Delayed Intestinal Absorption of Levothyroxine
Abstract
We report four female patients with nodular goiter (in two of the four due to Hashimoto's thyroiditis) and one male patient with frank hypothyroidism due to Hashimoto's thyroiditis in whom TSH-suppressive or replacement L-T4 therapy failed to suppress or, respectively, normalize serum TSH. As is typical in our country, our patients took L-T4 15-20 min before a light breakfast. Gastrointestinal or other diseases and drugs known to interfere with the intestinal absorption of L-T4 were not the cause of this failure. The gastrointestinal absorption test of L-T4 (1000 micrograms) was performed in four patients; in three patients it revealed peculiar abnormalities in that (i) the absorption peak was > 70% but occurred at 4 hr vs an average of 2 hr in 12 euthyroid controls (EC) and 3 hr in the 10 primary hypothyroid controls (HC); (ii) 50% of the maximal absorption occurred at 110 min vs 45 min in EC and 50 min in HC; (iii) the maximal increment in T4 absorption was between 90 and 120 min (+111%) vs between 30 and 60 min in EC (+312%) and HC (+354%). In sum, only the first part of the absorption curve of T4 was shifted to the right (in three of the four women) and this shift was more pronounced and extended to the second part of the curve in the fourth patient; in this last patient absorption peak was 44% at 180 min. Based on these results, we obtained full suppression or normalization of TSH by postponing breakfast for at least 60 min after T4 ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)
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Ingestion of food and LT4 in close proximity was associated with an LT4 absorption curve characterized by delayed absorption.
“The ingestion of food and LT4 in close proximity to each other was associated with an LT4 absorption curve that was characterized by delayed absorption.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [121]
In a case report, four patients who had failure to suppress TSH while consuming breakfast within 20 minutes of LT4 ingestion underwent absorption testing (121).
“In another case report, four patients who had failure to suppress their TSH values while consuming their breakfast within 20 minutes of their LT4 ingestion underwent absorption testing (121).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [121]
When LT4 is co-administered with food, absorption is reduced compared with absorption in the fasting state.
“When LT4 is co-administered with food, absorption is reduced compared with absorption in the fasting state.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [121]
After a 1-month period of delaying breakfast by 60 minutes, the patients achieved suppression of TSH values, suggesting correction of impaired absorption, although absorption testing was not repeated.
“After a 1-month period of delaying breakfast by 60 minutes, the patients were seen to achieve suppression of their TSH values, suggesting correction of the impaired absorption, although absorption testing was not repeated to confirm this.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [121]
Consuming breakfast within 20 minutes after taking LT4 resulted in higher TSH compared with breakfast 60 minutes after LT4, suggesting impaired absorption with a separation of less than 60 minutes.
“Consuming breakfast within 20 minutes after taking LT4 resulted in a higher TSH, compared with when these same patients had breakfast 60 minutes after taking their LT4, suggesting impaired absorption with a separation of less than 60 minutes.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [121]
Four of six studies examining timing of LT4 administration showed that timing influences serum TSH values in hypothyroid patients receiving treatment.
“Four studies (121,126,128,129), out of the six studies examining this issue (121,128-131), have shown that the timing of LT4 administration influences the serum TSH values of hypothyroid patients receiving treatment.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [121]
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- Authors
- BENVENGA, S., BARTOLONE, L., SQUADRITO, S., GIUDICE, F. L., & TRIMARCHI, F.
- Affiliations
- University of Messina (IT)
- ORCID
- BENVENGA, SALVATORE
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 1995-08
- Volume
- 5
- Issue
- 4
- Pages
- 249-253
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2025704325
- Cited by
- 156
- References
- 9
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 3 · 2023: 3 · 2022: 10 · 2021: 13 · 2020: 5 · 2019: 8 · 2018: 9 · 2017: 10 · 2016: 11 · 2015: 7 · 2014: 14 · 2013: 7 · 2012: 8
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- levothyroxine, intestinal absorption, delayed absorption, Hashimoto's thyroiditis, nodular goiter, hypothyroidism, TSH suppression, breakfast timing
- MeSH terms
- Adult, Female, Food, Goiter, Nodular, Humans, Intestinal Absorption, Kinetics, Male, Thyroiditis, Autoimmune, Thyrotropin, Thyroxine
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