Acute elevation of interleukin 6 and matrix metalloproteinase 9 during the onset of pituitary apoplexy in Cushing’s disease



Pituitary apoplexy is a rare endocrine emergency. The purpose of this study is to characterize physiological changes involved in pituitary apoplexy, especially during the acute phase.


A Cushing’s disease patient experienced corticotroph releasing hormone (CRH)-induced pituitary apoplexy during inferior petrosal sinus sampling (IPSS). The IPSS blood samples from the Cushing’s disease patient were retrospectively analyzed for cytokine markers. For comparison, we also analyzed cytokine markers in blood samples from two pituitary ACTH-secreting microadenoma patients and one patient with an ectopic ACTH-secreting tumor.


Acute elevation of interleukin 6 (IL-6) and matrix metalloproteinase 9 (MMP9) was observed in the IPSS blood sample on the apoplectic hemorrhagic site of the tumor. In contrast, such a change was not observed in the blood samples from the contralateral side of the apoplexy patient and in other IPSS samples from two non-apoplexy Cushing’s disease patient and a patient with ectopic Cushing’s syndrome.


IL-6 and MMP9 may be involved in the acute process of pituitary apoplexy in Cushing’s disease.

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This study is supported by grants from the University of Minnesota (UMF0011528 to TA, AHC Grant-in-Aid 212588 to TA) and a grant from the NIH (R01AR064195 to YK). We are grateful to Dr. Yasumasa Iwasaki for critical reading, to Cailin McMahon and Mathew Pappas for editorial assistance, to Justin Wang for his excellent technical assistance and to Michael Ehrhardt at the Cytokine reference laboratory for blood sample assays.

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Corresponding author

Correspondence to Takako Araki.

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The authors have no multiplicity of interest to disclose.

Ethical approval

Study protocols were approved by the University of Minnesota Institutional Review Board (protocol #00005168). Informed consent was obtained from patients over 18 years of age, who were diagnosed with Cushing’s syndrome and underwent the IPSS procedure.

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Araki, T., Sangtian, J., Ruanpeng, D. et al. Acute elevation of interleukin 6 and matrix metalloproteinase 9 during the onset of pituitary apoplexy in Cushing’s disease. Pituitary (2021).

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  • Pituitary apoplexy
  • IL-6
  • MMP9
  • Cushing's disease
  • CRH