CLN Article

Diagnostic Profiles

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Patients Newly Diagnosed With Hyperlipidemia Not Being Tested for Thyroid Dysfunction

A retrospective analysis at Boston University Medical Center (BMC) found that contrary to guideline recommendations, only about half of patients with newly diagnosed hyperlipidemia were screened for thyroid dysfunction (JAMA Intern Med 2014;174:287–9). The findings demonstrate the need for more awareness of the guidelines, as well as further study to understand why there is a low rate of thyroid screening in patients with newly diagnosed hyperlipidemia.

Guidelines of the National Cholesterol Education Program, the American Association of Clinical Endocrinologists, and the American Thyroid Association all recommend screening patients newly diagnosed with hyperlipidemia before putting them on lipid-lowering therapy.

The researchers reviewed medical records of nearly 8,800 adult patients managed between 2003 to 2011 at BMC’s general internal medicine or family medicine clinics. The patients all had total serum cholesterol levels ≥200 mg/dL or low-density lipoprotein cholesterol levels ≥160 mg/dL. The authors excluded from their investigation any patients who previously had been prescribed lipid-lowering or thyroid medications.

Overall, 49.5% of patients had their serum thyroid-stimulating hormone (TSH) levels tested within 6 months of hyperlipidemia diagnosis. Of these, 5.2% had elevated TSH levels, and 1.7% had TSH >10 mIU/L, the point at which levothyroxine treatment generally is recommended. In addition, 18.3% of patients had peripheral thyroid function testing, and of these 2.6% had overt hypothyroidism.

The authors also found that about 50% of patients with elevated TSH levels were prescribed levothyroxine. However, 30% of those with TSH levels >10 mIU/L did not receive thyroid medications. Among the patients who went on levothyroxine, 75% did not require a lipid-lowering agent within 1 year.

β-amyloid Brain Deposits, Cholesterol Fractions Linked

In a cross-sectional study of seniors, elevated β-amyloid (Aβ) was associated with cholesterol fractions in a pattern similar to that found in coronary artery disease (JAMA Neurol 2014;71:195–200). The findings suggest that a better understanding of how serum lipids modulate Aβ could offer new approaches to slowing Aβ deposition in the brain, thereby reducing the incidence of Alzheimer’s disease.

The study involved 74 patients with a mean age of 78 who were recruited from stroke clinics and community senior facilities. In total, 33 were cognitively normal, 38 had mild cognitive impairment, and three had mild dementia.

The authors conducted the study because cholesterol, which is vital to neuronal structure and function, also plays an important role in Aβ synthesis, deposition, and clearance. Apolipoprotein E (APOE) is the primary cholesterol transporter in the brain, and an APOE gene allele has been associated with earlier and higher Aβ levels in the brain. The epidemiological evidence about a link between serum cholesterol and development of Alzheimer’s disease, however, is complicated.

The mean fasting total cholesterol was 171 mg/dL, and mean low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were 92 mg/dL and 54 mg/dL, respectively. The researchers measured Aβ via the Global PIB Index, which averages c-11-labeled Pittsburgh Compound B retention in areas of the brain prone to amyloidosis.

After running a series of multiple linear regression models that controlled for age and APOE ε4 allele, the researchers found independent associations among the levels of LDL-C, HDL-C, and PIB Index. The authors suggested that “this is the first human experimental evidence” of a direct relationship between cholesterol fractions in blood and amyloid deposition in the brain.

Elevated Cardiac Troponin Levels Linked to Post-Operative Myocardial Injury, Death in Noncardiac Surgery Patients

Myocardial injury after noncardiac surgery (MINS) is common and associated with substantial mortality, according to findings from the vascular events in noncardiac surgery patients cohort evaluation (VISION) (Anesthesiology 2014;120:564–78).

The authors conducted the study because of emerging evidence that some patients experience myocardial injury in the perioperative period which, while not meeting the diagnostic criteria for myocardial infarction, still puts these individuals at risk for poor prognosis. VISION is a large, international, prospective cohort study evaluating complications after noncardiac surgery.

The authors defined MINS as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days of noncardiac surgery, with a peak cardiac troponin T (cTn) level of 0.03 ng/mL as the threshold for MINS.

This study involved 15,065 patients at least 45 years of age who underwent inpatient, noncardiac surgery and had cTn levels measured during the first 3 post-operative days. Patients whose cTn elevations were adjudicated as having non-ischemic etiologies, such as sepsis, were excluded.

The researchers found that MINS independently predicted 30-day mortality, with an adjusted hazard ratio of 3.87, and that it explained about 34% of deaths that occur within 30 days after noncardiac surgery, the highest population-attributable risk of the perioperative complications explored in this study.

Overall 8% of subjects had MINS, but only about 40% of them would have met the universal definition of myocardial infarction and <16% experienced ischemic symptoms. According to the authors, these findings highlight the need for clinical trials to establish strategies to prevent and treat this important complication of surgery.

FT4 Immunoassay Misclassifies Hypothyroidism in Comparison to LC-MS/MS

A pilot study found that in comparison to liquid chromatography-tandem mass spectrometry (LC-MS/MS), the direct analogue immunoassay method for measuring serum free thyroxine (FT4) concentrations results in many patients being misclassified as having subclinical hypothyroidism, when they actually have overt hypothyroidism (Clin Chim Acta 2014;430:121–4).

The authors were interested in exploring the performance of FT4 direct analogue immunoassays because they are known to be influenced by changes in binding protein concentrations, and appear to perform poorly in individuals with thyroid disease. At the same time, LC-MS/MS has been shown to correlate better with log thyroid stimulating hormone (TSH) and with the gold standard equilibrium dialysis method.

The study involved 53 outpatient samples received at the NIH Clinical Center with elevated TSH levels but FT4 concentrations within the laboratory reference interval. In all, 17 samples were excluded because the patients they came from had known thyroid disease or were receiving thyroid hormone replacement therapy or other medications known to affect FT4 or TSH values. From the remaining 40 samples, 65% (26) had either or both FT4 or free triiodothyronine (FT3) levels below LC-MS/MS reference levels. The researchers also found bias between the LC-MS/MS and immunoassay values, with FT4 immunoassay values being on average 48% lower than LC-MS/MS values and FT3 immunoassay values being on average 36% higher.

The authors indicated they intended to confirm these findings in a larger follow-up study in which they first measure FT4 via LC-MS/MS with selected samples analyzed with immunoassay.