Improvement in imaging technique has resulted in detection o f increased number of adrenal incidentalomas, thus they are being found incidentally in millions o f people w orldw ide2. It is a common problem; up to 7% o f all patients over 60 may harbor a benign growth.
Because the incidence o f adrenal incidentalomas increases with age, appropriate management o f adrenal incidentalomas will be a growing public health challenge for the aging society.
The medical imaging technique o f magnetic resonance imaging or MRI makes use o f strong magnetic fields and radio waves to form images o f the body. It has a wide variety of applications in hospitals, from medical diagnosis to staging and follow-up o f disease. With the advancement o f biomedical research more advance and sensitive M RIs have been developed. According to a recent article in Stanford News, scientists from Stanford and IBM have improved the sensitivity of magnetic resonance imaging by 100 million times using a new technique for measuring tiny magnetic forces. Which allows dramatic improvement o fresolving power, achieving a resolution down to 4 nanometers (nm). W hereas on one hand increased sensitivity o f MRI would be a very helpful diagnostic tool in clinical setting, on the other hand it will increase the number o f incidental findings like incidentalomas. As incidentalomas are not clinically apparent there is a risk o f over diagnosis with them. Incidentalomas are commonly found in following organs adrenal glands, kidneys, pituitary gland, thyroid gland, parathyroid gland, lungs, liver and lumbosacral spine. The differential diagnosis for adrenal incidentaloma is nonfunctioning adenoma, pheochromocytoma,
cortisol producing adenoma, aldosteronoma, adrenocortical carcinoma, adrenal cyst, ganglioneuroma and myelolipoma.
About 5% to 47% o f the adrenal incidentalomas may secrete mild amounts o f cortisol without symptoms o f Cushing’s syndrome. This is referred to as Subclinical Cushing Syndrome Cortisol causes insulin resistance by affecting both insulin-dependent glucose uptake in the peripheral tissues and enhancing gluconeogenesis in the liver
Cortisol also increases vagal stimulation o f insulin secretion with its central action Cortisol impairs endothelium-dependent vasodilatation and increases vascular smooth muscle contractility . Evidence suggests that there is a link between cortisol excess and atherosclerosis. Carotid intima media thickness, is a marker o f systemic atherosclerosis
There has been quite a number o f studies on adrenal incidentalomas and their association with the adverse cardiovascular risk profile but there are limited studies carried out that assess the association between cardiovascular events and adrenal incidentalomas8,9 In our study It was found that the patients with functional adrenal incidentaloma group had increased risk of cardiovascular events like stroke, ischemic heart disease, arrhythmia, heart failure when compared to nonfunctional adrenal incidentaloma group, Odds Ratio=3.63 was highly significant with 95% C.1=2.227-5.938. Z value=5.159, p value=0.000 which was also statistically significant, i squared=.000 indicating that there was minimum heterogeneity.
It was also found that functional adrenal incidentaloma group have an increased risk of hypertension as compared nonfunctional adrenal incidentaloma group, Odds Ratio =1.871 with 95% C.I= 1.302-2.688 was statistically significant. Z value=3.389, p value=.001 which was also statistically significant, i squared=43.006 which indicates medium to low
The risk o f diabetes mellitus was also increased in functional adrenal incidentaloma group when compared nonfunctional adrenal incidentaloma group, Odds Ratio =2.706, with 95%C.I=1.623 -4 .5 1 1 was statistically significant. Z value= 3.819, p value=.000 was also statistically significant, i sq=.000 which indicates minimum heterogeneity.
Our results also demonstrate that adrenal incidentaloma group (which includes both functional and nonfunctional adrenal incidentalomas ) have a 2.9 times increased risk of hypertension when compared to healthy control group, OR= 2.918 with 95% C.I= (1.184 -7.195) which is statistically significant, Z value=2.326, p value=.020 which is also statistically significant, i squared= 24.325 which indicates medium to low heterogeneity There are also increased levels o f fasting blood glucose in adrenal incidentaloma group when compared to healthy control group as shown by effect size=0.281 with 95%C.I=0
.014-0.549 which is statistically significant, z value=2.064, p value=.039 is also statistically significant, i sq.=.000 indicating minimum heterogeneity. Adrenal incidentaloma group have an increased levels o f carotid intima media thickness when compared to healthy control group, effect size= l.805 with 95% C.I= 1.437 -2.174 which is statistically significant =_z value=9.602 p value= .000 is also statistically significant. However i sq. = 95.370 indicating high heterogeneity Adrenal incidentaloma group have a small increase in levels o f fibrinogen as compared to healthy control g roup ,effect size point estimate=0.658 with 95 % C.I=(0.311- 1.004) which is statistically significant, z value=3.724, p value=0.000 which is also statistically
significant, however i sq.=95.822 indicating high heterogeneity.
