P-61 From Cushing to Nelson Syndrome: Diagnostic challenges and Surgical Dilemma

Abstract

Abstract Introduction Diagnosis of the origin of ACTH-dependent Cushing's syndrome (CS) can be difficult in some cases, especially when MRI of the pituitary gland does not reveal an adenoma. Inferior petrosal (IPSS) or cavernous sinus sampling (CSS) with CRH stimulation helps confirm the central origin in most cases. CSS also helps lateralize the tumor within the pituitary gland with a sensitivity of 80%. Because transsphenoidal pituitary surgery is successful in the majority of MRI-negative cases, bilateral adrenalectomy is performed less frequently. Even with advanced radiologic studies, the origin may not be detected. Adrenalectomy may be an option in these cases. However, loss of feedback inhibition of the hypothalamic-pituitary-adrenal axis; can lead to aggressive transformation of an existing ACTH-secreting pituitary adenoma into Nelson's syndrome within 1-5 years. Clinical Case A 46-year-old female patient complaining of hot flashes and unable to lose weight was evaluated for CS and referred to the Department of Neurosurgery for a pituitary adenoma (Table 1). Since the adenoma was <6mm CSS with CRH stimulation was performed. The results did not support central origin (Table 2). Ectopic ACTH secretion was considered, but without finding the origin of the tumor on radiological examination, and treatment with ketoconazole and metyrapone was started for CS. However the patient then discontinued outpatient follow-up. The patient presented to our clinic 6 years later with a new pituitary MRI showing tumor growth (Fig.1b). She complained of fatigue and obesity. She was depressed and anxious. The skin on her face, hands and hump was dark and patchy (Fig.1c). During these years, she consulted several endocrinologists. MRI was performed annually. Brain MRI had showed a fronto-basal extraaxial mass lesion. The patient underwent microsurgical resection and pathology revealed a microcystic meningioma (WHO grade I). 3 months later bilateral nodular hyperplasia of adrenal gland was detected; she underwent bilateral laparoscopic adrenalectomy (no neoplasia). ACTH gradually increased up to 418pg/ml; the diagnosis of Nelson's syndrome was established. The patient underwent endoscopic transsphenoidal adenomectomy. The ACTH level was found to be 12pg/ml on the 2nd postoperative day. Pathological examination revealed a ACTH secreting pituitary adenoma (Ki-67:7%). CS patients suffer from emotional lability due to the effects of elevated cortisol and to the physical changes of their body. Proximal muscle weakness and obesity causes fatigue symptoms. The diagnosis is often delayed until complications occur. Differential diagnosis could be difficult and challenging. Patient's emotional lability could adversely affect treatment/follow-up compliance. The presented case had meningioma resection which could be delayed until remission from CD and bilateral adrenalectomy which could be avoided by endoscopic pituitary surgery. This case is a good example of the need for pituitary centers of excellence.Figure.Fig.1.a. MRI scan of the pituitary gland at first admission shows (a) a lesion extending posteriorly inferior to the right half of the pituitary gland, hyperintense at T2-weighted, iso-hypointense at T1-w, with heterogeneous contrast enhancement consistent with pituitary microadenoma (4mm*2mm) Fig.1.b. Progression in size of the adenoma (6mm*4mm) Fig.1.c. Darkening of the skin due to hypersecretion of ACTH. Table 1.Cavernous sinus sampling with corticotropin-releasing hormone stimulation Table 2.Laboratory tests in different times