Key Points
- Obtain a lipid panel in adults with endocrine disorders to assess triglyceride (TG) levels and to calculate LDL cholesterol (LDL-C).
- Treat adults with type 2 diabetes (T2D) and other cardiovascular (CV) risk factors with a statin in addition to lifestyle modifications, aiming for an LDL-C goal of <70 mg/dL.
- Consider statin therapy, irrespective of the CV risk score, in adults with type 1 diabetes who are age 40 years and older, or have a history of diabetes of at least 20 years, or either microvascular complications, chronic kidney disease (CKD) stages 1-4, or obesity.
- Rule out hypothyroidism in patients with hyperlipidemia before treatment with lipid lowering medications. In patients with hypothyroidism re-evaluate the lipid profile when the patient is euthyroid.
- Consider statin therapy as adjunct to lifestyle modifications in adults with persistent endogenous Cushing’s syndrome or adults taking chronic glucocorticoid therapy above replacement levels.
- For treatment of dyslipidemia in post-menopausal women, use statins, rather than hormone therapy, because statins reduce atherosclerotic cardiovascular disease (ASCVD).
- Evaluate and treat lipids and other CV risk factors in women who enter menopause early (before the age of 40-45 years).
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. (1|⊕⊕⊕◯)
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.
Table 1. Lipids and Lipoproteins in Select Endocrine Disorders
| Disease | LDL-C | HDL-C | TG | Lp(a) |
|---|---|---|---|---|
| T2D | No change or ↑ | Normal or ↓ | ↑ | -------- |
| Type 1 diabetes | No change or ↑ | Normal or ↓ | ↑ | -------- |
| Obesity | No change or ↑ | ↓ | ↑ | ------- |
| Hypothyroidism | No change or ↑ | Normal or ↑ | Normal or ↑ | Normal or ↑ |
| Subclinical hypothyroidism | No change or ↑ | Normal or ↓ | Normal | Normal |
| Hyperthyroidism | ↓ | Normal or ↓ | Normal or ↑ | ↓ |
| Cushing syndrome/disease | No change or ↑ | Normal or ↓ | ↑ | Normal or ↑ |
| Chronic glucocorticoid therapy | No change or ↑ | Normal or ↑ | Normal or ↑ | -------- |
| Adult growth hormone deficiency (GHD) | ↑ | Normal or ↓ | Normal or ↑ | Normal |
| Acromegaly | No change or ↑ | Normal or ↓ | ↑ | ↑ |
| Polycystic ovary syndrome (PCOS) | No change or ↑ | ↓ | ↑ | ↑ |
| Menopause vs pre-menopause | ↑ | Normal or ↓ | Normal | Normal or ↑ |
| Oral HRT for menopause | ↓ | ↑ | ↑ | ↓ |
| Male Hypogonadism | ↑ | Normal or ↓ | ↑ | Normal or ↑ |
| Testosterone replacement for male hypogonadism | No change or ↓ | Normal or ↓ | Normal or ↓ | ↓ |
| Anabolic steroid abuse | ↑ | ↓ | Normal or ↑ | ↓ |
| Gender affirming hormone therapy: | ||||
| Transmen | ↑ | ↓ | ↑ | --------- |
| Transwomen | ----------- | ----------- | ↑ | --------- |
Note: Evidence is limited on the effects of transgender hormone therapy on lipids.
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. (1|⊕⊕⊕◯)
- 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. (2|⊕⊕⊕◯)
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.
- 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. (2|⊕⊕◯◯)
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.
Table 2. Assessment of ASCVD Risk in Patients with Endocrine Diseases
| Suggested Steps in Risk Assessment |
|---|
| Determine if the patient has established ASCVD or long-standing diabetes. If not, proceed with risk assessment. |
| Calculate 10-year risk using the Pooled Cohort Equations (http://static.heart.org/riskcalc/app/index.html#!/baseline-risk) |
| Assess for presence of additional risk enhancing factors. |
| The Endocrine Society considers persistent Cushing syndrome and Cushing disease, high dose chronic glucocorticoid therapy, and possibly adult GHD, acromegaly, and hypothyroidism as risk enhancing factors. |
| In borderline to intermediate risk patients (10-year ASCVD risk 5%–19.9%) consider a CAC score, particularly when risk enhancing factors are present. |
| Conduct a clinician-patient risk discussion, including discussion of lifetime risk and lifetime lipid-lowering treatment benefit, along with patient preferences. |
Figure 1. CVD Events per 1,000 Person-Years by Strata of CAC and LDL-C
Source: Reproduced with permission from Martin SS, Blaha M, Blankenstein R, Agatston A, Rivera JJ, Virani SS, Ouyang P, Jones SR, Blumenthal RS, Budoff MJ, Nasir K. “Dyslipidemia, CAC, and incident ASCVD: implications for statin therapy from the multi-ethnic study of atherosclerosis.” Circulation, 2014; 129(1):77-86.
Table 3. Proposed Decision-Making Approach to Selective Use of CAC Measurement for Risk Prediction
| Using 10-year ASCVD Risk Estimate plus CAC Score to Guide Statin Therapy | |||||
|---|---|---|---|---|---|
| Patient’s 10-year ASCVD risk estimate | <5% | 5%–7.4% | 7.5%–19.9% | ≥20% | |
| Consulting ASCVD risk estimate alone | Statin not recommended | Consider statin | Recommend statin | Recommend statin | |
| Consulting ASCVD risk estimate + CAC | If CAC score = 0 | Statin not recommended | Statin generally not recommended | Statin generally not recommended | Recommend statin |
| If CAC score >0 | Statin may be considered | Recommend statin | Recommend statin | Recommend statin | |
| Does CAC score modify treatment plan? | X CAC less effective for this population | ✔ CAC can reclassify risk up or down | ✔ CAC can reclassify risk up or down | X CAC not effective for this population | |
Source: From Greenland P, Blaha MJ, Budoff MJ, Erbel R, Watson KE. “Coronary Calcium Score and CV Risk.” J Am Coll Cardiol. 2018; 72(4): 434-447.
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. (1|⊕◯◯◯)
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.
- 2.2 In patients with TG-induced pancreatitis, we suggest against the use of acute plasmapheresis as first-line therapy to reduce TG levels. (2|⊕◯◯◯)
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.
- 2.3 In patients without diabetes who have TG-induced pancreatitis, we suggest against the routine use of insulin infusion. (2|⊕◯◯◯)
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 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. (2|⊕⊕⊕◯)
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.
- 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. (2|⊕◯◯◯)
Technical Remark:
- Bile acid sequestrants are contraindicated when TG are above 500 mg/dL (5.6 mmol/L).
