Plasma prolactin levels in the inferior petrosal sinuses in various pituitary disorders during perihypophyseal phlebography

The use of intercavernous sinus phlebography for the diagnosis and neurosurgical treatment of pituitary adenomas has enabled the collection of selective venous samplings of the inferior petrosal sinuses (IPSs), where prolactin (PRL) levels can be measured before the hormone becomes excessively diluted in the systemic circulation. In the present study, plasma PRL levels were studied in the right and/or left IPS and, simultaneously, in the peripheral circulation of: (1) normoprolactinemic patients affected with various pituitary disorders which required phlebographic procedures; (2) hyperprolactinemic patients with negative radiological and computed tomographic (CT) signs of pituitary adenomas and (3) adenomatous hyperprolactinemic patients. In the 17 normoprolactinemic patients, the plasma PRL concentration in the IPSs was significantly higher (3.5 times; p less than 0.01) than in the peripheral circulation. In the 11 hyperprolactinemic patients with negative radiological and CT signs of pituitary adenomas, the central gradient for PRL was significantly higher (2.8 times; p less than 0.05) than in the peripheral circulation. No significant difference was detected between PRL concentrations in the left and right IPSs. In the 11 adenomatous hyperprolactinemic patients, there was a significant (p less than 0.01) central gradient for PRL 3.8 times higher than in the peripheral circulation on the ipsilateral side of the tumor. Furthermore, the plasma PRL concentration in the ipsilateral IPS was significantly higher (3.4 times; p less than 0.05) than that in the contralateral sinus. In conclusion, the present study shows that a clear-cut concentration gradient exists between plasma PRL levels in the IPSs and in the peripheral circulation of normoprolactinemic and hyperprolactinemic patients with negative radiological and CT signs of pituitary adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Selective venous sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome.

Bilateral simultaneous inferior petrosal sinus sampling, associated with the oCRH stimulation test (100 micrograms i.v. as a bolus) was performed in 22 patients with Cushing's syndrome and no signs of pituitary abnormalities. Catheters were inserted into both femoral veins. More than one site in the superior and inferior vena cava was sampled before reaching the inferior petrosal sinuses. Blood samples for ACTH and beta-endorphin were gently aspirated from both petrosal sinuses and from a peripheral vein simultaneously. Blood was drawn at 0, 5, 10 and 15 min after oCRH injection. Seventeen of 22 patients showed an ipsilateral to peripheral vein ratio higher than 1.5, and 12 patients showed a lateralization of ACTH levels after oCRH stimulation. Seventeen patients underwent transsphenoidal pituitary surgery. Nine patients had a pituitary adenoma at the expected side; 1 at the contralateral side, while in 2 it was central. Three of 4 patients in whom the ipsilateral/peripheral ratio was less than 1.5 had the highest ACTH levels at the superior or inferior vena cava, not responsive to oCRH stimulation. One of these had a mediastinal and one a pulmonary mass. The third one, with an occult ectopic source, is still under investigation. At immunohistochemical and biological in vitro studies, both tumors were shown to secrete ACTH. In 13 patients in whom both beta-endorphin and ACTH measurements were performed, these hormones showed similar patterns of response. In conclusion, simultaneous bilateral petrosal sinus catheterization is a useful tool in the differential diagnosis of Cushing's syndrome as concerning pituitary and ectopic forms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unilateral Proptosis (Exophthalmos) Caused by Axillary-Subclavian Venous Thrombosis in a Patient with Upper Extremity Arteriovenous Dialysis Fistula

Arterialization of orbital veins is most often due to dural arteriovenous malformations of the cavernous sinus area. We report an unusual case of unilateral proptosis (exophthalmos) caused by arterialized retrograde venous flow in the external jugular vein and cavernous sinus in a patient with an upper extremity hemodialysis fistula and ipsilateral acute central venous thrombosis. The patient’s symptoms improved after surgical closure of the hemodialysis fistula.     

Pituitary tumour localization in patients with Cushing's disease by magnetic resonance imaging. Is there a place for petrosal sinus sampling?

