Bilateral inferior petrosal sinus sampling

Bilateral inferior petrosal sinus sampling

Inferior petrosal sinus sampling (IPSS) is an invasive procedure in which adrenocorticotropic hormone (ACTH) levels are sampled from the veins that drain the pituitary gland; these levels are then compared with the ACTH levels in the peripheral blood to determine whether a pituitary tumor (as opposed to an ectopic source of ACTH) is responsible for ACTH-dependent Cushing syndrome. IPSS can also be used to establish on which side of the pituitary gland the tumor is located.

Bilateral inferior petrosal sinus sampling (BIPSS) is considered the gold standard test for anatomical localization for Cushing’s disease where radiology has been inconclusive 1).

In a metaanalysis of 21 studies, the overall sensitivity and specificity of BIPSS were found to be 96% and 100% respectively 2).

Anatomical localization of pituitary adenoma can be challenging in adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome, and bilateral inferior petrosal sinus sampling (BIPSS) is considered gold standard in this regard. Stimulation using corticotropin releasing hormone (CRH) improves the sensitivity of BIPSS.

In essence, it tests to see the source of the raised ACTH levels in a patient with diagnosed Cushing’s syndrome and high or normal serum ACTH levels. The inferior petrosal sinus is where the pituitary gland drains. Therefore, a sample from here showing raised ACTH compared to the periphery suggests that it is a pituitary cause of Cushing’s, i.e. Cushing’s disease. Equivocal levels of ACTH indicate ectopic or Paraneoplastic Cushing’s Syndrome. The sample is usually taken after administration of Corticotropin-releasing hormone or, more recently, DDAVP, which have been shown to increase ACTH production in active ACTH-producing pituitary tumors. Increasingly, it is known as a gold-standard method for diagnosing Cushing’s disease.

To increase the sensitivity, the sampling is repeated after peripheral administration of oCRH. Following this a peak central to peripheral plasma ACTH ratio of 3 or more occurring 3-5 minutes after oCRH stimulation is highly indicative of Cushing disease.

see Inferior petrosal sinus sampling with desmopressin.

Asymmetric inferior petrosal sinuses (IPS) are not infrequently encountered during bilateral IPS sampling. There is little data on whether IPS symmetry influences success in predicting the adenoma side in patients with ACTH-dependent Cushing’s syndrome (CS).

BIPSS was performed in 38 patients with a mean age of 45 ± 15 years. The overall technical success rate was 97% for bilateral cannulation. Asymmetric IPS were observed in 11 (39%) patients with Cushing’s disease (CD). A side-to-side ACTH ratio was not significantly different between patients with symmetric outflow and those with asymmetric outflow at baseline (8.6 ± 2.7 versus 16.4 ± 6.0; P = 0.45), but ratios were significantly different after ovine corticotropin-releasing hormone (oCRH) stimulation (6.0 ± 2.5 versus 35.7 ± 22.5; P = 0.03). BIPSS correctly predicted the side of the adenoma in 25 (96%) patients with CD. Prediction was better when the venous outflow was symmetric (100%) rather than asymmetric (93%), although the difference was not significant (P = 0.42). Remission from CS was achieved in 32 patients (87%), independent of the symmetry of IPS.

Bearing in mind the sample size of this audit, asymmetric IPS at least do not seem to diminish the accuracy of diagnosis of ACTH-dependent CS, nor do they influence the clinical outcome 3).


Most often, BIPSS is performed by sampling ACTH peripherally and from both IPSs before and after CRH (Acthrel; Ben Venue Laboratories, Ohio, USA) administration. In the US, CRH is typically given at a dose of 1 μg/kg, by slow intravenous push over 30 seconds; in other countries, a typical dose is 100 μg. Conscious sedation is preferred to allow for the monitoring of symptoms suggesting complications. A 6-French sheath is advanced into the right femoral vein, and a five-French sheath into the left femoral vein. The larger sheath allows for sampling from the common femoral vein, while a 5-French catheter is in place distally. Subsequently, 3,000–5,000 units of heparin are given to prevent cavernous sinus and other venous thrombosis.

Next, 5-French Davis catheters are advanced through each femoral vein sheath into the contralateral internal jugular vein, followed by 2.8-French microcatheters, directed medially at the C1–2 level to access the orifice of the IPS 4). without entering clival veins 5). Both catheters are positioned symmetrically.

Once catheter positions are confirmed, two baseline ACTH specimens are collected from the right femoral sheath (peripheral specimen) and both IPSs. CRH is then administered peripherally. Repeat ACTH sampling from the periphery and both IPSs is obtained 3 minutes, 5 minutes, 10 minutes, and 15 minutes after the injection of CRH. Samples are collected in tubes that are placed on ice before transport to the laboratory. Upon completion of sampling, both femoral sheaths are removed, and manual compression is used to obtain hemostasis before transferring patients to the recovery room for a rest of approximately 4 hours.

Case series

Pereira et al. evaluated all patients that undergone bilateral inferior petrosal sinus sampling in a tertiary center, between January 1995 and March 2018. The probable diagnosis of Cushing’s disease was made when the basal central/peripheral gradient was>2 and/or>3 after stimulation with a corticotrophin-releasing hormone. The localization was suggested when the inter-sinus gradient was>1.4. The results obtained were compared with the post-operatory results: compatible histology and positive immunohistochemistry to adrenocorticotrophic hormone and/or the presence of criteria of cure. Sensitivity, specificity and predictive positive value were calculated.

