9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

Official reprint from UpToDate®

www.uptodate.com
© 2022 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Desmopressin (DDAVP) stimulation test

Authors: André Lacroix, MD, Hershel Raff, PhD
Section Editor: Lynnette K Nieman, MD
Deputy Editor: Kathryn A Martin, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Aug 2022. | This topic last updated: Dec 03, 2021.

INTRODUCTION

Arginine-vasopressin (AVP) is the natural human nonapeptide, which (in addition to its
antidiuretic, vasoconstrictive, glycogenolytic, and platelet aggregation actions) plays an
important role in the regulation of the corticotropin (ACTH)-adrenal axis. AVP and some of
its analogs, such as porcine 8-lysine-vasopressin (LVP) and desmopressin (1-deamino, 8-D
arginine-vasopressin), have been used in a number of clinical settings. If corticotropin-
releasing hormone (CRH) is available, it is the peptide of choice for the differential diagnosis
of Cushing's syndrome. Desmopressin is used as an alternative when CRH is not available
and is considered the vasopressin analog of choice to use for the postoperative
surveillance of patients with ACTH-dependent Cushing's syndrome and for the diagnosis of
pseudo-Cushing's syndrome [1].

This topic will review the various stimulation tests using the vasopressin analog
desmopressin (DDAVP) in evaluating the pituitary-adrenal axis with a focus on pituitary
disease. (See "Corticotropin-releasing hormone stimulation test" and "Insulin-induced
hypoglycemia test" and "Initial testing for adrenal insufficiency: Basal cortisol and the ACTH
stimulation test".)

Desmopressin testing for bleeding disorders is reviewed elsewhere. (See "von Willebrand
disease (VWD): Treatment of minor bleeding, use of DDAVP, and routine preventive care",
section on 'DDAVP trial'.)

VASOPRESSIN PHYSIOLOGY

Arginine-vasopressin (AVP) is synthesized in the magnocellular neurons of the supraoptic

and paraventricular nuclei and is stored in neurosecretory granules in the axons, which
https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 1/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

project to the posterior pituitary. In addition, AVP is co-secreted with corticotropin-releasing

hormone (CRH) from smaller parvocellular neurons in a section of the paraventricular
nuclei, which project their axons to the median eminence and portal system of the pituitary
stalk [2]. At this site, AVP promotes the secretion of corticotropin (ACTH) via activation of
arginine-vasopressin receptor 1B (AVPR1B, previously named V1B or V3 receptor) present in
corticotropes [3].

Cortisol inhibits the secretion of both CRH and AVP from the paraventricular nuclei [4].
Cortisol deficiency decreases this inhibitory effect, leading to a persistent rise in
vasopressin release, water retention, and hyponatremia [2,4,5]. The AVPR2 receptors on the
cortical and medullary collecting kidney tubules mediate the antidiuretic response via the
migration of aquaporin-2 water channels [6]. AVPR2 on vascular endothelium can modulate
the release of factor VIII and von Willebrand factor [7]. Both AVPR1A and AVPR1B activate
phospholipase C [3,8,9], while the AVPR2 is coupled to adenylyl cyclase [10,11].

AVP are expected to bind to all three receptors; desmopressin is a preferential AVPR2
receptor-selective agent and has only limited effects on AVPR1A and AVPR1B. (See
"Hyponatremia and hyperkalemia in adrenal insufficiency".)

CLINICAL USES

Arginine-vasopressin (AVP), 8-lysine-vasopressin (LVP), and terlipressin have been used in a

number of clinical settings [12]. In general, these have been abandoned (due primarily to
vasopressor actions and the availability of other tests), and desmopressin is the only
peptide that is currently used. Desmopressin stimulation tests have been used to:

● Distinguish between the causes of ACTH-dependent Cushing's syndrome (Cushing's

disease and ectopic ACTH syndrome)

● The desmopressin test is used most commonly in countries where corticotropin-

releasing hormone (CRH) is not available, although there are some that suggest that
desmopressin is equivalent or even superior.