OBJECTIVE We wished to analyse the relative value and diagnostic accuracy of bilateral simultaneous inferior petrosal sinus blood sampling for plasma ACTH measurements when compared with pituitary magnetic resonance imaging (MRI) for the preoperative localization of microadenoma (tumour diameter <10 mm) within the pituitary fossa in patients with Cushing's disease. DESIGN Pituitary MRIs were assessed blind and independently. The sinus blood sampling was performed before and after administration of corticotrophin releasing hormone (CRH). The ratios of the ACTH concentrations in plasma samples from the inferior petrosal sinuses to the concentrations in peripheral blood plasma samples (the IPS:P ratio) and the ratios of the ACTH concentrations in samples from both inferior petrosal sinuses (the inter-sinus gradient) were calculated. PATIENTS Twenty consecutive patients with Cushing's disease were prospectively studied. All but two patients subsequently underwent transsphenoidal exploration of the pituitary fossa. RESULTS In three of 20 patients (15%), positioning of catheter tips in both inferior petrosal sinuses was unsuccessful. The diagnosis of Cushing's disease was confirmed by the greater basal IPS: P ratio amounting to 3; 2 0 in 13 of 17 patients (76%), and amounting to > 3 0 in CRH-stimulated peak samples in 15 of 17 patients (88%). Anatomical variations of the inferior petrosal sinus, precluding reliable conclusions about lateralization of pituitary venous ACTH drainage, were observed in five of 20 patients (25%). Adding the three patients with technical failure and one patient who presented with a macroadenoma (tumour diameter 11 mm), this left interpretable data with regard to lateralization of the microadenomas in only 11 of 20 patients (55%). In 15 of 20 patients (75%) a pituitary microadenoma was found at MRI. In 14 of these 15 patients (93%) a tumour was indeed found at that position at subsequent transsphenoidal operation. Concordance between the lateralization by the intersinus gradient and microadenoma localization by MRI was observed in six of 11 cases (55%) when using basal samples and in seven of 11 cases (64%) when using peak samples obtained after stimulation with CRH. Concordance between the lateralization by the intersinus gradient and subsequent microadenoma localization at surgery was observed in seven of 11 patients (64%) before and in eight of 11 cases (73%) after CRH stimulation. Reversal of the intersinus gradient after CRH stimulation, suggesting a shift in the lateralization to the contralateral side of the gland, was found in three of 12 cases (25%). CONCLUSIONS Bilateral simultaneous inferior petrosal sinus blood sampling for plasma ACTH measurements before and after CRH stimulation successfully confirmed the diagnosis of pituitary dependent Cushing's disease in 15 of 17 patients (88%) in whom this diagnosis was suspected on the basis of conventional biochemical testing. Magnetic resonance imaging, however, is superior to bilateral simultaneous inferior petrosal sinus blood sampling for the localization/lateralization of pituitary microadenomas in patients with Cushing's disease. Therefore, bilateral simultaneous inferior petrosal sinus blood sampling should be reserved for the assessment of those patients with Cushing's syndrome in whom either the results of biochemical tests are equivocal and/or subsequent pituitary magnetic resonance imaging gives unconvincing results.     

经面静脉入路栓塞治疗海绵窦区硬脑膜动静脉瘘

目的探讨经面静脉途径治疗海绵窦区硬脑膜动静脉瘘（arteriovenous fistula，AVF）的方法和疗效。方法回顾性分析经面静脉途径（导管置入股静脉-面静脉-角静脉-眼上静脉-海绵窦）治疗7例海绵窦区硬脑膜AVF的病例资料，其中5例患者岩下窦闭塞；1例患者岩下窦开放，但其AVF所在的海绵窦和岩下窦之间无交通；1例患者的瘘与岩下窦相通。对该患者先行经岩下窦栓塞海绵窦后部，然后再经面静脉途径栓塞海绵窦前部。其他6例患者只经面静脉途径行栓塞治疗。结果血管造影显示，7例患者的角静脉和眼上静脉的走行清晰，其中有1例眼上静脉闭塞的患者，由于导管无法置入闭塞的眼上静脉，导致经静脉途径治疗终止。其余6例患者经面静脉入路用弹簧圈栓塞海绵窦治疗后，4例达到完全栓塞，2例临床症状明显好转。结论相对其他静脉途径而言，经股静脉-面静脉入路是血管内治疗海绵窦区硬脑膜AVF的一种很有价值的方法，即使该入路对术者手术技能要求较高，但仍然不失为一种安全和有效的血管内治疗方法。     

