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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.

Adolescent↗

Petrositis.

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Bone Diseases↗

The limited ability of inferior petrosal sinus sampling with corticotropin-releasing hormone to distinguish Cushing's disease from pseudo-Cushing states or normal physiology.

To determine whether petrosal sinus sampling is useful to distinguish patients with mild or intermittent Cushing's disease from normal subjects and individuals with pseudo-Cushing states, we performed bilateral inferior petrosal sinus sampling for ACTH before and after the administration of CRH in 7 eucortisolemic volunteers, 8 hypercortisolemic patients with pseudo-Cushing states, and 40 patients with ACTH-dependent Cushing's disease whose urinary free cortisol excretion was within the range found in patients with, pseudo-Cushing states (< 1000 nmol/day; < 360 micrograms/day). The ACTH level, the ratio of the inferior petrosal sinus ACTH to the peripheral venous ACTH concentration (the IPS:P ratio), and the greater ratio of right to left or left to right petrosal sinuses (the R:L ratio) were compared in patients with and without Cushing's disease. Maximal petrosal ACTH values were significantly elevated in patients with Cushing's disease compared to patients with pseudo-Cushing states before CRH administration (P < 0.001), but not after CRH. Maximal petrosal plasma ACTH values after the administration of CRH as high as 808 pmol/L (3670 pg/mL) and 469 pmol/L (2130 pg/mL) were found in patients with pseudo-Cushing states and in normal volunteers, respectively, whereas maximal petrosal ACTH levels as low as 10 pmol/L (46 pg/mL) were observed in patients with surgically proven Cushing's disease. Maximal and minimal IPS:P ratios were significantly greater in patients with Cushing's disease than in subjects without Cushing's disease before, but not after, CRH treatment. R:L ratios did not differ among groups either before or after CRH. All of the subjects without Cushing's disease showed large R:L gradients, consistent with the notion of one dominant petrosal sinus containing a greater percentage of pituitary effluent. The ACTH concentrations, IPS:P ratios, and R:L ratios exhibited great overlap between those with and without Cushing's disease, which resulted in a diagnostic accuracy of 81% at best for the diagnosis of Cushing's disease. We conclude that petrosal sinus sampling is of limited usefulness in distinguishing either normal individuals or patients with pseudo-Cushing states from those with mild Cushing's disease. This limited usefulness must be recognized when interpreting the results of petrosal sinus sampling in patients with mild or intermittent hypercortisolism who may have a pseudo-Cushing state. Because of these limitations, petrosal sinus sampling should be reserved for patients with clear clinical and biochemical evidence of Cushing's syndrome.

Adrenocortical Hyperfunction↗

Internal jugular vein sampling in adrenocorticotropic hormone-dependent Cushing's syndrome: a comparison with inferior petrosal sinus sampling.

