Abstract
Purpose
To compare TSH levels of hypothyroid patients treated with liquid LT4 at breakfast or 30 min before breakfast.
Patients and methods
Subjects, aged 18–75 years old, were eligible if they presented hypothyroidism, due to Hashimoto’s thyroiditis or after thyroidectomy for proven benign goiter. Seven hundred ninety-eight patients were recruited and enrolled in the study. Thirty-seven subjects withdrew from the trial. A total of 761 patients (mean age 46.2 ± 10.8 years) completed the study. The starting dose of LT4 was determined through clinical judgment, taking into account TSH levels, estimated residual thyroid function, age, body weight and comorbidities. All patients underwent TSH, fT4, and fT3 evaluation to verify achievement of euthyroidism with their initial fasting state assumption of LT4 after 8 weeks of therapy. If euthyroidism was not achieved, an appropriately adjusted LT4 dose was administered for 8 weeks, after which thyroid function parameters were checked again. If euthyroidism was achieved, the patients were asked to take LT4 at breakfast and hormone levels were checked again after 6 months.
Results
At the end of the study period, no significant differences in serum TSH level were observed whether LT4 was ingested at breakfast or 30 min prior in a fasting state: 2.61 ± 1.79 vs. 2.54 ± 1.86 mIU/L, respectively (p = 0.455).
Conclusions
This study confirms in a large set of patients that a liquid LT4 formulation can be taken directly at breakfast and potentially improve therapeutic compliance.
Similar content being viewed by others
References
Vanderpump PJ, Tunbrldge WM, French JM, Appleton D, Bates D et al (1995) The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol 43:55–68
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC (2000) The Colorado thyroid disease prevalence study. Arch Internal Med 160:526–534
Aoki Y, Belin RM, Clickner R, Jeffries R, Phillips L et al (2007) Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999–2002). Thyroid 17:1211–1223
Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR et al (2014) American Thyroid Association Task Force on Thyroid Hormone Replacement 2014 Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on thyroid hormone replacement. Thyroid 24:1670–1751
Vaidya B, Pearce SH (2008) Management of hypothyroidism in adults. BMJ 337:a801
Biondi B, Bartalena L, Chiovato L, Lenzi A, Mariotti S, Pacini F et al (2016) Recommendations for treatment of hypothyroidism with levothyroxine and levotriiodothyronine: a 2016 position statement of the Italian Society of Endocrinology and the Italian Thyroid Association. J Endocrinol Invest 39:1465–1474
Parle JV, Franklyn JA, Cross KW, Jones SR, Sheppard MC (1993) Thyroxine prescription in the community: serum thyroid stimulating hormone level assays as an indicator of undertreatment or overtreatment. Br J Gen Pract 43:107–109
Liwanpo L, Hershman JM (2009) Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab 23:781–792
Dusing R, Lottermoser K, Mengden T (2001) Compliance with drug therapy-new answers to an old question. Nephrol Dial Transplant 16:1317–1321
Vita R, Saraceno G, Trimarchi F, Benvenga S (2013) A novel formulation of l-thyroxine (LT4) reduces the problem of LT4 malabsorption by coffee observed with traditional tablet formulations. Endocrine 43:154–160
Centanni M, Benvenga S, Sachmechi I (2017) Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report. J Endocrinol Invest 40:1289–1301
Cappelli C, Pirola I, Daffini L, Formenti A, Iacobello C et al (2016) A double-blind placebo-controlled trial of liquid thyroxine ingested at breakfast: results of the TICO study. Thyroid 26:197–202
Esposito D, Rotondi M, Accardo G, Vallone G, Conzo G, Docimo G et al (2017) Influence of short-term selenium supplementation on the natural course of Hashimoto’s thyroiditis: clinical results of a blinded placebo-controlled randomized prospective trial. J Endocrinol Invest 40:83–89
Wenzel KW, Kirschsieper HE (1997) Aspects of the absorption of oral l-thyroxine in normal man. Metabolism 26:1–8
Benvenga S, Bartolone L, Pappalardo MA, Russo A, Lapa D et al (2008) Altered intestinal absorption of l-thyroxine caused by coffee. Thyroid 18:293–301
Bach-Huynh TG, Nayak B, Loh J, Soldin S, Jonklaas J (2009) Timing of levothyroxine administration affects serum thyrotropin concentration. JCEM 94:3905–3912
Perez CL, Araki FS, Graf H, de Carvalho GA (2013) Serum thyrotropin levels following levothyroxine administration at breakfast. Thyroid 23:779–784
Liel Y, Harman-Boehm I, Shany S (1996) Evidence for a clinically important adverse effect of fiber-enriched diet on the bioavailability of levothyroxine in adult hypothyroid patients. J Clin Endocrinol Metab 81:857–885
Bell DS, Ovalle F (2001) Use of soy protein supplement and resultant need for increased dose of levothyroxine. Endocr Pract. 7:193–194
Vita R, Fallahi P, Antonelli A, Benvenga S (2014) The administration of l-thyroxine as soft gel capsule or liquid solution. Expert Opin Drug Deliv 11:1103–1111
Cappelli C, Rotondi M, Pirola I, Agosti B, Formenti A, Zarra E et al (2012) Thyreotropin levels in diabetic patients on metformin treatment. Eur J Endocrinol 167:261–265
Cappelli C, Rotondi M, Pirola I, Agosti B, Gandossi E, Valentini U et al (2009) TSH-lowering effect of metformin in type 2 diabetic patients: differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients. Diabetes Care 32:1589–1590
Vita R, Di Bari F, Benvenga S (2017) Oral liquid levothyroxine solves the problem of tablet levothyroxine malabsorption due to concomitant intake of multiple drugs. Expert Opin Drug Deliv 14:467–472
Ferrara R, Ientile V, Arcoraci V, Ferrajolo C, Piccinni C et al (2017) Treatment pattern and frequency of serum TSH measurement in users of different levothyroxine formulations: a population-based study during the years 2009-2015. Endocrine 58(1):143–152
Negro R, Valcavi R, Agrimi D, Toulis KA (2014) Levothyroxine liquid solution versus tablet for replacement treatment in hypothyroid patients. Endocr Pract 1:1–20
Cappelli C, Pirola I, Daffini L, Gandossi E, Agosti B et al (2014) Thyroid hormonal profile in elderly patients treated with two different levothyroxine formulations: a single institute survey. Eur Geriatr Med 5:382–385
Acknowledgements
We thank the patients who volunteered to participate in this study.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
Any no funds have been provided for this study.
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional ethics committee 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.
Rights and permissions
About this article
Cite this article
Pirola, I., Gandossi, E., Brancato, D. et al. TSH evaluation in hypothyroid patients assuming liquid levothyroxine at breakfast or 30 min before breakfast. J Endocrinol Invest 41, 1301–1306 (2018). https://doi.org/10.1007/s40618-018-0867-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-018-0867-3