Cardio-metabolic consequences of mild adrenal glucocorticoid excess

Patients with incidentally identified adrenal adenoma (adrenal incidentaloma), and low excess cortisol secretion, defined as morning cortisol concentration 50 - 140 nmol/L after 1 mg dexamethasone will identified. Dexamethasone is administered via oral capsule as part of routine clinical care to evaluate for autonomous cortisol secretion in all patients with adrenal incidentaloma. As such, prior to study enrolment, patients will have had this test performed by their usual endocrinologist or treating physician. Study investigators will review incoming referrals to the Endocrine Department at Flinders Medical Centre and the Lyell McEwin Hospital to identify potential participants who have adrenal incidentaloma and have already had a 1mg dexamethasone test performed to identify patients with adrenal incidentaloma and mild autonomous cortisol secretion and a control group of patients with non-functioning adrenal incidentaloma. Participant commitment will consist of one study visit to the Endocrine Research Unit lasting 5-6 hours and 24 hour blood pressure monitoring on one occasion only. Following a 10 hour overnight fast, participants will attend the Endocrine Research Unit at Southern Adelaide Diabetes and Endocrine Services at 0800 on the study day. Baseline anthropometric measures including height, weight and waist circumference will be collected. An intravenous cannula will be inserted into the antecubital fossa and baseline blood samples for glycated haemoglobin (HbA1c), insulin and glucose will be collected. The following investigative procedures will be performed: 1. Endothelial function, will be evaluated via peripheral arterial tonometry. This will be performed using an Endo-Pat 2000 device (Itamar Medical). A finger plethysmograph will be placed on each hand. This will record finger arterial pulsatile volume changes. Baseline readings will be performed, after which local ischaemia is induced in one arm by inflating a blood pressure cuff to suprasystolic pressures for 5 mins. The blood pressure cuff will then be deflated, and the change in pulse amplitude will be used to estimate endothelial function. 2. Insulin sensitivity, will be estimated from measurements of glucose and insulin before and every 30 minutes for 2 hours after a mixed meal (10kcal/kg, 45% carbohydrate, 15% protein, 40% fat) using the Matsuda index. 3. Fat oxidation, will be evaluated using indirect calorimetry which will be performed using a ventilated hood technique (Parvo Medics True One 2400 Metabolic Measurement System, Parvo Medics, Sandy, UT). This will be performed fasting and 120 mins following the meal. Indirect calorimetry is the method by which type and rate of substrate utilisation and energy metabolism is estimated from gas exchange measurements. Substrate oxidation and resting energy expenditure will be calculated using equations of Ferrannini. Diet-induced thermogenesis will be calculated as the percentage increase in energy expenditure after the mixed-meal. 4. Body composition and bone mineral density at the hip and spine, will be quantified by dual energy X-ray (DEXA), which will quantify lean body mass, total fat mass and central abdominal fat and bone mineral density. 5. 24 hour ambulatory blood pressure, will be evaluated using oscillometric methods using the Mobil-O-Graph PWA (I.E.M. GmbH, Germany). Blood pressure cuff will be worn for 24 hours on the upper arm and blood pressure measurements will be taken every hour. Participants will commence 24 hour ambulatory blood pressure monitoring at the completion of the study day outlined above and will return it to SADES the following day.