What is the appropriate dose of desmopressin to use for Bilateral Inferior Petrosal Sinus Sampling (BIPSS) Procedures? How should it be administered, and what should the timing be with regards to sampling?

Comment by InpharmD Researcher

Clinical outcomes data on desmopressin (DDAVP) stimulation testing for bilateral inferior petrosal sinus sampling (BIPSS) is limited to predominantly retrospective cohort studies in pediatric and adult patients with Cushing’s disease. DDAVP has been evaluated against ovine corticotropin-releasing hormone (CRH) at a standard, fixed dose of 10 mcg administered as a single intravenous bolus, especially in the setting of CRH being commercially unavailable in North American markets. Clinical practice guidelines recommend DDAVP administration during the stimulation phase after two prestimulation adrenocorticotropic hormone (ACTH) or prolactin samples are drawn, with additional timed samples collected at 3, 5, 10, and 15 minutes post-stimulation to capture the ACTH peak. Samples are generally drawn from a peripheral line and both inferior petrosal sinuses.

Background

A 2026 multidisciplinary panel developed standardized recommendations for bilateral inferior petrosal sinus sampling (BIPSS) technique for adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome using a modified Delphi approach based on the Society of Vascular and Interventional Neurology (SVIN) framework. Desmopressin was designated as a reasonable, evidence-based alternative stimulant to corticotropin-releasing hormone (CRH) when ovine CRH is unavailable (as in the U.S., Canada, Brazil, Argentina, and Mexico; Class of Recommendation I, Level of Evidence B-NR, based on non-randomized observational evidence). The guideline specifies a fixed desmopressin dose of 10 mcg intravenously (IV), administered as a bolus during the stimulation phase after two prestimulation ACTH/prolactin samples are drawn, with additional timed samples collected at 3, 5, 10, and 15 minutes post-stimulation to capture the ACTH peak (diagnostic peaks typically occur 5–10 minutes post-stimulation). A referenced meta-analysis reported comparable diagnostic performance between desmopressin and CRH, with CRH sensitivity/specificity 98%/100% vs desmopressin 96%/100%). No weight-based adjustments or pediatric dosing were addressed, as pediatric studies were excluded from this guideline. [1]

A 2022 mini-review evaluated desmopressin's role as a BIPSS secretagogue and diagnostic aid amid lack of availability of ovine CRH in North American and several other markets. No dose-titration data specific to BIPSS were reported; the review references the original dose-response work establishing 10 mcg IV bolus as the standard dose, with basal, 5-minute post-injection, and 15-minute post-injection ACTH sampling. Diagnostic thresholds for BIPSS varied by study, with peak/base ACTH ratios ranging from >2 to >2.8 to >3 in different studies. A pooled meta-analysis of 11 studies representing 612 patients found comparable BIPSS sensitivity/specificity for desmopressin (0.96/1.0) vs CRH (0.98/1.0). Hyponatremia was theoretically plausible but unreported in BIPSS studies; however, 12-hour fluid restriction is still recommended with desmopressin use for BIPSS. The authors concluded that desmopressin is an effective, safe CRH alternative for BIPSS stimulation, though dosing thresholds for positivity remain inconsistent across studies and lack external validation; the lack of consensual criteria of normal or abnormal response to desmopressin in its various uses underscores the need for further research on its usefulness. [2]

Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-5 for your response.

Bilateral inferior petrosal sinus sampling using desmopressin or corticotropic-releasing hormone: a single-center experience
Design	Single-center, retrospective study N= 20
Objective	To evaluate the safety and diagnostic accuracy of using desmopressin (DDAVP) in bilateral inferior petrosal sinus sampling (BIPSS) compared to corticotropin-releasing hormone (CRH)
Study Groups	BIPSS with DDAVP (n= 20)
Inclusion Criteria	Patients with presumed adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome based on laboratory results such as 24 h urine free cortisol level, late night salivary cortisol level, plasma ACTH level, dexamethasone suppression test, and imaging studies
Exclusion Criteria	Not specified
Methods	BIPSS procedures were performed using DDAVP and CRH. Catheters were positioned in both inferior petrosal sinuses (IPS) and then baseline samples were collected from a peripheral (P) line and both sinuses. After peripheral intravenous infusion of 10 mg DDAVP in normal saline, samples were collected at 3, 5, 10, and 15 minutes. Diagnostic criteria included IPS/P ACTH ratios of ≥2 at baseline or ≥3 after stimulation. Lateralization was defined as an ACTH intersinus gradient of ≥1.4. Heparin was administered intraprocedurally based on weight, averaging 4000 units intravenously.
Duration	April 2012 to February 2013
Outcome Measures	Primary: Safety and diagnostic accuracy Secondary: Comparison of ACTH ratios between DDAVP and CRH stimulation
Baseline Characteristics		All patients (N= 20)
	Age, mean years (range)	38 (12-84)
	Female	16 (80%)
	Common symptoms - Weight gain	15 (75%)
	Common symptoms - Skin changes	15 (75%)
	Common symptoms - Facial rounding	13 (65%)
Results		BIPSS with DDAVP (N= 20)
	Successful bilateral cannulation	100%
	Centralization and lateralization criteria met	18 patients
	Sensitivity for BIPSS with DDAVP	94.5%
	ACTH-secreting adenoma on pathology	18 patients
	Calculated sensitivity for BIPSS with DDAVP was 94.4%. There was also no significant difference in the biochemical results produced by BIPSS using either DDAVP or CRH. All 18 patients with centralizing BIPSS suggestive of Cushing disease demonstrated an ACTH-secreting adenoma on pathology review.
Adverse Events	No complications observed during or immediately following procedures. Specifically, no thromboembolic events were encountered with DDAVP use.
Study Author Conclusions	DDAVP is a safe alternative to CRH for BIPSS, producing comparable diagnostic results with no significant difference in biochemical outcomes.
Critique	The study provides valuable insights into the use of DDAVP as an alternative to CRH in BIPSS, demonstrating its safety and efficacy. However, the small sample size and single-center design may limit the generalizability of the findings. Additionally, the inability to calculate specificity due to follow-up issues is a limitation.

