In 29 consecutive patients with adrenocorticotropin (ACTH)-dependent Cushing’s syndrome, we compared the usefulness of multiple baseline ACTH evaluations (10/29), multiple hormone evaluation (29/29) and ACTH-releasing hormone (CRH) stimulation (21/29) during simultaneous and bilateral inferior petrosal sinus sampling. The basal inferior petrosal sinus/periphery ratio for ACTH concentrations was greater than 2 in 18 of the 29 patients and CRH challenge caused the appearance of an inferior petrosal sinus/periphery ratio greater than 3 in 6 other patients. The presence of an ACTH-secreting adenoma was surgically proven in all the 24 patients who had an ACTH inferior petrosal sinus/periphery ratio greater than 2 basally or greater than 3 after the CRH test but also in 1 patient who had an inferior petrosal sinus/periphery ratio lower than 2 basally or 3 after the CRH test. In 4 patients, both the very high peripheral ACTH levels, the inferior petrosal sinus/periphery ratio and the complete lack of ACTH increase after CRH indicated the presence of an ectopic ACTH syndrome: a bronchial carcinoid was found in 2 patients, whereas the site of the tumor is still unknown in the remaining 2. An ACTH intersinus gradient greater than 1.4 was found in 23 patients. Among these 23 patients, the side of the adenoma was correctly predicted in 19 patients and wrongly in 4. In the 10 patients receiving ACTH level evaluation three times before performing the CRH test, no difference of ACTH concentrations was detected in 7 either in the periphery or in inferior petrosal sinuses, while in the remaining 3 patients the ACTH inferior petrosal sinus/periphery ratio became greater than 2 indicating Cushing’s disease. The presence of an intersinus gradient greater than 1.4 for β-endorphin was found basally in 19/29 patients (65.5%) whereas after CRH challenge in 21/29 patients. Moreover, in 4/21 patients (19%) it was clearer than the ACTH intersinus gradient in localizing the pituitary adenoma. Furthermore, in 13 patients a significant intersinus gradient, either basally or after CRH challenge, was found also for GH and/or PRL (44.8%) and in 5 patients for TSH, FSH and/or LH (17.3%). All the 4 patients with proven or suggested ectopic ACTH production had no intersinus gradient for whichever pituitary hormone was considered. In conclusion, the diagnostic accuracy of the inferior petrosal sinus sampling in our series was of 96.5% (28/29 cases) when considering basal and CRH-stimulated ACTH levels in the inferior petrosal sinuses and periphery. On the contrary, the multiple basal ACTH evaluation does not seem to be necessary when CRH is performed during the test, but may be helpful in a minority of cases when CRH test is not available. The multiple hormone evaluation, in particular β-endorphin level assay, might be performed in doubtful cases after the ACTH level determination is obtained, as it can help to indicate the presence of a pituitary microadenoma in the majority of patients.
