Correspondence

Delayed Severe Hypertriglyceridemia from Tamoxifen

N Engl J Med 1997; 337:281-282July 24, 1997

Article

To the Editor:

The effects of estrogen-replacement therapy on lipid metabolism — mainly, a reduction in levels of low-density lipoprotein (LDL) and modest increases in triglycerides and high-density lipoprotein (HDL) — have been well documented. However, estrogens may prove harmful in women with underlying hypertriglyceridemia, leading to profoundly high triglyceride levels and ensuing pancreatitis.1 What is less widely known is that tamoxifen, used clinically for its antiestrogenic properties, may have a paradoxical estrogenic effect on lipid metabolism, with the same potential complication.

We describe a 58-year-old woman who was referred for severe hypertriglyceridemia. In July 1992, she underwent segmental mastectomy for T1N0M0 infiltrating ductal adenocarcinoma of the breast. Adjuvant therapy included external-beam radiation and tamoxifen (10 mg by mouth two times a day). Three months after surgery, a multiphasic chemistry panel revealed a triglyceride level of 795 mg per deciliter. She had a known history of familial hypertriglyceridemia, with her most recent recorded triglyceride level (283 mg per deciliter) five years before her surgery. Triglyceride levels were measured at least twice a year while she was taking tamoxifen, and at no time did her triglyceride level exceed 770 mg per deciliter on a low-fat diet. However, in October 1996 a lipid panel obtained in the fasting state revealed a triglyceride level of 4420 mg per deciliter, a cholesterol level of 750 mg per deciliter, and an HDL level of 20 mg per deciliter. She had no signs or symptoms of pancreatitis, but the serum amylase level was elevated at 83 IU per liter. Tamoxifen was immediately discontinued, and she was given gemfibrozil (600 mg by mouth two times a day). Three weeks later her triglyceride level had fallen to 218 mg per deciliter, with a cholesterol level of 279 mg per deciliter, an HDL level of 37 mg per deciliter, an LDL level of 198 mg per deciliter, and an amylase level of 30 IU per liter.

Three cases of severe hypertriglyceridemia due to tamoxifen therapy have been reported. Each patient had previously had hypertriglyceridemia. Although two patients recovered with tamoxifen withdrawal, diet, and medication (gemfibrozil and clofibrate),1,2 the third patient had fulminant pancreatitis and died of multiorgan failure, with a peak triglyceride level of 3673 mg per deciliter.3 Tamoxifen (and estrogen) induces hypertriglyceridemia by stimulating the endogenous production of triglycerides, which overloads serum clearance by lipoprotein lipase and hepatic triglyceride lipase. Substantial triglyceride buildup occurs only when these enzymes are already saturated, as in patients with familial hypertriglyceridemia or familial combined hyperlipidemia. The rarity of these disorders may explain why trials assessing the effect of tamoxifen on lipid metabolism show only modest elevations in serum triglyceride levels.4,5

Tamoxifen should be used cautiously in patients who have hypertriglyceridemia in the fasting state before treatment is begun. Our experience has shown that dangerous lipid abnormalities may occur years into therapy, and therefore vigilance must be maintained until the tamoxifen is discontinued.

Keith T. Kanel, M.D.
Norman Wolmark, M.D.
Allegheny University of the Health Sciences, Pittsburgh, PA 15212

Paul D. Thompson, M.D.
University of Pittsburgh Medical Center, Pittsburgh, PA 15261

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Citing Articles (6)

Citing Articles

1. 1

   Masataka Sawaki, Ai Idota, Hiroki Uchida, Sumiyo Noda, Shigenori Sato, Toyone Kikumori, Tsuneo Imai. (2011) The Effect of Toremifene on Lipid Metabolism Compared with That of Tamoxifen in vitro. Gynecologic and Obstetric Investigation 71:3, 213-216
   CrossRef

2. 2

   Hakan Alagozlu, Mehmet Cindoruk, Selahattin Unal. (2006) Tamoxifen-Induced Severe Hypertriglyceridaemia and Acute Pancreatitis. Clinical Drug Investigation 26:5, 297-302
   CrossRef

3. 3

   Zeng-Ming Lin, Yi-Ho Young. (2005) Investigating the causes of vertigo in breast cancer survivors. European Archives of Oto-Rhino-Laryngology 262:5, 432-436
   CrossRef

4. 4

   M. Elisaf, E. Bairaktari, N. Pavlidis. (2000) Correspondence. The Breast 9:4, 238
   CrossRef

5. 5

   U Veronesi, P Maisonneuve, A Costa, V Sacchini, C Maltoni, C Robertson, N Rotmensz, P Boyle. (1998) Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. The Lancet 352:9122, 93-97
   CrossRef

6. 6

   &NA;. (1997) Tamoxifen. Reactions Weekly &NA;:664, 12
   CrossRef