Inferior petrosal sinus ACTH and prolactin responses to CRH in ACTH-dependent Cushing’s syndrome: a single centre experience from the United Kingdom

Abstract

Inferior petrosal sinus sampling (IPSS) of ACTH with CRH stimulation helps distinguish pituitary ACTH-dependent Cushing's syndrome from the ectopic ACTH syndrome (EAS). The usefulness of the paradoxical response of other pituitary hormones including prolactin to CRH remains controversial. Data from 33 IPSS procedures carried out at the Walton Centre for Neurology and Neurosurgery in Liverpool were analyzed. Patients were selected for this procedure if they had been diagnosed with ACTH dependent Cushing's syndrome and the majority had no obvious pituitary adenoma on Magnetic Resonance Imaging. Satisfactory simultaneous bilateral catheterization was accomplished in 23/33 (success rate 70%). The diagnostic sensitivity of a basal central/peripheral ACTH ratio >2.0 and >3 post-CRH was 94%. In two patients with subsequently confirmed EAS the maximal central/peripheral ACTH ratio was <2.0 on basal samples and did not change following CRH. The maximal central/peripheral prolactin ratio was noted at 5 min post-CRH, coinciding with the maximal central/peripheral ACTH ratio. The intersinus gradient (ISG) of ACTH was paralleled by a consistent ISG of prolactin and in 7 out of 9 patients (with successful bilateral IPSS and unilateral adenomas) the ISG of prolactin correctly lateralized the microadenoma whereas the ISG of ACTH correctly lateralized in 8 out of 9 patients. Neither of the patients with EAS achieved a central/peripheral prolactin ratio >2 in the basal state and >3 post-CRH. Bilateral catheterization of inferior petrosal sinuses can be successful in up to 70% of cases. Prolactin measurements do not have superior lateralizing capability compared with ACTH but may be useful in the differential diagnosis of pituitary-driven from EAS.

Bilateral inferior petrosal sinus sampling

“…This hypothesis, based on the assumption that the hormones measured drained symmetrically in the two sides of the pituitary, was not consistently confirmed and conversely an intersinus, and central/peripheral gradient also for these hormones was repeatedly documented (96, 97, 98, 99). More recent reports on the use of PRL in addition to ACTH to correctly localize the pituitary adenoma site in CD have given conflicting result (100, 101). …”

Latest diagnostic approaches to determine the cause of ACTH-dependent Cushing’s syndrome, in the South African setting

“…A central to peripheral prolactin ratio of greater than 1.8:1 is considered to indicate appropriate IPSS. [23][24][25][26][27] In our case the central to peripheral IPS prolactin ratio at baseline was 1:1 in the left compared with 3:1 for the right IPS. This signifies that the left IPS essentially sampled peripheral blood.…”

“…28 Using the prolactin correction additional cases of PC could be correctly detected, without decreasing the specificity. [23][24][25][26][27] This may avoid an unnecessary repeat of IPSS.…”

Cushing Syndrome

“…40 This chance has been mitigated by the measurement of prolactin in the IPS samples to verify proper catheter placement and venous drainage. [41][42][43][44] When the lack of an IPS to peripheral ACTH gradient indicates ectopic ACTH, prolactin should be measured in the IPS and peripheral samples. This strategy prevents a fruitless search for an ectopic ACTH-secreting neoplasm in patients with a pituitary adenoma and anomalous pituitary venous drainage.…”