OBJECTIVE: Distinguishing between pituitary-dependent Cushing's syndrome (CS) and occult ectopic ACTH syndrome can be extremely difficult. Bilateral inferior petrosal sinus sampling has been shown to have the highest diagnostic accuracy in this subtype evaluation. Internal jugular vein sampling (IJVS) has been reported as a potentially safer invasive alternative, but data are limited. Our objective was to compare the sensitivity and specificity of bilateral IJVS and bilateral inferior petrosal sinus sampling (IPSS) in patients with ACTH-dependent CS. DESIGN: We prospectively collected blood samples from the inferior petrosal sinus and internal jugular vein of consecutive patients with ACTH-dependent CS. PATIENTS: The study group included 35 patients: 32 with pituitary-dependent CS (positive immunohistochemical findings for ACTH pituitary tumour or biochemical cure after pituitary surgery) and three with histologically proven ectopic ACTH syndrome. MEASUREMENTS: Inferior petrosal sinus sampling and bilateral IJVS were performed simultaneously before and after administration of corticotropin-releasing hormone (CRH), and ratios of central-to-peripheral ACTH concentrations were calculated. RESULTS: The basal IJVS central-to-peripheral ACTH ratios were diagnostic for pituitary-dependent CS (> 2) in 15 patients (46.9%), as were basal inferior petrosal sinus sampling central-to-peripheral ACTH ratios in 29 patients (90.6%). The post-CRH IJVS central-to-peripheral ACTH ratios were diagnostic for pituitary-dependent disease (> 3) in 24 patients (75%), as were post-CRH inferior petrosal sinus sampling central-to-peripheral ACTH ratios in 28 patients (87.5%). In the three patients with ectopic ACTH CS, the IJVS and inferior petrosal sinus sampling pre- and post-CRH ACTH ratios were correctly negative. The overall sensitivity of combined pre- or post-CRH was 81.3% for IJVS and 93.8% for inferior petrosal sinus sampling. Because of the difference between mean ratios in the two techniques, new criteria for IJVS were mathematically calculated: a pre-CRH central-to-peripheral ACTH ratio of 1.59 and a post-CRH central-to-peripheral ACTH ratio of 2.47 maximized sensitivity and specificity when both of these are equally taken into consideration. CONCLUSION: In conclusion, IJVS is not superior to inferior petrosal sinus sampling for establishing the cause of ACTH-dependent CS. When new criteria of basal (> 1.6) and post-CRH (> 2.5) central-to-peripheral ACTH gradients were applied to ACTH ratios from IJVS, the sensitivity of this test was maximized. However, confirmatory inferior petrosal sinus sampling is recommended when there is a lack of a central-to-peripheral ACTH gradient and when there is only a gradient above the cut-off on basal (pre-CRH) sampling.

ACTH Syndrome, Ectopic↗

Presence and localization of neurotrophin receptor tyrosine kinase (TrkA, TrkB, TrkC) mRNAs in visceral afferent neurons of the nodose and petrosal ganglia.

The presence of mRNAs to the high affinity tyrosine kinase (Trk) receptors for neurotrophins was studied in visceral afferent neurons of the nodose and petrosal ganglia of adult and neonatal rats using in situ hybridization histochemistry. Neurons containing TrkA mRNA were found in the adult nodose and petrosal ganglia. About 10% of nodose ganglion neurons and 38% of petrosal ganglion neurons contained TrkA mRNA. The nodose and petrosal ganglia from 1 day old neonates also expressed TrkA mRNA. No TrkB mRNA-containing neurons were detected in the adult nodose and petrosal ganglia, whereas TrkB mRNA was detected in 1 day old neonatal nodose and petrosal ganglia. TrkC mRNA was found in about 9% of nodose ganglion neurons and 11% of petrosal ganglion neurons of adult rats. Likewise, low but detectable levels of TrkC mRNA were seen in 1 day old neonatal nodose and petrosal ganglia. These data demonstrate the presence of TrkA and TrkC in the adult nodose and petrosal ganglia and provide a substrate for the ongoing neurotrophin-induced regulation of these placodally derived visceral afferent neurons. The altered expression of Trk receptor mRNAs in the nodose and petrosal ganglia between the adult and neonatal rats may reflect developmentally regulated changes in neurotrophin responsiveness.

Aging↗

Petrosal sinus sampling: technique and rationale.