● Stimulate ACTH secretion from corticotroph tumors during petrosal sinus sampling.
Most often, desmopressin is used as a substitute for CRH, but some studies have
evaluated the combination.

● Distinguish between Cushing's syndrome and pseudo-Cushing's syndrome (Dex-CRH

versus desmopressin tests).

DESMOPRESSIN STIMULATION TEST PROCEDURE

https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 2/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

The test is usually performed in the morning with the patient fasting. An intravenous (IV)
line is established 30 minutes before the test is begun. Blood samples for measurement of
plasma corticotropin (ACTH) and serum cortisol are obtained 15 minutes and immediately
before and 15, 30, 45, 60, 90, and 120 minutes after the injection of desmopressin [13,14].
Shorter and longer versions of this test have been used [15-19]. In fact, sampling 15
minutes and immediately before, and at 15, 30, 45 and 60 minutes seems to perform as well
as the 120-minute test [18].

The recommended dose of desmopressin is 10 mcg IV [13,14], although lower doses (5 to 8

mcg) have been used successfully [13,17,20].

Interpretation — It was expected that desmopressin, initially thought to be a selective

AVPR2 receptor agent, would not stimulate ACTH and cortisol levels in normal individuals.
However, as many as 10 percent of normal subjects do respond [13,16,17], presumably
because of low-level pituitary expression of AVPR2 [21].

Side effects — Desmopressin is an AVPR2 preferential agonist and lacks the

vasoconstrictive, pallor, and abdominal discomfort mediated by the AVPR1A action of the
natural vasopressins. However, it shares their effect on platelets.

ACTH-DEPENDENT CUSHING'S SYNDROME

The desmopressin test is used in the evaluation of corticotropin (ACTH)-dependent

Cushing's syndrome [1,22-24]. The lack of commercial availability of corticotropin-releasing
hormone (CRH) in certain countries and the lower cost of desmopressin has contributed to
its increased use.

Identifying the cause — Desmopressin can be used for the differential diagnosis of

Cushing's syndrome. At low doses (1 ng/kg/min), desmopressin fails to potentiate the effect
of CRH on ACTH release in most normal subjects [25]. At a higher dose (10 mcg intravenous
[IV]), it causes an increase in plasma ACTH and serum cortisol concentrations in most
patients with Cushing's disease [13,15,26-28], suggesting that the test could be used to
diagnose this condition.

In patients with Cushing's disease, using criteria of a 30 or 50 percent increase in plasma

ACTH in response to desmopressin, 95 and 81 percent of patients respond, respectively;
using the criterion of a greater than 20 percent increase in serum cortisol, 80 to 85 percent
of patients respond [13,15,27-30]. However, in some reports, 8 of 25 (32 percent) of patients
with ectopic ACTH syndrome, mostly benign carcinoid tumors, also responded
[13,15,17,27,28,31-34].

https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 3/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

Desmopressin has a relatively low affinity for the AVPR1B receptor [9,35] that is found on
normal pituitary corticotrophs, on most adenomatous corticotrophs, and on some ACTH-
secreting bronchial carcinoid adenomas [36]. It was unclear whether this response to
desmopressin was mediated by abnormal expression of the AVPR2 on the cells of the
corticotroph adenomas and ectopic ACTH-producing tumors [28] or by increased
expression of the AVPR1B [33]. However, a study in patients with Cushing's disease suggests
that the ACTH response to desmopressin correlates better with AVPR2 expression levels
than with AVPR1B [21]. A higher in vivo response to desmopressin than that observed in
corticotroph adenoma cultures (compared with high in vitro CRH response) suggested that
other unidentified mechanisms to stimulate ACTH release may also be implicated [37].
Responsiveness to desmopressin has been observed in a bronchial carcinoid tumor in vitro
[34].

Combined with CRH — When desmopressin is given in combination with corticotropin-

releasing hormone (CRH), virtually all patients with Cushing's disease have an increase in
plasma ACTH concentrations, using the criterion of a 35 percent rise after CRH with
desmopressin [32,38]. Some clinicians use the combined test routinely, but it is more
expensive.

