False-Negative Inferior Petrosal Sinus Sampling in Young-Onset Cushing Disease: What Happens Next

Introduction: False-negative results during inferior petrosal sinus sampling (IPSS) may complicate the diagnostic evaluation of patients with ACTH-dependent Cushing syndrome (CS). The management of these patients can be confusing for clinicians and lead to delayed management. Methods: We studied patients with young-onset (<21 years old) CD who underwent IPSS during their diagnostic evaluation. For all patients, diagnosis of CD was eventually confirmed based on histologic evaluation of a resected pituitary tumor or remission after transsphenoidal surgery. Results: We recorded a rare incidence of false-negative IPSS results in 5 out of the 142 IPSS procedures (3.5%), performed in 4 unique patients. Patients with negative IPSS did not differ in demographic (age and sex) or biochemical (diurnal ACTH/cortisol or 24-hour urinary free cortisol) data from the remaining. Additional workup was performed in three of the four patients including evaluation for ectopic sources of CS and repeat IPSS. Two of these patients also received medical treatment for suppression of cortisol production. One patient decided to proceed with pituitary exploration without additional evaluation. All patients finally underwent surgery and achieved remission. Discussion/Conclusion: In patients with CD, IPSS may rarely lead to false-negative results. Management of these patients usually includes screening for ectopic sources of ACTH/CRH secretion, repeating IPSS if ectopic workup is negative, and considering medical management until final diagnosis of the source of hypercortisolism is made.