PMON93 Adenoma Size & Inferior Petrosal Sinus Sampling in Cushing's Disease Diagnosis - Smoke & Mirrors?

BACKGROUND: The current guidelines on Cushing's Disease management recommend surgically resecting adenomas larger than 10 mm in size.(1) For smaller adenomas, inferior petrosal sinus sampling (IPSS) is considered the gold standard to distinguish between Cushing's disease and ectopic ACTH production. We report a case where IPSS testing and the size of the adenoma on MRI were misleading in determining the final diagnosis, prompting us to challenge the existing guidelines. CLINICAL CASE: A 40-year-old female with a past medical history of hyperlipidemia, obesity (BMI 42) and prediabetes presented with secondary infertility, galactorrhea, headaches, blurred vision and weight gain (30 lbs) over the past year. Physical examination was notable for acanthosis nigricans of the neck and bilateral milky nipple discharge. Prolactin level was elevated to 46.9 ng/ml (n 4.8-23.3 ng/mL). ACTH was elevated to 83.5 pg/mL (n 7.2-63.3 pg/mL) and cortisol to 17.4 ug/dL (n 2.7-10.5 ug/dL). Salivary cortisol was elevated to 0.216 ug/dL (n <0.112 ug/dL), 24-hour urinary cortisol elevated to 60.2 ug (n <45 ug) and on 1 mg dexamethasone suppression testing, morning cortisol was elevated to 7.2 ug/dL (n <1.8 ug/dL). MRI revealed a 6×7×7 mm right sided pituitary mass. Referral to Neurosurgery for resection was made. Neurosurgery recommended bilateral IPSS for pre-operative tumour lateralisation. 10 ug of DDAVP was used to increase test sensitivity. Central to peripheral ACTH ratio was 1: 1. No significant laterality was noted. In the absence of other identifiable sources on CT imaging, endoscopic endonasal surgical resection was pursued. On pathology, the adenoma was immunoreactive for ACTH, confirming Cushing's Disease. Post-operative morning cortisol was 1.3 ug/dL. The patient was started on hydrocortisone 50 mg in the morning and 20 mg in the afternoon with outpatient taper two weeks following discharge to prednisone 10 mg daily. CONCLUSION: Current guidelines recommend surgery for adenomas >10 mm in size, IPSS for adenomas < 6 mm and further diagnostics (IPSS or serum CRH and DDAVP stimulation tests plus whole-body CT) for those 6-9 mm. IPSS is strongly preferred. (1) IPSS is operator dependent and has low efficacy in tumour lateralisation. With the advent of high-resolution CT imaging and emerging data corroborating non-invasive stimulation tests,(2) it may be time to shift away from IPSS as a first line test for adenomas irrespective of size. IPSS can present a costly, invasive, oft misleading, and hence superfluous testing strategy; it is high time the medical community re-evaluates its reliance on it.References1. Fleseriu M et al. Consensus on diagnosis and management of Cushing's disease: a guideline update. Lancet Diabetes Endocrinol. 2021 Dec;9(12): 847-875.2.Caroline Frete et al. Non-invasive Diagnostic Strategy in ACTH-dependent Cushing's Syndrome, The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 10, October 2020, Pages 3273–3284 Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.