Question: If you have been in practice for 15 years or more, what changes have you seen in the Cushing’s medical community regarding treatment, medical therapies, theories on causes, etc.? Before we had any medications available, what did Cushing’s patients do if surgery and/or radiation didn’t work or they weren’t a candidate for either?
Answer: In the 1960s and 1970s bilateral adrenalectomy was often used to treat Cushing’s disease. With the refinement of pituitary microsurgery, bilateral adrenalectomy has become much less popular because of its obvious shortcomings (adrenal insufficiency, risk of Nelson’s syndrome). Although there are more medications available nowadays, the role of medical therapy remains adjunctive in patients with Cushing’s disease (for example, it is often used as a “bridge” until radiation therapy takes effect in patients who cannot be cured by pituitary surgery).
In the past, it was debated whether Cushing’s disease is caused by a pituitary adenoma or hypothalamic dysfunction. With the recognition of monoclonal pituitary adenomas in patients undergoing pituitary microsurgery, it has become clear that (generally benign) pituitary tumors underlie Cushing’s disease. More recent discoveries, including the detection of USP8 gene mutations in a substantial proportion of these tumors, have begun shedding more light on the molecular underpinnings of this condition.
By Dr. Nicholas Tritos, Massachusetts General Hospital, Boston, MA (Fall 2018)
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