Background Reliable laboratory assays are of paramount importance in the field of endocrinology, as our ability to make diagnoses and recommend the appropriate treatment, rely heavily on them. Clinical Case A 36-year-old woman presented to our clinic with a history of a 30-pound weight gain over the course of a year and hypertension that was sub-optimally controlled on two antihypertensive medications. On physical exam she exhibited facial plethora, moon facies, central obesity, dorsocervical fat pad, and reddish abdominal striae. Laboratory data revealed a 24 hr urine free cortisol 277 mcg/24 h (n ≤ 45 mcg/24 h), 8 am cortisol after 1 mg dexamethasone suppression test 19.2 mcg/dL (cut-off <1.8 mcg/dL) with a dexamethasone level 179 ng/dL (n 140-295 ng/dL). Serum DHEAS <15 mcg/dL (n 35-430 mcg/dL) which was suggestive of an adrenal source of cortisol. CT scan of the adrenals revealed a 3.0×2.3 cm right adrenal nodule, 14 HU, relative washout of 58%, absolute washout of 68%, consistent with an adenoma. However, plasma ACTH was 20 pg/mL (n 0-46 pg/mL) which was suggestive of an ACTH-dependent etiology. Repeat ACTH levels through our local lab ranged between 17-27 pg/mL. An MRI of the brain was obtained which showed a normal pituitary gland without evidence of an adenoma. Due to the discrepancy between the clinical picture and the ACTH levels, the patient's case was discussed with the medical director of our local lab. It was decided to obtain another sample for ACTH which was tested for heterophile antibodies but did not yield any meaningful results. The patient denied being on any supplements that could interfere with the ACTH assay. The sample was then sent out to an outside lab with a plasma ACTH level <1 pg/mL (n 7.2-63 pg/mL), which was consistent with the patient's clinical presentation of an adrenal source of cortisol excess. Further investigation revealed that our local lab used a Siemens Immulite assay which was likely detecting interference, whereas the outside lab used the Roche Elecsys assay. In previous studies, the Roche assay has highly correlated with intact ACTH that has been measured by HPLC-MS/MS. The patient was started on ketoconazole and has been referred for right adrenalectomy. Clinical Lessons Heterophile antibodies and ACTH fragments are common culprits of ACTH immunoassay interference, but they can be difficult to detect if there is not a high index of suspicion. Erroneous laboratory results can lead clinicians to perform unnecessary procedures and delay patient care. This case highlights the importance of a reliable plasma ACTH assay to inform clinical judgment. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

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Background: Quantifying ten-year cardiovascular risk can be challenging. Different online risk calculators provide different risk estimates and online risk calculators use only one point in time. However, risk factors occur over the lifetime of the individual. Purpose: This manuscript provides three solutions to improving ten-year cardiovascular risk assessment in individuals at intermediate risk. Methods: Measuring Lipoprotein(a)-Lp(a) is recommended for assessing cardiovascular risk in all individuals who are in the intermediate risk category by standard online risk calculators. Lp(a) is primarily determined by genetic inheritance. It has the undesirable properties of being proatherosclerotic, proinflammatory, and prothrombotic. Measuring apolipoprotein B (apo B) provides a good index of the number of atherosclerotic particles present. Studies have demonstrated that small, dense LDL cholesterol particles are more atherogenic than larger, less dense LDL cholesterol particles. Measuring high sensitivity C-reactive protein (hsCRP) provides a good estimation of the degree of inflammation in the vascular system. Inflammation is a critical component of heart attacks and strokes. It is increased in diabetes and obesity. Treatment to reduce inflammation results in a reduction of cardiovascular events, independent of lipid values. Results: The above three risk factors should be measured in all patients with an intermediate risk score. Routine assays are readily available at a reasonable cost. They are independent risk factors for cardiovascular disease. Their recommendation is based on the pathophysiology of atherosclerotic cardiovascular disease. Successful therapy will result in the decrease of each of these risk factors. Conclusion:The recommended approach will improve the assessment of cardiovascular risk and guide the physician and patient to the correct treatment recommendations.