Severe Hypercholesterolemia in Two Children

Background: Extreme elevations of low-density lipoprotein cholesterol (LDL-C) levels are generally consistent with genetic mutations affecting lipid or lipoprotein metabolism, as seen in familial hypercholesterolemia (FH). A detailed family history, medical history, and routine labs are key in determining the underlying cause to support appropriate clinical decision-making. We report two children with severe hypercholesterolemia and discuss evaluation and treatment. Case 1: A 2-yr-old Hispanic female presented for possible FH after routine lab test reported a severely elevated LDL-C of 370 mg/dL. The medical and family histories were unremarkable. Additional tests were ordered to rule out 2nd causes of hypercholesterolemia; her free T4 was low and her TSH elevated. Upon further questioning, the mother stated that the child was diagnosed with congenital hypothyroidism at birth and was started on thyroid hormone, but had been without it for 5 mos. Within 6 weeks of resuming levothyroxine, LDL-C was normal (78 mg/dL). Case 2: A 16-yr-old male was referred for evaluation after a cholesterol-screening test, performed by his PCP, reported an LDL-C of 213 mg/dL. His past medical history was unremarkable and he denied the use of medications. Both parents denied any significant family history. Additional studies revealed a low free T4 and an elevated TSH. He was found to have thyroid antibodies, consistent with the clinical impression of Hashimoto’s disease. Upon treatment with levothyroxine, thyroid function studies and LDL-C were normal (106 mg/dL). Summary: FH is a common genetic mutation that is frequently encountered in primary care. Although severe elevations in LDL-C are generally consistent with genetic mutations in lipid or lipoprotein metabolism, secondary causes must be considered. Both patients presented for evaluation of FH but were diagnosed with hypothyroidism. The dramatic decline of their LDL-C values within 6 weeks of treatment with levothyroxine emphasizes the importance of ruling out secondary causes of hypercholesterolemia. Thyroid dysfunction can lead to alteration of lipid metabolism due to the effects of low thyroid hormone on HMG-CoA reductase, LDL receptor expression, and high-density lipoprotein. Conclusions: While severe elevations of LDL-C can be caused by genetic mutations affecting lipid and lipoprotein metabolism, secondary causes of hypercholesterolemia should be excluded prior to counseling, genetic testing, and implementation of lipid-lowering therapy.