Full Guideline: Lipid Management in Patients with Endocrine Disorders
JCEM | December 2020 (Online October 2020)
Connie Newman (Chair), Michael J. Blaha, Jeffrey B. Boord, Bertrand Cariou, Alan Chait, Henry Fein, Henry Ginsberg, Ira Goldberg (Co-Chair), M. Hassan Murad, Savitha Subramanian, and Lisa R. Tannock
The 2020 guideline on lipid management in patients with endocrine disorders:
- Emphasizes assessing lipid profiles in patients with endocrine diseases to reduce the risk of ASCVD.
- Focuses on the consideration of statin therapy and lipid-lowering effects (if any) in patients with certain endocrine disorders.
Resources
Essential Points
- Obtain a lipid panel in adults with endocrine disorders.
- Treat adults with type 2 diabetes and other cardiovascular risk factors with a statin in addition to lifestyle modifications.
- Consider statin therapy, irrespective of the cardiovascular risk score, in adults with type 1 diabetes who are age 40 years and older.
- Rule out hypothyroidism before treatment with lipid-lowering medications. In patients with hypothyroidism, re-evaluate the lipid profile when the patient has thyroid hormone levels in the normal range.
- Consider statin therapy in addition to lifestyle modifications in adults with Cushing syndrome.
- Use statins rather than hormone therapy to treat high cholesterol in post-menopausal women.
- Evaluate and treat lipids and other cardiovascular risk factors in women who enter menopause early (before the age of 40-45 years).
+ 2 HYPERTRIGLYCERIDEMIA
- 2.1 In adults with fasting triglyceride levels over 500 mg/dL (5.6 mmol/L), we recommend pharmacologic treatment as adjunct to diet and exercise to prevent pancreatitis. (1⊕OOO)
Technical Remarks:
- Patients with triglyceride levels over 1000 mg/dL (11.3 mmol/L) often do not get an adequate response to medications and therefore, control of diabetes, modification of diet, and weight loss are essential.
- 2.2 In patients with triglyceride-induced pancreatitis, we suggest against the use of acute plasmapheresis as first-line therapy to reduce triglyceride levels. (2⊕OOO)
Technical Remark:
- Plasmapheresis may be useful in those who do not respond to conventional methods of lowering triglycerides, such as individuals who have extraordinarily elevated triglyceride levels (e.g., over 10,000 mg/dL [112.9 mmol/L]) or in extremely high-risk situations such as pregnancy.
- 2.3 In patients without diabetes who have triglyceride-induced pancreatitis, we suggest against the routine use of insulin infusion. (2⊕OOO)
Technical Remark:
- When uncontrolled diabetes is present, insulin therapy should be used to normalize glucose levels.
- 2.4 In adults who are on statins and still have moderately elevated triglyceride levels >150 mg/dL (1.7 mmol/L), and who have either atherosclerotic cardiovascular disease or diabetes plus two additional risk factors, we suggest adding eicosapentaenoic acid ethyl ester to reduce the risk of cardiovascular disease. (2⊕⊕⊕O)
Technical Remarks:
- Risk factors include traditional risk factors and risk-enhancing factors.
- The dose of eicosapentaenoic acid ethyl ester is 4 grams/day.
- If eicosapentaenoic acid ethyl ester is not available or accessible, then it is reasonable to consider a fibrate.
- 2.5 In patients with elevated triglycerides (>150 mg/dL to 499 mg/dL [1.7 mmol/L to 5.6 mmol/L]), we suggest checking triglycerides before and after starting a bile acid sequestrant. (2⊕OOO)
Technical Remarks:
- Bile acid sequestrants are contraindicated when triglycerides are above 500 mg/dL (5.6 mmol/L).
+ 3 TYPE 2 DIABETES MELLITUS
- 3.1 In adults with type 2 diabetes and other cardiovascular risk factors, we recommend statin therapy in addition to lifestyle modification in order to reduce cardiovascular risk. (1⊕⊕⊕⊕)
Technical Remarks:
- High intensity statins should be chosen in patients with atherosclerotic cardiovascular disease, or those with risk factors for atherosclerotic cardiovascular disease or risk enhancing factors.
- Statins should not be used in women who are pregnant or trying to become pregnant.
- In patients over the age of 75, continuation of statin treatment or initiation of statin treatment depends upon atherosclerotic cardiovascular disease risk, prognosis, potential interacting medications, polypharmacy, mental health and the wishes of the patient.
- 3.2 In adults with type 2 diabetes and other cardiovascular risk factors, we suggest lowering low-density lipoprotein cholesterol to achieve a goal of low-density lipoprotein cholesterol <70 mg/dL (1.8 mmol/L) in order to reduce cardiovascular risk. (2⊕OOO)
Technical Remarks:
- A statin should be added to lifestyle modifications if low-density lipoprotein cholesterol is > 70 mg/dL (1.8 mmol/L).