Table 1 References:
[3] Deipolyi AR, Alexander B, Rho J, Hirsch JA, Oklu R. Bilateral inferior petrosal sinus sampling using desmopressin or corticotropic-releasing hormone: a single-center experience. J Neurointerv Surg. 2015;7(9):690-693. doi:10.1136/neurintsurg-2014-011262

The effects of sampling lateralization on bilateral inferior petrosal sinus sampling and desmopressin stimulation test for pediatric Cushing's disease
Design	Retrospective, single-center analysis in China N= 16
Objective	To evaluate the sensitivity of bilateral inferior petrosal sinus sampling (BIPSS) before and after desmopressin stimulation in pediatric Cushing disease (CD), and to explore related factors of false-negative results and meanings of sampling lateralization
Study Groups	All patients (N= 16)
Inclusion Criteria	Children and adolescents (≤18 years old) diagnosed with CD undergoing BIPSS
Exclusion Criteria	Not specified
Methods	Retrospective analysis of 16 pediatric CD patients who underwent 17 BIPSS procedures. CD was diagnosed if inferior petrosal sinus (IPS) to peripheral adrenocorticotropic hormone (ACTH) ratio was >2 at baseline or >3 after desmopressin stimulation. Sampling lateralization was defined if interpetrosal sinus gradient was >1.4. Gadolinium-based magnetic resonance imaging (MRI) of the pituitary gland was conducted. All patients underwent surgery for confirmation. Desmopressin stimulation test was conducted after successful catheterization and sampling at 0 min. Peripheral and inferior petrosal sinus blood samples were simultaneously collected 3, 5, and 10 min after intravenous injection of 10 mcg of desmopressin.
Duration	2006 to 2017
Outcome Measures	Primary: Sensitivity of BIPSS before and after desmopressin stimulation Secondary: Sampling lateralization rate, accuracy of MRI in predicting tumor lateralization
Baseline Characteristics		All patients (N= 16)
	Age, mean years (range)	15.5 ± 2.9 (9.8–18.7)
	Female	10 (62.5%)
	Height, cm	152.5 ± 13.7
	Weight, kg	65.0 ± 17.2
	ACTH, ng/L	56.6 ± 23.2
	24 h UFC, mcg	495.0 (233.8, 654.4)
	Duration of disease >1 year	12 (75%)
Results		Before stimulation	After stimulation
	Sensitivity	64.7% (11/17)	83.3% (10/12)
	Sampling lateralization rate by BIPSS without desmopressin stimulation was only 62.5%, and the accordant rate with actual tumor lateralization was only 50%. Desmopressin stimulation not only failed to improve the efficacy and accuracy of tumor lateralization, but also led to contradictory results. The accuracy of MRI in predicting the tumor lateralization was 80%.
Adverse Events	No severe adverse effects occurred during BIPSS procedures.
Study Author Conclusions	The sensitivity of BIPSS in pediatric CD was low at baseline, but increased after desmopressin stimulation. Sampling lateralization cannot accurately indicate the tumor lateralization, but the absence of sampling lateralization with low ACTH at IPS is a hint of false-negative cases in BIPSS.
Critique	The study provides valuable insights into the use of BIPSS in pediatric CD, highlighting the increased sensitivity with desmopressin stimulation. However, the small sample size and retrospective design may limit the generalizability of the findings. Additionally, the study does not explore alternative methods for improving diagnostic accuracy beyond desmopressin stimulation.

