Osilodrostat Therapy and 11C-methionine PET to Improve Corticotroph Adenoma Detection

Cushing's disease is a rare condition where the body produces too much of a hormone called cortisol. Cortisol helps with metabolism, the immune system, and managing stress. But too much cortisol can lead to problems like weight gain, high blood pressure, diabetes, and changes in appearance, such as a round face or a hump on the back. People with Cushing's disease often gain weight around their belly and may get stretch marks. They might also feel emotional changes, tiredness, or weakness. This disease is usually caused by a small, non-cancerous growth in the pituitary gland called a 'pituitary adenoma.' The pituitary gland is a small organ at the base of the brain and controls many important functions. When someone is diagnosed with Cushing's disease, doctors typically use an MRI scan to look for the adenoma in the pituitary gland. If found, the adenoma can often be removed through surgery, which often cures the disease. This is the standard treatment for patients with Cushing's disease. However, MRIs only find the adenoma in about 60% of the time. If surgery isn't possible because the adenoma can't be located, doctors may use medication to lower cortisol levels. In addition to the MRI, doctors might use a special PET/CT scan to find the adenoma. This PET/CT scan is not available everywhere, so the investigators refer our patients to Cambridge Hospital for this scan, which uses a special dye called 11C-methionine. The investigators then review the scan with the teams from Imperial and Cambridge. If the PET/CT scan shows where the adenoma is, the patient will be offered surgery. However, finding the adenoma can be challenging because they are often small and hard to distinguish from normal tissue. If the adenoma isn't visible, the investigators will use medical treatment to lower cortisol. After a period of medical treatment, another MRI scan and PET/CT scan will be done to see if the adenoma has become clearer. This second PET/CT scan would not normally be part of routine clinical care. The investigators will then compare the results of the two scans to see if the special dye is showing a stronger signal, which can help us find the adenoma more accurately and improve the chance of curing Cushing's disease with surgery.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

All participants must meet all of the following inclusion criteria:

* age 18 years and older newly diagnosed with Cushing's disease and no/ an equivocal surgical target on MRI pituitary or
* age 18 years and older and previously undergone pituitary surgery for Cushing's disease and clinical and biochemical evidence of persistent/ recurrent hypercortisolaemia and no/ an equivocal surgical target on MRI pituitary.

Exclusion Criteria:

Potential participants will be ineligible to enter the study if they meet any of the following exclusion criteria:

* Absolute contraindication to osilodrostat therapy and/or 11C methionine PET.
* Pregnancy or unwillingness to use secure contraception for the study duration (female participants only).
* Unable to comply with study visit schedule.

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