Endocrine Abstracts

Cushing’s syndrome (CS) is a severe disease associated with elevated morbidity and mortality rates, up to four times higher than those of general population. Whether the positive effects of cortisol-lowering medications is widely documented in overt CS cases, its impact on mild or subclinical CS remains unclear since limited clinical investigations have been performed in patients with subclinical hypercortisolism. In this study, we retrospectively analysed clinical data from patients with mild CS treated with either Ketoconazole or Metyrapone. Inclusion criteria were: serum cortisol levels after dexamethasone suppression test >50 nmol/l, slight increase of urinary free cortisol (UFC) levels (<2 times the upper limit of normal) and/or impaired circadian rhythm of cortisol. Our aim was to evaluate the effects of steroidogenesis inhibitors on UFC, late-night salivary cortisol (LNSC), ACTH, metabolic parameters, and blood pressure in these patients. Twenty-five patients (20F and 5 M) met the inclusion criteria, with 12 diagnosed with adrenal CS and 13 with Cushing’s Disease. Fifteen patients were treated with Metyrapone and ten with Ketoconazole. Significant reduction in UFC levels were observed after 6 (median [IQR] levels 120 [65 – 162] nmol/24 h, P 0, 021) and 12 months of treatment (74 [48 – 146], P 0, 008) compared to baseline (178 [116 – 255], along with a reduction in LNSC (baseline 3.7 [3.4 – 5.1] nmol/l, 12 months 2.7 [1.7 – 3.6] P 0, 022) and increase in ACTH levels at 12 months (baseline 17.7 [6.7 – 43.8] ng/l, 12 months (33 [7.9 – 58.5], P 0, 033). However, metabolic parameters such as glucose, HbA1c, LDL cholesterol, waist circumference and blood pressure did not change over time. The subgroup analysis of patients treated with Metyrapone also showed an improvement of glucose metabolism both at 6 and 12 months. Conversely, patients treated with Ketoconazole did not experience any of these changes. Additionally, we considered patients treated for more than 12 months. Sixteen patients were included, with follow-up period which ranged from 13 to 125 months. We observed a significant reduction in UFC, total cholesterol, LDL (baseline 124 [102.75 – 144.3] mg/dl, last follow-up 87.2 [75.7 – 111.3], P 0, 028) and an increase in ACTH levels. To conclude, metyrapone might be considered to control mild/subclinical CS. Although no metabolic effects were observed after 6-12 months of treatment, an improvement in lipid profile was observed in patients treated for a longer period. Further studies are needed to evaluate the metabolic and cardiovascular implications of medical therapy in these patients.