Bilateral simultaneous sampling of the inferior petrosal sinuses is an extremely sensitive, specific, and accurate test for diagnosing Cushing disease and distinguishing between that entity and the ectopic ACTH syndrome. It is also valuable for lateralizing small hormone-producing adenomas within the pituitary gland. The inferior petrosal sinuses connect the cavernous sinuses with the ipsilateral internal jugular veins. The anatomy of the anastomoses between the inferior petrosal sinus, the internal jugular vein, and the venous plexuses at the base of the skull varies, but it is almost always possible to catheterize the inferior petrosal sinus. In addition, variations in size and anatomy are often present between the two inferior petrosal sinuses in a patient. Advance preparation is required for petrosal sinus sampling. Teamwork is a critical element, and each member of the staff should know what he or she will be doing during the procedure. The samples must be properly labeled, processed, and stored. Specific needles, guide wires, and catheters are recommended for this procedure. The procedure is performed with specific attention to the three areas of potential technical difficulty: catheterization of the common femoral veins, crossing the valve at the base of the left internal jugular vein, and selective catheterization of the inferior petrosal sinuses. There are specific methods for dealing with each of these areas. The sine qua non of correct catheter position in the inferior petrosal sinus is demonstration of reflux of contrast material into the ipsilateral cavernous sinus. Images must always be obtained to document correct catheter position. Special attention must be paid to two points to prevent potential complications: The patient must be given an adequate dose of heparin, and injection of contrast material into the inferior petrosal sinuses and surrounding veins must be done gently and carefully. When the procedure is performed as outlined, both inferior petrosal sinuses can be catheterized in more than 98% of patients. The complication rate is low, and the theoretical risk of major morbidity or death is less than 1% (neither has yet occurred, to our knowledge). The most common complication is groin hematoma.

ACTH Syndrome, Ectopic↗

Usefulness of inferior petrosal sinus venous endocrine markers in Cushing's disease.

Bilateral and simultaneous sampling of the inferior petrosal sinuses in patients with Cushing's disease has been used to establish the presence and laterality of adrenocorticotropic hormone (ACTH)-producing microadenomas prior to transsphenoidal surgery. Successful preoperative lateralization depends upon equivalent dilution of pituitary venous blood on the two sides since samples which are diluted by unequal amounts of non-pituitary blood may lead to erroneous results. To assure valid sampling results, the use of other pituitary hormones, measured simultaneously, has been proposed to correct the ACTH concentrations from the inferior petrosal sinuses against unequal dilution by non-pituitary venous blood. This proposal presumes that ACTH-secreting microadenomas will not cause unequal delivery of the other pituitary hormones into the two inferior petrosal sinuses. The inferior petrosal sinus concentrations of prolactin (PRL), thyrotropin (TSH), and the alpha subunit of human chorionic gonadotropin (alpha-HCG) were evaluated as indicators of pituitary venous blood dilution in 11 patients with Cushing's disease. Four patients with ectopic ACTH syndrome served as controls. Blood was withdrawn simultaneously from catheters in both inferior petrosal sinuses and from a peripheral vein for measurement of ACTH, PRL, TSH, and alpha-HCG. The ACTH concentrations were then corrected for dilution by non-pituitary blood by dividing the ACTH concentration from each side by the ratio of the inferior petrosal sinus to peripheral blood concentrations of PRL, TSH, and alpha-HCG for that side. At surgery, all 11 patients had ACTH-secreting microadenomas on the side predicted by the uncorrected ACTH concentrations. However, in three patients the corrected ACTH values would have led to erroneous results. Among the 18 sets of corrected inferior petrosal sinus measurements in these three patients, the corrected ACTH values failed to show an inferior petrosal sinus gradient in six and localized the tumor to the side opposite the adenoma in four. Incorrect lateralization was obtained with each of the hormones (PRL, TSH, and alpha-HCG) used for correction. Furthermore, the ipsilateral (side of tumor)-to-contralateral inferior petrosal sinus gradient of ACTH in patients with Cushing's disease was generally paralleled by a significant inferior petrosal sinus gradient of PRL, TSH, and alpha-HCG to the side of the tumor, whereas patients with the ectopic ACTH syndrome tended not to exhibit lateralizing (side-to-side) gradients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗

Inferior petrosal sinus arginine vasopressin concentrations in normal volunteers and patients with Cushing's disease.

