RESUMEN
CONTEXT: Patients with nonfunctioning adenomas (NFA), adenomas with mild autonomous cortisol secretion (MACS) and Cushing syndrome (CS) demonstrate an increased cardiovascular risk. OBJECTIVE: 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 subjects (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, BMI, 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 TRL size (odds ratio (OR) ranging from 1.22 to 2.08) and total LDLP (OR ranging from 1.22 to 1.75) and decreased LDL and HDL size compared to referent subjects. In fully adjusted analysis, LDLP concentrations remained elevated in all patient categories (odds ratios ranging from 1.31 to 1.84). Total cholesterol, LDL cholesterol, triglycerides and apolipoprotein B 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 subjects 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.
RESUMEN
OBJECTIVE: Patients with nonfunctioning adrenal adenomas (NFA) and mild autonomous cortisol secretion (MACS) demonstrate an increased risk of chronic kidney disease (CKD), however factors associated with CKD are unknown. We aimed to identify the factors associated with CKD and assess the impact of adrenalectomy on kidney function in patients with NFA or MACS. DESIGN: Single-center cohort study of patients with NFA and MACS, 1999-2020. METHODS: MACS was diagnosed based on post-dexamethasone cortisol (DST) ≥ 1.8 mcg/dL. Age, sex, dysglycemia, hypertension, therapy with statin, angiotensin converting enzyme inhibitor, or angiotensin II receptor blocker were included in the multivariable analysis. Outcomes included estimated glomerular filtration rate (eGFR) at the time of diagnosis with MACS or NFA and post-adrenalectomy delta eGFR. RESULTS: Of 972 patients, 429 (44%) had MACS and 543 (56%) had NFA. At the time of diagnosis, patients with MACS had lower eGFR (median 79.6 vs 83.8â ml/min/1.73m2, p < 0.001) than patients with NFA. In a multivariable analysis, factors associated with lower eGFR were older age, hypertension, and higher DST. In 204 patients (MACS: 155, 76% and NFA: 49, 24%) treated with adrenalectomy, post adrenalectomy eGFR improved in both groups starting at 18 months up to 3.5 years of follow up. Factors associated with increased eGFR were younger age, lower pre-adrenalectomy eGFR and longer follow-up period. CONCLUSION: DST cortisol is an independent risk factor for lower eGFR in patients with adrenal adenomas. Both patients with MACS and NFA demonstrate an increase in eGFR post-adrenalectomy, especially younger patients with lower eGFR pre-adrenalectomy.
RESUMEN
The AMP-activated kinase (AMPK) is an important enzyme involved in the regulation of cell metabolism, whose activity is regulated by several mechanisms, mainly the increased concentration of AMP. This enzyme catalyze the phosphorylation of several regulatory proteins implicated in the metabolism of lipids and carbohydrates, upregulating their catabolism. Thus, the AMPK plays an important role in the pathophysiology of some diseases, such as metabolic syndrome and type 2 diabetes mellitus, which have a high prevalence among Mexican population. Because of this, the AMPK has become a relevant target for several drugs used in the management of these pathologies, e.g. metformin and pioglitazone.
La cinasa activada por AMP (AMPK) es una enzima crucial en la regulación del metabolismo energético celular, cuya actividad se encuentra regulada por diversos mecanismos, entre los cuales el principal es el aumento en la concentración intracelular de AMP. Esta enzima cataliza la fosforilación de múltiples proteínas reguladoras de las vías metabólicas de lípidos y de hidratos de carbono, con lo que favorecen su catabolismo. Debido a esto, ejerce un papel importante en la fisiopatología de enfermedades como el síndrome metabólico y la diabetes mellitus tipo 2, las cuales tienen una alta prevalencia en la población mexicana. En vista de lo anterior, la AMPK se ha convertido en diana terapéutica relevante en el que actúan diversos fármacos utilizados en el manejo de estas patologías, como es el caso de la metformina y la pioglitazona.