title: Marked lowering of high-density lipoprotein cholesterol levels due to high dose bexarotene therapy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA; Division of Endocrinology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA; Lipid Cinic, Parkland Memorial Hospital, Dallas, TX, USA.
authors.forename: Samata
authors.initials: S
authors.lastname: Basani
authors.affiliation: Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA; Lipid Cinic, Parkland Memorial Hospital, Dallas, TX, USA. Electronic address: Abhimanyu.Garg@utsouthwestern.edu.
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Garg
mesh_terms: D000328:Adult; D000077610:Bexarotene; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D008875:Middle Aged; D013764:Tetrahydronaphthalenes / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D008075:Lipoproteins, HDL; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene
keywords: Bexarotene; Dyslipidemia; Low HDL; Retinoids