High LDL Particle and APOB Concentrations in Patients With Adrenal Cortical Adenomas

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2024 Jun 13

PMID 38870260

Authors

Rashi Sandooja

Jasmine Saini

Annop Kittithaworn

Raul Gregg-Garcia

Prerna Dogra

Elizabeth Atkinson

Kai Yu

Vanessa Fell

Vinaya Simha

Margery A Connelly

Robin P F Dullaart

Irina Bancos

Affiliations

Soon will be listed here.

Abstract

Context: Patients with nonfunctioning adenomas (NFAs), adenomas with mild autonomous cortisol secretion (MACS) and Cushing syndrome (CS) demonstrate an increased cardiovascular risk.

Objective: This work aimed to determine the extent of lipoprotein abnormalities in NFA, MACS, and CS.

Methods: We conducted a single-center, cross-sectional study of patients with NFA (n = 167), MACS (n = 213), CS (n = 142), and referent individuals (n = 202) between January 2015 and July 2022. Triglyceride-rich lipoprotein particles (TRLP), low-density lipoprotein particles (LDLP), high-density lipoprotein particles (HDLP), their subclasses and sizes were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, body mass index, smoking, hypertension, diabetes and lipid-lowering drug therapy.

Results: In age- and sex-adjusted analysis, all patients categories demonstrated increased very large TRLP, large TRLP, and greater TRLP size (odds ratio [OR], 1.22-2.08) and total LDLP (OR, 1.22-1.75) and decreased LDL and HDL size compared to referent individuals. In fully adjusted analysis, LDLP concentrations remained elevated in all patient categories (OR, 1.31-1.84). Total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B (ApoB) were also higher in all patient categories in age- and sex-adjusted analysis, with ApoB remaining elevated in all patient categories in fully adjusted analysis. Similar LDLP and ApoB elevations were observed in all patient categories after excluding individuals on lipid-lowering therapy.

Conclusion: Patients with overt, mild, and even absent cortisol excess demonstrate lipoprotein profile abnormalities, in particular, high LDLP and ApoB concentrations, which conceivably contribute to high cardiometabolic risk.

References

Patrova J, Mannheimer B, Lindh J, Falhammar H . Mortality in Patients With Nonfunctional Adrenal Tumors. JAMA Intern Med. 2023; 183(8):832-838. PMC: 10294015. DOI: 10.1001/jamainternmed.2023.2442. View

Ribeiro Cavalari E, de Paula M, Arruda M, Carraro N, Martins A, de Souza K . Nonfunctioning adrenal incidentaloma: A novel predictive factor for metabolic syndrome. Clin Endocrinol (Oxf). 2018; 89(5):586-595. DOI: 10.1111/cen.13822. View

Prete A, Subramanian A, Bancos I, Chortis V, Tsagarakis S, Lang K . Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study. Ann Intern Med. 2022; 175(3):325-334. DOI: 10.7326/M21-1737. View

Di Dalmazi G, Vicennati V, Garelli S, Casadio E, Rinaldi E, Giampalma E . Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing's syndrome: a 15-year retrospective study. Lancet Diabetes Endocrinol. 2014; 2(5):396-405. DOI: 10.1016/S2213-8587(13)70211-0. View

Taskinen M . Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia. 2003; 46(6):733-49. DOI: 10.1007/s00125-003-1111-y. View

Zhang C, Li D, Kaur R, Ebbehoj A, Singh S, Atkinson E . Cardiometabolic Outcomes and Mortality in Patients with Adrenal Adenomas in a Population-based Setting. J Clin Endocrinol Metab. 2021; 106(11):3320-3330. PMC: 8530703. DOI: 10.1210/clinem/dgab468. View

Steffen B, Guan W, Remaley A, Paramsothy P, Heckbert S, McClelland R . Use of lipoprotein particle measures for assessing coronary heart disease risk post-American Heart Association/American College of Cardiology guidelines: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2014; 35(2):448-54. PMC: 4304970. DOI: 10.1161/ATVBAHA.114.304349. View

Mora S, Otvos J, Rifai N, Rosenson R, Buring J, Ridker P . Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation. 2009; 119(7):931-9. PMC: 2663974. DOI: 10.1161/CIRCULATIONAHA.108.816181. View

Sampson M, Ling C, Sun Q, Harb R, Ashmaig M, Warnick R . A New Equation for Calculation of Low-Density Lipoprotein Cholesterol in Patients With Normolipidemia and/or Hypertriglyceridemia. JAMA Cardiol. 2020; 5(5):540-548. PMC: 7240357. DOI: 10.1001/jamacardio.2020.0013. View

10.

Shalaurova I, Connelly M, Garvey W, Otvos J . Lipoprotein insulin resistance index: a lipoprotein particle-derived measure of insulin resistance. Metab Syndr Relat Disord. 2014; 12(8):422-9. PMC: 4175429. DOI: 10.1089/met.2014.0050. View

11.

Ebbehoj A, Li D, Kaur R, Zhang C, Singh S, Li T . Epidemiology of adrenal tumours in Olmsted County, Minnesota, USA: a population-based cohort study. Lancet Diabetes Endocrinol. 2020; 8(11):894-902. PMC: 7601441. DOI: 10.1016/S2213-8587(20)30314-4. View

12.

Higgs J, Quinn A, Seely K, Richards Z, Mortensen S, Crandall C . Pathophysiological Link between Insulin Resistance and Adrenal Incidentalomas. Int J Mol Sci. 2022; 23(8). PMC: 9032410. DOI: 10.3390/ijms23084340. View

13.

Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray K, Thompson A . Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009; 302(18):1993-2000. PMC: 3284229. DOI: 10.1001/jama.2009.1619. View

14.

Bancos I . Adrenal Incidentalomas: Insights Into Prevalence. Ann Intern Med. 2022; 175(10):1481-1482. DOI: 10.7326/M22-2600. View

15.

Elhassan Y, Alahdab F, Prete A, Delivanis D, Khanna A, Prokop L . Natural History of Adrenal Incidentalomas With and Without Mild Autonomous Cortisol Excess: A Systematic Review and Meta-analysis. Ann Intern Med. 2019; 171(2):107-116. DOI: 10.7326/M18-3630. View

16.

Howard B, Abbott W, Egusa G, Taskinen M . Coordination of very low-density lipoprotein triglyceride and apolipoprotein B metabolism in humans: effects of obesity and non-insulin-dependent diabetes mellitus. Am Heart J. 1987; 113(2 Pt 2):522-6. DOI: 10.1016/0002-8703(87)90625-9. View

17.

Nieman L, Biller B, Findling J, Murad M, Newell-Price J, Savage M . Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015; 100(8):2807-31. PMC: 4525003. DOI: 10.1210/jc.2015-1818. View

18.

. 2. Classification and Diagnosis of Diabetes: . Diabetes Care. 2020; 44(Suppl 1):S15-S33. DOI: 10.2337/dc21-S002. View

19.

Taskinen M, NIKKILA E, PELKONEN R, Sane T . Plasma lipoproteins, lipolytic enzymes, and very low density lipoprotein triglyceride turnover in Cushing's syndrome. J Clin Endocrinol Metab. 1983; 57(3):619-26. DOI: 10.1210/jcem-57-3-619. View

20.

Tauchmanova L, Rossi R, Biondi B, Pulcrano M, Nuzzo V, Fazio S . Patients with subclinical Cushing's syndrome due to adrenal adenoma have increased cardiovascular risk. J Clin Endocrinol Metab. 2002; 87(11):4872-8. DOI: 10.1210/jc.2001-011766. View