The usefulness of combined biochemical tests in the diagnosis of Cushing’s disease with negative pituitary magnetic resonance imaging

Abstract

Objective: The etiological diagnosis of ACTH-dependent Cushing's syndrome is often a problem. In fact, no endocrine or radiological examination can conclusively distinguish the ectopic from the pituitary source of disease. The aim of our study was to evaluate the role of stimulation and suppression endocrine tests in the diagnostic and therapeutic approach of patients with Cushing's disease (CD) and negative pituitary magnetic resonance imaging (MRI), considering their post-surgical outcome in comparison with patients with CD and positive MRI. Patients and methods: We retrospectively analyzed 31 patients (25 women and 6 men, median age 40G 15 years) with a confirmed diagnosis of CD who underwent transsphenoidal pituitary surgery by the same neurosurgeon between 2001 and 2005. Preoperative endocrine assessment included corticotropin-releasing hormone (CRH), desmopressin (dDAVP), and overnight 8 mg dexamethasone suppression tests (8-DST) in all patients. Fifteen patients had a normal pituitary MRI and sixteen had a clearly evident pituitary microadenoma. Bilateral inferior petrosal sinus sampling (BIPSS) was performed in patients with discordant biochemical results or with signs and symptoms highly suggestive of an ectopic source of ACTH. Post-surgical median follow-up was 38.4G22.0 months. Results: Among patients with negative MRI, 60% had concordant positive endocrine tests and underwent neurosurgery without other examinations. BIPSS was performed in three other patients prompted by discordant endocrine tests (negative dDAVP) and in two patients with clinical suspicion of ectopic disease. Among patients with positive MRI, 87% underwent neurosurgery without BIPSS that was performed in two patients because of negative concomitant response to dDAVP and CRH tests. A pituitary adenoma, confirmed by pathological examination, was found in 40 and 81% of patients with negative and positive MRI respectively (P!0.05), corticotroph hyperplasia resulted more frequent in the group with negative MRI. Remission rate was not different between patients with negative and positive MRI (73 and 75% respectively; PZ0.61) and between patients with negative MRI who did not undergo BIPSS and patients with positive MRI (PZ0.56). The recurrence rate was also similar between groups (PZ0.64), but higher, although not statistically different (PZ0.07) in patients with corticotroph hyperplasia at histology. Conclusions: An accurate evaluation of presurgical endocrine tests results enabled us to reduce the number of BIPSS in patients with a negative MRI without any fallout on their post-surgical outcome. In the hands of an expert pituitary surgeon, the outcome after surgery and the subsequent recurrence rate are much the same in patients with negative or positive MRI.European Journal of Endocrinology 156 241-248

Latest diagnostic approaches to determine the cause of ACTH-dependent Cushing’s syndrome, in the South African setting

“…17 However, DDAVP is freely available in South Africa and a concordant DDAVP test adds to diagnostic accuracy for PC when used in combination with other positive tests. 18 As our patient did not demonstrate a more than 6 mm pituitary lesion on MRI, which was discordant with the pronounced pituitary localisation on HDDST, we proceeded to perform IPSS without a DDAVP stimulation test. If MRI and HDDST are discordant (as was the case in our patient), IPSS is inevitable and a DDAVP stimulation test before proceeding to IPSS will add no further diagnostic value.…”

Desmopressin test during petrosal sinus sampling: a valuable tool to discriminate pituitary or ectopic ACTH-dependent Cushing’s syndrome

“…This procedure has been initially reported to have 100% sensitivity and specificity (6). However, since the first published series in the early 1990s, other reports have shown the technique to have much less discriminatory power (7)(8)(9)(10)(11)(12).…”

Inferior petrosal sinus sampling: Final solution to a riddle called “Cushing's syndrome”

“…In only 36e78% of cases MRI is able to localize the adenoma in pituitary because of very small sized adenoma or diffuse corticotroph hyperplasia. 7 However, dynamic studies have improved sensitivity but, still in many cases MRI fail to localize the adenoma as happened in our case. 8 About 10% of general population may be harboring incidentaloma in pituitary, which may result in false positivity and failed surgery.…”