An assessment of petrosal sinus sampling for localization of pituitary microadenomas in children with Cushing disease

CONTEXT: Pituitary adenomas in Cushing disease (CD) are usually small and difficult to visualize. Bilateral inferior petrosal venous sampling (BIPSS) before and after ovine CRH stimulation is reserved for patients who have ACTH-dependent Cushing syndrome and negative magnetic resonance imaging (MRI) or positive MRI but inconsistent biochemical data. OBJECTIVE: The objective of the study was to evaluate the usefulness of BIPSS as a tool for localization of a pituitary adenoma in children with CD. DESIGN: The study was a retrospective review of the records of 141 children who were admitted for evaluation of CD from 1982 to 2004. SETTING: The study was conducted at a tertiary care center. INTERVENTIONS AND OUTCOME MEASURES: Lateralization of ACTH secretion during BIPSS was compared with MRI and surgical findings for the localization of a microadenoma. RESULTS: A total of 94 patients, 49 males and 45 females with an age range of 5.3 to 18.7 yr (13 +/- 3.2 yr), underwent BIPSS. Localization of a microadenoma by BIPSS agreed with surgical location in only 58% of the cases (95% confidence interval, 43-66). The combined use of information from the MRI and inferior petrosal venous sampling did not predict the location of the tumor more frequently than MRI alone (P > 0.1), which in this study localized a lesion in 39% of the patients (95% confidence interval, 28-50). The procedure was completed successfully in all patients, and no serious complications were recorded. CONCLUSIONS: Although BIPSS was safe and well tolerated in an experienced center, lateralization of the ACTH gradient during BIPSS was a poor predictor of the site of the adenoma in children with CD.     

The role of desmopressin in bilateral and simultaneous inferior petrosal sinus sampling for differential diagnosis of ACTH-dependent Cushing's syndrome

OBJECTIVE: Bilateral inferior petrosal sinus sampling (BIPSS) with corticotrophin-releasing hormone (CRH) stimulation is currently the gold standard test for the differential diagnosis of ACTH-dependent Cushing's syndrome. Reports on the use of desmopressin in this approach are limited. The aim of this study was to evaluate the use of desmopressin during BIPSS in a cohort of patients with ACTH-dependent Cushing's syndrome. DESIGN: A retrospective case-record study. PATIENTS: Fifty-six patients with confirmed ACTH-dependent Cushing's syndrome underwent BIPSS with desmopressin stimulation when presenting negative pituitary tumour imaging. MEASUREMENTS: Central to peripheral (CEN:PER) ACTH gradient, lateralization of the ACTH source and surgical tumour confirmation were evaluated. RESULTS: A CEN:PER ACTH gradient was found in 40 patients under basal conditions (CEN:PER >or= 2) and in 47 patients after desmopressin stimulation (CEN:PER >or= 3). Ectopic ACTH-producing tumours (three lung carcinoid tumour, one thymus carcinoid tumour and one thymus hyperplasia) were confirmed in five out of nine patients without the CEN:PER ACTH gradient, and four cases were false negative for Cushing's disease. Lateralization (IPS:IPS >or= 1.4) was observed in 80.8% of patients under basal conditions (38/47) and in 97.8% after desmopressin (46/47), and it was surgically confirmed in 78.7%. There were no false-positive cases. Sensitivity and specificity were 92.1% and 100%, respectively. CONCLUSIONS: Desmopressin improves the differential diagnosis of ACTH-dependent Cushing's syndrome by amplifying the CEN:PER and IPS:IPS ACTH gradients, and is therefore a useful ACTH secretagogue in BIPSS.     

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.     

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.     

Bilateral inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin-dependent Cushing's syndrome: a comparison with other diagnostic tests

To compare bilateral inferior petrosal sinus sampling (IPSS) with high dose dexamethasone (HDD) and CRH testing (using recently proposed stringent response criteria) in the differential diagnosis of ACTH-dependent Cushing's syndrome, we reviewed 53 consecutive cases. The main analysis was limited to 45 cases with confirmed diagnosis: 44 with pituitary dependency, proven by confirmatory histology and/or significant biochemical improvement after pituitary surgery, and 1 with ectopic ACTH syndrome. After HDD (2 mg every 6 h for 48 h), 21 of the 44 pituitary cases met the stringent more than 90% suppression criterion. Twenty-three of the 44 pituitary cases also underwent CRH testing; 16 of 23 met a stringent response criterion of a more than 50% serum cortisol rise. For HDD and CRH testing combined, 8 of 23 fulfilled both stringent criteria, 10 of 23 had discordant results, and 5 of 23 failed to fulfil either of the stringent criteria for pituitary dependency. IPSS was performed in all 44 of the proven pituitary cases; 36 had petrosal/peripheral ACTH ratios of 2.0 or more without CRH stimulation. Thus, in patients with proven pituitary disease, stringent response criteria to HDD and CRH testing were fulfilled by only 48% and 70%, respectively. IPSS, which gave direct evidence of pituitary ACTH secretion in 82% of the cases, is therefore considered necessary in a significant proportion of cases.     

