Top

Endocrine

Published in:

01-07-2018 | Meta-Analysis

Liquid L-thyroxine versus tablet L-thyroxine in patients on L- thyroxine replacement or suppressive therapy: a meta-analysis

Authors: Irakoze Laurent, Siying Tang, Manirakiza Astère, Kan Ran Wang, Shuhua Deng, Ling Xiao, Qi Fu Li

Published in: Endocrine | Issue 1/2018

Abstract

Purpose

To compare the effectiveness of liquid L-T4 (L-thyroxine) and tablet L-T4 in patients on L-T4 replacement or suppressive therapy.

Methods

The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All prospective or randomized controlled studies (RCTs) comparing liquid L-T4 and tablet L-T4 in patients on L-T4 replacement or suppressive therapy were included in the analysis.

Results

Overall, the initial search of the four databases identified 1278 published studies; of these, eight studies were ultimately included in the meta-analysis. TSH (thyroid stimulating hormone) levels were significantly suppressed in patients on liquid L-T4 compared with those on tablet L-T4, in patients on L-T4 suppressive therapy with L-T4 malabsorption (Mean Difference (MD) = −2.26, 95% Confidence Interval (CI): −3.59, −0.93; P = 0.0009)). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 suppressive therapy without malabsorption (MD = 0.08, 95% CI: −0.31, 0.47; P = 0.69). TSH levels were significantly normalized in patients on liquid L-T4 compared with those on tablet L-T4, in Patients on L-T4 replacement therapy with L-T4 malabsorption (MD = −3.20, 95% CI: −5.08, −1.32; P = 0.0009). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 replacement therapy without malabsorption (MD = 0.91, 95% CI: −0.03, 1.86; P = 0.06).

Conclusion

Liquid L-T4 is more efficient than tablet L-T4 in patients on L-T4 replacement or suppressive therapy with malabsorption. No significant differences were observed in patients without malabsorption. Further studies should be conducted to verify these findings.

Available only for authorised users

J.R. Garber, R.H. Cobin, H. Gharib, J.V. Hennessey, I. Klein, J.I. Mechanick, R. Pessah-Pollack, P.A. Singer, K.A. Woeber, Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr. Pract. 18(6), 988–1028 (2012). https://doi.org/10.4158/ep12280.gl CrossRefPubMed

B. Biondi, L. Wartofsky, Treatment with thyroid hormone. Endocr. Rev. 35(3), 433–512 (2014). https://doi.org/10.1210/er.2013-1083 CrossRefPubMed

B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel, Y.E. Nikiforov, F. Pacini, G.W. Randolph, A.M. Sawka, M. Schlumberger, K.G. Schuff, S.I. Sherman, J.A. Sosa, D.L. Steward, R.M. Tuttle, L. Wartofsky, 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 26(1), 1–133 (2016). https://doi.org/10.1089/thy.2015.0020 CrossRefPubMedPubMedCentral

J. Przytulska, K. Tupikowski, G. Bednarek-Tupikowska, [Thyroid dysfunction in patients treated with tyrosine kinase inhibitors]. Pol. Merkur. Lek. 36(211), 42–44 (2014)

L. Bianchi, L. Rossi, F. Tomao, A. Papa, F. Zoratto, S. Tomao, Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma. Endocr. Relat. Cancer 20(5), R233–R245 (2013). https://doi.org/10.1530/erc-13-0201 CrossRefPubMed

P. Wolf, Y. Winhofer, M. Krssak, M. Krebs, Heart, lipids and hormones. Endocr. Connect. 6(4), R59–r69 (2017). https://doi.org/10.1530/ec-17-0031 CrossRefPubMedPubMedCentral

M. Gutch, S. Rungta, S. Kumar, A. Agarwal, A. Bhattacharya, S.M. Razi, Thyroid functions and serum lipid profile in metabolic syndrome. Biomed. J. 40(3), 147–153 (2017). https://doi.org/10.1016/j.bj.2016.12.006 CrossRefPubMedPubMedCentral

A.P. Delitala, G. Fanciulli, G.M. Pes, M. Maioli, G. Delitala, Thyroid Hormones, Metabolic Syndrome and Its Components. Endocr. Metab. Immune Disord. Drug Targets 17(1), 56–62 (2017). https://doi.org/10.2174/1871530317666170320105221 CrossRefPubMed

R.B. Lv, Q.G. Wang, C. Liu, F. Liu, Q. Zhao, J.G. Han, D.L. Ren, B. Liu, C.L. Li, Low versus high radioiodine activity for ablation of the thyroid remnant after thyroidectomy in Han Chinese with low-risk differentiated thyroid cancer. OncoTargets Ther. 10, 4051–4057 (2017). https://doi.org/10.2147/ott.s135145 CrossRef

10.

