Endocrine Abstracts

Introduction Primary bilateral macronodular adrenal hyperplasia (PBMAH) is potentially responsible for variable degree of cortisol excess. In patients with PBMAH the complete remission of cortisol hypersecretion can be achieved only by performing bilateral adrenalectomy, leading to a persistent hypocortisolism and to a consequent need of a lifelong glucocorticoid replacement therapy. Therefore, bilateral adrenalectomy is worth doing only in patients with severe hypercortisolism, while a medical treatment could be a valid alternative for patients with mild Cushing’s syndrome (mCS), particularly in the presence of possibly related clinical conditions (i.e. diabetes, hypertension and bone fragility). In this scenario, steroid synthesis inhibitors, such as metyrapone, have been proposed as possible therapeutic options. We report two cases of PBMAH with mCS treated with low doses of metyrapone (mean dose of 500 mg). Before and after 6 months of therapy, an assessment of clinical consequences of mCS was performed with a 24-hour ambulatory blood pressure monitoring (ABPM) and an oral glucose tolerance test (OGTT).

Case reports: Case 1. A 68 years old male with history of scarcely controlled arterial hypertension. The basal OGTT was consistent with a diabetes diagnosis (fasting glucose levels 128 mg/dl, 2-hour OGTT glucose levels 202 mg/dl). After 6 months of treatment, he achieved: i) the remission of diabetes (fasting glucose levels 97 mg/dl. 2-hour OGTT glucose levels 122 mg/dl) with no changes in anti-diabetic therapies; ii) the ABPM documented improvement in mean blood pressure values (147/80 mmHg and 121/63 mmHg, respectively before and 6 months after treatment). Case 2. A 79 years old female with a history of osteoporosis with 4 clinical vertebral fractures, arterial hypertension and depressive disorder. Before starting the therapy, she had an impaired fasting glucose (104 mg/dl) with a normal response to the glucose load (post-OGTT glucose levels 96 mg/dl). After six months of therapy, we observed: i) the normalization of basal glucose levels (90 mg/dl) and the persistence of a normal OGTT response (132 mg/dl); ii) the important reduction of anti-hypertensive medications with ABPM documented stable mean blood pressure values (119/68 mmHg); iii) the striking amelioration of the depressive disorder and cognitive function. In both patients metyrapone was well tolerated without signs or symptoms of hypocortisolism. In the first patient, potassium levels decreased during the treatment period but remaining within the normal range.

Discussion: Our observations suggest that low doses of metyrapone are well-tolerated and can improve blood pressure and glycemic control in PBMAH and mCS