Reduction of false-negative results in inferior petrosal sinus sampling with simultaneous prolactin and corticotropin measurement

Endocr Pract. 2011 Jan-Feb;17(1):33-40. doi: 10.4158/EP10067.OR.


Objective: To investigate the value of prolactin as an independent marker of catheter placement to improve the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in patients with corticotropin-dependent Cushing syndrome.

Methods: In this retrospective cohort study, we reviewed hospital records of patients who underwent IPSS procedures at the Cleveland Clinic between 1997 and 2009. Serum prolactin and plasma corticotropin levels were measured prospectively in peripheral and inferior petrosal sinus (IPS) samples.

Results: Forty-one patients underwent 42 IPSS procedures at our institution during the study period. Among 35 patients with Cushing disease, 1 patient had erroneous IPSS results: all pre-corticotropin-releasing hormone (CRH) and post-CRH IPS to peripheral (IPS:P) ACTH ratios were less than 2 and less than 3, respectively. Despite radiologic evidence of appropriate IPS catheter placement, concurrent IPS:P prolactin ratios indicated that successful IPS venous sampling was not achieved. A second case with equivocal IPSS results could also be explained by corresponding IPS:P prolactin ratios. During IPSS, all patients with an identifiable ACTH-staining adenoma localizing to 1 side of the pituitary gland (n = 22) who demonstrated absent IPS:P ACTH gradients (<2 before or <3 after CRH administration) on the ipsilateral side of the corticotroph adenoma had corresponding IPS:P prolactin ratios less than 1.3.

Conclusions: Measurement of prolactin during IPSS testing may reduce false-negative results in patients with Cushing disease who do not demonstrate an appropriate central-to-peripheral ACTH gradient. In our series, all false-negative IPS:P ACTH ratios had a corresponding IPS:P prolactin ratio less than 1.3.

MeSH terms

  • Adrenocorticotropic Hormone / blood*
  • Adult
  • Aged
  • Cushing Syndrome / blood*
  • Cushing Syndrome / diagnosis*
  • False Negative Reactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Petrosal Sinus Sampling / methods*
  • Prolactin / blood*
  • Retrospective Studies
  • Sensitivity and Specificity
  • Young Adult


  • Adrenocorticotropic Hormone
  • Prolactin