Endocrine Abstracts

Cushing’s Disease (CD) is severe clinical condition due to an ACTH-secreting pituitary tumor. Here we present the case of a 25-years old male who came to our attention for hypertension, moon face, acanthosis nigricans, abdominal purple striae and central obesity. The diagnosis of CD was based on the presence of high plasma cortisol after dexamethasone suppression test and elevated urinary free cortisol levels (UFC, 6-fold higher the upper limit of normality (ULN)). The pituitary MRI revealed a small lesion (5.5 mm), which was removed by transsphenoidal surgery, and it was later on confirmed as a corticotroph tumor at the pathology report. Surgery led to a slight improvement of symptoms. However, two months after the intervention, the patient experienced a worsening of the clinical picture, and the following biochemical assessment was suggestive of an early disease relapse. First, pasireotide was administered, although with low efficacy in reducing cortisol secretion. Then, a novel steroidogenesis-inhibitor, available only for investigational use in the context of a clinical trial, was started, but the patient withdrawn due to safety concerns. Therefore, low dose metyrapone was prescribed. However, severe gastrointestinal side effects occurred, and the drug was discontinued after few months. Furthermore, during imaging follow-up, the suspicion for a recurrent pituitary lesion was raised. Following a multidisciplinary discussion, inferior petrosal sinus sampling was performed, confirming the disease recurrence. Based on the expected low success rate, the team avoided a second surgery. Ketoconazole (600 mg/day) was then administered, leading for the first time to UFC normalization. Unfortunately, the patient developed severe nausea, headache and fatigue, and the dosage was reduced (400 mg/day). As expected, cortisol levels raised and cabergoline (1 mg/week) was then added. Combination therapy led to partial disease control, but a further disease relapse was observed. Therefore, radiosurgery was performed, and the newly available steroidogenesis-inhibitor, osilodrostat, was started as bridge therapy due to persistent hypercortisolism. Osilodrostat was titrated up to 5 mg/day, leading to biochemical control (UFC normalization) with no side effects. At 7-months follow-up, the patient is currently proceeding with this latter treatment schedule, with no safety issues. Our case report highlights the difficulties encountered during the management of CD. The patient underwent surgery, radiotherapy and six different types of drugs before achieving disease control without adverse events. Therefore, clinical predictors of drug safety and efficacy are strongly needed in a challenging disease such as CD.