In patients with Cushing's disease (CD), basal inferior petrosal sinus arginine vasopressin (AVP) concentrations are greater than peripheral levels and are further increased by the administration of CRH. AVP has an interpetrosal sinus gradient similar to that for ACTH, leading to the hypotheses that petrosal sinus AVP might either be derived from the corticotroph adenoma or be important for adenoma formation. To determine whether petrosal sinus AVP is truly increased in patients with CD, we compared inferior petrosal sinus and peripheral venous AVP and ACTH levels in 23 patients with CD and 9 healthy volunteers before and after iv ovine CRH. In both groups, AVP and ACTH showed interpetrosal lateralization, such that greater levels of both hormones were found at each time point in a single dominant petrosal sinus. When both hormones exhibited lateralization (an intersinus gradient > 1.5), ACTH and AVP always lateralized together. In patients with CD, the ACTH interpetrosal sinus lateralization correctly identified the side of the pituitary containing the tumor in 75% of evaluable patients, whereas the AVP interpetrosal sinus lateralization identified 63% (P = NS). Ovine CRH stimulated AVP in both the dominant and nondominant petrosal sinuses in patients with CD. Although basal AVP in the dominant petrosal sinus was not significantly different in patients with CD and normal volunteers (144 +/- 85 vs. 13.0 +/- 4.3 pmol/L; P = 0.058), dominant petrosal sinus AVP was significantly elevated in patients with CD compared to normal volunteers at 3 min (269 +/- 122 vs. 45.1 +/- 30.0 pmol/L; P < 0.05) and 5 min (315 +/- 120 vs 40.2 +/- 23.6 pmol/L; P < 0.05) after ovine CRH administration. Peripheral venous AVP levels were similar in all groups. We conclude that lateralization of AVP secretion occurs in both patients with CD and normal volunteers, but there is greater CRH-stimulated AVP secretion in the inferior petrosal sinuses of patients with CD.

Adrenocorticotropic Hormone↗

Bilateral sequential inferior petrosal sinus sampling with corticotrophin-releasing hormone stimulation in the diagnosis of Cushing's disease.

OBJECTIVE: The demonstration of a central to peripheral ACTH gradient in a hypercortisolaemic patient is diagnostic of Cushing's disease. We tried to determine whether single blood samples for ACTH obtained sequentially from each of the inferior petrosal sinuses following human corticotrophin-releasing hormone (hCRH) stimulation can reliably establish such a gradient. DESIGN: Prospective study. PATIENTS: Seventeen patients with clinical and biochemical features of Cushing's syndrome. METHODS: After the administration of hCRH, the patients underwent bilateral sequential inferior petrosal sinus sampling, with a single blood sample obtained from each of the inferior petrosal sinuses sequentially, along with a peripheral venous sample. The petrosal sinus catheter was withdrawn immediately after obtaining a blood sample. Patients did not require indwelling catheters in the petrosal sinuses, nor heparinisation. RESULTS: Bilateral sequential inferior petrosal sinus sampling correctly identified a pituitary source of ACTH, as shown by a central to peripheral ACTH ratio >2, in all patients in whom the procedure was successfully carried out. All patients underwent transsphenoidal pituitary surgery resulting in remission. CONCLUSIONS: The simplified method of inferior petrosal sinus sampling, using a single sequential sample from each of the inferior petrosal sinuses, following initial hCRH stimulation, is as accurate as the more complex test using multiple bilateral simultaneous inferior petrosal sinus samples. It avoids the use of indwelling cerebral venous catheters and is therefore unlikely to cause brain stem damage.

Adult↗

Vasopressin levels in Cushing's disease: inferior petrosal sinus assay, response to corticotrophin-releasing hormone and comparison with patients without Cushing's disease.