There is increasing evidence that several cardio metabolic risk factors such as diabetes mellitus and hypertension, occur with higher prevalence in nonfunctional adrenal incidentaloma patients compared to age-matched healthy subjects In a recent study of 92 patients with adrenal incidentalomas, predominantly nonfunctional adrenal incidentaloma the rates of hypertension and diabetes were three- and fivefold higher respectively, than those reported in the general population
A study conducted by Yener et a l.35 analyzed carotid intima media thickness values of subjects with nonfunctional adrenal incidentaloma and reported significantly increased carotid intima media thickness in these patients. The difference was determined to be due to the higher body mass indices o f the adrenal incidentaloma group. When the adrenal incidentaloma group was compared with a body mass index -matched control group, there was no significant difference between the carotid intima media thickness values o f the two groups.
Coagulation system disturbances are strongly associated with insulin-resistant state and fibrinogen levels are a part o f it, our results showed that fibrinogen levels were increased in adrenal incidentaloma group vs. healthy control group but the results o f the test had high heterogeneity.
Chronic cortisol excess has been implicated in central obesity, systemic arterial hypertension, impaired glucose tolerance, insulin resistance, altered lipid profile, and hypercoagulability these factors confer increased cardiovascular risk which can lead to adverse cardiovascular events like stroke, heart failure, arrhythmia, ischemic heart disease,and myocardial infarction. Thus mild hypercortisolism can lead to increased mortality, due to cardiovascular events.
On diagnosis o f an adrenal incidentaloma the two important things to consider are its size and its radiographic appearance. Adrenal incidentalomas >4 cm are recommended for complete removal by Adrenalectomy. Adrenal incidentalomas <4 cm may also be recommended for removal if they are hormonally active, otherwise observation is recom m ended. Hormonal evaluation o f adrenal incidentalomas include 1 -mg overnight dexamethasone suppression test, 24-hour urinary specimen for measurement o f fractionated metanephrines and catecholamines, blood plasma aldosterone concentration and plasma
renin activity, if hypertension is present On CT scan, benign adrenal incidentalomas are typically o f low radiographic density (due to fat content) and show rapid washout o f contrast medium. If the hormonal evaluation is negative and imaging suggests benign lesion, follow up should be considered. Imaging at 6,12, and 24 months and repeat hormonal evaluation yearly for 4 years is often recommended.
Hypertension is a predictor o f major cardiovascular events and total mortality in the elderly . lOmmHg reduction in systolic blood pressure is associated with a one third decrease in risk o f stroke in subjects aged 60 to 79 y ears.Thus adequate control o f hypertension is important in adrenal incidentaloma patients. Also management and control o f blood glucose levels, hyperlipidemia and weight reduction are key elements in decreasing the risk of cardiovascular disease in these patients.
According to some authors, patients with adrenal incidentalomas should be followed only with clinical and radiological examinations. 29-30 Other authors claim that the high prevalence of cardiovascular risk factors in patients with adrenal masses, both Subclinical Cushing Syndrome and non-functioning tumors, requires surgical treatment, especially in patients
with hypertension, obesity, and diabetes.29,31,32 This meta-analysis has some limitations. The total number of studies which were included is quite small and there was no optimal quality for some of the studies included. Few studies were measuring our primary outcome o f interest and some studies had m issing data thus we could not include them in our analysis. Studies had different comparison arms, some were comparing different types o f adrenal incidentalomas like functional vs. nonfunctional, and others were comparing functional and nonfunctional adrenal incidentalomas with healthy control group. Detailed subgroup analysis was not done as part o f this meta-analysis. Thus the matter o f adrenal incidentalomas and their relation with adverse cardiovascular profile is still a matter o f debate and many aspects are still inconclusive. There is requirement for further research regarding the risk o f cardiovascular disease, cardiovascular events and the mortality due to the cardiovascular events in patients with adrenal incidentalomas.