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BackgroundFK506 binding protein 51 (FKBP5) is a co-chaperone regulator of the glucocorticoid receptor (GR). Recent studies have reported increased FKBP5 mRNA in the circulation from patients with Cushing disease (CD) which returned to comparable levels seen in healthy controls following successful trans-nasal trans-sphenoidal (TNTS) surgical corticotroph tumor removal. However, the expression of circulating FKBP5 mRNA levels in other pituitary tumor subtypes and its specificity to corticotroph tumors is unknown.MethodsPre-operative blood was collected from consecutive patients undergoing TNTS for pituitary tumors (n = 57) at our center between 2015 and 2019. Total RNA was isolated from whole blood using RiboPure blood RNA isolation kit and real-time qPCR was used to quantitate circulating FKBP5 mRNA expression.ResultsConsistent with the prior report, higher circulating FKBP5 mRNA levels were observed in 20 patients with CD prior to surgical tumor removal, compared to 21 healthy controls (p < 0.0005) and compared to 8 patients harboring gonadotroph pituitary tumors (p < 0.05) and 6 patients with silent corticotroph pituitary tumors (p < 0.05). However, circulating FKBP5 mRNA levels were higher in 10 patients with prolactin (PRL)-secreting pituitary tumors compared to healthy controls (p < 0.05), and did not differ between patients with CD and patients with growth hormone secreting tumors (GH-omas).ConclusionsAlthough we confirm that circulating FKBP5 mRNA is higher in patients with corticotroph tumors compared to healthy subjects, measurement of circulating FKBP5 does not appear to be helpful to distinguish corticotroph tumors from other pituitary tumor sub-types.

ObjectiveImmune checkpoint inhibitors are approved to treat multiple cancers. We report life-threatening hepatic failure in 2 consecutive patients with Cushing syndrome that were treated with ketoconazole (KTZ) in combination with 2 different programmed cell death protein 1 (PD-1) inhibitors, Nivolumab and Pembrolizumab.MethodsThe first patient suffered from corticotroph pituitary carcinoma and the second from metastatic adrenal cortical carcinoma. They were both treated with KTZ for tumor-associated hypercortisolism.ResultsHepatic function was normal on KTZ prior to initiation of PD-1 inhibitors, after which they rapidly developed severe hepatic dysfunction. In both cases, liver biopsy was consistent with drug-induced hepatic injury. Liver function fully recovered on discontinuing KTZ and the PD-1 inhibitors along with methylprednisone therapy.ConclusionAntifungal azole therapy is commonly used in oncology patients who may be co-treated with PD-1 inhibitors. Although the specific combination of KTZ and PD-1 inhibitors to treat Cushing syndrome may be relatively uncommon, we recommend careful monitoring of hepatic function using a combination PD-1 inhibitors and azole antifungal agents, especially KTZ, due to the potential of life-threatening hepatic failure.