BACKGROUND: Higher vasopressin (AVP) levels have been found in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma than in the contralateral one, suggesting a potential pathogenetic role of AVP in Cushing's disease. DESIGN: In order to investigate AVP release, plasma ACTH and AVP concentrations were assayed in the inferior petrosal sinuses and in the peripheral blood before and after CRH stimulation. PATIENTS: Twenty patients with Cushing's disease and 12 with other pituitary diseases were subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes. Ten healthy sex and age-matched subjects served as control for peripheral AVP values. MEASUREMENTS: Plasma ACTH concentrations were measured by RIA using commercial kits. Plasma AVP concentrations were assayed by RIA in acetone extracts of 1-2 ml plasma. RESULTS: Plasma AVP levels in the inferior petrosal sinuses were significantly higher in Cushing's disease than in patients with other pituitary diseases (P < 0.05) and in both groups AVP levels were higher in the inferior petrosal sinuses than in the peripheral blood (P < 0.01). In Cushing's disease, ACTH, but not AVP levels, were higher in the inferior petrosal sinus ipsilateral to the adenoma than in the contralateral one (P < 0.01). Seven patients showed a significant ACTH and AVP increase (greater than 50% of baseline) after CRH stimulation in the inferior petrosal sinus ipsilateral to the adenoma. Conversely, no change was found in AVP levels in the remaining 13 patients. When AVP values were analyzed in relation to surgical cure, higher inferior petrosal sinus levels (P < 0.05) were found in 6 patients with poor outcome: 4 of these patients had significantly decreased plasma AVP concentrations (by 32-43% of baseline) after CRH bolus. Peripheral AVP levels were similar in healthy subjects and patients with Cushing's disease whereas they were significantly reduced in patients with other pituitary diseases (P < 0.002). CONCLUSIONS: The results of this study show that patients with Cushing's disease and poor surgical outcome had the highest AVP levels in our series. CRH administration caused different effects on AVP levels: it increased them in 35% of patients whereas there was no response in the remaining patients. On the basis of these findings, it is hypothesized that AVP might be involved in the persistence of ACTH hypersecretion in a subset of patients poorly responsive to surgery.

Adenoma↗

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 intersinus 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 > or = 2.0 in 13 of 17 patients (76%), and amounting to > or = 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.

Adenoma↗

Corticotropin-releasing hormone administration increases alpha-melanocyte-stimulating hormone levels in the inferior petrosal sinuses in a subset of patients with Cushing's disease.

The effect of corticotropin (ACTH)-releasing hormone (CRH) administration on alpha-melanocyte-stimulating hormone (alpha-MSH), ACTH and beta-endorphin (beta-EPH) was evaluated in the inferior petrosal sinuses and in the periphery of 30 patients affected with Cushing's disease subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes. Baseline PRL levels, sensitivity to dexamethasone and surgery outcome were compared to alpha-MSH response. CRH bolus did not modify alpha-MSH concentrations either in the inferior petrosal sinuses or in the periphery in the 30 patients considered as a whole. In 7 of 30 patients, however, a greater than 50% increase over baseline alpha-MSH levels (from 50 to 115.5%) was recorded in the inferior petrosal sinus ipsilateral to the adenoma (from 42.9 +/- 1.7 to 76.4 +/- 4.6 ng/l; p < 0.001), whereas no change was found in the contralateral inferior petrosal sinus or in the periphery. Conversely, as expected, ACTH and beta-ELI significantly increased in all the patients after CRH both in the inferior petrosal sinuses and in the periphery (particularly in the inferior petrosal sinus ipsilateral to the adenoma). No difference in sensitivity to dexamethasone (urinary cortisol percent decrease: 66.4 +/- 4.9 vs. 67.8 +/- 3.4) and surgery outcome (chi 2 test: p = 0.7) was found between patients with alpha-MSH response to CRH and patients without such a response. By contrast, baseline PRL levels, although being normal in both groups, were significantly higher in patients with alpha-MSH response to CRH (18.1 +/- 1.6 vs. 10.1 +/- 0.7 micrograms/l; p < 0.001). In conclusion, the results of the present study suggest that in a subset of patients with Cushing's disease (23.3% of our series) alpha-MSH may be released after the administration of CRH together with ACTH and beta-EPH by adenomatous corticotrophs. In this subset of patients, PRL levels may be in the upper normal range.

Adolescent↗

[Simultaneous and bilateral catheterization of inferior petrosal sinuses in the diagnosis of Cushing's syndrome: basal multiple sampling and after ACTH-releasing hormone test].