- Low-density lipoprotein cholesterol should be <55 mg/dL (1.4 mmol/L) in patients with established cardiovascular disease or multiple risk factors.
- Additional low-density lipoprotein -lowering therapy (ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitor) may be needed if the low-density lipoprotein cholesterol goal is not reached with statins.
- Risk factors include traditional risk factors and risk-enhancing factors.
- 3.3 In adults with type 2 diabetes on a statin at low-density lipoprotein goal with residual triglycerides over 150 mg/dL (1.7 mmol/L) and with two additional traditional risk factors or risk-enhancing factors, we suggest adding eicosapentaenoic acid ethyl ester to reduce cardiovascular risk. (2⊕⊕⊕O)
Technical Remarks:
- Consider 4 grams/day of eicosapentaenoic acid ethyl ester.
- If eicosapentaenoic acid ethyl ester is not available or accessible, then it is reasonable to consider a fibrate such as fenofibrate.
- 3.4 In adults with type 2 diabetes with chronic kidney disease stages 1–4 and post renal transplant, we suggest statin therapy, irrespective of the cardiovascular risk score, to reduce cardiovascular risk. (2⊕OOO)
Technical Remarks:
- When selecting the statin, consider the renal clearance of the statin. Pitavastatin, pravastatin and rosuvastin all have at least partial clearance through the kidney whereas atorvastatin, fluvastatin, lovastatin, and simvastatin are cleared via the liver.
- All statins require dose adjustments in chronic kidney disease except for atorvastatin and fluvastatin.
- 3.5 In adults with type 2 diabetes and diabetic retinopathy, we suggest fibrates in addition to statins to reduce retinopathy progression. (2⊕OOO)
Technical Remarks:
- This recommendation applies regardless of triglyceride levels.
- The preferred fibrate is fenofibrate.
+ 4 TYPE 1 DIABETES MELLITUS
- 4.1 In adults with type 1 diabetes age 40 years and older and/or with duration of diabetes greater than 20 years, and/or microvascular complications, we suggest statin therapy, irrespective of the cardiovascular risk score, to reduce cardiovascular risk. (2⊕OOO)
Technical Remarks:
- Low-density lipoprotein should be the primary target for lipid-lowering therapy.
- Consider therapy if low-density lipoprotein is over 70 mg/dl (1.8 mmol/L).
- Statins should not be used in women who are pregnant or trying to become pregnant.
- 4.2 In adults with type 1 diabetes with chronic kidney disease in stages 1–4, we suggest statin therapy, irrespective of the cardiovascular risk score, to reduce cardiovascular risk. (2⊕OOO)
Technical Remarks:
- Low-density lipoprotein should be the primary target for lipid-lowering therapy.
- Consider therapy if low-density lipoprotein is over 70 mg/dL (1.8 mmol/L).
- When selecting the statin, consider the renal clearance of the statin: Pitavastatin, pravastatin and rosuvastatin all have at least partial clearance through the kidney whereas atorvastatin, fluvastatin, lovastatin, and simvastatin are cleared via the liver.
- All statins require dose adjustments in chronic kidney disease except for atorvastatin and fluvastatin.
- Ezetimibe can be added to the statin if required to lower low-density lipoprotein cholesterol further. No dose adjustments of ezetimibe are needed in chronic kidney disease.
- 4.3 In adults with type 1 diabetes with obesity, or with high triglycerides and low high-density lipoprotein cholesterol, we suggest statin therapy, irrespective of the cardiovascular risk score, to reduce cardiovascular risk. (2⊕OOO)
Technical Remarks:
- Low-density lipoprotein should be the primary target for lipid-lowering therapy.
- Consider therapy if low-density lipoprotein is over 70 mg/dL (1.8 mmol/L).
- 4.4 In adults with type 1 diabetes and diabetic retinopathy, we suggest statin therapy, irrespective of the cardiovascular risk score, to reduce cardiovascular risk. (2⊕OOO)
Technical Remarks:
- Low-density lipoprotein should be the primary target.
- Consider therapy if low-density lipoprotein cholesterol is over 70 mg/dL (1.8 mmol/L).
+ 5 OBESITY
- 5.1 In individuals who have obesity, we advise assessment of components of the metabolic syndrome and body fat distribution to accurately determine the level of cardiovascular disease risk. (Ungraded Good Practice Statement)
Technical Remarks:
- Diagnosis of Metabolic Syndrome requires the presence of three of the following criteria:
- Elevated triglycerides ≥150 mg/dL (1.7 mmol/L) or on triglycerides-lowering medication
- Reduced high-density lipoprotein cholesterol <50 mg/dL (1.3 mmol/L) in women and < 40 mg/dL (1.0 mmol/L) in men
- Systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg or on blood pressure medication
- Elevated waist circumference (men ≥40 in [102 cm] and women ≥35 in [88 cm]), except for East and South Asian (men ≥35 in [90 cm] and women ≥31.5 in [80 cm])
- Hyperglycemia (but not yet with type 2 diabetes) is defined by cutoffs for prediabetes according to fasting blood glucose, oral glucose tolerance and/or hemoglobin A1c
- Body fat distribution can be assessed in clinical practice by measuring the waist size or the waist/hip ratio.
