Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe

Rgia A. Othman, Semone B. Myrie, David Mymin, Jean-Baptiste Roullet, Andrea De Barber, Robert D. Steiner, Peter J.H. Jones

Research output: Contribution to journalArticle

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Abstract

Objectives: To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE). Study design: Eight patients with sitosterolemia (16-56 years of age) were studied during 14 weeks off EZE therapy and 14 weeks on EZE (10 mg/day). Serum thyroid biomarkers (free triiodothyronine [FT3], free thyroxine [FT4], FT3/FT4 ratio, thyroid-stimulating hormone), 5α-stanols (sitostanol and cholestanol), and cholestanol precursors (total cholesterol and its synthesis marker lathosterol, and 7α-hydroxy-4-cholesten-3-one cholestenol) were measured at baseline and during the 14 weeks off EZE and on EZE. Results: EZE increased FT3/FT4 (10% ± 4%; P = .02). EZE reduced plasma and red blood cells sitostanol (-38% ± 6% and -20% ± 4%; all P < .05) and cholestanol (-18% ± 6% and -13% ± 3%; all P < .05). The change in plasma cholestanol level on EZE inversely correlated with the change in FT3/FT4 (r = -0.86; P = .01). EZE lowered total cholesterol (P < .0001) and did not affect 7α-hydroxy-4-cholesten-3-one cholestanol. EZE increased (P < .0001) lathosterol initially, but the level was not sustained, resulting in similar levels at week 14 off EZE and on EZE. Conclusion: In patients with STSL, 5α-stanols levels might be associated with thyroid function. EZE reduces circulating 5α-stanols while increasing FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status. Trial registration: ClinicalTrials.gov NCT01584206.

Original languageEnglish (US)
JournalJournal of Pediatrics
DOIs
StateAccepted/In press - Jan 19 2017

Fingerprint

Thyroid Hormones
Cholestanol
Thyroid Gland
Sitosterolemia
Ezetimibe
Biomarkers
Cholesterol
Triiodothyronine
Thyrotropin
Thyroxine
Erythrocytes

Keywords

  • 7α-hydroxy-4-cholesten-3-one
  • Cholestanol
  • Lathosterol
  • Phytosterolemia
  • Sitostanol
  • Total cholesterol

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Othman, R. A., Myrie, S. B., Mymin, D., Roullet, J-B., De Barber, A., Steiner, R. D., & Jones, P. J. H. (Accepted/In press). Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe. Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2017.05.049

Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe. / Othman, Rgia A.; Myrie, Semone B.; Mymin, David; Roullet, Jean-Baptiste; De Barber, Andrea; Steiner, Robert D.; Jones, Peter J.H.

In: Journal of Pediatrics, 19.01.2017.

Research output: Contribution to journalArticle

Othman, RA, Myrie, SB, Mymin, D, Roullet, J-B, De Barber, A, Steiner, RD & Jones, PJH 2017, 'Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe', Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2017.05.049
Othman RA, Myrie SB, Mymin D, Roullet J-B, De Barber A, Steiner RD et al. Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe. Journal of Pediatrics. 2017 Jan 19. https://doi.org/10.1016/j.jpeds.2017.05.049
Othman, Rgia A. ; Myrie, Semone B. ; Mymin, David ; Roullet, Jean-Baptiste ; De Barber, Andrea ; Steiner, Robert D. ; Jones, Peter J.H. / Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe. In: Journal of Pediatrics. 2017.
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abstract = "Objectives: To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE). Study design: Eight patients with sitosterolemia (16-56 years of age) were studied during 14 weeks off EZE therapy and 14 weeks on EZE (10 mg/day). Serum thyroid biomarkers (free triiodothyronine [FT3], free thyroxine [FT4], FT3/FT4 ratio, thyroid-stimulating hormone), 5α-stanols (sitostanol and cholestanol), and cholestanol precursors (total cholesterol and its synthesis marker lathosterol, and 7α-hydroxy-4-cholesten-3-one cholestenol) were measured at baseline and during the 14 weeks off EZE and on EZE. Results: EZE increased FT3/FT4 (10{\%} ± 4{\%}; P = .02). EZE reduced plasma and red blood cells sitostanol (-38{\%} ± 6{\%} and -20{\%} ± 4{\%}; all P < .05) and cholestanol (-18{\%} ± 6{\%} and -13{\%} ± 3{\%}; all P < .05). The change in plasma cholestanol level on EZE inversely correlated with the change in FT3/FT4 (r = -0.86; P = .01). EZE lowered total cholesterol (P < .0001) and did not affect 7α-hydroxy-4-cholesten-3-one cholestanol. EZE increased (P < .0001) lathosterol initially, but the level was not sustained, resulting in similar levels at week 14 off EZE and on EZE. Conclusion: In patients with STSL, 5α-stanols levels might be associated with thyroid function. EZE reduces circulating 5α-stanols while increasing FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status. Trial registration: ClinicalTrials.gov NCT01584206.",
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AU - De Barber, Andrea