E. Fiore, P. Vitti, Serum TSH and risk of papillary thyroid cancer in nodular thyroid disease. J. Clin. Endocrinol. Metab. 97(4), 1134–1145 (2012). https://doi.org/10.1210/jc.2011-2735 CrossRefPubMed

11.

E. Garcia-Garcia, M. Lopez-Gonzalez, R. Cabello-Laureano, E. Navarro-Gonzalez, Multinodular goiter in children: treatment controversies. J. Pediatr. Endocrinol. Metab. 30(8), 847–850 (2017). https://doi.org/10.1515/jpem-2016-0368 CrossRefPubMed

12.

P. Fallahi, S.M. Ferrari, A. Antonelli, In patients with subclinical hypothyroidism while in therapy with tablet L-T4, the liquid L-T4 formulation is more effective in restoring euthyroidism. Endocr. Pract. 23(2), 170–174 (2017). https://doi.org/10.4158/ep161545.or CrossRefPubMed

13.

R. Vita, G. Saraceno, F. Trimarchi, S. Benvenga, A novel formulation of L-thyroxine (L-T4) reduces the problem of L-T4 malabsorption by coffee observed with traditional tablet formulations. Endocrine 43(1), 154–160 (2013). https://doi.org/10.1007/s12020-012-9772-2 CrossRefPubMed

14.

M. Skelin, T. Lucijanic, D. Amidzic Klaric, A. Resic, M. Bakula, A.M. Liberati-Cizmek, H. Gharib, D. Rahelic, Factors affecting gastrointestinal absorption of levothyroxine: a review. Clin. Ther. 39(2), 378–403 (2017). https://doi.org/10.1016/j.clinthera.2017.01.005 CrossRefPubMed

15.

M. Ruchala, E. Szczepanek-Parulska, A. Zybek, The influence of lactose intolerance and other gastro-intestinal tract disorders on L-thyroxine absorption. Endokrynol. Pol. 63(4), 318–323 (2012)PubMed

16.

N.T. Williams, Medication administration through enteral feeding tubes. Am. J. Health-Syst. Pharm. 65(24), 2347–2357 (2008). https://doi.org/10.2146/ajhp080155 CrossRefPubMed

17.

R. Vita, P. Fallahi, A. Antonelli, S. Benvenga, The administration of L-thyroxine as soft gel capsule or liquid solution. Expert Opin. Drug Deliv. 11(7), 1103–1111 (2014). https://doi.org/10.1517/17425247.2014.918101 CrossRefPubMed

18.

G.J. Canaris, N.R. Manowitz, G. Mayor, E.C. Ridgway, The Colorado thyroid disease prevalence study. Arch. Intern. Med. 160(4), 526–534 (2000)CrossRefPubMed

19.

D. Brancato, A. Scorsone, G. Saura, L. Ferrara, A. Di Noto, V. Aiello, M. Fleres, V. Provenzano, Comparison of TSH levels with liquid formulation versus tablet formulations of levothyroxine in the treatment of adult hypothyroidism. Endocr. Pract. 20(7), 657–662 (2014). https://doi.org/10.4158/ep13418.or CrossRefPubMed

20.

P. Fallahi, S.M. Ferrari, A. Antonelli, Oral L-thyroxine liquid versus tablet in patients with hypothyroidism without malabsorption: a prospective study. Endocrine 52(3), 597–601 (2016). https://doi.org/10.1007/s12020-015-0836-y CrossRefPubMed

21.

P. Fallahi, S.M. Ferrari, I. Ruffilli, A. Antonelli, Reversible normalisation of serum TSH levels in patients with autoimmune atrophic gastritis who received L-T4 in tablet form after switching to an oral liquid formulation: a case series. BMC Gastroenterol. 16, 22 (2016). https://doi.org/10.1186/s12876-016-0439-y CrossRefPubMedPubMedCentral

22.

M. Grussendorf, R. Vaupel, K. Wegscheider, [Bioequivalence of L-thyroxine tablets and a liquid L-thyroxine solution in the treatment of hypothyroid patients]. Med. Klin. 99(11), 639–644 (2004). https://doi.org/10.1007/s00063-004-1096-4 CrossRef

23.

G. Ianiro, F. Mangiola, T.A. Di Rienzo, S. Bibbo, F. Franceschi, A.V. Greco, A. Gasbarrini, Levothyroxine absorption in health and disease, and new therapeutic perspectives. Eur. Rev. Med. Pharmacol. Sci. 18(4), 451–456 (2014)PubMed

24.