The hypoplastic inferior petrosal sinus: a potential source of false-negative results in petrosal sampling for Cushing's disease

Our purpose was to describe the hypoplastic or plexiform inferior petrosal sinus as a potential cause of false-negative sampling results in patients with Cushing's disease. Five hundred and one patients with surgically proven Cushing's disease and negative or equivocal magnetic resonance imaging scans of the pituitary gland underwent petrosal sinus sampling. Four patients (0.8%) with surgically proven Cushing's disease had false-negative results of petrosal sinus sampling. Retrograde inferior petrosal sinograms in these patients were reviewed to evaluate the anatomy of the inferior petrosal sinuses for abnormalities that could have contributed to this misdiagnosis. In addition, the retrograde inferior petrosal sinograms of 100 consecutive patients were reviewed to establish the frequency of asymmetric and/or hypoplastic inferior petrosal sinuses. All four patients with false-negative results of petrosal sampling demonstrated a hypoplastic or plexiform inferior petrosal sinus ipsilateral to an ACTH-secreting microadenoma. When the sampling catheter was in the hypoplastic petrosal sinus, retrograde sinograms from the contralateral side demonstrated anomalous drainage patterns on the side of the hypoplastic sinus. Because the negative results of petrosal sinus sampling false-suggested the presence of the ectopic ACTH syndrome, curative transsphenoidal surgery in these four patients was delayed up to 31 months. We conclude that the presence of a unilateral hypoplastic or plexiform inferior petrosal sinus can result in anomalous drainage from the pituitary gland that may lead to false-negative sampling results in patients with Cushing's disease.     

Relative contributions of inferior petrosal sinus sampling and pituitary imaging in the investigation of children and adolescents with ACTH-dependent Cushing's syndrome.

Selective transsphenoidal microadenomectomy is the first line treatment of childhood Cushing's disease, with accurate preoperative localization of the corticotroph adenoma an important step in its investigation. Inferior petrosal sinus sampling (IPSS) for ACTH after CRH stimulation is a recognized investigation in adults, but there are few data in the pediatric age range. We report the relative contributions of IPSS and pituitary imaging in 11 patients, aged 10.7-18.8 yr, presenting with Cushing's disease. All underwent transsphenoidal surgery (TSS). IPSS was performed without complication. Sampling was from the inferior petrosal sinuses in 7 patients and the high jugular veins in 4 (patients 2, 4, 5, and 10). The central to peripheral ACTH (IPS/P) ratios were more than 2 (2.5-157.2) in 10 of 11 patients, confirming central ACTH secretion. In 3 patients with high jugular sampling, IPS/P ratio ranged from 2.5-21.1. In the fourth patient with high jugular sampling (IPS/P ratio, 0.95), a central adenoma was identified surgically, and the patient was cured after TSS. The interpetrosal sinus ACTH gradient (IPSG) was more than 1.4 (2.1-20.8) in 10 patients, indicating lateralization of ACTH secretion to the right side in 6 patients and to the left in 4. IPSG ratios were 2.1-8.5 in 3 patients with high jugular sampling. Pituitary imaging (computed tomography and or magnetic resonance imaging) was reported to identify an adenoma in 5 of 11 patients. At operation a tumor was visualized by the same surgeon in all 11 cases. In 9 patients with lateralization on IPSS, the correct side of the tumor was confirmed at surgery. In a 10th patient with a negative IPSG, a central tumor was present. Thus, IPSS gave a 91% prediction of correct tumor localization. In only 1 of 5 patients with an adenoma reported on pituitary imaging was this localization confirmed at surgery, a prediction rate of only 9%. After TSS, 8 patients were cured, 1 was in remission, and 2 required pituitary irradiation. In 73% of patients undergoing IPSS, localization of the adenoma was followed by surgical cure or remission. Pituitary scanning was therefore relatively unhelpful in localizing the adenoma. In experienced hands, however, IPSS was feasible in this age group, safe, and strongly predictive of the site of the adenoma, leading to a high rate of successful surgical outcome.     

