Last updated March 16, 2022

Lipid Management in Patients with Endocrine Disorders

Assessment

1. Screening and Cardiovascular Disease Risk Assessment

Measurement of Lipids

1.1 In adults with endocrine disorders, we recommend a lipid panel for the assessment of TG levels and for calculating LDL-C. Technical Remarks:
  • Non-fasting lipid panels are acceptable for initial screening.
  • If TG levels are elevated or if genetic dyslipidemia is suspected, repeat a fasting lipid panel.
  • If lipoprotein(a) [Lp(a)] levels are measured, fasting or non-fasting samples can be obtained.
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CV Risk Assessment

1.2 In adults with endocrine disorders, we recommend conducting a CV risk assessment by evaluating traditional risk factors, including calculation of 10-year ASCVD risk using a tool such as the Pooled Cohort Equations. ()
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1.3 In adults with endocrine disorders at borderline or intermediate risk (10-year ASCVD risk 5%–19.9%), particularly those with additional risk-enhancing factors, in whom the decision about statin treatment and/or other preventive interventions is uncertain, we suggest measuring coronary artery calcium (CAC) to inform shared decision-making. ()

Technical Remarks:

  • Borderline and intermediate CV risk are defined as 5%–7.4% and 7.5%–19.9% 10-year ASCVD risk using the Pooled Cohort Equations.
  • Risk enhancing factors are additional features, including diseases, that enhance the risk of ASCVD beyond the risk associated with major risk factors and/or the calculated 10-year risk of ASCVD.
  • In patients with additional risk-enhancing factors, including elevated Lp(a) as described below, risk assessment should consider traditional 10-year ASCVD risk assessment and the presence of risk-enhancing factors. The CAC score should be considered when risk assessment and treatment decisions remain uncertain.
  • At present we suggest measuring CAC as the preferred tool for assessment of subclinical atherosclerosis. Other techniques to assess atherosclerotic burden are being developed.
  • CAC=0 marks very low risk of ASCVD. In patients with baseline CAC=0, evidence suggests that it is reasonable to repeat a CAC scan after 5–7 years in low risk patients, 3–5 years in borderline to intermediate risk patients, and in 3 years for high risk patients or those with diabetes.
  • In patients without diabetes or ASCVD and with LDL >70 mg/dL (1.8 mmol/L), and 10 year ASCVD risk, >7.5%, or 10 year ASCVD risk 5–7.4% plus one or more risk enhancing factors, or CAC score over the 75th percentile for age, sex, and race, or CAC score >100, the initiation of a statin, as adjunct to diet and exercise, is advised after a discussion of the risk/benefit with the patient.
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1.4 In adult patients with a family history of premature ASCVD, or a personal history of ASCVD or family history of high Lp(a), we suggest measuring Lp(a) to inform decision making about short-term and lifetime ASCVD risk and the need to intensify LDL-C–lowering therapy.
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Technical Remarks:

  • Lp(a) ≥50 mg/dL (125 nmol/L) enhances risk of ASCVD.
  • Lp(a) testing does not need to be repeated if it has previously been measured (i.e., in childhood or early adulthood).
  • It is not yet known whether reducing Lp(a) reduces ASCVD risk.
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Hypertriglyceridemia

2. Hypertriglyceridemia

2.1 In adults with fasting TG levels over 500 mg/dL (5.6 mmol/L), we recommend pharmacologic treatment as adjunct to diet and exercise to prevent pancreatitis. ()

Technical Remark:

  • Patients with TG 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.
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In patients with triglyceride-induced pancreatitis, we suggest against the use of acute plasmapheresis as first-line therapy to reduce triglyceride levels. ()

Technical Remark:

  • Plasmapheresis may be useful in those who do not respond to conventional methods of lowering TG such as individuals who have extraordinarily elevated TG levels (e.g., over 10,000 mg/dL [112.9 mmol/L]) or in extremely high-risk situations such as pregnancy.
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2.3 In patients without diabetes who have TG-induced pancreatitis, we suggest against the routine use of insulin infusion. ()

Technical Remark:

  • When uncontrolled diabetes is present, insulin therapy should be used to normalize glucose levels.
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2.4 In adults who are on statins and still have moderately elevated TG levels >150 mg/dL (1.7 mmol/L), and who have either ASCVD or diabetes plus two additional risk factors, we suggest adding eicosapentaenoic acid (EPA) ethyl ester to reduce the risk of CVD. ()

Technical Remarks:

  • Risk factors include traditional risk factors and risk-enhancing factors.
  • The dose of EPA ethyl ester is 4 gms/day.
  • If EPA ethyl ester is not available or accessible, then it is reasonable to consider a fibrate.
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2.5 In patients with elevated TG (>150 mg/dL to 499 mg/dL [1.7 mmol/L to 5.6 mmol/L]), we suggest checking TG before and after starting a bile acid sequestrant. ()

Technical Remark:

