Adrenal incidentalomas are clinically silent masses discovered inadvertently during diagnostic imaging procedures performed for unrelated reasons. Radiological studies report a frequency of these masses around 3% in the age of 50 years, which increases up to 10% in the elderly. Mild hypercortisolism, recently redefined as possible autonomous cortisol secretion (pACS), is characterized by an incomplete suppression of the hypothalamic-pituitary-adrenal axis without the typical signs of overt cortisol hypersecretion (1,2). It is well known that overt hypercortisolism (Cushing's Syndrome) is associated with cardiovascular disease and in particular with left ventricular hypertrophy and hypertension, typically not presenting nocturnal blood pressure-dipping (3). Current retrospective data revealed that even asymptomatic patients with adrenal incidentalomas and pACS suffer from a higher rate of cardiovascular events and mortality than patients with normal HPA-axis suppression (4). Our group recently described on European Journal of Endocrinology that mild autonomous cortisol secretion can sustain early cardiac and vascular remodeling, showing that both mean left ventricular mass index and prevalence of left ventricular hypertrophy was higher in pACS than in non-functioning adenomas patients (5). Despite hypertension is one of the most common clinical features of patients with mild hypercortisolism, prospective studies documenting circadian blood pressure profile in these patients are lacking. The aim of this study is to assess 24-h ambulatory blood pressure monitoring (ABPM) in patients with adrenal incidentalomas and mild hypercortisolism, focusing on the impact of dipping and non-dipping profiles.
(1) Debono M et al. Curr Opin Endocrinol Diabetes Obes 2015
(2) Fassnacht M et al.Eur J Endocrinol 2016
(3) Pivonello R, Isidori AM et al.Lancet Diabetes Endocrinol 2016
(4) Morelli V, et al. Eur J Endocrinol 2017
(5) Sbardella E. Minnetti M. et al. Eur J Endocrinol 2018
In 2015, our group besides the ABC Study Group (Altogether to Beat Cushing's syndrome) wrote a comprehensive review about the controversies in the pathophysiology of hypertension of Cushing¿s syndrome on Journal of Hypertension (1). The mechanisms through which hypercortisolism induces hypertension are complex and only partially understood, involving the renin¿angiotensin system, the mineralocorticoid activity, the sympathetic nervous system, and the vasoregulatory system, together with indirect mechanisms. A tendency towards higher blood pressure is seen in adrenal over pituitary tumors associated with Cushing's syndrome. This difference might be related to the specific vasoactive effects of adrenal sex steroids (androgens, estrogen and their metabolites), which are generally suppressed in cortisol-secreting adrenal tumors. No nocturnal blood pressure dipping (i.e., decrease by 10% of daytime values) was observed in most of patients during active overt hypercortisolism. As well Cushing's syndrome, the association of pACS due to an adrenal incidentaloma and hypertension has been shown in several studies. Mild hypercortisolism appears to have a higher prevalence in patients with resistant hypertension compared to the general hypertensive population. Chronic exposure to glucocorticoids, even mild, can induces metabolic and cardiovascular disturbances, which are mediated by glucocorticoid and mineralocorticoid receptors and modified by local metabolism of glucocorticoids by the 11ß-hydroxysteroid dehydrogenase enzymes. Glucocorticoids also have several direct effects on endothelial system such as impairing endothelium dependent vasodilatation and increasing perivascular inflammation. Several retrospective studies found that hypertension was significantly higher in patients with pACS compared with those with nonfunctioning tumors (2,3,4). Casual blood pressure (CBP) measurements using a standard sphygmomanometer have traditionally constituted the principal modality for the assessment and management of hypertension. However, ambulatory blood pressure monitoring (ABPM) provides abundant information on blood pressure (BP), including heart rate, all BP readings for test periods, BP variability, BP load, BP average, distribution pattern of BP, reduction percentage of BP, and summary statistics for overall 24-hour, daytime and nighttime periods. These data could help to correctly understand and characterize the molecular mechanism or pathway through which mild autonomous secretion can induce cardiac damage and underline the importance of careful monitoring of cardiovascular risk in this subgroup of patients.
(1) Isidori AM, et al. J Hypertens 2015 33 44-60.
(2) Terzolo M, et al. Endocrinology and Metabolism Clinics of North America 2005
(3) Tauchmanova L, et al. Journal of Clinical Endocrinology and Metabolism 2002
(4) Morelli V. et al, Clin Endocrinol (Oxf). 2010