AU - Steiner, Robert D.

AU - Jones, Peter J.H.

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N2 - Objectives: To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE). Study design: Eight patients with sitosterolemia (16-56 years of age) were studied during 14 weeks off EZE therapy and 14 weeks on EZE (10 mg/day). Serum thyroid biomarkers (free triiodothyronine [FT3], free thyroxine [FT4], FT3/FT4 ratio, thyroid-stimulating hormone), 5α-stanols (sitostanol and cholestanol), and cholestanol precursors (total cholesterol and its synthesis marker lathosterol, and 7α-hydroxy-4-cholesten-3-one cholestenol) were measured at baseline and during the 14 weeks off EZE and on EZE. Results: EZE increased FT3/FT4 (10% ± 4%; P = .02). EZE reduced plasma and red blood cells sitostanol (-38% ± 6% and -20% ± 4%; all P < .05) and cholestanol (-18% ± 6% and -13% ± 3%; all P < .05). The change in plasma cholestanol level on EZE inversely correlated with the change in FT3/FT4 (r = -0.86; P = .01). EZE lowered total cholesterol (P < .0001) and did not affect 7α-hydroxy-4-cholesten-3-one cholestanol. EZE increased (P < .0001) lathosterol initially, but the level was not sustained, resulting in similar levels at week 14 off EZE and on EZE. Conclusion: In patients with STSL, 5α-stanols levels might be associated with thyroid function. EZE reduces circulating 5α-stanols while increasing FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status. Trial registration: ClinicalTrials.gov NCT01584206.

AB - Objectives: To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE). Study design: Eight patients with sitosterolemia (16-56 years of age) were studied during 14 weeks off EZE therapy and 14 weeks on EZE (10 mg/day). Serum thyroid biomarkers (free triiodothyronine [FT3], free thyroxine [FT4], FT3/FT4 ratio, thyroid-stimulating hormone), 5α-stanols (sitostanol and cholestanol), and cholestanol precursors (total cholesterol and its synthesis marker lathosterol, and 7α-hydroxy-4-cholesten-3-one cholestenol) were measured at baseline and during the 14 weeks off EZE and on EZE. Results: EZE increased FT3/FT4 (10% ± 4%; P = .02). EZE reduced plasma and red blood cells sitostanol (-38% ± 6% and -20% ± 4%; all P < .05) and cholestanol (-18% ± 6% and -13% ± 3%; all P < .05). The change in plasma cholestanol level on EZE inversely correlated with the change in FT3/FT4 (r = -0.86; P = .01). EZE lowered total cholesterol (P < .0001) and did not affect 7α-hydroxy-4-cholesten-3-one cholestanol. EZE increased (P < .0001) lathosterol initially, but the level was not sustained, resulting in similar levels at week 14 off EZE and on EZE. Conclusion: In patients with STSL, 5α-stanols levels might be associated with thyroid function. EZE reduces circulating 5α-stanols while increasing FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status. Trial registration: ClinicalTrials.gov NCT01584206.

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