Absence of intercavernous venous mixing: evidence supporting lateralization of pituitary microadenomas by venous sampling

Preoperative lateralization of endocrine-active pituitary tumors may be possible by bilateral inferior petrosal sinus (IPS) sampling for hormone measurement. The reliability of this technique depends on unilateral drainage of blood from the adenoma within the pituitary gland, in its course from the gland to the ipsilateral cavernous sinus, and from the cavernous sinus to the junction of the IPS and the internal jugular vein. Anatomical studies demonstrate unilateral drainage of each hemihypophysis into the ipsilateral cavernous sinus. The degree of mixing of blood between the cavernous sinuses, via the intercavernous sinus, and between the IPSs, via the basilar plexus, is unknown. We determined the extent of mixing of blood flowing from the superior orbital vein to the junction of the IPS and the internal jugular vein in four rhesus monkeys. After catheterization of a superior orbital vein and both IPSs, 99Tc-colloidal sulfur was infused into the superior orbital vein while blood samples were taken simultaneously from both IPSs and a peripheral vein at 3-min intervals. Mean relative radioactivity was 100 +/- 14% (+/- SEM) in the ipsilateral IPS, 8 +/- 2% in the contralateral IPS, and 3 +/- 1% in a peripheral vein. Isotope reaching the ipsilateral IPS before recirculation from the periphery was 10- to 313-fold more concentrated than in the contralateral IPS. These findings suggest that mixture of blood between the cavernous sinuses and between the IPSs is insignificant and support the capability of preoperative lateralization of pituitary microadenomas by bilateral and simultaneous IPS sampling.     

Routine inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing's syndrome: early recognition of the occult ectopic ACTH syndrome.

The clinical, biochemical, and radiographic features of ectopic ACTH-dependent Cushing's syndrome are often indistinguishable from those of pituitary ACTH-dependent hypercortisolism (Cushing's disease). We prospectively evaluated 29 patients with ACTH-dependent hypercortisolism by means of bilateral inferior petrosal sinus ACTH sampling with ovine CRH (oCRH) stimulation. Patients with Cushing's disease (n = 20), had a maximal basal inferior petrosal sinus to peripheral ACTH ratio (IPS:P-ACTH) of 11.7 +/- 4.4 (+/- SE) from the dominant IPS, which increased to 50.8 +/- 18.3 after oCRH administration. Bilateral IPS sampling was necessary to correctly identify patients with Cushing's disease, since the maximal basal nondominant IPS:P-ACTH was less than 2.0 in over 50% of the patients and remained less than 2.0 after oCRH administration in one third. In contrast, patients with occult ectopic ACTH-secreting neoplasms (n = 9) had maximal basal IPS:P-ACTH of 1.2 +/- 0.1 that did not change after oCRH administration. Occult ectopic ACTH-secreting neoplasms were found in 7 of 9 patients from 0.4-14 yr after the recognition of Cushing's syndrome, and 4 of these patients had intermittent hypercortisolism with prolonged periods of remission. Selective endobronchial lavage for ACTH correctly localized a radiologically occult ACTH-secreting bronchial carcinoid in 1 patient, and magnetic resonance imaging identified a similar neoplasm in a patient with a normal chest computed tomographic scan. Basal ACTH and urinary free cortisol excretion were significantly higher in patients with ectopic ACTH than in those with Cushing's disease, but overlap existed between groups. High dose dexamethasone suppression testing inaccurately classified 24% of patients, and radiological imaging of the pituitary and adrenal glands was misleading. The occult ectopic ACTH syndrome is a common form of ACTH-dependent hypercortisolism that cannot be distinguished from Cushing's disease with routine clinical studies. The accurate differential diagnosis of ACTH-dependent Cushing's syndrome requires bilateral inferior petrosal sinus ACTH sampling with oCRH stimulation.     