经未显影静脉窦栓塞治疗硬脑膜动静脉瘘

目的探讨经未显影静脉窦栓塞治疗硬脑膜动静脉瘘（DAVF）的可行性、安全性及有效性。方法回顾性分析92例经未显影静脉窦栓塞治疗的DAVF患者的临床资料，其中病变位于海绵窦区91例，侧窦区1例。经颈内静脉的起始段探查未显影岩下窦，进入引流静脉窦内栓塞海绵窦区DAVF；通过颈内静脉探查未显影乙状窦，进入静脉窦栓塞侧窦区DAVF。首选可控纤毛弹簧圈进行栓塞，待血流减慢以后，用游离纤毛弹簧圈继续栓塞。若仍存在少量瘘口，通过静脉窦内注射液体栓塞剂（25％～33％Glubran或Onyx18），观察置管的成功率、安全性和栓塞的疗效。术后6个月通过电话、门诊或DSA随访。结果92例患者中，均未出现并发症，无死亡病例。1例海绵窦区DAVF患者置管失败；其余91例患者均顺利置管，并成功进行静脉栓塞。所有患者栓塞后即刻造影，均未见异常静脉窦早显，瘘口消失，达到了影像学上治愈。置管成功率及治愈率均为99％（91／92）。术后6个月对38例进行随访，无一例DAVF复发。对其余患者进行电话或门诊随访。所有患者临床症状好转或消失。结论经未显影静脉窦栓塞治疗DAVF，尤其对于海绵窦区DAVF，经未显影岩下窦超选择置管进行栓塞，具有较高的可行性、安全性及有效性，可作为海绵窦区DAVF的首选常规治疗方法。     

Bilateral and simultaneous venous sampling of inferior petrosal sinuses for ACTH and PRL determination: preoperative localization of ACTH-secreting microadenomas

We report our experience on venous sampling of the inferior petrosal sinuses for basal and CRH-stimulated ACTH and PRL gradients in 8 patients with surgically proven Cushing's disease who had normal preoperative neuroradiological studies. In 7 patients basal plasma ACTH concentrations in the inferior petrosal sinus ipsilateral to the tumor were higher than in the contralateral sinus; the gradients were enhanced by oCRH administration. In one out of two patients who had previously undergone unsuccessful pituitary microsurgery, neither basal nor oCRH-induced ACTH increases led to correct localization of the microadenoma within the pituitary. In 4 out of 7 patients basal serum PRL concentrations in the inferior petrosal sinus ipsilateral to the tumor were higher than in the contralateral; only two out of 4 showed an increase in PRL levels after oCRH injection. Our study confirms that simultaneous and bilateral venous sampling of inferior petrosal sinuses is a valuable means to identify the site of microadenomas in patients with Cushing's disease without neuroradiological evidence of the tumor. This procedure may give misleading results in patients previously operated on. Unilateral or predominant increases of PRL concentration during catheterization of the inferior petrosal sinuses, when present, always lateralize to the side of the corticotroph adenoma, providing a possible additional signal of the presence of the tumor.     

Petrosal sinus sampling for diagnosis of Cushing's disease: evidence of false negative results

