ODP302 Cushing's Disease: A Challenging Diagnosis in Patients with Underlying Co-Morbidities
Authors: Campbell Spencer , Goyal Itivrita , Lim Jonea , Punni Emma 
Published: November 2022

Introduction

Cushing's disease (CD) is a rare endocrine disorder with significant morbidity and mortality. This case is a complicated ACTH (adrenocorticotropic hormone)-dependent hypercortisolism with a negative pituitary MRI inthe setting of underlying liver cirrhosis and chronic kidney disease. Hypercortisolism work up was challenging due to liver and kidney disease.

Case Presentation

A 42-year-old woman with a history of liver cirrhosis(MELDscore: 19) and stage 3b chronic kidney disease (CKD) presented with nausea, vomiting and abdominal pain. She reported proximal muscle weakness. On examination, she had central adiposity with large purple abdominal striae and proximal muscle wasting. Medical history was pertinent for uncontrolled hypertension and type 2 diabetes mellitus. Due to concern for Cushing's syndrome, an overnight 1 mg dexamethasone suppression test (DST) was performed. She had an inappropriately elevated morning cortisol of 10.1 mcg/dL (n &lt; 1.8 mcg/dL), but suboptimal dexamethasone level of 104 ng/dL (140-295 ng/dL), suggesting incomplete absorption secondary to emesis. A repeat DST was not performed given concerns for reduced dexamethasone clearance with her underlying renal and liver disease. Her 24-hour urine free cortisol (UFC) was elevated at 55 ug/24 hr (6-42 ug/24 hr). A repeat 24-hour UFC was again elevated at 265 ug/24 hr (6-42 ug/24 hr). Three late night salivary cortisol levels were also elevated at 0.231 ug/dL, 0.429 ug/dL and 0.19 ug/dL (n &lt;0. 01-0. 09 ug/dL). Diagnosis of Cushing's syndrome was confirmed. ACTH level obtained was detectable at 70.1 pg/mL (7.2-63.3 pg/mL), suggestive of ACTH-dependent Cushing's syndrome. Pituitary MRI without contrast was obtained due to CKD. MRI reported no pituitary abnormalities. High dose DST was not performed due to concerns for aforementioned reduced dexamethasone clearance and due to lack of availability of CRH (corticotropin-releasing hormone), CRH stimulation testing was not done. She underwent inferior petrosal sinus sampling (IPSS) which showed central to peripheral ACTH ratio of 2.11 at baseline and ratios of 3.53, 3.45 and 3.32 at 5 minutes, 10 minutes and 15 minutes respectively after vasopressin stimulation, solidifying the diagnosis of Cushing's disease. Patient is now scheduled for an exploration of the sella via endoscopic endonasal approach.

Conclusion

This case highlights the limitations of biochemical tests and imaging modalities in the workup of hypercortisolism, notably in patients with underlying liver and kidney disease. The ordering physician should be mindful of the caveats associated with each biochemical testing. ACTH-dependent Cushing's syndrome can be difficult to diagnose properly in the setting of a negative pituitary MRI. IPSS, although an expensive and invasive test, has the best diagnostic accuracy. This case further demonstrates the importance of performing an IPSS to diagnose CD and distinguish from an ectopic source when imaging is non-diagnostic.

Presentation: No date and time listed