X.S. Qi, Y.X. Bao, M. Bai, W.D. Xu, J.N. Dai, X.Z. Guo, Nonselective beta-blockers in cirrhotic patients with no or small varices: A meta-analysis. World J. Gastroenterol. 21(10), 3100–3108 (2015). https://doi.org/10.3748/wjg.v21.i10.3100 CrossRefPubMedPubMedCentral

25.

X. Wan, W. Wang, J. Liu, T. Tong, Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med. Res. Methodol. 14, 135 (2014). https://doi.org/10.1186/1471-2288-14-135 CrossRefPubMedPubMedCentral

26.

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(12), 4481–4486 (2014). https://doi.org/10.1210/jc.2014-2684 CrossRefPubMed

27.

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(4), 467–472 (2017). https://doi.org/10.1080/17425247.2017.1290604 CrossRefPubMed

28.

D. Ribichini, G. Fiorini, A. Repaci, V. Castelli, L. Gatta, D. Vaira, R. Pasquali, Tablet and oral liquid L-thyroxine formulation in the treatment of naïve hypothyroid patients with Helicobacter pylori infection. Endocrine 57(3), 394–401 (2017). https://doi.org/10.1007/s12020-016-1167-3 CrossRefPubMed

29.

I. Pirola, L. Daffini, E. Gandossi, D. Lombardi, A. Formenti, M. Castellano, C. Cappelli, Comparison between liquid and tablet levothyroxine formulations in patients treated through enteral feeding tube. J. Endocrinol. Invest 37(6), 583–587 (2014). https://doi.org/10.1007/s40618-014-0082-9 CrossRefPubMed

30.

M. Giusti, L. Mortara, N. Machello, E. Monti, G. Pera, M. Marenzana, Utility of a liquid formulation of levo-thyroxine in differentiated thyroid cancer patients. Drug Res. 65(6), 332–336 (2015). https://doi.org/10.1055/s-0034-1384535 CrossRef

31.

P. Fallahi, S.M. Ferrari, S. Camastra, U. Politti, I. Ruffilli, R. Vita, G. Navarra, S. Benvenga, A. Antonelli, TSH normalization in bariatric surgery patients after the switch from L-thyroxine in tablet to an oral liquid formulation. Obes. Surg. 27(1), 78–82 (2017). https://doi.org/10.1007/s11695-016-2247-4 CrossRefPubMed

32.

C. Cappelli, I. Pirola, E. Gandossi, C. Casella, D. Lombardi, B. Agosti, F. Marini, A. Delbarba, M. Castellano, TSH variability of patients affected by differentiated thyroid cancer treated with levothyroxine liquid solution or tablet form. Int J. Endocrinol. 2017, 7053959 (2017). https://doi.org/10.1155/2017/7053959 CrossRefPubMedPubMedCentral

33.

S. Benvenga, F. Di Bari, R. Vita, Undertreated hypothyroidism due to calcium or iron supplementation corrected by oral liquid levothyroxine. Endocrine 56(1), 138–145 (2017). https://doi.org/10.1007/s12020-017-1244-2 CrossRefPubMed

34.

I. Pirola, A.M. Formenti, E. Gandossi, F. Mittempergher, C. Casella, B. Agosti, C. Cappelli, Oral liquid L-thyroxine (L-t4) may be better absorbed compared to L-T4 tablets following bariatric surgery. Obes. Surg. 23(9), 1493–1496 (2013). https://doi.org/10.1007/s11695-013-1015-y CrossRefPubMedPubMedCentral

35.

C. Cappelli, I. Pirola, L. Daffini, A. Formenti, C. Iacobello, A. Cristiano, E. Gandossi, E. Agabiti Rosei, M. Castellano, A double-blind placebo-controlled trial of liquid thyroxine ingested at breakfast: results of the TICO study. Thyroid 26(2), 197–202 (2016). https://doi.org/10.1089/thy.2015.0422 CrossRefPubMed

36.

S. Morelli, G. Reboldi, S. Moretti, E. Menicali, N. Avenia, E. Puxeddu, Timing of breakfast does not influence therapeutic efficacy of liquid levothyroxine formulation. Endocrine 52(3), 571–578 (2016). https://doi.org/10.1007/s12020-015-0788-2 CrossRefPubMed

37.

A.M. Formenti, G. Mazziotti, R. Giubbini, A. Giustina, Treatment of hypothyroidism: all that glitters is gold? Endocrine 52(3), 411–413 (2016). https://doi.org/10.1007/s12020-016-0882-0 CrossRefPubMed

38.

M. Centanni, L. Gargano, G. Canettieri, N. Viceconti, A. Franchi, G. Delle Fave, B. Annibale, Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. New Engl. J. Med. 354(17), 1787–1795 (2006). https://doi.org/10.1056/NEJMoa043903 CrossRefPubMed

39.

