TY - JOUR
T1 - Marked lowering of high-density lipoprotein cholesterol levels due to high dose bexarotene therapy
AU - Basani, Samata
AU - Garg, Abhimanyu
N1 - Funding Information:
A.G. received research grants from Pfizer , Bristol-Myers Squibb , AstraZeneca , and Aegerion and is a consultant for Bristol-Myer Squibb, AstraZeneca, Amgen, Eli Lilly, BioMarin, Hyperion Therapeutics, Back Bay Life Sciences, MEDACorp, Gerson Lehman Group, Ipsen Bioscience, Engage Health, BioMedical Insight, Intellisphere, Health Advances, and Tekmira, BioMarin, Hyperion Therapeutics, Back Bay Life Sciences, MEDACorp, Gerson Lehman Group, Ipsen Bioscience, Engage Health, BioMedical Insight, Intellisphere, Health Advances, and Tekmira, BioMarin, Hyperion Therapeutics, Back Bay Life Sciences, MEDACorp, Gerson Lehman Group, Ipsen Bioscience, Engage Health, BioMedical Insight, Intellisphere, Health Advances, and Tekmira.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Context Bexarotene is a retinoid X receptor agonist, which is currently used for the treatment of cutaneous T-cell lymphoma (CTCL). It is known to induce central hypothyroidism as well as dyslipidemia including elevation of triglycerides (TG) and low-density lipoprotein cholesterol along with slight lowering of high-density lipoprotein cholesterol (HDL-C). Marked lowering of HDL-C has never been previously reported in bexarotene-treated patients and whether it is related to hypothyroidism remains unclear. Case Report A 49-year-old African female with a history of CTCL on treatment with bexarotene of 300 mg/d, presented with serum total cholesterol level of 249 mg/dL (6.4 mmol/L), TG level of 92 mg/dL (1.03 mmol/L), HDL-C level of 78 mg/dL (2.02 mmol/L), thyroid stimulating hormone (TSH) of 0.68 μIU/mL, and free thyroxine level of 0.5 ng/dL. Six months later, on increasing the bexarotene dose to 600 mg daily, serum TG increased to 310 mg/dL (3.5 mmol/L) and HDL-C dropped to 3 to 5 mg/dL (0.077-0.13 mmol/L), whereas the TSH was undetectable (0.01 μIU/mL). Despite adequate levothyroxine replacement to 225 μg daily resulting in free thyroxine levels up to 1.5 ng/dL, HDL-C remained extremely low of 4 to 9 mg/dL (0.103-0.233 mmol/L). Bexarotene was discontinued due to poor response of CTCL, 3 months after which her HDL-C levels returned to baseline of 80 to 90 mg/dL (2.07-2.33 mmol/L). Conclusions High dose bexarotene can markedly lower HDL-C levels, which normalize on discontinuation of the drug. Lowering of HDL-C with bexarotene may be due to an increase in cholesterol ester transfer protein activity and appears to be independent of central hypothyroidism.
AB - Context Bexarotene is a retinoid X receptor agonist, which is currently used for the treatment of cutaneous T-cell lymphoma (CTCL). It is known to induce central hypothyroidism as well as dyslipidemia including elevation of triglycerides (TG) and low-density lipoprotein cholesterol along with slight lowering of high-density lipoprotein cholesterol (HDL-C). Marked lowering of HDL-C has never been previously reported in bexarotene-treated patients and whether it is related to hypothyroidism remains unclear. Case Report A 49-year-old African female with a history of CTCL on treatment with bexarotene of 300 mg/d, presented with serum total cholesterol level of 249 mg/dL (6.4 mmol/L), TG level of 92 mg/dL (1.03 mmol/L), HDL-C level of 78 mg/dL (2.02 mmol/L), thyroid stimulating hormone (TSH) of 0.68 μIU/mL, and free thyroxine level of 0.5 ng/dL. Six months later, on increasing the bexarotene dose to 600 mg daily, serum TG increased to 310 mg/dL (3.5 mmol/L) and HDL-C dropped to 3 to 5 mg/dL (0.077-0.13 mmol/L), whereas the TSH was undetectable (0.01 μIU/mL). Despite adequate levothyroxine replacement to 225 μg daily resulting in free thyroxine levels up to 1.5 ng/dL, HDL-C remained extremely low of 4 to 9 mg/dL (0.103-0.233 mmol/L). Bexarotene was discontinued due to poor response of CTCL, 3 months after which her HDL-C levels returned to baseline of 80 to 90 mg/dL (2.07-2.33 mmol/L). Conclusions High dose bexarotene can markedly lower HDL-C levels, which normalize on discontinuation of the drug. Lowering of HDL-C with bexarotene may be due to an increase in cholesterol ester transfer protein activity and appears to be independent of central hypothyroidism.
KW - Bexarotene
KW - Dyslipidemia
KW - Low HDL
KW - Retinoids
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U2 - 10.1016/j.jacl.2015.08.004
DO - 10.1016/j.jacl.2015.08.004
M3 - Article
C2 - 26687705
AN - SCOPUS:84949640070
SN - 1933-2874
VL - 9
SP - 832
EP - 836
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
IS - 6
ER -