ingestion 6–8 h later. Sixteen women accepted [group I; liquid (n = 9), capsule (n = 7)], while 34 continued tablet L-T4 [group II, (n = 34)].

Results

After 3 months, in group I, TSH decreased significantly (1.23 ± 0.49 vs. 1.80 ± 0.37 mU/L, P < 0.01), as did FG (80.7 ± 7.9 vs. 83.4 ± 6.3 mg/dL, P < 0.05); CHOL, SBP, and DBP decreased, though insignificantly. In contrast, in group II, TSH, FG, CHOL, SBP increased insignificantly, and DBP increased borderline significantly (69.7 ± 9 vs. 66.3 ± 6.5, P < 0.10). Compared to baseline (before adding CC), in group I, TSH was significantly lower (P < 0.01) and the other indices similar; in group II, TSH, FG, and SBP were significantly higher (P < 0.05), DBP borderline significantly higher (P < 0.10) and CHOL insignificantly higher. Performance of liquid L-T4 and capsule L-T4 was similar.

Conclusion

Delaying CC ingestion even by 6–8 h after taking tablet L-T4 is not entirely satisfactory, unlike liquid or softgel L-T4.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Change history

  • 28 June 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

References

  1. C.R. Schneyer, Calcium carbonate and reduction of levothyroxine efficacy [letter]. JAMA 279, 750 (1998)

    Article  CAS  PubMed  Google Scholar 

  2. N. Singh, P.N. Singh, J.M. Hershman, Effect of calcium carbonate on the absorption of levothyroxine. JAMA 283, 2822–2825 (2000)

    Article  CAS  PubMed  Google Scholar 

  3. I. Zamfirescu, H.E. Carlson, Absorption of levothyroxine when coadministered with various calcium formulations. Thyroid 21, 483–486 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. S. Benvenga, F. Di Bari, R. Vita, Undertreated hypothyroidism due to calcium or iron supplementation corrected by oral liquid levothyroxine. Endocrine 56, 138–145 (2017)

    Article  CAS  PubMed  Google Scholar 

  5. P. Colucci, C. Seng Yue, M. Ducharme, S. Benvenga, A review of the pharmacokinetics of levothyroxine for the treatment of hypothyroidism. Eur. Endocrinol. 9, 40–47 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  6. S. Benvenga, When thyroid hormone replacement is ineffective? Curr. Opin. Endocrinol. Diabetes Obes. 20, 467–477 (2013)

    Article  CAS  PubMed  Google Scholar 

  7. E. Morini, A. Catalano, A. Lasco, N. Morabito, S. Benvenga, l-thyroxine malabsorption due to calcium carbonate impairs blood pressure, total cholesterolemia, and fasting glycemia. Endocrine (2018). https://doi.org/10.1007/s12020-018-1798-7

  8. J.R. Garber, R.H. Cobin, H. Gharib et al. Clinical practice guidelines for hypothyroidism for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid 22, 1200–1235 (2012)

    Article  CAS  PubMed  Google Scholar 

  9. I.L. Klein, S. Danzi, in Werner and Ingbar’s the Thyroid: a Fundamental and Clinical Text, ed. by L.E Bravermann, D.S Cooper (Wolters Kluver, Lippincott, Willimas & Wilkins, Philadelphia, 2013), p. 575–582

  10. B.O. Asvold, L.J. Vatten, T.I. Nilsen, T. Bjøro, The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study. Eur. J. Endocrinol. 156, 181–186 (2007)

    Article  CAS  Google Scholar 

  11. T.N. Le, F.S. Celi, E.P. Wickham 3rd, Thyrotropin levels are associated with cardiometabolic risk factors in euthyroid adolescents. Thyroid 26, 1441–1449 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. B. Xu, H. Yang, Z. Wang, T. Yang, H. Guo, P. Cheng, W. He, M. Sun, H. Chen, Y. Duan, Elevated thyroid stimulating hormone levels are associated with metabolic syndrome in a Chinese community-based population of euthyroid people aged 40 years and older. J. Biomed. Res. 30, 476–482 (2016)

    PubMed  PubMed Central  Google Scholar 

  13. I.M. Benseñor, A.C. Goulart, C. Molina Mdel, É.J. de Miranda, I.S. Santos, P.A. Lotufo, Thyrotropin levels, insulin resistance, and metabolic syndrome: a cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Metab. Syndr. Relat. Disord. 13, 362–369 (2015)

    Article  CAS  PubMed  Google Scholar 

  14. A. Javed, P.B. Balagopal, A. Vella, P.R. Fischer, F. Piccinini, C. Dalla Man, C. Cobelli, P.D. Giesler, J.M. Laugen, S. Kumar, Association between thyrotropin levels and insulin sensitivity in euthyroid obese adolescents. Thyroid 25, 478–484 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. J. Alam, M.N.-E.-T.M. Mukti, M. Hoque, I. Ali, M. Kamal, S.C. Mallik, S. Choudhury, Cross sectional evaluation of thyroid hormone levels in non-diabetic and diabetic patients in Bangladeshi population. Asian J. Biol. Sci. 6, 228–233 (2013)