A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing's disease and the occult ectopic adrenocorticotropin syndrome

The clinical, biochemical, and radiological features of pituitary ACTH-dependent Cushing's syndrome (CS) [Cushing's disease (CD)] are often indistinguishable from those of occult ectopic ACTH-dependent CS (oEAS). We have evaluated, retrospectively, the results of simultaneous bilateral inferior petrosal sinus (IPS) ACTH sampling before and after CRH stimulation in 128 patients with ACTH-dependent CS: 107 patients with CD, 6 with oEAS, 1 with an adrenal adenoma, 1 with a pituitary gangliocytoma, and 1 with Nelson's syndrome; while, in the remaining 12, the source remains unclear. One hundred seven patients received human-sequence CRH (hCRH), and 11 received ovine CRH; another 6 patients underwent stimulation with desmopressin and hCRH, and 4 with desmopressin alone. A successful bilateral IPS catheterization and sampling (IPSCS) rate of 87.5% was obtained only after considerable experience had been gained. Sixty-nine patients with CD underwent successful bilateral IPSCS: the IPS-to-peripheral ratio of plasma ACTH value (IPS/P) rose from 9.5 +/- 1.4 to a maximum ratio of 55.8 +/- 7.5 in 67 patients, after CRH stimulation. The maximum ratio was obtained at 5 min in 60 of the 69 patients with CD; however, all 69 patients obtained a ratio of more than 2, at that time. In contrast, the 6 patients with occult ACTH-secreting neoplasms had a maximal IPS/P ratio of 1.3 +/- 0.16, and this did not change after CRH stimulation. A bilateral IPS/P ratio more than 2, obtained 5 min after CRH stimulation, had a sensitivity of 97% and a specificity of 100% in diagnosing CD. Two patients with proven active CD had an IPS/P ratio of less than 2. After successful bilateral IPSCS, the gradients between the IPS ACTH concentrations [IPS ACTH gradient (IPSG)] of more than 1.4, at 5 min after CRH stimulation, had a sensitivity of 83% in correctly lateralizing the pituitary microadenoma, compared with 72% sensitivity for magnetic resonance imaging (MRI) scanning. Furthermore, when IPSG and MRI findings were contradictory, IPSG was more often correct than MRI scanning. Although oEAS is a relatively uncommon cause of ACTH-dependent hypercortisolism (5.5% in our series), the accurate diagnosis of ACTH-dependent CS and localization of an intrapituitary microadenoma requires bilateral IPSCS with CRH stimulation, provided that the appropriate technical experience is available. hCRH is as effective a secretagogue as ovine CRH, and either may be used. The value of the combination of CRH and desmopressin stimulation requires more detailed investigation.     

Cavernous and inferior petrosal sinus sampling in the evaluation of ACTH-dependent Cushing's syndrome

OBJECTIVE: Central venous sampling (CVS) is used frequently in the evaluation of ACTH-dependent Cushing's syndrome. However, several controversies exist including the diagnostic accuracy, the sampling site of choice (cavernous sinus vs. inferior petrosal sinus) and the use of lateralization data in tumour localization. We have analysed our experience with CVS to address these controversies. DESIGN: We retrospectively reviewed CVS data in patients with ACTH-dependent Cushing's syndrome, in whom cavernous sinus sampling (CSS), inferior petrosal sinus sampling (IPSS) and IPSS after administration of ovine corticotrophin releasing hormone (oCRH) were performed. PATIENTS: Data on 95 patients were analysed, including 79 patients with suspected Cushing's disease (CD) and 16 patients with suspected ectopic ACTH syndrome (EAS). RESULTS: For the differential diagnosis of ACTH-dependent Cushing's syndrome, the diagnostic accuracy of IPSS after oCRH stimulation was 97% compared to 86% for CSS. While no single sampling site was perfect in diagnostic accuracy, sampling both CS and IPS achieved a combined diagnostic accuracy of 100%. Lateralization data predicted tumour location in 62-68% of the patients with various central venous drainage patterns and in 77-80% of the patients with symmetrical drainage. CSS was not significantly superior to IPSS in tumour lateralization. In patients with suspected CD based on CVS and in whom an adenoma was not found on magnetic resonance imaging (MRI) and not located by the surgeon intraoperatively, hemihypophysectomy based on lateralization data was successful in only 10 of the 18 patients (56%) with various central venous drainage patterns and in 5 of 10 patients with symmetrical drainage. CONCLUSION: CVS is a powerful method for differentiating CD from the EAS. CSS without oCRH was not superior to IPSS after oCRH stimulation; however, we achieved a 100% diagnostic accuracy if at least two sites were sampled. Tumour localization by CVS did not accurately predict the tumour site at surgery and should not be used to guide surgical resection.     

