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A young man with dry skin and nodules on elbows and buttocks

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A 32-year-old man sought consultation for dry flaky skin, painless nodules on elbows and buttocks, constipation, cold intolerance, muscle aches and diminished appetite of 4 months duration. On examination he had the features shown in his palms (figure 1), elbows (figure 2) and gluteal region (figure3).


What are the abnormalities shown in the figures?
What is the disorder which has unmasked these abnormalities?



Figure 1 shows palmar xanthomas, which are planar xanthomas in the palmar creases. They are virtually pathognomonic of type III hyperlipoproteinaemia, also known as familial dysbetalipoproteinaemia.1 Figure 2 shows tubero-eruptive xanthomas on the elbows. Figure 3 shows tuberous xanthomas in the gluteal region. Tuberous and tubero-eruptive xanthomas are also seen in but are less specific for this disorder. Salient features of type III hyperlipoproteinaemia are listed in box FB1.

Figure FB1
Figure FB2


Detailed clinical evaluation revealed that patient had obesity, hypothyroid facies, moderate diffuse non-tender thyromegaly, proximal myopathy, bradycardia and delayed relaxation of tendon jerks. There was no history of coronary or peripheral vascular disease.

Investigations revealed fasting cholesterol 11 mmol/l (normal range 4.3–6.18 mmol/l); fasting triglycerides 5.4 mmol/l (<1.8 mmol/l); VLDL cholesterol/ triglyceride ratio >0.3 (0.2), plasma lipoprotein electrophoresis demonstrated broad band in beta migrating lipoprotein region (type III pattern), fasting plasma glucose 4.2 mmol/l (4.2–6.1 mmol/l); thyroid-stimulating hormone 48 mU/l (0.4–5.0 mU/l); thyroxine 51 nmol/l (64–154 nmol/l); fine needle aspiration cytology of thyroid showed diffuse lymphocytic infiltration with germinal centre formation, obliteration of thyroid follicles, and fibrosis. Destruction of epithelial cells was seen, and few larger epithelial cells with oxyphilic changes in the cytoplasm (Askanazy cells) were present. Thyroid peroxidase antibodies were positive. This was consistent with primary hypothyroidism due to Hashimoto's thyroiditis. Liver enzymes, chest X-ray, electrocardiogram and serum immune electrophoresis were normal. Isoelectric focussing of plasma for apo-E2 homozygosity or apo-E genotyping of DNA obtained from leucocytes could not be done.


Alterations in thyroid functions affect plasma lipids significantly,2 and hypothyroidism is a common cause of secondary hyperlipidaemia. All patients with significant hyperlipidaemia must be screened for hypothyroidism. The classic manifestation of hypothyroidism is increased levels of plasma LDL cholesterol. Another abnormality is increased plasma triglyceride levels.3 HDL cholesterol levels are normal or slightly lower in hypothyroidism. Elevated plasma cholesterol levels in hypothyroidism are associated with decreased LDL catabolism by way of the LDL receptor pathway,4 and with an increased risk for atherosclerosis. Subclinical hypothyroidism can also lead to hypercholesterolaemia, which regresses with thyroid hormone therapy.5

A predisposition to increased triglyceride levels is due to impaired lipoprotein lipase activity in hypothyroidism. This can exacerbate the hypertriglyceridaemia of an underlying genetic triglyceride disorder, and chylomicronaemia can occur. Hypothyroidism interferes with remnant metabolism by impaired lipoprotein clearance, and individuals with E2/E2 genotype may present with marked lipid elevations and tubero-eruptive xanthomas. Thus, hypothyroidism can modulate the clinical expression of type III hyperlipoproteinaemia.6 7Type III hyperlipoproteinaemia associated with hypothyroidism responds dramatically to thyroid hormone replacement therapy.7

This patient was managed with thyroid hormone replacement therapy and institution of the National Cholesterol Education Programme step I diet. His tubero-eruptive and palmar xanthomas, features of hypothyroidism, and lipid and thyroid hormone abnormalities regressed completely over a period of 14 weeks. He is now asymptomatic and is being followed up in the thyroid clinic on thyroxine and diet therapy. There was no family history of similar disorder, or premature coronary/peripheral vascular disease. Screening of first-degree relatives for type III hyperlipoproteinaemia is planned.

Final diagnosis

Type III hyperlipoproteinaemia with phenotypic exacerbation by primary hypothyroidism.