In 22 patients with ACTH-dependent Cushing's syndrome we have performed multiple ACTH evaluations, baseline and after ACTH-releasing hormone (CRH), during simultaneous bilateral inferior petrosal sinus sampling. The basal inferior petrosal sinus/periphery ratio for ACTH was > 2 in 11/22 patients, CRH challenge caused the appearance of an inferior petrosal sinus/periphery ratio > 3 in 6 other patients. An ACTH-secreting adenoma was surgically proven in 17 patients with ACTH inferior petrosal sinus/periphery ratio > 2 basally or > 3 after CRH and in 1 patient with an inferior petrosal sinus/periphery ratio < 2 basally or 3 after CRH. In 4 patients the very high peripheral ACTH levels, the inferior petrosal sinus/periphery ratio and the lack of ACTH increase after CRH indicated the presence of an ectopic ACTH syndrome. An ACTH intersinus gradient > 1.4 was found in 11 patients. Among these patients the adenoma was correctly localised in 6 and wrongly in 5 patients. In conclusion, the diagnostic accuracy of the inferior petrosal sinus sampling was of 95.4% (21/22 cases) considering basal and CRH-stimulated ACTH levels. The multiple basal ACTH evaluation does not seem to be necessary associated with CRH-test, but may be helpful in some cases.

Adenoma↗

Inferior petrosal sinus AVP in patients with Cushing's syndrome.

OBJECTIVE: In both normal volunteers and patients with Cushing's disease, one dominant inferior petrosal sinus (IPS) contains higher concentrations of AVP and ACTH than the contralateral (non-dominant) IPS, but ovine corticotrophin-releasing hormone (oCRH)-stimulated AVP in the petrosal sinuses is greater in Cushing's disease than in normal volunteers. To distinguish whether greater oCRH-releasable AVP might be specifically related to the presence of a pituitary corticotrophinoma, or be due to hypercortisolism per se, we compared IPS AVP in patients with Cushing's disease with those of patients with other causes of Cushing's syndrome. PATIENTS: Twenty-three patients with Cushing's disease, 16 patients with the syndrome of ectopic ACTH and seven patients with Cushing's syndrome of adrenal origin. MEASUREMENTS: AVP and ACTH, measured both before and 3, 5 and 10 minutes after oCRH in the petrosal sinuses, and in a peripheral vein. RESULTS: In all three groups, AVP concentrations were lateralized such that most of the AVP was found in one, dominant IPS. oCRH significantly increased IPS ACTH only in patients with Cushing's disease (p < 0.001), whereas it significantly increased dominant IPS AVP levels in all three patient groups (P < 0.01). However, neither dominant nor non-dominant IPS AVP (basal or oCRH-stimulated) were significantly different among patients with Cushing's disease, ectopic ACTH or Cushing's syndrome of adrenal origin. Basal and oCRH-stimulated IPS AVP were negatively correlated with urine free cortisol. CONCLUSIONS: Inferior petrosal sinus AVP levels are similar in all forms of Cushing's syndrome, and thus the higher inferior petrosal sinus AVP levels in patients with Cushing's disease compared with normal volunteers are unlikely to be related specifically to the presence of the pituitary corticotrophinoma. While AVP may play a role in pituitary corticotroph tumourigenesis or may be secreted by some pituitary corticotroph tumours, the observation that CRH-stimulated inferior petrosal sinus AVP levels are higher in Cushing's disease than in normal volunteers appears most likely to be related to the low endogenous CRH levels induced by hypercortisolism, rather than a consequence of Cushing's disease itself. We hypothesize that low endogenous CRH leads to increased sensitivity of central nervous system CRH receptors to exogenous CRH, and thus to greater ovine CRH-stimulated AVP.

ACTH Syndrome, Ectopic↗

Simultaneous and bilateral inferior petrosal sinus sampling for the diagnosis of Cushing's syndrome: comparison of multihormonal assay, baseline multiple sampling and ACTH-releasing hormone test.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Studies on the coexistence of substance P with other putative transmitters in the nodose and petrosal ganglia.