Jugular venous sampling: an alternative to petrosal sinus sampling for the diagnostic evaluation of adrenocorticotropic hormone-dependent Cushing's syndrome

Bilateral sampling of the inferior petrosal sinuses (IPSS) to distinguish Cushing's disease from the ectopic ACTH syndrome is accurate but risky and technically difficult. Bilateral sampling of the internal jugular vein (JVS) is simpler and presumably safer. To compare jugular and petrosal sinus venous sampling for distinguishing Cushing's disease from ectopic ACTH syndrome, we studied 74 patients with surgically proven Cushing's disease, 11 with surgically confirmed, and three with occult ectopic ACTH secretion. Patients underwent JVS and IPSS with administration of CRH on separate days. Ratios of central-to-peripheral ACTH in venous samples were calculated. At 100% specificity, IPSS correctly identified 61 of 65 patients with Cushing's disease [sensitivity, 94%; confidence interval (CI), 84-98%]. When patients with abnormal venous drainage were excluded, sensitivity was 98% (CI, 90-100%). JVS had a sensitivity of 83% (CI, 71-91%) at 100% specificity. Receiver operated characteristics plot areas under the curve were similar (0.968 +/- 0.020 and 0.974 +/- 0.016, area under the curve +/- se, JVS vs. IPSS). Although petrosal sampling had better diagnostic accuracy, CIs overlapped (95% CI, 90-100% vs. 86% CI, 78-94%). Centers with limited sampling experience may choose to use the simpler JVS and refer patients for IPSS when the results are negative.     

The value of inferior petrosal sinus sampling in diagnosis and treatment of Cushing's disease

OBJECTIVE While microsurgical selective adenomectomy is the best method available at present for the treatment of Cushing's disease, its success depends to a large degree on precise preoperative intrapituitary microadenoma localization. This study compares the results of intrapituitary adenoma localization obtained with inferior petrosal sampling, computerized tomography and magnetic resonance imaging with the adenoma localization as found at surgery. DESIGN The results of inferior petrosal sampling for intrapituitary localization of ACTH-producing pituitary adenomas were compared in a retrospective study with the results of computerized tomography, magnetic resonance imaging, surgical and pathological findings. Special attention was paid to the intersinus ACTH relation. PATIENTS Thirty-eight patients (33 women and 5 men) of 11-68 years of age suffering from pituitary-dependent Cushing's disease were studied. Patients with ectopic ACTH-secreting tumours and and recurrent pituitary adenomas were excluded. MEASUREMENTS Blood samples were obtained simultaneously from both inferior petrosal sinuses and a peripheral vein before and 5, 10, 15 and 20 minutes after stimulation with 60 /μg/m² human corticotrophin-releasing hormone (hCRH). RESULTS of the adenomas in our series, 42% had a diameter of 3 mm or less. Only 6 of 20 adenomas examined by computerized tomography and 11 of 29 examined by magnetic resonance imaging were identified correctly. Inferior petrosal sinus sampling produced significantly better results, particularly when combined with a stimulation test with hCRH: for 29 of 38 adenomas examined, the location was predicted correctly with these techniques. Analysis of the intersinus adrenocorticotrophin concentration ratio showed that the best right-central-left discrimination was obtained with values of 1.3 and 1.4. CONCLUSIONS We conclude that inferior petrosal sinus ACTH sampling after hCRH stimulation is the best method available for the intrapituitary localization of microadenomas causing Cushing's disease provided that the appropriate technique of blood sampling is used meticulously.     

Selective venous sampling for ACTH in Cushing's syndrome: differentiation between Cushing disease and the ectopic ACTH syndrome

We performed selective venous catheterization and sampling for ACTH in six patients with ACTH-secreting pituitary adenomas (Cushing's disease) and four patients with occult ectopic ACTH-secreting neoplasms. In five patients with Cushing's disease in whom the inferior petrosal sinus could be catheterized, ACTH levels were unequivocally higher than simultaneous peripheral values: The ratio was greater than 2.0, with a range of 2.2 to 16.7. In contrast, the inferior petrosal sinus-to-peripheral ACTH ratio in three patients with ectopic ACTH secretion was less than 1.5. In the fourth patient, an arteriovenous gradient of 6.8 was shown 2 years before a bronchial carcinoid tumor was clinically apparent. Central-to-peripheral ACTH ratios at the level of the jugular bulb and jugular vein were not diagnostic. We conclude that selective venous ACTH sampling from the inferior petrosal sinus is a reliable and useful aid in the differential diagnosis of Cushing's syndrome when standard clinical and biochemical studies are inconclusive.     