  • Bile acid sequestrants are contraindicated when TG are above 500 mg/dL (5.6 mmol/L).
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Diabetes

3. Type 2 Diabetes Mellitus

3.1 In adults with T2D and other CV risk factors, we recommend statin therapy in addition to lifestyle modification in order to reduce CV risk. ()

Technical Remarks:

  • High intensity statins should be chosen in patients with ASCVD or those with risk factors for ASCVD 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 ASCVD risk, prognosis, potential interacting medications, polypharmacy, mental health and the wishes of the patient.
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3.2 In adults with T2D and other CV risk factors, we suggest lowering LDL-C to achieve a goal of LDL-C <70 mg/dL (< 1.8 mmol/L) in order to reduce CV risk. ()

Technical Remarks:

  • A statin should be added to lifestyle modifications if LDL-C is >70 mg/dL (1.8 mmol/L).
  • LDL-C should be <55 mg/dL(1.4 mmol/L) in patients with established CVD or multiple risk factors.
  • Additional LDL-lowering therapy (ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitor [PCSK9]) may be needed if the LDL-C goal is not reached with statins.
  • Risk factors include traditional risk factors and risk-enhancing factors.
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3.3 In adults with T2D on a statin at LDL goal with residual TG over 150 mg/dL (1.7 mmol/L) and with two additional traditional risk factors or risk-enhancing factors, we suggest adding EPA ethyl ester to reduce CV risk. ()

Technical Remarks:

  • Consider 4 g/d of EPA ethyl ester.
  • If EPA ethyl ester is not available or accessible, then it is reasonable to consider a fibrate such as fenofibrate.
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3.4 In adults with T2D with chronic kidney disease stages 1–4 and post renal transplant, we suggest statin therapy, irrespective of the CV risk score, to reduce CV risk.

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Technical Remarks:

  • 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 CKD except for atorvastatin and fluvastatin.
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3.5 In adults with T2D and diabetic retinopathy, we suggest fibrates in addition to statins to reduce retinopathy progression. ()

Technical Remarks:

  • This recommendation applies regardless of TG levels.
  • The preferred fibrate is fenofibrate.
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4. Type 1 Diabetes Mellitus

4.1 In adults with type 1 diabetes (T1D) 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 CV risk score, to reduce CV risk. ()

Technical Remarks:

  • LDL should be the primary target for lipid-lowering therapy.
  • Consider therapy if LDL is over 70 mg/dl (1.8 mmol/L).
  • Statins should not be used in women who are pregnant or trying to become pregnant.
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4.2 In adults with T1D with CKD in stages 1–4, we suggest statin therapy, irrespective of the CV risk score, to reduce CV risk. ()

Technical Remarks:

  • LDL should be the primary target for lipid-lowering therapy.
  • Consider therapy if LDL 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 CKD except for atorvastatin and fluvastatin.
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4.3 In adults with T1D with obesity, or with high TG and low high-density lipoprotein cholesterol (HDL-C), we suggest statin therapy, irrespective of the CV risk score, to reduce CV risk. ()

Technical Remarks:

  • LDL should be the primary target for lipid-lowering therapy.
  • Consider therapy if LDL is over 70 mg/dL (1.8 mmol/L).
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4.4 In adults with T1D and diabetic retinopathy, we suggest statin therapy, irrespective of the CV risk score, to reduce CV risk. ()

Technical Remarks:

  • LDL should be the primary target.
  • Consider therapy if LDL-C is over 70 mg/dL (1.8 mmol/L).
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Obesity

5. Obesity

5.1 In individuals who have obesity, we advise assessment of components of the metabolic syndrome (MetS) and body fat distribution to accurately determine the level of CVD risk. ()

Technical Remarks:

  • Diagnosis of MetS requires the presence of three of the following criteria:
    • Elevated TGElevated TGElevated TGElevated TGElevated TGElevated TGElevated TG ≥150 mg/dL (1.7 mmol/L) or on TG-lowering medication
    • Reduced HDL-C <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 T2D) is defined by cutoffs for prediabetes according to fasting blood glucose, oral glucose tolerance and/or HbA1c.
  • 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.
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5.2 In individuals who have obesity, we suggest lifestyle measures as first-line treatment to reduce plasma TG to lower CV and pancreatitis risk. ()

Technical Remarks:

  • Reductions in LDL-C and increases in HDL-C are modest compared to the decrease in TG with lifestyle measures that produce weight loss.
  • Lifestyle therapy-induced changes in the lipid profile in obesity have not been shown to reduce CVD events.
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5.3 In individuals who have obesity, we recommend assessment of 10-year risk for ASCVD to guide the use of lipid-lowering therapy. ()

Technical Remarks:

  • Calculation of 10-year risk for ASCVD may be done using the Pooled Cohort Equations.
  • Elevated LDL-C is predictive of CV risk.
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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 CVD and pancreatitis. ()

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 and when the weight is stable.
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5.5 In individuals with obesity, (body mass index >40 or >35 kg/m with comorbidities) who undergo bariatric surgery, we suggest measurement of the lipid profile after bariatric surgery to assess 2CV risk. ()