A total of 49 patients were evaluated (75.5% female; mean age 45.4±16.3 years old). Bilateral inferior petrosal sinus sampling was compatible with Cushing’s disease in 27 out of 28 confirmed cases in histology or by criteria of cure, and was compatible with ectopic secretion in the 2 cases confirmed as ectopic secretion of adrenocorticotrophic hormone (sensitivity 96.4%; specificity 100%). The lateralization calculated was concordant with the results after surgery in 17 out of 27 patients with Cushing’s disease – predictive positive value of 63%. Magnetic resonance had a higher predictive value to lateralization – 70.0%.

Bilateral inferior petrosal sinus sampling is a safe and reliable procedure to diagnose Cushing’s disease, with great sensitivity and specificity. Nevertheless, the capacity of this procedure to lateralize the lesion inside the pituitary is limited 6).



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Tomycz ND, Horowitz MB. Inferior petrosal sinus sampling in the diagnosis of sellar neuropathology. Neurosurg Clin N Am. 2009 Jul;20(3):361-7. doi: 10.1016/ Review. PubMed PMID: 19778704.

Doppman JL, Oldfield E, Krudy AG, Chrousos GP, Schulte HM, Schaaf M, Loriaux DL. Petrosal sinus sampling for Cushing syndrome: anatomical and technical considerations. Work in progress. Radiology. 1984 Jan;150(1):99-103. PubMed PMID: 6316418.

Pereira CA, Ferreira L, Amaral C, Alves V, Xavier J, Ribeiro I, Cardoso H. Diagnostic accuracy of Bilateral Inferior Petrosal Sinus Sampling: The Experience of a Tertiary Centre. Exp Clin Endocrinol Diabetes. 2019 Aug 19. doi: 10.1055/a-0981-5973. [Epub ahead of print] PubMed PMID: 31426111.

Cerebral venous sinus thrombosis treatment

Cerebral venous sinus thrombosis treatment

Hydration with IV fluids and IV anticoagulation are part of the initial treatment for cranial sinus thrombosis (CST). Prior to initiation of treatment, blood for hypercoagulopathy tests is drawn.

Severity of cerebral venous thrombosis (CVT) may require the transfer to intensive care unit (ICU).

Treatment is with anticoagulants and rarely thrombolysis (enzymatic destruction of the blood clot).

Batroxobin may promote venous sinus recanalization and attenuate CVT-induced stenosis. Further randomized study of this promising drug may be warranted to better delineate the amount of benefit 1).


Current guidelines recommend anticoagulation after cerebral venous sinus thrombosis (CVT) even in the setting of intracranial hemorrhage, but the timing of initiation is unclear.

A literature review demonstrated a wide variation of timing for anticoagulation initiation in patients with CVT and intracranial hemorrhage. Most started anticoagulation within 24 hours of admission with similar functional neurological recovery. Current guidelines on the treatment of CVT, even with intracranial hemorrhage, recommend anticoagulation. Most reports in the literature state initiation of anticoagulation within 24 hours. However, the literature does not definitively state when to initiate anticoagulation in a patient with CVT, intracranial hemorrhage, thrombectomy, and decompressive hemicraniectomy 2).

Given that there is usually an underlying cause for the disease, tests may be performed to look for these. The disease may be complicated by raised intracranial pressure, which may warrant surgical intervention such as the placement of a shunt.

There are several other terms for the condition, such as cerebral venous and sinus thrombosis, (superior) sagittal sinus thrombosis, dural sinus thrombosis and intracranial venous thrombosis as well as the older term cerebral thrombophlebitis.

Indications for endovascular intervention

● Persistent ischemic symptoms despite anticoagulation therapy.

● Contraindication to anticoagulation and/or anti-platelet therapy including hemorrhagic infarct 3).

● Impending risk of stroke.

Endovascular treatment

Chemical Thrombolysis: A catheter may be advanced to the involved sinus or close to it, through the femoral vein. The advantage of local administration is that, a larger amount of tPA actually reaches the clot vs systemic administration through a peripheral vein. Usually, 2–5mg are administered through the thrombus and then an infusion started at a rate of 1 mg/hr, usually for 12 hours. If clot burden is still there on angiography, the infusion may be continued for longer, until the clot resolves.

For CST, the infusion may be prepared in a concentration of 1 mg/10 ml (0.1 mg/ml), for a rate of 10 ml/hr.

Mechanical Thrombolysis: Similar to arterial embolic stroke, devices such as Stentriever or Penumbra may be used for clot extraction. Additionally, devices intended for other sites e.g., clot extraction from dialysis fistula, have also been used in cranial sinuses 4).

The challenge during endovascular intervention is negotiating the sigmoid-transverse sinus junction especially when using bulkier catheters e.g., AngioJet.



Ding JY, Pan LQ, Hu YY, Rajah GB, Zhou D, Bai CB, Ya JY, Wang ZA, Jin KX, Guan JW, Ding YC, Ji XM, Meng R. Batroxobin in combination with anticoagulation may promote venous sinus recanalization in cerebral venous thrombosis: A real-world experience. CNS Neurosci Ther. 2019 May;25(5):638-646. doi: 10.1111/cns.13093. Epub 2019 Jan 23. PubMed PMID: 30675757; PubMed Central PMCID: PMC6488911.

Pizzi MA, Alejos DA, Siegel JL, Kim BY, Miller DA, Freeman WD. Cerebral Venous Thrombosis Associated with Intracranial Hemorrhage and Timing of Anticoagulation after Hemicraniectomy. J Stroke Cerebrovasc Dis. 2016 Jun 16. pii: S1052-3057(16)30098-2. doi: 10.1016/j.jstrokecerebrovasdis.2016.05.025. [Epub ahead of print] PubMed PMID: 27321968.
3) , 4)

Khan SH, Adeoye O, Abruzzo TA, Shutter LA, Ringer AJ. Intracranial dural sinus thrombosis: novel use of a mechanical thrombectomy catheter and review of management strategies. Clin Med Res. 2009; 7:157– 165
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