Visceral afferent neurons of the nodose and petrosal ganglia are immunoreactive (ir) for many neurotransmitters [e.g., substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP), and dopamine (tyrosine hydroxylase-ir; TH)]. Coexistence of SP-ir with NKA-, CGRP-, or TH-ir was studied in individual neurons of the rat ganglia using fluorescence immunocytochemistry. SP- and NKA-ir were present in equal numbers of cells and were consistently colocalized. SP- and CGRP-ir were found to be similarly distributed in scattered cells, concentrated mostly in the rostral pole of the nodose ganglion and in the petrosal ganglion. SP-ir completely coexisted with CGRP-ir. However, there was at least twice the number of CGRP-ir neurons as SP-ir neurons, and thus CGRP-ir neurons that did not contain SP-ir were also present. In contrast, SP- and TH-ir had different distributions in both the nodose and the petrosal ganglia. SP-ir was located in the more rostral regions of both the nodose and petrosal ganglia, whereas TH-ir was detected throughout the entire nodose ganglion and only in the most caudal region of the petrosal ganglion. There was no coexistence of SP- and TH-ir. These data demonstrate the differential localization and coexistence of putative transmitters in visceral sensory neurons in the nodose and petrosal ganglia.

Animals↗

The petrosal of Omomys carteri and the evolution of the primate basicranium.

The first omomyine petrosals, those of Omomys carteri, are described. Omomys probably had a tympanic bulla and canals for the intratympanic carotid circulation derived from the petrosal bone. The stapedial and promontory canals were complete, large and subequal. The posterior carotid foramen entered the bulla posteromedially. The intratympanic portion of the facial nerve was fully enclosed in bone, the stapedius fossa is extrabullar and the parotic fissure is patent. The mastoid was pneumatized from the epitympanic recess and a supracochlear cavity may have been present. The Omomys petrosals exhibit a generic omomyiform morphology, exhibiting no features that can be interpreted as autapomorphies and only one feature shared with adapiforms. The monophyly of Omomyiformes is based on other cranial characters, dental and postcranial characters assessed elsewhere. The similarity of the Shanghuang petrosal to the petrosals of omomyiforms, as well as the ambiguous evidence of its association, suggest that an omomyiform affinity for that petrosal cannot be ruled out.

Animals↗

Peripheral deafferentation alters calcitonin gene-related peptide mRNA expression in visceral sensory neurons of the nodose and petrosal ganglia.

Visceral sensory neurons of the glossopharyngeal and vagus nerves are located in the petrosal and nodose ganglia, respectively. Our previous studies showed that peripheral axotomy which removes afferent input to visceral sensory perikarya decreased the number of calcitonin gene-related peptide (CGRP)-immunoreactive (ir) neurons in the petrosal but not the nodose ganglion. To evaluate axotomy-induced changes in CGRP mRNA expression, we used in situ hybridization histochemistry with 35S-labeled oligonucleotide probes. CGRP mRNA-containing neurons were studied 1, 3, 7 and 14 days after peripheral deafferentation of the left nodose and petrosal ganglia via transection of the left cervical vagus, superior laryngeal, glossopharyngeal and carotid sinus nerves. The numbers of CGRP mRNA-containing neurons in the deafferented petrosal ganglion were significantly reduced at 3, 7 and 14 days compared to either intact or sham-operated control ganglia. However, the density of hybridization product in the positively-labeled petrosal ganglion cells was not significantly changed. The numbers of CGRP mRNA-containing neurons in the deafferented nodose ganglion were significantly reduced at 3 and 7 days. These data suggest that axotomy-induced changes in CGRP-ir neurons of the petrosal ganglion correlate with changes in CGRP mRNA and probably result from altered CGRP gene expression. In addition, in situ hybridization histochemistry revealed changes in CGRP neurons of the nodose ganglion which were not apparent with immunocytochemistry.

Afferent Pathways↗