MON-016 - Clinical Challenges in Inferior Petrosal Sinus Sampling: Lessons from Three Distinct Outcomes

ABSTRACT
Inferior petrosal sinus sampling (IPSS) is the gold standard test for the diagnosis of Cushing’s disease (CD) with high accuracy. IPSS differentiates pituitary from ectopic ACTH sources in ACTH-dependent Cushing’s syndrome (CS). Anatomical variations, procedural deviations, and technical limitations can lead to misleading results. We are presenting three cases illustrating key challenges of IPSS.
Case Summaries:
Case 1: A 48-year-old female with a history of type 2 diabetes and hypertension was evaluated for CS due to her cushingoid appearance. Biochemical tests supported a diagnosis of Cushing's disease, and MRI revealed a 5 mm lesion in the right sellar region, suggesting a pituitary microadenoma. IPSS confirmed CD with right-sided lateralization. The patient underwent transsphenoidal surgery (TSS), which confirmed an ACTH-secreting corticotroph adenoma.
Case 2: A 40-year-old female with type 2 diabetes mellitus had an incidental finding of a 10mm cystic mass in the right pituitary gland on an MRI. Rapid weight gain occurred over the past year. Biochemical tests confirmed CD, and she underwent TSS, which revealed a Rathke cleft cyst and no adenoma. Despite surgery, her cortisol levels remained high, and work up again was consistent with CD. She has been a smoker since age 13. CT Chest was negative for lung cancer. Post-surgical MRI showed a small remnant cyst in the right pituitary gland. IPSS confirmed a pituitary source without clear lateralization. This conflicting finding led to a plan for extensive surgical exploration.
Case 3:
A 39-year-old female presented with clinical symptoms of CS. Only biochemical testing was positive for CD (24-hour urine cortisol, 8 am ACTH with cortisol, 3 midnight saliva cortisol, 1 mg dexamethasone suppression test, 8 mg dexamethasone suppression test). An MRI of the brain showed a possible Rathke's cleft cyst. The patient underwent an IPSS. However, during the procedure, cosyntropin was mistakenly administered instead of CRH or DDAVP, rendering the IPSS results non-interpretable.
Discussion
These cases highlight the pitfalls of IPSS.
The first IPSS confirmed a pituitary source with right-sided lateralization; the second confirmed a pituitary source without clear lateralization; and the third was indeterminate due to an error in the stimulation protocol, with cosyntropin used instead of CRH or DDAVP.
Recognizing these challenges is crucial for preventing misdiagnosis and effectively integrating the IPSS with imaging and clinical data.
Conclusion
Proper technical execution, understanding of anatomy, and close adherence to standardized protocols are key to the successful IPSS. Surgical decisions should not be based solely on IPSS.

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