Retnakaran Ravi, Connelly Philip W, Goguen Jeannette
Department of Medicine, Division of Endocrinology, St. Michael's Hospital and Health Centre, 61 Queen Street East, Toronto, Ontario, Canada.
Endocr Pract. 2005 Nov-Dec;11(6):394-8. doi: 10.4158/EP.11.6.394.
To illustrate the potential abnormalities in lipoprotein metabolism associated with type III hyper-lipoproteinemia and the modulation of their clinical expression by thyroid hormone and estrogenic status.
An illustrative case, with associated clinical and laboratory data, is presented, and relevant clinical and pathophysiologic studies from the literature are reviewed.
A 35-year-old woman, at 7 months after delivery of her first child, presented to her family physician with a complaint of painful eruptions on the palms of her hands. On evaluation, she was found to have new hypothyroidism and severe hypertriglyceridemia (>1,569 mg/dL). Thyroxine replacement was initiated, and she was referred to the lipid clinic. When seen in the lipid clinic shortly thereafter, her triglyceride level had normalized, but her low-density lipoprotein (LDL) fraction was strikingly elevated (representing a combination of elevated intermediate-density lipoprotein and LDL cholesterol). On physical examination, palmar xanthomas were noted, suggestive of type III hyperlipoproteinemia. This diagnosis was further supported by homozygosity at the apolipoprotein E (apo E) gene locus for the apo E2 allele implicated in this condition. Ultimately, with attainment of euthyroidism in the subsequent weeks, the lipid profile normalized, with the LDL cholesterol concentration particularly reduced at 55 mg/dL.
Clinical expression of type III hyperlipoproteinemia necessitates interaction between an underlying genetic defect of lipoprotein metabolism (apo E2 homozygosity) and a secondary metabolic insult such as, in the current case, hypothyroidism and possibly breast-feeding-mediated hypoestrogenemia. As such, in patients with type III hyperlipoproteinemia, it is essential to search for exacerbating factors, particularly because the amelioration of such factors may rectify the effects of the underlying dyslipidemia.
阐述与Ⅲ型高脂蛋白血症相关的脂蛋白代谢潜在异常情况，以及甲状腺激素和雌激素状态对其临床表型的调节作用。
呈现一个伴有相关临床和实验室数据的实例，并复习文献中的相关临床和病理生理学研究。
一名35岁女性，在其首次分娩7个月后，因双手掌出现疼痛性皮疹而就诊于家庭医生。经评估，发现她患有新发甲状腺功能减退和严重高甘油三酯血症（>1569mg/dL）。开始进行甲状腺素替代治疗，并将她转诊至脂质门诊。此后不久在脂质门诊就诊时，她的甘油三酯水平已恢复正常，但低密度脂蛋白（LDL）部分显著升高（代表中密度脂蛋白和LDL胆固醇升高）。体格检查发现掌部黄色瘤，提示Ⅲ型高脂蛋白血症。载脂蛋白E（apo E）基因位点纯合子为与该病相关的apo E2等位基因，这进一步支持了该诊断。最终，在随后几周甲状腺功能恢复正常后，血脂谱恢复正常，LDL胆固醇浓度尤其降至55mg/dL。
Ⅲ型高脂蛋白血症的临床表型需要脂蛋白代谢的潜在遗传缺陷（apo E2纯合子）与继发性代谢损伤之间相互作用，如本例中的甲状腺功能减退以及可能由母乳喂养介导的低雌激素血症。因此，对于Ⅲ型高脂蛋白血症患者，寻找加重因素至关重要，特别是因为改善这些因素可能纠正潜在血脂异常的影响。
