A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences

Objective: Cross-sectional studies have reported that TSH above or close to the upper normal limit correlates with unfavorable metabolic and cardiovascular outcomes. Certain medications impair intestinal absorption of levothyroxine (L-T4), resulting in undertreated hypothyroidism (viz. failure of se...

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Main Authors: Salvatore Benvenga, Rachele Pantano, Giovanna Saraceno, Luigi Lipari, Antonio Alibrando, Santi Inferrera, Giuseppe Pantano, Giuseppe Simone, Sebastiano Tamà, Riccardo Scoglio, Maria Giovanna Ursino, Carmen Simone, Antonino Catalano, Umberto Alecci
Format: Article
Language:English
Published: Elsevier 2019-06-01
Series:Journal of Clinical & Translational Endocrinology
Online Access:http://www.sciencedirect.com/science/article/pii/S2214623719300237
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spelling doaj-3eb10e07ba0a47108734329646cfd1bf2020-11-24T23:55:26ZengElsevierJournal of Clinical & Translational Endocrinology2214-62372019-06-0116A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequencesSalvatore Benvenga0Rachele Pantano1Giovanna Saraceno2Luigi Lipari3Antonio Alibrando4Santi Inferrera5Giuseppe Pantano6Giuseppe Simone7Sebastiano Tamà8Riccardo Scoglio9Maria Giovanna Ursino10Carmen Simone11Antonino Catalano12Umberto Alecci13Dipartimento di Medicina Clinica e Sperimentale, Università di Messina, Messina, Italy; Programma Interdipartimentale di Endocrinologia Molecolare Clinica e Salute Endocrina della Donna, AOU Policlinico G. Martino, Messina, ItalyDipartimento di Medicina Clinica e Sperimentale, Università di Messina, Messina, ItalyIstituto Auxologico Italiano, Verbania, ItalyMedico di Medicina Generale, ASP 5, Messina, ItalyMedico di Medicina Generale, ASP 5, Messina, ItalyMedico di Medicina Generale, ASP 5, Messina, ItalyMedico di Medicina Generale, ASP 5, Messina, ItalyMedico di Medicina Generale, ASP 5, Messina, ItalyMedico di Medicina Generale, ASP 5, Messina, ItalyMedico di Medicina Generale, ASP 5, Messina, ItalySocietà Italiana di Medicina Generale, Firenze, ItalyBiologo Nutrizionista, Endocrinologia dell’Infanzia, dell’Adolescenza e della Donna, Università di Messina, ItalyDipartimento di Medicina Clinica e Sperimentale, Università di Messina, Messina, Italy; Corresponding author at: Department of Clinical and Experimental Medicine, University Hospital of Messina, Via C. Valeria, 98125 Messina, Italy.Medico di Medicina Generale, ASP 5, Messina, ItalyObjective: Cross-sectional studies have reported that TSH above or close to the upper normal limit correlates with unfavorable metabolic and cardiovascular outcomes. Certain medications impair intestinal absorption of levothyroxine (L-T4), resulting in undertreated hypothyroidism (viz. failure of serum TSH to reach target levels, if hypothyroidism is primary).Further to evaluating the magnitude of sub-optimally treated primary hypothyroidism as a result of co-ingestion of those medications, we wished to ascertain whether the above complications would occur during a low number of years under polypharmacy. Method: In this retrospective study in collaboration with 8 family physicians, we enrolled adults with primary hypothyroidism under L-T4 therapy that, for 2 years minimum, was not associated with those medications (non-exposure, baseline) and that, for another 2 years minimum, it was (exposure). Outcomes were serum levels and proportions of serum TSH levels >4.12 mU/L, and proportions of complications. Complications were aggravation of pre-existing or de novo onset of any of metabolic syndrome, impaired fasting glycemia (IFG), diabetes mellitus, dyslipidemia, hypertension, coronary heart disease (CHD), cerebrovascular disease (CVD). Result: A total of 114 patients were enrolled. Duration of exposure to the interfering medication was 32.1 ± 6.9 months (median 31; range 24–55). Compared with non-exposure, the exposure period resulted in greater TSH levels (2.81 ± 3.62 [median 1.79] vs 1.27 ± 1.34 [median 0.93], P = 2.2 × 10−20) and proportions of values >4.12 mU/L (18.5% vs 4.7%, P = 1.2 × 10−7). Seventy-six patients (67%) had complications, whose rates of TSH >4.12 mU/L were greater than in the 36 complication-free patients (22% vs 11%, P = 0.018). Conclusion: During a median period of 31 months, there are relevant consequences for L-T4 treated adult hypothyroid patients resulting from hyperthyrotropinemia caused by medications impairing L-T4 absorption. This should be taken into account by future guidelines on hypothyroidism management. Keywords: Subclinical hypothyroidism, Levothyroxine malabsorption, Diabetes mellitus, Dyslipidemia, Hypertension, Cardiovascular diseaseshttp://www.sciencedirect.com/science/article/pii/S2214623719300237
