Skip to main content
Top
Published in: Endocrine 3/2019

01-09-2019 | Levothyroxine | Original Article

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

Authors: Elisabetta Morini, Antonino Catalano, Antonino Lasco, Nunziata Morabito, Salvatore Benvenga

Published in: Endocrine | Issue 3/2019

Login to get access

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.
Literature
1.
go back to reference C.R. Schneyer, Calcium carbonate and reduction of levothyroxine efficacy [letter]. JAMA 279, 750 (1998)CrossRefPubMed C.R. Schneyer, Calcium carbonate and reduction of levothyroxine efficacy [letter]. JAMA 279, 750 (1998)CrossRefPubMed
2.
go back to reference N. Singh, P.N. Singh, J.M. Hershman, Effect of calcium carbonate on the absorption of levothyroxine. JAMA 283, 2822–2825 (2000)CrossRefPubMed N. Singh, P.N. Singh, J.M. Hershman, Effect of calcium carbonate on the absorption of levothyroxine. JAMA 283, 2822–2825 (2000)CrossRefPubMed
4.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
5.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
6.
go back to reference S. Benvenga, When thyroid hormone replacement is ineffective? Curr. Opin. Endocrinol. Diabetes Obes. 20, 467–477 (2013)CrossRefPubMed S. Benvenga, When thyroid hormone replacement is ineffective? Curr. Opin. Endocrinol. Diabetes Obes. 20, 467–477 (2013)CrossRefPubMed
8.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
9.
go back to reference 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 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.
go back to reference 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)CrossRef 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)CrossRef
11.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
12.
go back to reference 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)PubMedPubMedCentral 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)PubMedPubMedCentral
13.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
14.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
15.
go back to reference 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)CrossRef 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)CrossRef
16.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
17.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
18.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
19.
go back to reference V. Velkoska Nakova, B. Krstevska, M. Bosevski, Ch Dimitrovski, V. Serafimoski, Dyslipidaemia and hypertension in patients with subclinical hypothyroidism. Prilozi 30, 93–102 (2009)PubMed V. Velkoska Nakova, B. Krstevska, M. Bosevski, Ch Dimitrovski, V. Serafimoski, Dyslipidaemia and hypertension in patients with subclinical hypothyroidism. Prilozi 30, 93–102 (2009)PubMed
21.
go back to reference 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)CrossRef 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)CrossRef
22.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
23.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
24.
go back to reference R. Luboshitzky, A. Aviv, P. Herer, L. Lavie, Risk factors for cardiovascular disease in women with subclinical hypothyroidism. Thyroid 12, 421–425 (2002)CrossRefPubMed R. Luboshitzky, A. Aviv, P. Herer, L. Lavie, Risk factors for cardiovascular disease in women with subclinical hypothyroidism. Thyroid 12, 421–425 (2002)CrossRefPubMed
25.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
26.
go back to reference 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)CrossRef 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)CrossRef
27.
go back to reference 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)PubMedPubMedCentral 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)PubMedPubMedCentral
28.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
29.
go back to reference A. Iqbal, Y. Figenschau, R. Jorde, Blood pressure in relation to serum thyrotropin: the Tromsø study. J. Hum. Hypertens. 20, 932–936 (2006)CrossRefPubMed A. Iqbal, Y. Figenschau, R. Jorde, Blood pressure in relation to serum thyrotropin: the Tromsø study. J. Hum. Hypertens. 20, 932–936 (2006)CrossRefPubMed
30.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
31.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
32.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
33.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
34.
go back to reference C. Virili, A. Antonelli, M.G. Santaguida, S. Benvenga, M. Centanni, Gastrointestinal malabsorption of thyroxine. Endocr. Rev. 40(1), 118–136 (2019)CrossRefPubMed C. Virili, A. Antonelli, M.G. Santaguida, S. Benvenga, M. Centanni, Gastrointestinal malabsorption of thyroxine. Endocr. Rev. 40(1), 118–136 (2019)CrossRefPubMed
35.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
36.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
37.
38.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
39.
go back to reference 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)CrossRef 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)CrossRef
Metadata
Title
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
Authors
Elisabetta Morini
Antonino Catalano
Antonino Lasco
Nunziata Morabito
Salvatore Benvenga
Publication date
01-09-2019
Publisher
Springer US
Published in
Endocrine / Issue 3/2019
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-019-01908-x

Other articles of this Issue 3/2019

Endocrine 3/2019 Go to the issue

Endocrine Imaging

Uremic leontiasis ossea