The present study aimed at evaluating the anterior pituitary hormone levels in the inferior petrosal sinuses and in the peripheral blood of 55 patients affected by various pituitary disorders and undergoing perihypophysial phlebography on neurosurgical indication or for diagnostic purposes. The results indicated that in 6 patients with Cushing's disease and in 4 with hyperprolactinemia the secreting adenoma could be localized by inferior petrosal sinus sampling. Furthermore, the concentrations of all the pituitary hormones were found to be higher in the right and/or in the left inferior petrosal sinus than in peripheral blood, showing a clear gradient between central and peripheral samples. Moreover, the evaluation of hormone central/peripheral concentration ratios revealed noteworthy differences, namely, that central/peripheral concentration ratios of GH, ACTH, and PRL were significantly higher than those of TSH, FSH, and LH (p<0.01). On the contrary, no significant differences were found when the concentration ratios of GH, ACTH and PRL or TSH, FSH and LH were compared among themselves. This finding may be attributed to at least two factors: the increased pulsatility and the relatively short biological halftime of polypeptic hormones (GH, ACTH, and PRL) compared with glycoprotein hormones (TSH, FSH, and LH).The hormones secreted by the anterior pituitary gland reach the inferior petrosal sinuses (IPSs) via small hypophysial veins and intercavernous si¬ nuses. More distally, in the jugular bulb, blood flowing from the inferior petrosal sinuses is mixed with blood originating from different regions of the brain (1,2). Therefore, the determination of pituitary hormone levels in blood collected from inferior petrosal sinuses can mean a direct ap¬ proach in the study of the pituitary secretory ac¬ tivity. The use of perihypophysial phlebography for the diagnosis and presurgical evaluation of var¬ ious pituitary disorders, in the past and more re¬ cently limited to only Cushing's syndrome, has en¬ abled the collection of selective blood samplings in the inferior petrosal sinuses.In a previous report (3) we determined plasma PRL levels in normoprolactinemic patients with different pituitary disorders, and in non-adenomatous hyperprolactinemic and adenomatous hyperprolactinemic patients. The study demonstrated the existence of a gradient between plasma PRL levels in the inferior petrosal sinuses and in periph¬ eral blood in all the groups of patients and, in par¬ ticular, the presence in patients bearing PRL-secreting adenomas of a PRL gradient ipsilateral to the tumour.The aim of the present study was to evaluate the anterior pituitary hormone levels in the inferior petrosal sinuses and in the peripheral blood of seven groups of patients affected by various pitu¬ itary disorders.
The aim of this retrospective study was to evaluate the existence of a multihormonal gradient between the inferior petrosal sinuses in various pituitary diseases: Cushing's disease (8 cases), acromegaly (4 cases), prolactinomas (7 cases), GH, PRL-secreting adenoma (1 case), functionless adenoma (2 cases), empty sella (3 cases) and in non-tumoral hyperprolactinemia (5 cases). A significant intersinus gradient (more than 1.4:1) was recorded for GH, ACTH and PRL in 16 patients (80%), but in only 9 patients (45%) out of the 20 with hormone-secreting tumors for TSH, FSH and LH. Moreover, of the 10 patients in the remaining groups, only in two cases was a significant intersinus gradient present: one for GH and one for LH. In conclusion, the finding of a multihormonal release in the inferior petrosal sinus ipsilateral to the adenoma is reported, for the first time, in patients with GH- and PRL-secreting adenomas. The possible explanation for such a finding may be either an increased blood flow in this site of sampling or a pituitary multihormone release through a paracrine mechanism primed by the tumoral hypersecreted hormone. In addition, the pulsatile secretory pattern and the short half-life of polypeptide hormones may contribute to better demonstrate this phenomenon in respect to glycoprotein hormones.
Twenty-six consecutive patients with ACTH-dependent Cushing syndrome were subjected to simultaneous, bilateral inferior petrosal sinus sampling for ACTH assay before and after ACTH-releasing hormone (CRH) stimulation. The baseline ACTH inferior petrosal sinus/periphery (IPS/P) ratio was > or = 2 in 12 of 26 patients (46%), whereas the CRH-stimulated IPS/P ratio was > or = 3 in 19 of 26 patients (73%). A pituitary adenoma, ACTH-secreting at immunostaining, was surgically proved in all of the 19 patients who had an ACTH IPS/P ratio > or = 2 basally or > or = 3 after the CRH test but also in three other patients who did not have such ratios. The value of the basal IPS/P ratio and the complete lack of ACTH increase after CRH led to the diagnosis of an ectopic ACTH syndrome in four patients: a bronchial carcinoid was found in three patients, and the site of the tumor was still unknown in the other. In conclusion, the CRH test improved the diagnostic accuracy of inferior petrosal sinus sampling from 61.5% (12 pituitary, 4 ectopic) to 92.0% (19 pituitary, 4 ectopic). Thus it should be performed during the diagnostic process.
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