OBJECTIVE While inferior petrosal sinus (IPS) sampling correctly diagnoses pituitary-dependent Cushing's syndrome if a significant ratio of plasma ACTH between the IPS and the peripheral blood is demonstrated, little has been said about the significance of a negative ratio in Cushing's disease (e.g. a false-negative result). This study evaluates the results of IPS sampling in patients with Cushing's disease, and compares them with both imaging findings and transsphenoidal examination. DESIGN The results of IPS sampling were retrospectively compared with both imaging findings and transsphenoidal examination. IPS samples were obtained before and 2, 5 and 10 minutes after intravenous administration of 100 μg of CRH. PATIENTS Thirty-two patients with Cushing's disease were evaluated. All subsequently underwent transsphenoidal examination of the pituitary gland. MEASUREMENTS The ratio of the ACTH concentrations at the IPS and in the peripheral blood (IPS : P ratio), and the ratio of the ACTH concentrations between the IPSs (interpetrosal ratio) were calculated. Radiographic evaluation of the pituitary gland was performed with magnetic resonance imaging (MRI, 29 cases) or computed tomography imaging (CT, 3 cases). RESULTS Transsphenoidal examination of the pituitary gland revealed a microadenoma in 27 cases. Radiological imaging showed a signal compatible with a microadenoma in 22 cases (68.8%), and correctly located the tumour at the side found at surgery in 14 of the 22 cases with positive transsphenoidal findings (MRI 13 cases, CT 1 case, overall 63.6%). Successful bilateral catheterization was accomplished in 30 patients (93.8%). Samples before and after CRH stimulation were drawn in 24 cases. No major complications were observed with the technique. IPS catheterization correctly predicted Cushing's disease (by means of a significant IPS : P ACTH ratio) in 27 of the 30 patients (90%) with basal sampling, and in 23 of the 24 cases with samples drawn before and after CRH administration (95.8%). Taking into account the 12 patients with a lateral microadenoma shown at transsphenoidal examination, IP sinus ACTH ratio was in agreement with the side recorded by the neurosurgeon in 8/12 cases (66.7%). MRi correctly located the tumour in 8/12 patients (66.7%). One patient showed no significant IPS : P ACTH ratio in any set of samples. His MRI showed no sign of a microadenoma. Two years later, another pituitary MRI evaluation showed a midline hypodense signal. The transsphenoidal examination revealed a microadenoma and the post-operative plasma cortisol and urinary free cortisol fell to 293 nmol/l and 100 nmol/24 h, respectively. CONCLUSIONS Only when a significant IPS : P ACTH ratio is present can Cushing's disease be established by IPS sampling. The absence of a significant IPS : P ACTH ratio does not necessarily imply ectopic secretion of ACTH, nor does it exclude Cushing's disease. The results of lateralization by IPS sampling do not remove the need for a thorough transsphenoidal examination of the contents of the sella turcica.     

Galanin is released by adrenocorticotropin-secreting pituitary adenomas in vivo and in vitro

Galanin, a brain-gut peptide, is also synthesized and released by the pituitary. In man, galanin-like immunoreactivity and galanin messenger RNA have been detected specifically in normal and tumoral corticotropes, but little is known about the production and release of galanin by the human pituitary. We evaluated galanin release by 5 ACTH-secreting pituitary adenomas in culture and plasma galanin concentrations in the inferior petrosal sinuses (IPSs) of 15 patients with Cushing's disease before and after CRH administration. For comparison, the galanin response to CRH was evaluated in 8 normal controls. Galanin secretion by pituitary tumor cultures ranged from 30-230 pmol/4 h. Incubation with CRH induced an increase in galanin concentrations (100 pM CRH: 151 +/- 32%; 1 nM CRH: 232 +/- 43%; 10 nM CRH: 246 +/- 35%; and 100 nM CRH: 270 +/- 44% unstimulated levels at 24 h, P < 0.05). The stimulatory effect of CRH seemed to be dose-dependent. Basal and CRH-stimulated ACTH and galanin concentrations also exhibited a strong positive correlation in single tumor cultures. At IPS sampling, mean basal plasma galanin concentrations in the dominant IPS were somewhat higher than those registered at the periphery (18.6 +/- 1.94 vs. 15.8 +/- 1.60 pmol/L, P = 0.05). Administration of CRH induced a modest but significant increase in galanin concentrations at all three sampling sites. No correlations were found between ACTH and galanin levels in the IPSs and at the periphery. Different from what was observed in patients with Cushing's disease, CRH did not modify plasma galanin concentrations in normal subjects. In conclusion, this study demonstrates that galanin is released by human tumoral corticotropes and responds to CRH. The role of locally produced galanin is, as yet, unknown but may possibly be that of a autocrine/paracrine modulator.     

Preliminary observations using endocrine markers of pituitary venous dilution during bilateral simultaneous inferior petrosal sinus catheterization in Cushing's syndrome: Is combined CRF and TRH stimulation of value?

