Can petrosal sinus ACTH and prolactin responses to CRH help localize the tumour in Cushing's disease due to pituitary microadenomas?
C Daousi, T Nixon, C Hayden, PM Foy, M Diver & IA MacFarlane
Aims: The majority of patients with Cushing's disease have pituitary microadenomas and preoperative localization can be helpful during transphenoidal surgery. Inferior petrosal sinus sampling (IPSS) of ACTH and responses to CRH may show higher levels on the side ipsilateral to the tumour, although this remains controversial. A few small studies suggested a prolactin response to CRH during IPSS. We assessed whether prolactin responses to CRH can help lateralize the microadenoma.
Subjects and methods: 18 patients with proven Cushing's disease who underwent IPSS were studied. ACTH and prolactin levels were measured in both petrosal sinuses and peripheral blood before and after stimulation with CRH. 13 patients were found intraoperatively to have unilateral pituitary microadenomas and 5 midline/bilateral microadenomas.
Results: Stimulation with CRH caused a significant increase in both ACTH and prolactin levels in the IPS samples. Prolactin levels however did not rise in the peripheral blood. The maximal IPS:peripheral (P) prolactin ratio was noted at 5 minutes post-CRH, coinciding with the maximal IPS:P ACTH ratio. In the unilateral tumours the mean ACTH level was significantly higher in the ipsilateral IPS compared to the contralateral IPS in both basal and post-CRH samples. The mean prolactin level at each timepoint was also higher on the side ipsilateral to the tumour. In central/bilateral tumours higher ACTH levels on one side were also paralleled by higher prolactin levels on the same side.
Comments: We have found that both ACTH and prolactin respond to i.v. CRH. We confirm that IPS ACTH levels pre and post-CRH can help lateralize a microadenoma. We also observed a consistent intersinus gradient of prolactin in patients with ACTH-secreting microadenomas. The mechanism of higher concentrations of prolactin in IPS samples from the side ipsilateral to the microadenoma is unclear. It may be paracrine stimulation of prolactin secretion from anterior pituitary tissue surrounding the ACTH adenoma.