Table 2 References:
[4] Chen S, Chen K, Lu L, et al. The effects of sampling lateralization on bilateral inferior petrosal sinus sampling and desmopressin stimulation test for pediatric Cushing's disease. Endocrine. 2019 Mar;63(3):582-591. doi:10.1007/s12020-018-1779-x

Use Of Desmopressin In The Differential Diagnosis Of Cushing’s Syndrome: Recent Experience At The NIH
Design	Retrospective review N= 16
Objective	To evaluate the use of desmopressin in the differential diagnosis of Cushing’s syndrome, particularly in distinguishing between Cushing's disease and ectopic adrenocorticotropic hormone (ACTH) secretion (EAS)
Study Groups	Cushing's disease (n= 11) Ectopic ACTH secretion (n= 4) Occult EAS (n= 1)
Inclusion Criteria	Patients with pathologically-confirmed Cushing's syndrome who underwent petrosal sinus sampling or desmopressin stimulation testing
Exclusion Criteria	Not specified
Methods	Retrospective review of 16 patients who underwent petrosal sinus sampling or desmopressin stimulation testing using a 10 mcg IV dose at time 0 minutes. ACTH and cortisol levels were measured at various time points to assess response. Percent response was calculated according to previous reports using the mean of-15 and 0 min and the mean of 15 and 30 min, or peak, ACTH values and the mean of 30 and 45 min, or peak, F levels. For petrosal sinus sampling, ACTH was measured at -5, -1, 3, 5, and 10 min from left and right petrosal veins and a peripheral site.
Duration	Not specified
Outcome Measures	Primary: ACTH and cortisol response to desmopressin stimulation test Secondary: Correlation between petrosal sinus sampling and stimulation test values
Baseline Characteristics	Not provided
Results		Cushing's disease (n= 11)	Ectopic ACTH secretion (n= 4)	Occult EAS (n= 1)
	Positive cortisol response >20% at 30/45 min	9/11	1/4	0/1
	Positive peak cortisol response	10/11	3/4	0/1
	Positive ACTH response >35% at 15/30 min	9/11	2/4	0/1
	Positive peak ACTH response	10/11	3/4	0/1
Adverse Events	Not specified
Study Author Conclusions	Desmopressin stimulation testing shows a robust ACTH and cortisol response in Cushing's disease, but ectopic ACTH secretion patients also responded, especially at peak values. Negative stimulation test responses suggest ectopic ACTH secretion, while positive responses require confirmation by petrosal sinus sampling or other tests.
Critique	The study is limited by its small sample size and retrospective design, which may affect the generalizability of the findings. The overlap in response between Cushing's disease and ectopic ACTH secretion patients reduces the specificity of the desmopressin stimulation test, necessitating further confirmatory testing. Additionally, these findings were available in a published abstract form, limiting access to the full study methodology and results for verification.

Table 3 References:
[5] McGlotten R, Nieman LK. THU039 Use Of Desmopressin In The Differential Diagnosis Of Cushings Syndrome: Recent Experience At The NIH. J Endocr Soc. 2023 Oct 5;7(Suppl 1):bvad114.1119. doi:10.1210/jendso/bvad114.1119