OBJECTIVE We determined whether the measurement of hormones in pituitary blood permits correction for dilution by non-pituitary blood during bilateral simultaneous inferior petrosal sinus blood sampling in Cushing's syndrome. DESIGN Bilateral simultaneous inferior petrosal sinus blood sampling was performed after combined hCRF and TRH stimulation. Peak ACTH concentrations were corrected for the TSH and PRL inter-sinus ratio, assuming uniform secretion of both hormones into each inferior petrosal sinus. PATIENTS Eight patients with clinical and biochemical features of Cushing's syndrome. MEASUREMENTS Basal and stimulated ACTH, TSH and PRL concentrations were measured after bilateral simultaneous inferior petrosal sinus blood sampling and simultaneously from a peripheral forearm vein. RESULTS Basal central peripheral ACTH ratio misdiagnosed four of eight patients as having non-pituitary disease. Peak uncorrected ACTH central:peripheral ratio erroneously suggested two of eight patients had non-pituitary disease. ACTH central: peripheral ratio corrected by TSH and PRL correctly predicted pituitary-dependent disease in all eight cases and provided correct lateralization data in four of five patients with a unilateral pituitary microadenoma. CONCLUSION This study suggests that measuring other hormones in pituitary blood after TRH stimulation can offer a simple and reliable method for correcting for dilution by non-pituitary blood during bilateral simultaneous inferior petrosal sinus blood sampling in Cushing's syndrome.     

Melatonin Concentration in the Cerebral Vascular Sinuses of Sheep and Evidence for Its Episodic Release

Blood was collected from the cerebral sinuses and from the jugular vein of 5 ewes during both the day and night. Cerebral sinus samples were collected by means of a permanently indwelling cannula (roughly every 5 min) while jugular vein samples were collected by venipuncture (roughly every 10 min). In each of the 5 animals mean nighttime melatonin concentrations were greater at night than during the day. In 2 animals, cerebral sinus plasma melatonin concentrations were greater than in the jugular vein; in 2 animals the sinus and jugular plasma had similar melatonin levels; in 1 ewe jugular vein blood melatonin levels exceeded those in the cerebral sinus plasma. These differences among animals are presumably due to slight positional differences in the cerebral venous cannula placement. In several animals episodic release of melatonin was apparent. Whereas the episodes were most obvious in the cerebral venous blood at night, they were also apparent in 1 case in the jugular vein plasma and in 1 animal during the day. When episodes appeared they occurred about every 15-20 min.     

Adrenocorticotropic hormone and beta-endorphin concentrations in the inferior petrosal sinuses in Cushing's disease and other pituitary diseases.

Aim of the present study was the evaluation of ACTH and beta-endorphin-like-immunoreactivity (beta-ELI) in the inferior petrosal sinuses (IPS's) and in the peripheral blood of patients with Cushing's disease (Group 1), with GH- or PRL-secreting adenomas or nontumoral hyperprolactinemia (Group 2). These patients had undergone selective and bilateral simultaneous IPS sampling for diagnostic purposes or for neurosurgical indications. In the patients of Group 1, ACTH and beta-ELI levels were higher in the IPS ipsilateral than in the contralateral to the adenoma and in the periphery (p < 0.001). In the patients of Group 2 ACTH and beta-ELI levels were higher in the IPS's than in the peripheral blood (p < 0.001) and, in the 9 patients with GH- or PRL-secreting adenomas, they were higher in the IPS ipsilateral than in the contralateral to the adenoma and in the periphery (p < 0.05). A significant correlation exists between ACTH and beta-ELI in the periphery (p < 0.01; r = 0.72), in the IPS ipsilateral (p < 0.05; r = 0.54) and contralateral (p < 0.01; r = 0.66) to the adenoma in Group 1, but not in Group 2. In conclusion, higher beta-ELI levels were detected in the IPS's than in the peripheral blood not only in patients with Cushing's disease but also in those with other pituitary diseases not involving ACTH secretion. The absence of correlation between ACTH and beta-ELI in patients not bearing Cushing's disease suggests that in these conditions corticotrophs release ACTH and beta-endorphin in an independent manner.     