    Article  CAS  Google Scholar 

  16. H.T. Park, G.J. Cho, K.H. Ahn, J.H. Shin, S.C. Hong, T. Kim, J.Y. Hur, Y.T. Kim, K.W. Lee, S.H. Kim, Thyroid stimulating hormone is associated with metabolic syndrome in euthyroid postmenopausal women. Maturitas 62, 301–305 (2009)

    Article  CAS  PubMed  Google Scholar 

  17. A. Giandalia, G.T. Russo, E.L. Romeo, A. Alibrandi, P. Villari, A.A. Mirto, G. Armentano, S. Benvenga, D. Cucinotta, Influence of high-normal serum TSH levels on major cardiovascular risk factors and Visceral Adiposity Index in euthyroid type 2 diabetic subjects. Endocrine 47, 152–160 (2014)

    Article  CAS  PubMed  Google Scholar 

  18. J.E. Jun, S.M. Jin, J.H. Jee, J.C. Bae, K.Y. Hur, M.K. Lee, S.W. Kim, J.H. Kim, TSH increment and the risk of incident type 2 diabetes mellitus in euthyroid subjects. Endocrine 55, 944–953 (2017)

    Article  CAS  PubMed  Google Scholar 

  19. V. Velkoska Nakova, B. Krstevska, M. Bosevski, Ch Dimitrovski, V. Serafimoski, Dyslipidaemia and hypertension in patients with subclinical hypothyroidism. Prilozi 30, 93–102 (2009)

    CAS  PubMed  Google Scholar 

  20. Y. Zhang, P. Lu, L. Zhang, X. Xiao, Association between lipids profile and thyroid parameters in euthyroid diabetic subjects: a cross-sectional study. BMC Endocr. Disord. 15, 12 (2015). https://doi.org/10.1186/s12902-015-0008-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. V.L. Langén, T.J. Niiranen, P. Puukka, J. Sundvall, A.M. Jula, V.L. Langén, T.J. Niiranen, P. Puukka, J. Sundvall, A.M. Jula, Association between thyroid-stimulating hormone and blood pressure in adults: an 11-year longitudinal study. Clin. Endocrinol. 84, 741–747 (2016)

    Article  CAS  Google Scholar 

  22. T. Ittermann, D. Tiller, C. Meisinger, C. Agger, M. Nauck, R. Rettig, A. Hofman, T. Jørgensen, A. Linneberg, J.C. Witteman, O.H. Franco, K.H. Greiser, K. Werdan, A. Döring, A. Kluttig, B.H. Stricker, H. Völzke, High serum thyrotropin levels are associated with current but not with incident hypertension. Thyroid 23, 955–963 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Y. Duan, W. Peng, X. Wang, W. Tang, X. Liu, S. Xu, X. Mao, S. Feng, Y. Feng, Y. Qin, K. Xu, C. Liu, C. Liu, Community-based study of the association of subclinical thyroid dysfunction with blood pressure. Endocrine 35, 136–142 (2009)

    Article  CAS  PubMed  Google Scholar 

  24. R. Luboshitzky, A. Aviv, P. Herer, L. Lavie, Risk factors for cardiovascular disease in women with subclinical hypothyroidism. Thyroid 12, 421–425 (2002)

    Article  PubMed  Google Scholar 

  25. D. Liu, F. Jiang, Z. Shan, B. Wang, J. Wang, Y. Lai, Y. Chen, M. Li, H. Liu, C. Li, H. Xue, N. Li, J. Yu, L. Shi, X. Bai, X. Hou, L. Zhu, L. Lu, S. Wang, Q. Xing, W. Teng, A cross-sectional survey of relationship between serum TSH level and blood pressure. J. Hum. Hypertens. 24, 134–138 (2010)

    Article  CAS  PubMed  Google Scholar 

  26. W.X. Jian, J. Jin, L. Qin, W.J. Fang, X.R. Chen, H.B. Chen, Q. Su, H.L. Xing, Relationship between thyroid-stimulating hormone and blood pressure in the middle-aged and elderly population. Singap. Med. J. 54, 401–405 (2013)

    Article  Google Scholar 

  27. L. Petrosyan, Relationship between high normal TSH levels and metabolic syndrome components in type 2 diabetic subjects with euthyroidism. J. Clin. Transl. Endocrinol. 2, 110–113 (2015)

    PubMed  PubMed Central  Google Scholar 

  28. B.O. Asvold, T. Bjøro, T.I. Nilsen, L.J. Vatten, Association between blood pressure and serum thyroid-stimulating hormone concentration within the reference range: a population-based study. J. Clin. Endocrinol. Metab. 92, 841–845 (2007)