Diagnostic performance of desmopressin stimulation test in pediatric Cushing’s disease
Design	Retrospective cohort study N= 64 (Peripheral Stimulation Test), N= 30 (BIPSS)
Objective	To evaluate the diagnostic performance of the desmopressin (DDAVP) stimulation test in pediatric patients with Cushing’s disease (CD), and to compare its accuracy and safety profile to the ovine corticotropin-releasing hormone (oCRH) stimulation test
Study Groups	Peripheral Stimulation Test: DDAVP (n= 32), CRH (n= 32) BIPSS: DDAVP (n= 15), CRH (n= 15)
Inclusion Criteria	Pediatric patients with a final diagnosis of CD who underwent peripheral or BIPSS stimulation testing with either DDAVP or oCRH between 2021 and 2025
Exclusion Criteria	Not specified
Methods	Patients underwent peripheral or BIPSS stimulation testing with DDAVP or oCRH. DDAVP was administered as 10 mcg IV push over 30s, while oCRH was administered as 1 mcg/kg (max 100 mcg) IV push. Samples were collected at specified intervals post-administration to measure cortisol and ACTH levels. Sensitivity was calculated based on predefined criteria for cortisol and adrenocorticotropic hormone (ACTH) increases.
Duration	2021 to 2025
Outcome Measures	Primary: Sensitivity of DDAVP and oCRH stimulation tests for cortisol and ACTH Secondary: Central-to-peripheral ACTH ratios in BIPSS
Baseline Characteristics		DDAVP (n= 32)	CRH (n= 32)	p-value	DDAVP (n= 15)	CRH (n= 15)	p-value
	Sex; Male	17 (53%)	17 (53%)	1	9 (60%)	9 (60%)	1
	Age (years)	13.1 (3.4)	13.2 (3.2)	0.97	12.0 (3.6)	12.0 (3.4)	1
	Initial diagnosis	27 (84%)	31 (97%)	0.20	14 (93%)	14 (93%)	1
	Disease duration (years)	2.5 [1.8, 3.0]	3.0 [1.6, 3.3]	0.35	2.0 [1.5, 2.5]	2.7 [1.1, 3.4]	0.46
	Tumor size (mm)	4.0 [0.5, 6.1]	5.0 [0.5, 6.3]	1	0.5 [0.5, 1.8]	0.5 [0.5, 2.0]	0.98
	MRI Negative	11 (34.4%)	12 (37.5%)	1	11 (73.3%)	11 (73.3%)	1
Results		DDAVP	CRH	p-value
	Peripheral Stimulation Test - Sensitivity for Cortisol	96.9%	93.8%	p > 0.05
	Peripheral Stimulation Test - Sensitivity for ACTH	81.3%	96.9%	p > 0.05
	BIPSS - Sensitivity for Baseline Ratios	73.3%	93.3%	p = 0.33
	BIPSS - Sensitivity for Stimulated Ratios	80%	100%	p = 0.22
	Central-to-peripheral ACTH ratios were similar across groups.
Adverse Events	No major adverse events reported. One patient in the CRH group reported mild headache, which resolved spontaneously. No episodes of hyponatremia or venous thrombosis were recorded.
Study Author Conclusions	Although the DDAVP stimulation test demonstrates lower diagnostic accuracy compared to the CRH test, it still provides sufficient sensitivity and given its availability and lower cost, it represents a pragmatic alternative to CRH stimulation.
Critique	The study provides valuable insights into the use of DDAVP as a diagnostic tool for pediatric Cushing's disease, especially in settings where oCRH is unavailable. However, the retrospective design and the small sample size may limit the generalizability of the findings. Additionally, the study does not address potential variability in test performance across different clinical settings or populations

Table 4 References:
[6] Omotosho YB, Chang R, Kassin M, Groat E, Quillian A, Parker R, Tatsi C. Diagnostic performance of desmopressin stimulation test in pediatric cushing's disease. Pituitary. 2025 Dec 20;29(1):19. doi:10.1007/s11102-025-01610-4

Catheterization of the petrosal sinus: possible advantage of desmopressin stimulation in Cushing disease
Design	Case report
Case presentation	A 26-year-old woman presenting with cyclical ACTH-dependent Cushing’s syndrome characterized by intermittent hypercortisolism and normal urinary free cortisol levels underwent bilateral inferior petrosal sinus sampling (BIPSS) using desmopressin stimulation. Desmopressin was administered intravenously (10 mcg), and ACTH levels were measured in the inferior petrosal sinuses and peripheral circulation at multiple time points up to 30 minutes post-infusion. Eucortisolemia was confirmed during the procedure, with a basal serum cortisol of 6.31 mcg/dL and urinary free cortisol within normal limits, conditions which would typically contraindicate CRH-stimulated BIPSS due to insufficient hypercortisolism to suppress normal corticotroph responsiveness. Despite this, significant central-to-peripheral ACTH gradients were observed after desmopressin stimulation, notably with ACTH levels reaching >1500 pg/mL in the petrosal sinuses, confirming a pituitary source of ACTH secretion. Surgical resection of the detected pituitary microadenoma, confirmed on MRI as a 0.9 × 0.9 × 0.6 cm lesion, was followed by immunohistochemical analysis revealing strong ACTH positivity in 80–90% of tumoral cells and T-Pit positivity in 80%, corroborating the diagnosis of Cushing disease. Postoperative follow-up demonstrated clinical remission supported by normalized overnight dexamethasone-suppressed serum cortisol and 24-hour urinary free cortisol levels.
Study Author Conclusions	This case underscores the potential advantage of desmopressin-stimulated BIPSS in diagnosing cyclic Cushing’s disease even during eucortisolemic phases, highlighting that vasopressin receptor-mediated ACTH release in pituitary adenomas is not dependent on hypercortisolism-induced suppression of normal corticotrophs. The findings suggest that desmopressin stimulation may overcome limitations associated with CRH stimulation in cyclic disease and facilitate earlier diagnosis, although further validation in larger cohorts is necessary to confirm clinical applicability.

Table 5 References:
[7] Garmes HM, Siqueira SC, Daniel KB, et al. Catheterization of the petrosal sinus: possible advantage of desmopressin stimulation in Cushing disease. Arch Endocrinol Metab. 2026 Jun 25;70(4):e260064. doi:10.20945/2359-4292-2026-0064