C. Cappelli, I. Pirola, E. Gandossi, A. Formenti, M. Castellano, Oral liquid levothyroxine treatment at breakfast: a mistake? Eur. J. Endocrinol. 170(1), 95–99 (2014). https://doi.org/10.1530/eje-13-0693 CrossRefPubMed

40.

R. Negro, R. Valcavi, D. Agrimi, K.A. Toulis, Levothyroxine liquid solution versus tablet for replacement treatment in hypothyroid patients. Endocr. Pract. 20(9), 901–906 (2014). https://doi.org/10.4158/ep13378.or CrossRefPubMed

41.

I. Muller, P. Yap, P. Steinmann, B.P. Damons, C. Schindler, H. Seelig, N.S. Htun, N. Probst-Hensch, M. Gerber, R. du Randt, U. Puhse, C. Walter, J. Utzinger, Intestinal parasites, growth and physical fitness of schoolchildren in poor neighbourhoods of Port Elizabeth, South Africa: a cross-sectional survey. Parasites Vectors 9(1), 488 (2016). https://doi.org/10.1186/s13071-016-1761-5 CrossRefPubMedPubMedCentral

42.

K. Thevakumar, J.R. Chandren, G.I. Perez-Perez, E.G. Chua, L.K. Teh, M.Z. Salleh, J.A. Tan, A.H. Leow, K.L. Goh, A.C. Tay, B.J. Marshall, J. Vadivelu, M.F. Loke, L.P. Wong, Assessment of risk and Sero-Prevalence of Helicobacter pylori colonization among remote Orang Asli Tribes in Peninsula Malaysia. PloS One 11(7), e0159830 (2016). https://doi.org/10.1371/journal.pone.0159830 CrossRefPubMedPubMedCentral

43.

I. Sachmechi, D.M. Reich, M. Aninyei, F. Wibowo, G. Gupta, P.J. Kim, Effect of proton pump inhibitors on serum thyroid-stimulating hormone level in euthyroid patients treated with levothyroxine for hypothyroidism. Endocr. Pract. 13(4), 345–349 (2007). https://doi.org/10.4158/ep.13.4.345 CrossRefPubMed

44.

N. Bahreini Esfahani, N. Ganjali Dashti, M. Ganjali Dashti, M.I. Noorv, P.B. Koon, R.A. Talib, S.H. Lubis, Dietary predictors of overweight and obesity in Iranian adolescents. Iran. Red. Crescent Med. J. 18(9), e25569 (2016). https://doi.org/10.5812/ircmj.25569 CrossRefPubMedPubMedCentral

45.

G.A. Bray, G. Fruhbeck, D.H. Ryan, J.P. Wilding, Management of obesity. Lancet 387(10031), 1947–1956 (2016). https://doi.org/10.1016/s0140-6736(16)00271-3 CrossRefPubMed

46.

G. Fruhbeck, Bariatric and metabolic surgery: a shift in eligibility and success criteria. Nat. Rev. Endocrinol. 11(8), 465–477 (2015). https://doi.org/10.1038/nrendo.2015.84 CrossRefPubMed

47.

A.D. Miller, K.M. Smith, Medication and nutrient administration considerations after bariatric surgery. Am. J. Health-Syst. Pharm. 63(19), 1852–1857 (2006). https://doi.org/10.2146/ajhp060033 CrossRefPubMed

48.

E. Peroni, M.C. Vigone, S. Mora, L.A. Bassi, C. Pozzi, A. Passoni, G. Weber, Congenital hypothyroidism treatment in infants: a comparative study between liquid and tablet formulations of levothyroxine. Horm. Res Paediatr. 81(1), 50–54 (2014). https://doi.org/10.1159/000356047 CrossRefPubMed

Title: Liquid L-thyroxine versus tablet L-thyroxine in patients on L- thyroxine replacement or suppressive therapy: a meta-analysis
Authors: Irakoze Laurent
Siying Tang
Manirakiza Astère
Kan Ran Wang
Shuhua Deng
Ling Xiao
Qi Fu Li
Publication date: 01-07-2018
Publisher: Springer US
Published in: Endocrine / Issue 1/2018
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-018-1574-8

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Liquid L-thyroxine versus tablet L-thyroxine in patients on L- thyroxine replacement or suppressive therapy: a meta-analysis

Abstract

Purpose

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2018

Thyroid cancer-related bone metastases: increasingly good prospects for treatment

Kisspeptin and LH pulsatile temporal coupling in PCOS patients

Alteration in skeletal muscle mass in women with subclinical hypercortisolism

Lactate induces expression and secretion of fibroblast growth factor-21 by muscle cells

Increased cortisol metabolism in women with pregnancy-related hypertension

Comment on Microsurgical therapy of pituitary adenomas

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page