- Waist size measurement in people with body mass index greater than 35 kg/m2 has potential limitations.
- 5.2 In individuals who have obesity, we suggest lifestyle measures as first-line treatment to reduce plasma triglycerides to lower cardiovascular and pancreatitis risk. (2⊕OOO)
Technical Remarks:
- Reductions in low-density lipoprotein cholesterol and increases in high-density lipoprotein cholesterol are modest compared to the decrease in triglycerides with lifestyle measures that produce weight loss.
- Lifestyle therapy–induced changes in the lipid profile in obesity have not been shown to reduce cardiovascular disease events.
- 5.3 In individuals who have obesity, we recommend assessment of 10-year risk for atherosclerotic cardiovascular disease to guide the use of lipid-lowering therapy. (1⊕⊕⊕O)
Technical Remarks:
- Calculation of 10-year risk for atherosclerotic cardiovascular disease may be done using the Pooled Cohort Equations.
- Elevated low-density lipoprotein cholesterol is predictive of cardiovascular risk.
- 5.4 In individuals who have obesity and are on pharmacological therapy for weight reduction, we suggest reassessment of the lipid profile to evaluate the risk of cardiovascular disease and pancreatitis. (2⊕OOO)
Technical Remark:
- As there are no data on the timing of lipid measurements after weight loss, we suggest reassessment of lipids after 5% weight loss and periodically thereafter, when the weight is stable.
- 5.5 In individuals with obesity, (body mass index > 40 or > 35 kg/m2 with comorbidities) who undergo bariatric surgery, we suggest measurement of the lipid profile after bariatric surgery to assess cardiovascular risk. (2⊕OOO)
Technical Remarks:
- Malabsorptive bariatric surgery procedures (e.g., Roux-en-Y gastric bypass) are more effective than restrictive procedures (e.g., banding, sleeve gastrectomy) in decreasing low-density lipoprotein cholesterol levels.
- Both restrictive and malabsorptive procedures decrease triglycerides.
- Reassess lipid profile 1 to 3 months after bariatric surgery and periodically thereafter and when the weight is stable.
+ 6 THYROID DISEASE
- 6.1 In patients with hyperlipidemia, we recommend ruling out hypothyroidism as the cause of the hyperlipidemia before treatment with lipid lowering medications. (1⊕⊕⊕⊕)
Technical Remark:
- Hypothyroidism can elevate both cholesterol and triglyceride levels, which improve with treatment.
- 6.2 In patients with hyperthyroidism, we recommend re-evaluating the lipid panel after the patient becomes euthyroid. (1⊕⊕⊕⊕)
Technical Remark:
- Changes in low-density lipoprotein cholesterol have been observed as early as 3 months after the patient is euthyroid.
- 6.3 In patients with overt hypothyroidism, we suggest against treating hyperlipidemia until the patient becomes euthyroid in order to more accurately assess the lipid profile. (2⊕OOO)
- 6.4 In patients with subclinical hypothyroidism (thyroid-stimulating hormone < 10 mIU/L) with associated hyperlipidemia, we suggest considering thyroxine treatment as a means of reducing low-density lipoprotein levels. (2⊕OOO)
Technical Remarks:
- Take into consideration the patient’s age and general health, the possibility of suppression of thyroid-stimulating hormone, and whether the patient has cardiovascular disease.
+ 7 EXCESS GLUCOCORTICOIDS
- 7.1 In adult patients with Cushing syndrome, we recommend monitoring the lipid profile in order to identify cases of dyslipidemia. (1⊕⊕OO)
Technical Remark:
- Monitor lipid profile at the time of diagnosis and periodically afterwards at the discretion of the treating physician.
Lipid-Lowering Therapy in Cushing Syndrome
- 7.2 In adults with persistent endogenous Cushing syndrome, we suggest statin therapy, as adjunct to lifestyle modification, to reduce cardiovascular risk irrespective of the cardiovascular risk score. (2⊕OOO)
Technical Remarks:
- Low-density lipoprotein cholesterol should be the primary target, and therapy should be considered if low-density lipoprotein cholesterol is over 70 mg/dL (1.8 mmol/L).
- Patients receiving mitotane therapy for Cushing syndrome commonly develop secondary dyslipidemia from therapy.
- Lipid lowering therapy may not be appropriate for patients with limited life expectancy, such as those with an underlying malignancy.