Hypophysopexy technique for radiosurgical treatment of cavernous sinus pituitary adenoma

Stereotactic radiosurgery is being used with increased frequency in the treatment of residual or recurrent pituitary adenomas. The major risk associated with radiosurgical treatment of residual or recurrent pituitary tumor adjacent to normal functional pituitary gland is radiation of the pituitary, which frequently leads to the development of hypopituitarism. The authors describe a technique of pituitary transposition to reduce the radiation dose to the normal pituitary gland in cases of planned radiosurgical treatment of residual pituitary adenoma within the cavernous sinus. A sellar exploration for tumor resection is performed, the pituitary gland is transposed from the region of the cavernous sinus, and a fat and fascia graft is interposed between the normal pituitary gland and the residual tumor in the cavernous sinus. The residual tumor may then be treated with stereotactic radiosurgery. The increased distance between the normal pituitary gland and the residual tumor facilitates treatment of the tumor with radiosurgery and reduces the radiation to the normal pituitary gland. An illustrative case of a young female with recurrent acromegaly and a pituitary adenoma invading the cavernous sinus is described.     

Corticotrophin releasing hormone (CRH1–41) stimulates the secretion of adrenocorticotrophin, vasopressin and oxytocin but not adrenocorticotrophin precursors: evidence from petrosal sinus sampling in man

To examine the relationship between corticotrophin releasing hormone (CRH), arginine vasopressin (AVP) and oxytocin (OXT) we have studied the responses of adenohypophyseal and neurohypophyseal hormones to CRH in eight patients (age 26-64 years, six female) with suspected pituitary-dependent Cushing's syndrome during bilateral, simultaneous inferior petrosal sinus catheterization. Blood samples were taken from both petrosal sinuses and a peripheral vein before, and at 5-min intervals for 15 min after, an intravenous injection of 100 micrograms human CRH1-41. CRH increased sinus AVP concentrations in all eight patients and OXT concentrations in four of five patients studied. Although AVP concentrations often increased in both sinuses, the side of maximal AVP rise was termed side(max-AVP). CRH did not affect peripheral or petrosal sinus mean concentrations of LH, FSH, GH or TSH. While there was no change in mean peripheral concentrations of AVP, OXT, ACTH, ACTH precursors or prolactin after CRH, sinus concentrations of OXT, ACTH and prolactin on side(max-AVP) were markedly elevated over contralateral values. CRH did not increase mean sinus concentrations of ACTH precursors. In seven patients with either no radiological abnormality or the pituitary fossa or a small adenoma the mean ACTH precursor/ACTH ratio in blood sampled from all sites was 2.1 +/- 0.16 (mean +/- SEM, n = 50). In a patient with a large, locally invasive tumour the mean ACTH precursor/ACTH molar ratio was 32.1 +/- 1.3 (n = 12; P less than 0.001), suggesting that alterations in this molar ratio may reflect the biological properties of the tumour. The source of CRH-stimulatable AVP and OXT remains uncertain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Accuracy of bilateral inferior petrosal or cavernous sinuses sampling in predicting the lateralization of Cushing's disease pituitary microadenoma: influence of catheter position and anatomy of venous drainage

Bilateral inferior petrosal sinus sampling (BIPSS) is the most reliable procedure for distinguishing Cushing's disease from ectopic ACTH secretion. However, it is less reliable at predicting the lateralization of the pituitary corticotroph microadenoma. We sought to determine whether this could be improved by taking into account the pattern of venous drainage and the precise location of the catheters. We retrospectively studied data from 86 patients who underwent BIPSS. Cushing's disease was predicted in 74 patients, of whom 69 underwent transsphenoidal surgery. Surgical cure was obtained in 65 patients, with identification of a corticotroph microadenoma in 58 cases. In 49 patients the location of the microadenoma predicted by the intersinus ACTH gradient could be compared with the pathologist's data. BIPSS accurately predicted the lateralization of the microadenoma in only 57% of these patients. Prediction was improved to 71% when both venograms and catheters were symmetric (35 patients). In this subgroup accuracy was 86% in patients with both catheters in the inferior petrosal sinuses compared with 50% in patients with both catheters in the cavernous sinuses (CS). Two transient sixth nerve palsies occurred during CS catheterization. Our data suggest that BIPSS results are much improved when venous drainage is symmetric. Catheterization of CS did not improve the results and was less safe.     

