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Cited by 72Thyroid Disorders and TreatmentsDigestive system and related healthThyroid and Parathyroid Surgery

Systematic appraisal of lactose intolerance as cause of increased need for oral thyroxine

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Cellini, Miriam, Santaguida, Maria Giulia, Gatto, Ilenia, Virili, Camilla, Del Duca, Susanna Carlotta, Brusca, Nunzia, Capriello, Silvia, Gargano, Lucilla +1 more·2014·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2014-1217
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Abstract

CONTEXT: An increased need for T4 has been described in patients with different gastrointestinal disorders. However, there is a lack of systematic studies assessing the need for T4 in hypothyroid patients with lactose intolerance, a widespread and often occult disorder. OBJECTIVE: The objective of the study was to assess the replacement T4 dose required in hypothyroid patients with lactose intolerance. DESIGN: This was a cohort study. SETTING: The study was conducted at an outpatient endocrinology unit in a University Hospital. PATIENTS: The replacement T4 dose has been analyzed, from 2009 to 2012, in 34 hypothyroid patients due to Hashimoto's thyroiditis and lactose intolerance and being noncompliant with a lactose-free diet. MAIN OUTCOME MEASURE: An individually tailored T4 dose was measured. RESULTS: In all patients with isolated Hashimoto's thyroiditis, target TSH (median TSH 1.02 mU/L) was obtained at a median T4 dose of 1.31 μg/kg/d. In patients with lactose intolerance, only five of 34 patients reached the desired TSH (median TSH 0.83 mU/L) with a similar T4 dose (1.29 μg/kg/d). In the remaining 29 patients, the T4 dose was progressively increased and the target TSH (median TSH 1.21 mU/L) was attained at a median T4 dose of 1.81 μg/kg/d (+38%, P < .0001). In six of these patients, other gastrointestinal disorders were diagnosed, and their median T4 requirement was higher (2.04 μg/kg/d; +55%; P = .0032). In the remaining 23 patients with isolated lactose intolerance, a median T4 dose of 1.72 μg/kg/d (+31% P < .0001) has been required to attain pharmacological thyroid homeostasis. CONCLUSIONS: These findings show that lactose intolerance significantly increased the need for oral T4 in hypothyroid patients.

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  • The median levothyroxine requirement in patients with lactose intolerance has been estimated to be approximately 31% higher compared to controls.

    “The median of levothyroxine requirement in patients with lactose intolerance has been estimated to be approximately 31% higher as compared to controls (113).”

    From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [113]

  • In patients with celiac disease, intestinal parasitosis, or other intestinal dysfunctions, TSH concentrations remained elevated even after treatment with increased doses.

    “In patients with celiac disease, intestinal parasitosis, or other intestinal dysfunctions, TSH concentrations remained elevated, even after treatment with increased doses (19, 23–26).”

    From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [26]

  • Lactose intolerance and celiac disease are among the most frequent intestinal diseases responsible for malabsorption and may both impair intestinal absorption of drugs and nutrients via hydrolysis and complexation.

    “In addition to surgery, lactose intolerance and celiac disease are among the most frequent intestinal diseases responsible for malabsorption. They may both impair intestinal absorption of drugs and nutrients via hydrolysis and complexation (25, 26, 55).”

    From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [26]

  • Primary hypothyroidism is refractory to oral thyroxine when there is biochemical or clinical evidence of hypothyroidism (TSH above the upper target level, usually 4.5 mU/L after a 6-week interval after the last dose increase) and/or unresolved hypothyroid symptoms, despite increasing levothyroxine dosages beyond 1.9 μg/kg daily.

    “Primary hypothyroidism is considered to be refractory to oral thyroxine when there is biochemical or clinical evidence of hypothyroidism [serum level of thyroid-stimulating hormone (TSH) above the upper target level, usually 4.5 mU/L following a 6-week interval after the dosage was last increased] and/or unresolved hypothyroid symptoms, despite increasing dosages of levothyroxine beyond 1.9 μg/kg”

    From Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report (2017) · cites this paper as [3]

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Research works printed but not linked: 4

  1. [3]3. Benvenga S, Bartolone L, Squadrito S, Lo Giudice F, Trimarchi F. Delayedintestinal absorption of levothyroxine. Thyroid . 1995;5(4): 249-253.
  2. [9]9. Montalto M, Curigliano V, Santoro L, et al. Managementandtreatment of lactose malabsorption. World J Gastroenterol . 2006;12(2): 187-191.
  3. [12]12. Swagerty DL, Walling AD, Klein RM. Lactose intolerance. AmFam Physician . 2002;65(9):1845-1850.
  4. [18]18. NeumannWL,CossE,RuggeM,GentaRM. Autoimmuneatrophic gastritis-pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol . 2013;10(9):529-541.

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Authors
Cellini, M., Santaguida, M. G., Gatto, I., Virili, C., Del Duca, S. C., Brusca, N., Capriello, S., Gargano, L., & Centanni, M.
Affiliations
  • Sapienza University of Rome (IT)
  • Department of Medico-Surgical Sciences and Biotechnologies (M.Cel., M.G.S., I.G., C.V., S.C.D.D., N.B., S.C., M.Cen.), “Sapienza” University of Roma, 00040, Latina, Italy
  • Endocrinology Unit (M.Cel., S.C.D.D., N.B., L.G., M.Cen.), Azienda Unita Sanitaria Locale Latina, 00040, Latina, Italy
Corresponding author
Centanni, Marco
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2014-08-01
Volume
99
Issue
8
Pages
E1454-E1458
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2014-1217
OpenAlex
W1976679490
Cited by
72
References
22
Citations by year
2026: 4 · 2025: 2 · 2024: 7 · 2023: 1 · 2022: 10 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 1
FWCI
6.17
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
Funders
Sapienza Università di Roma
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Keywords
lactose intolerance, hypothyroidism, levothyroxine dose, thyroid hormone replacement, Hashimoto's thyroiditis, gastrointestinal diseases
MeSH terms
Administration, Oral, Adolescent, Adult, Dose-Response Relationship, Drug, Female, Humans, Hypothyroidism, Lactose Intolerance, Male, Middle Aged, Patient Compliance, Thyroxine, Cohort Studies, Hormone Replacement Therapy, Hashimoto Disease, Diet, Carbohydrate-Restricted, Drug Dosage Calculations, Young Adult

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