collection DOAJ
language English
format Article
sources DOAJ
author Salvatore Benvenga
Rachele Pantano
Giovanna Saraceno
Luigi Lipari
Antonio Alibrando
Santi Inferrera
Giuseppe Pantano
Giuseppe Simone
Sebastiano Tamà
Riccardo Scoglio
Maria Giovanna Ursino
Carmen Simone
Antonino Catalano
Umberto Alecci
spellingShingle Salvatore Benvenga
Rachele Pantano
Giovanna Saraceno
Luigi Lipari
Antonio Alibrando
Santi Inferrera
Giuseppe Pantano
Giuseppe Simone
Sebastiano Tamà
Riccardo Scoglio
Maria Giovanna Ursino
Carmen Simone
Antonino Catalano
Umberto Alecci
A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences
Journal of Clinical & Translational Endocrinology
author_facet Salvatore Benvenga
Rachele Pantano
Giovanna Saraceno
Luigi Lipari
Antonio Alibrando
Santi Inferrera
Giuseppe Pantano
Giuseppe Simone
Sebastiano Tamà
Riccardo Scoglio
Maria Giovanna Ursino
Carmen Simone
Antonino Catalano
Umberto Alecci
author_sort Salvatore Benvenga
title A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences
title_short A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences
title_full A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences
title_fullStr A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences
title_full_unstemmed A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences
title_sort minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences
publisher Elsevier
series Journal of Clinical & Translational Endocrinology
issn 2214-6237
publishDate 2019-06-01
description Objective: Cross-sectional studies have reported that TSH above or close to the upper normal limit correlates with unfavorable metabolic and cardiovascular outcomes. Certain medications impair intestinal absorption of levothyroxine (L-T4), resulting in undertreated hypothyroidism (viz. failure of serum TSH to reach target levels, if hypothyroidism is primary).Further to evaluating the magnitude of sub-optimally treated primary hypothyroidism as a result of co-ingestion of those medications, we wished to ascertain whether the above complications would occur during a low number of years under polypharmacy. Method: In this retrospective study in collaboration with 8 family physicians, we enrolled adults with primary hypothyroidism under L-T4 therapy that, for 2 years minimum, was not associated with those medications (non-exposure, baseline) and that, for another 2 years minimum, it was (exposure). Outcomes were serum levels and proportions of serum TSH levels >4.12 mU/L, and proportions of complications. Complications were aggravation of pre-existing or de novo onset of any of metabolic syndrome, impaired fasting glycemia (IFG), diabetes mellitus, dyslipidemia, hypertension, coronary heart disease (CHD), cerebrovascular disease (CVD). Result: A total of 114 patients were enrolled. Duration of exposure to the interfering medication was 32.1 ± 6.9 months (median 31; range 24–55). Compared with non-exposure, the exposure period resulted in greater TSH levels (2.81 ± 3.62 [median 1.79] vs 1.27 ± 1.34 [median 0.93], P = 2.2 × 10−20) and proportions of values >4.12 mU/L (18.5% vs 4.7%, P = 1.2 × 10−7). Seventy-six patients (67%) had complications, whose rates of TSH >4.12 mU/L were greater than in the 36 complication-free patients (22% vs 11%, P = 0.018). Conclusion: During a median period of 31 months, there are relevant consequences for L-T4 treated adult hypothyroid patients resulting from hyperthyrotropinemia caused by medications impairing L-T4 absorption. This should be taken into account by future guidelines on hypothyroidism management. Keywords: Subclinical hypothyroidism, Levothyroxine malabsorption, Diabetes mellitus, Dyslipidemia, Hypertension, Cardiovascular diseases
url http://www.sciencedirect.com/science/article/pii/S2214623719300237
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