Simultaneous bilateral venous sampling for adrenocorticotropin in pituitary-dependent cushing's disease: evidence for lateralization of pituitary venous drainage

At present it is not established whether lateralization of pituitary venous drainage occurs in humans. To explore this possibility, we performed bilateral simultaneous inferior petrosal sinus sampling for ACTH in three patients with surgically proven ACTH-secreting pituitary microadenomas laterally located in the pituitary gland. In each patient, a gradient for ACTH correctly identified the location of the tumor. This finding suggests that pituitary venous drainage in humans is lateralized. These data also demonstrate that inferior petrosal sinus sampling needs to be bilateral before the pituitary origin of ACTH hypersecretion can be safely excluded in patients with Cushing's syndrome. In at least one and possibly two patients, the pituitary origin of ACTH excess would have been missed had we only sampled one inferior petrosal sinus. Finally, the demonstration of a left to right central gradient for PRL in addition to ACTH in one patient suggests that this technique may be useful in lateralizing functioning pituitary tumors other than ACTH-secreting tumors.     

Right atrial-jugular venous pressure gradients during CPR in children

OBJECTIVE: This study measured the internal jugular vein and right atrium pressures during pediatric CPR to detect and quantify venous pressure gradients across the thoracic inlet. DESIGN: Ten children from 2 months to 15 years old who underwent CPR had simultaneous pressure measurements recorded from the right atrium and jugular vein. RESULTS: The right atrium-jugular vein peak compression-phase gradient was 18.3 +/- 4.7 mm Hg (mean +/- SD), and the end-relaxation gradient was 0.7 +/- 0.6. Jugular vein pressure exceeded the right atrium only in the early-relaxation phase (right atrium-jugular vein = -2.1 +/- 1.2). Thoracic inlet venous valving persisted throughout the duration of CPR. CONCLUSION: There is a large venous gradient across the thoracic inlet during chest compressions in children, facilitating cerebral blood flow. This gradient reversed only in the early-relaxation phase. The data suggest that jugular venous return occurs only in the early-relaxation phase, whereas cerebral venous drainage persists throughout the CPR cycle.     

Cavernous sinus sampling is highly accurate in distinguishing Cushing's disease from the ectopic adrenocorticotropin syndrome and in predicting intrapituitary tumor location.

Inferior petrosal sinus sampling (IPSS) is used to distinguish pituitary Cushing's disease from occult cases of the ectopic ACTH syndrome, but is limited in that it requires the use of ovine CRH (oCRH) and is not highly accurate at predicting the intrapituitary location of tumors. This study was designed to determine whether cavernous sinus sampling (CSS) is as safe and accurate as IPSS, whether CSS can eliminate the need for oCRH stimulation, and whether CSS can accurately predict the intrapituitary location of tumors. Ninety-three consecutive patients with ACTH-dependent Cushing's syndrome were prospectively studied with bilateral, simultaneous CSS before and after oCRH stimulation. Prediction of a pituitary or ectopic ACTH source was based on cavernous/peripheral plasma ACTH ratios. Intrapituitary tumor location was predicted based on lateralization (side to side) ACTH ratios. These predictions were compared to surgical outcome in the 70 patients who had surgically proven pituitary (n = 65) or ectopic (n = 5) disease. CSS distinguished pituitary Cushing's disease from the ectopic ACTH syndrome in 93% of patients with proven tumors before oCRH administration and in 100% of patients with proven tumors after oCRH. It was as safe and efficacious as published IPSS results. CSS accurately predicted the intrapituitary lateralization of the tumor in 83% of all patients and 89% of those patients with good catheter position and symmetric venous flow. CSS is as safe and accurate as IPSS for distinguishing patients with pituitary Cushing's disease from those with the ectopic ACTH syndrome. In addition, CSS appears to be superior to IPSS for predicting intrapituitary tumor lateralization.