Identification of patients with Cushing's disease with negative pituitary adrenocorticotropin gradients during inferior petrosal sinus sampling: prolactin as an index of pituitary venous effluent

Inferior petrosal sinus sampling for ACTH differentiates pituitary ACTH-dependent Cushing's (CD) from the ectopic ACTH syndrome (EAS). Petrosal sinus to peripheral (IPS:P) ACTH ratios greater than 2.0 in the basal state or a peak greater than 3.0 after CRH are diagnostic of CD. However, false-negative rates of 1-10% have been reported. We report three patients with features of CD with peak IPS:P ACTH ratios less than 3.0 after CRH suggesting EAS. We compared IPS:P prolactin (PRL) as an index of pituitary venous effluent in these three index cases with 44 patients with CD and five with EAS. The dominant basal IPS:P PRL ratio was greater than 1.8 in all 49 patients but was less than 1.2 in the three index cases. The IPS:P ACTH ratio normalized to IPS:P PRL was greater than 0.8 in all CD patients but was less than 0.6 in EAS patients. The IPS:P ACTH ratios normalized to IPS:P PRL were greater than 1.2 in the index cases, which was similar to those with CD. The three index cases had clinical and biochemical remissions after pituitary surgery.PRL is an index of pituitary venous effluent during inferior petrosal sinus sampling in patients with CD who fail to have a peak IPS:P ACTH ratio greater than 3.0 after CRH. IPS:P PRL should be measured when results indicate EAS.     

Usefulness of the corticotropin-releasing hormone test during bilateral inferior petrosal sinus sampling for the diagnosis of Cushing's disease.

Inferior petrosal sinus blood sampling for ACTH measurement (IPSS) is used for the differential diagnosis of ACTH-dependent Cushing's syndrome and for the preoperative location of pituitary microadenomas. Intermittent ACTH secretion from pituitary adenomas may result in insignificant differences between petrosal and peripheral ACTH levels at the time of sampling. Thus, pituitary stimulation during IPSS may improve the procedure. The aim of the study was to evaluate the usefulness of CRH injection in combination with IPSS. Twenty-two patients with Cushing's disease (CD; 5 macroadenomas, 16 microadenomas, and 1 corticotroph hyperplasia) and 5 patients with ectopic ACTH syndrome were studied. Bilateral IPSS was successfully carried out on 25 patients. Patients with ectopic ACTH syndrome had, before and after CRH injection, central to peripheral ACTH gradients below 1.7. Four patients with CD had basal gradients below 1.4. After CRH administration all patients with CD had gradients above 3.2. Despite correct location of central catheters, the predicted location of pituitary microadenomas was erroneous in 41% of the cases. It was not improved after CRH injection. In conclusion, the combination of CRH injection with IPSS was useful for the differential diagnosis of ACTH-dependent Cushing's syndrome, as it increased the discrimination of the procedure. On the contrary, it was useless for the preoperative location of pituitary microadenomas, which was poorly predicted by IPSS.     

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.     

Preoperative localization of abnormal parathyroid tissue: Cumulative experience with venous sampling and arteriography

Selective venous catheterization has been utilized with radioimmunoassay for parathyroid hormone as a preoperative localization technic in 94 patients with primary hyperparathyroidism. Sampling from thyroid veins provided localizing data in 82 per cent of patients with adenoma and 74 per cent of patients with hyperplasia. Failures were due to inability to catheterize important draining thyroid veins. Large vein sampling was much less helpful, localizing disease in only 29 per cent of patients with adenoma and 13 per cent of patients with hyperplasia. Thyroid venous sampling was also successful in patients who had had previous neck surgery (72 per cent). In addition, this technic differentiated between adenoma and hyperplasia; 98 per cent of patients with unilateral gradients had adenoma; 85 per cent of patients with bilateral elevations had hyperplasia. Selective thyroid venous sampling was more reliable (78 per cent) than arteriography (39 per cent). Venous sampling alone would not be useful for diagnostic purposes because high concentrations of parathyroid hormone were also detected in the inferior thyroid veins of control populations.The results indicate that selective venous sampling and radioimmunoassay of parathyroid hormone are useful preoperative adjuncts to surgical exploration especially in patients who have had previous neck surgery.     

Comparison of anterior pituitary hormone levels in the inferior petrosal sinuses and peripheral blood in various pituitary disorders during perihypophysial phlebography.

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 less than 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).