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 LDL-C levels.
  • Both restrictive and malabsorptive procedures decrease TG.
  • Reassess lipid profile 1 to 3 months after bariatric surgery and periodically thereafter and when the weight is stable.
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Other Conditions

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. ()

Technical Remark:

  • Hypothyroidism can elevate both cholesterol and TG levels, which improve with treatment.
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6.2 In patients with hyperthyroidism, we recommend re-evaluating the lipid panel after the patient becomes euthyroid. ()

Technical Remark:

  • Changes in LDL-C have been observed as early as 3 months after the patient is euthyroid.
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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. ()
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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 LDL levels. ()

Technical Remark:

  • Take into consideration the patient’s age and general health, the possibility of suppression of thyroid-stimulating hormone, and whether the patient has CVD.
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7. Excess Glucocorticoids

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 CV risk irrespective of the CV risk score. ()

Technical Remarks:

  • LDL-C should be the primary target, and therapy should be considered if LDL-C 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.
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7.3 In adults with cured Cushing syndrome, we advise the approach to CV risk assessment and treatment be the same as in the general population. ()
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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 CV risk factors because of the increased risk of CVD. ()

Technical Remark:

  • Effects of glucocorticoid therapy on lipids and CV risk will vary based on dose of glucocorticoid, duration of treatment, and underlying disease/indication.
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8. Disorders Of Growth Hormone Secretion

Adult Growth Hormone Deficiency

8.1 In adults with GHD, we recommend obtaining a lipid profile at diagnosis to assess for dyslipidemia. ()
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8.2 In adults with GHD associated with hypopituitarism, we suggest assessment and treatment of lipids and other CV risk factors. ()

Technical Remarks:

  • LDL-C should be the primary target.
  • Consider therapy if LDL-C is over 70 mg/dL (1.8 mmol/L).
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8.3 In adult patients with GHD, we recommend against using growth hormone replacement solely to lower LDL-C to reduce CV risk. ()
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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. ()
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9. Polycystic Ovary Syndrome

Lipid Abnormalities

9.1 In women with polycystic ovary syndrome (PCOS), we recommend obtaining a fasting screening lipid panel at diagnosis to assess CV risk. ()

Technical Remarks:

  • PCOS is associated with CV risk factors.
  • Conduct lipid screening both before and intermittently during hormonal therapy.
  • In PCOS, hypertriglyceridemia is the most common lipid abnormality.
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Cardiovascular Risk

Effect of treatment of PCOS on lipids
9.2 In women with PCOS, we suggest against using lipid-lowering therapies to treat hyperandrogenism or infertility. ()
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10. Menopause And Hormonal Replacement

10.1 In postmenopausal women, we recommend treating dyslipidemia with statin therapy, rather than hormone therapy. ()

Technical Remarks:

  • Hormone therapy is a risk factor for increased CVD.
  • Hormone therapy is described as estrogen +/– progesterone/a progestin.
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10.2 In postmenopausal women on hormone therapy and with other risk factors for CVD, we recommend statin therapy to reduce CV risk. ()

Technical Remarks:

  • Hormone therapy is a risk factor for increased CVD.
  • Hormone therapy is described as estrogen +/– progesterone/a progestin.
  • Menopause may be associated with an increase in LDL-C and a decrease in HDL-C.
  • Risk factors may be traditional risk factors or risk-enhancing factors.
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10.3 In women who enter menopause early (<40–45 years old), we recommend assessment and treatment of lipids and other CV risk factors. ()

Technical Remarks:

  • Early menopause enhances CVD risk.
  • ASCVD risk should be calculated and followed after menopause.
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11. Hypogonadism 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 CVD risk. ()
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11.2 In patients with low HDL (<30 mg/dL [0.8 mmol/L]), especially in the absence of hypertriglyceridemia, we advise clinical or biochemical investigation of anabolic steroid abuse. ()

Technical Remark: Supraphysiological doses of androgens will reduce HDL-C levels.

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12. Gender-Affirming Hormone Therapy

12.1 In transwomen and transmen who have taken or are taking gender-affirming hormone therapy, we advise assessing CV risk by guidelines for non-transgender adults.
Technical Remark: There are no data to guide selection of a gender marker in risk calculators for individuals on gender-affirming hormone therapy.
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Recommendation Grading

Overview

Title

Lipid Management in Patients with Endocrine Disorders

Authoring Organization

Publication Month/Year

September 19, 2020

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings

Ambulatory, Long term care

Intended Users

Social worker, physician, diabetes educator

Scope

Assessment and screening, Management

Diseases/Conditions (MeSH)

D050171 - Dyslipidemias, D004700 - Endocrine System Diseases

Keywords

diabetes, cardiovascular disease, dyslipidemia, triglycerides, endocrine diseases, lipids

Supplemental Methodology Resources

Systematic Review Document, Systematic Review Document