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E4 Endocrinology
Hypertriglyceridemia and Pancreatitis
Serum triglyceride levels >10 mmol/L increases the risk of developing pancreatitis (even some reports of TG >5 mmol/L)
Dyslipidemias Toronto Notes 2019 SECONDARY HYPERTRIGLYCERIDEMIA
Etiology
• endocrine:obesity/metabolicsyndrome,hypothyroidism(moreforhighLDL,notTG),acromegaly, Cushing’s syndrome, DM
• renal: chronic renal failure, polyclonal and monoclonal hypergammaglobulinemia
• hepatic:chronicliverdisease,hepatitis,glycogenstoragedisease
• drugs:alcohol,corticosteroids,estrogen,hydrochlorothiazide,retinoicacid,β-blockerswithoutintrinsic
sympathomimetic action (ISA), anti-retroviral drugs, atypical antipsychotics, oral contraceptive pills • other: pregnancy
Table 3. Primary Hypercholesterolemias
Hypercholesterolemia
PRIMARY HYPERCHOLESTEROLEMIA
Hypercholesterolemia
Familial Hypercholesterolemia
Etiology/Pathophysiology Labs
Heterozygous: 1/200-1/250  LDL in USA TC Homozygous: 1/300 000 –
1/400 000 in USA
Autosomal codominant with high penetrance
More prevalent in French Canadian, Dutch, South African Afrikaner, Christian Lebanese populations
Most commonly due to defects in the normal LDL receptor
on cell membranes or ApoB
or gain of function mutation PCSK9
Most common cause of ↑ LDL TC Few mild inherited defects in  LDL cholesterol metabolism
In many cases, over-population TC+G of VLDL and associatedLDL  VLDL 2o to excess hepatic synthesis  LDL
of apolipoprotein B
Diagnosis
Heterozygous: Genetic testing (LDLR, ApoB, or PCSK9 mutation) or clinical criteria (Dutch Lipid Clinic Network criteria)
Homozygous:
Untreated LDL-C >13 mmol/L or treated >8 mmol/L Tendon or more rarely tuberous xanthoma >10 yr Elevated LDL-C levels consistent with heterozygous FH in both parents
Clinical Presentation
Tendinous xanthomatosis (achilles, patellar, and extensor tendons of hand)
Arcus cornealis
Xanthelasmata
Heterozygotes: premature CAD, 50%riskofMIinmenbyage30 Homozygotes: manifest CAD and other vascular disease early in childhood and can be fatal (in <20 yr olds)
Asymptomatic until vascular disease develops
No xanthomata
May have xanthelasma
Xanthelasmata (10% of cases) Premature CAD and other vascular disease
Obesity
Treatment
Maximally tolerated statin as initial drug therapy, addition of second drug (ezitimibe and/or PCSK9 inhibitor) as second line, third line for homozygotes is portacaval shunt or LDL apheresis; potential liver transplant
Refer to lipid specialist in drug-resistant hypercholesterolemia
Statins, ezetimibe, bile acid sequesterant, PCSK9 inhibitor
Weight reduction
Decrease simple carbohydrates, fat, cholesterol, and EtOH in diet Statins
Fibrates, ezetimibe, PCSK9 inhibitor Rarely niacin
Polygenic Hypercholesterolemia
Familial Combined Hyperlipidemia
Autosomal dominant
FH and Cardiovascular Risk Calculators
• Risk calculators such as Framingham and SCORE do not apply to patients with familial hypercholesterolemia
• Consider all adults with FH as “high risk”
Familial Combined Hyperlipidemia
SECONDARY HYPERCHOLESTEROLEMIA
Etiology
• endocrine:hypothyroidism(smalldenseLDLwithType2DMandobesity,withnormalLDLlevel) • renal:nephroticsyndrome
• immunologic:monoclonalgammopathy
• hepatic:cholestaticliverdisease(e.g.primarybiliarycirrhosis)
• A common disorder (1-2% of the population) • Contributes to 1/3 to 1/2 of familial coronary
artery disease
• nutritional:diet,anorexianervosa • drugs: cyclosporin, carbamazepine
Low High-Density Lipoprotein
PRIMARY CAUSES
Table 4. Primary Low HDL Cholesterol Levels
Disorder
Familial Hypoalphalipoproteinemia
Tangier Disease
Etiology/Pathophysiology
Autosomal dominant inheritance of a mutation in the ABCA1 or the APOA1 gene
Autosomal recessive inheritance of mutations in the ABCA1 gene
Impaired HDL-mediated cholesterol efflux from macrophages and impaired intracellular lipid trafficking
Clinical Presentation
Premature atherosclerosis Cerebrovascular disease
Mild hypertriglyceridemia Neuropathy
Enlarged, orange-coloured tonsils Premature atherosclerosis Splenomegaly
Hepatomegaly Corneal clouding DM 2
Treatment
Reduce the risk of atherosclerosis with
lifestyle changes, management of concomitant hypercholesterolemia, hypertriglyceridemia, and metabolic syndrome if present
Reduce the risk of atherosclerosis with
lifestyle changes, management of concomitant hypercholesterolemia, hypertriglyceridemia, and metabolic syndrome if present