Endocrine Abstracts

Adrenocorticotropic hormone (ACTH) adenomas causing Cushing’s disease (CD) have been recognized as an aggressive and invasive subtype of pituitary adenomas. Remission of CD without surgical or medical treatment is an extremely rare occurrence. Moreover, a clinically relevant peculiarity of these tumors, though rarely observed, is their ability to modify their clinical expression from a silent form to CD or vice versa, the latter even more unexpected. We describe the case of a 51-year-old woman referred to our clinic from the Gastroenterology Department in November 2018 with typical signs and symptoms of Cushing’s syndrome. The laboratory tests supported an ACTH dependent Cushing’s syndrome, with a high-normal ACTH and a high-dose dexamethasone suppression test with a more than 50% reduction of plasma cortisol, suggesting CD. Though initial, the brain MRI could not reveal a pituitary tumor, 10 months later a 6 mm pituitary microadenoma was described upon follow-up MRI. She was treated with metyrapone as part of the PROMPT study (a prospective multicenter, open-label, phase III/IV study). After a 12 weeks period of titration to achieve normal urine and serum cortisol levels, the patient entered the 6-month extension period during which she received 1500 mg of metyrapone daily, with significant clinical and biochemical (as defined by mean urine free cortisol (UFC) ≤ upper limit of normal) improvement. The treatment was stopped on 15 December 2019, according to study protocol and the patient was reevaluated 5 and, respectively, 6 months later. Surprisingly, she appeared much improved, though she did not receive any treatment to counteract hypercortisolism during this period. She had lost 18 kilograms and we could note the disappearance of cushingoid features as well as a remission of diabetes mellitus and arterial hypertension. These findings were further supported by the hormonal evaluation that excluded an active CD. Moreover, the pituitary-adrenal axis was normal (cortisol 8 a.m. = 6.9 µg/dl, ACTH = 29.3 pg/ml, 24-hour UFC = 152.3 µg/24 h), whereas the pituitary MRI revealed no pituitary mass as well as no signs of hemorrhage or infarction. There were no clinical and biochemical signs of recurrence 12 months later, in December 2020, either. This spontaneous remission from CD is puzzling and there seems to be no explanation for it. However, though regrowth of the pituitary adenoma and recurrence are even less encountered than spontaneous remission in CD, careful lifelong follow-up is mandatory in this patient.