    Article  CAS  PubMed  Google Scholar 

  29. A. Iqbal, Y. Figenschau, R. Jorde, Blood pressure in relation to serum thyrotropin: the Tromsø study. J. Hum. Hypertens. 20, 932–936 (2006)

    Article  CAS  PubMed  Google Scholar 

  30. O. Gumieniak, T.S. Perlstein, P.N. Hopkins, N.J. Brown, L.J. Murphey, X. Jeunemaitre, N.K. Hollenberg, G.H. Williams, Thyroid function and blood pressure homeostasis in euthyroid subjects. J. Clin. Endocrinol. Metab. 89, 3455–3461 (2004)

    Article  CAS  PubMed  Google Scholar 

  31. K. Saltiki, P. Voidonikola, K. Stamatelopoulos, E. Mantzou, C. Papamichael, M. Alevizaki, Association of thyroid function with arterial pressure in normotensive and hypertensive euthyroid individuals: a cross-sectional study. Thyroid Res. 1(1), 3 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. A. Tsuda, M. Inaba, M. Ichii, A. Ochi, Y. Ohno, S. Nakatani, S. Yamada, K. Mori, H. Tahara, E. Ishimura, Relationship between serum TSH levels and intrarenal hemodynamic parameters in euthyroid subjects. Eur. J. Endocrinol. 169, 45–50 (2013)

    Article  CAS  PubMed  Google Scholar 

  33. M. Laclaustra, Y. Hurtado-Roca, M. Sendin, M. Leon, M. Ledesma, E. Andres, A. Fernandez-Ortiz, E. Guallar, J.M. Ordovas, J.A. Casasnovas, Lower-normal TSH is associated with better metabolic risk factors: a cross-sectional study on Spanish men. Nutr. Metab. Cardiovasc. Dis. 25, 1095–1103 (2015)

    Article  CAS  PubMed  Google Scholar 

  34. C. Virili, A. Antonelli, M.G. Santaguida, S. Benvenga, M. Centanni, Gastrointestinal malabsorption of thyroxine. Endocr. Rev. 40(1), 118–136 (2019)

    Article  PubMed  Google Scholar 

  35. P.M. Mannucci, A. Nobili, L. Pasina, REPOSI Collaborators (REPOSI is the acronym of REgistro POliterapie SIMI, Società Italiana di Medicina Interna). Polypharmacy in older people: lessons from 10 years of experience with the REPOSI register. Intern. Emerg. Med. 13(8), 1191–1200 (2018)

    Article  PubMed  Google Scholar 

  36. R. Vita, G. Saraceno, F. Trimarchi, S. Benvenga, Switching levothyroxine from the tablet to the oral solution formulation corrects the impaired absorption of levothyroxine induced by proton-pump inhibitors. J. Clin. Endocrinol. Metab. 99, 4481–4486 (2014)

    Article  CAS  PubMed  Google Scholar 

  37. C. Virili, L. Giovanella, P. Fallahi, A. Antonelli, M.G. Santaguida, M. Centanni, P. Trimboli, Levothyroxine therapy: changes of TSH levels by switching patients from tablet to liquid formulation. A systematic review and meta-analysis. Front Endocrinol. 9, 10 (2018). https://doi.org/10.3389/fendo.2018.00010

    Article  Google Scholar 

  38. R. Vita, F. Di Bari, S. Benvenga, Oral liquid levothyroxine solves the problem of tablet levothyroxine malabsorption due to concomitant intake of multiple drugs. Expert. Opin. Drug Deliv. 14, 467–472 (2017)

    Article  CAS  PubMed  Google Scholar 

  39. C. Virili, P. Trimboli, F. Romanelli, M. Centanni, Liquid and softgel levothyroxine use in clinical practice: state of the art. Endocrine 54(1), 3–14 (2016)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Salvatore Benvenga.

Ethics declarations

Conflict of interest

S.B. received novel formulations of LT4 from IBSA Institute Biochimique (Lugano, Switzerland) and IBSA s.r.l. (Lodi, Italy) to be given to patients for conducting clinical studies. In addition, S.B. was an invited speaker at symposia organized by IBSA. However, IBSA had no role in any phase of the writing of this manuscript. The remaining authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of our institutional research committee at University Hospital of Messina and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morini, E., Catalano, A., Lasco, A. et al. In thyroxine-replaced hypothyroid postmenopausal women under simultaneous calcium supplementation, switch to oral liquid or softgel capsule l-thyroxine ensures lower serum TSH levels and favorable effects on blood pressure, total cholesterolemia and glycemia. Endocrine 65, 569–579 (2019). https://doi.org/10.1007/s12020-019-01908-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-019-01908-x

Keywords

Navigation