- 7.3 In adults with cured Cushing syndrome, we advise the approach to cardiovascular risk assessment and treatment be the same as in the general population. (Ungraded Good Practice Statement)
Lipid Management in Chronic Glucocorticoid Therapy
- 7.4 In adults receiving chronic glucocorticoid therapy above replacement levels, we suggest assessment and treatment of lipids and other cardiovascular risk factors because of the increased risk of cardiovascular disease. (2⊕OOO)
Technical Remark:
- Effects of glucocorticoid therapy on lipids and cardiovascular risk will vary based on dose of glucocorticoid, duration of treatment, and underlying disease/indication.
+ 8 DISORDERS OF GROWTH HORMONE SECRETION
Adult Growth Hormone Deficiency
- 8.1 In adults with growth hormone deficiency, we recommend obtaining a lipid profile at diagnosis to assess for dyslipidemia. (1⊕⊕⊕O)
- 8.2 In adults with growth hormone deficiency associated with hypopituitarism, we suggest assessment and treatment of lipids and other cardiovascular risk factors. (2⊕OOO)
Technical Remarks:
- Low-density lipoprotein cholesterol should be the primary target.
- Consider therapy if low-density lipoprotein cholesterol is over 70 mg/dL (1.8 mmol/L).
- 8.3 In adult patients with growth hormone deficiency, we recommend against using growth hormone replacement solely to lower low-density lipoprotein cholesterol to reduce cardiovascular risk. (1⊕⊕⊕O)
Growth Hormone Excess (Acromegaly)
- 8.4 In adults with acromegaly, we suggest measurement of the usual lipid profile before and after treatment of growth hormone excess. (2⊕OOO)
+ 9 POLYCYSTIC OVARY SYNDROME
Lipid Abnormalities
- 9.1 In women with polycystic ovary syndrome, we recommend obtaining a fasting screening lipid panel at diagnosis to assess cardiovascular risk. (1⊕⊕⊕O)
Technical Remarks:
- Polycystic ovary syndrome is associated with cardiovascular risk factors.
- Conduct lipid screening both before and intermittently during hormonal therapy.
- In polycystic ovary syndrome, hypertriglyceridemia is the most common lipid abnormality.
Cardiovascular Risk
Effect of treatment of polycystic ovary syndrome on lipids
- 9.2 In women with polycystic ovary syndrome, we suggest against using lipid-lowering therapies to treat hyperandrogenism or infertility. (2⊕OOO)
+ 10 MENOPAUSE AND HORMONAL REPLACEMENT
- 10.1 In postmenopausal women, we recommend treating dyslipidemia with statin therapy, rather than hormone therapy. (1⊕⊕OO)
Technical Remarks:
- Hormone therapy increases the risk of cardiovascular disease, specifically venous thromboembolism and stroke. However, the absolute risk of cardiovascular disease is lower in younger compared to older postmenopausal women.
- Hormone therapy is described as estrogen +/- progesterone/a progestin.
- 10.2 In postmenopausal women on hormone therapy and with other risk factors for cardiovascular disease, we recommend statin therapy to reduce cardiovascular risk. (1⊕⊕⊕⊕)
Technical Remarks:
- Hormone therapy is a risk factor for increased cardiovascular disease.
- Hormone therapy is described as estrogen +/– progesterone/a progestin.
- Menopause may be associated with an increase in low-density lipoprotein cholesterol and a decrease in high-density lipoprotein cholesterol.
- Risk factors may be traditional risk factors or risk-enhancing factors.
- 10.3 In women who enter menopause early (<40–45 years old), we recommend assessment and treatment of lipids and other cardiovascular risk factors. (1⊕⊕⊕O)
Technical Remarks:
- Early menopause enhances cardiovascular disease risk.
- Atherosclerotic cardiovascular disease risk should be calculated and followed after menopause.
+ 11 HYPOGONDADISM AND TESTOSTERONE REPLACEMENT AND ABUSE
- 11.1 In patients with low testosterone levels, we suggest testosterone therapy as symptomatically indicated, and not as an approach to improve dyslipidemia or cardiovascular disease risk. (2⊕⊕OO)
- 11.2 In patients with low high-density lipoprotein (<30 mg/dL [0.8 mmol/L]), especially in the absence of hypertriglyceridemia, we advise clinical or biochemical investigation of anabolic steroid abuse. (Ungraded Good Practice Statement)
Technical Remark:
- Supraphysiological doses of androgens will reduce high-density lipoprotein cholesterol levels.
+ 12 GENDER-AFFIRMING HORMONE THERAPY
- 12.1 In transwomen and transmen who have taken or are taking gender-affirming hormone therapy, we advise assessing cardiovascular risk by guidelines for non-transgender adults. (Ungraded Good Practice Statement)
Technical Remark:
- There are no data to guide selection of a gender marker in risk calculators for individuals on gender-affirming hormone therapy.