Some patients with ectopic ACTH secretion also respond [32,38,39]. Since obese subjects
without Cushing's syndrome may have a pronounced response to the combined CRH-AVP
(arginine-vasopressin) stimulation test, it is important to use the test only in the setting of
confirmed Cushing's syndrome [40]. (See "Corticotropin-releasing hormone stimulation
test".)

During petrosal sinus sampling — CRH is not commercially available in certain countries

or is more expensive than desmopressin. Desmopressin has therefore been used in place
of CRH to perform petrosal sinus sampling in small series [39,41-43]. There are differences
of opinion about when to use this test clinically.

Many clinicians perform petrosal sinus sampling with CRH without first determining if the
pituitary tumor responds to CRH. However, another approach is to test with desmopressin
first (which is less expensive than CRH), and if the tumor is very responsive, then use
desmopressin rather than CRH to stimulate ACTH during petrosal sinus sampling [44].

In a retrospective analysis of combined CRH and desmopressin testing during petrosal

sinus sampling in 47 patients with proven Cushing's disease and 7 with occult ectopic ACTH-
secreting tumors, a post-stimulation gradient >2 was seen in 46 of 47 and 0 of 7 patients
with Cushing's disease and ectopic ACTH, respectively (diagnostic accuracy of 98.7 percent)
[45]. However, desmopressin (alone or in combination with CRH) during inferior petrosal
sinus sampling may, on occasion, yield a false-positive diagnosis of Cushing's disease [46].
Some studies have found that the ACTH response to desmopressin during inferior petrosal
https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 4/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

sinus sampling had a sensitivity of 95 to 99 percent for the diagnosis of Cushing's disease
and was equivalent to CRH [47,48]. Similar to CRH [49], its use to accurately lateralize the
corticotroph tumor is of limited value [48]. Like with CRH [50-52], the measurement of
prolactin as an index of the adequacy of inferior petrosal sinus sampling venous sampling
is effective with desmopressin [53].

Cushing's disease versus pseudo-Cushing's syndrome — The desmopressin test may be

useful to distinguish patients with Cushing's disease from those with pseudo-Cushing's
syndrome [22]. Pseudo-Cushing's syndrome is best defined as physiologic hypercortisolism
and can occur in several disorders other than Cushing's syndrome [1]. Examples include
pregnancy, obesity, psychological or physical stress, depression, and chronic alcoholism.

Using a criterion for response of an ACTH increase of at least 4 pmol/L [54] or 6 pmol/L [30],
patients with pseudo-Cushing's syndrome are identified by a smaller increase
[16,30,31,54,55]. However, the false-positive and false-negative rates are approximately 10
percent. Furthermore, 13 to 60 percent of healthy subjects respond to desmopressin
(although less frequently than Cushing's disease patients). A subsequent study suggested
that use of an absolute increase in ACTH of 37 pg/mL (8.1 pmol/L) has a better sensitivity (88
percent) and specificity (96 percent) [18], but this criterion has not been tested widely. Thus,
caution must be used as desmopressin alone is not sufficiently specific to establish a
diagnosis of Cushing's syndrome [13,14,16,26]. (See "Causes and pathophysiology of
Cushing's syndrome", section on 'Pseudo-Cushing's syndrome'.)

In one head-to-head comparison, desmopressin testing had better specificity (90 percent)
but less sensitivity (82 percent) [54] or perhaps better [56] than the dexamethasone
suppressed-ovine CRH test (63 percent specificity; 100 percent sensitivity) for distinguishing
Cushing's disease from pseudo-Cushing's syndrome. Another study suggested that the
combination of dexamethasone (given in the evening) and desmopressin (8 mcg, IV), may
improve performance in differentiating Cushing's disease and pseudo-Cushing's syndrome,
but only nine subjects with pseudo-Cushing's syndrome were studied [20]. (See
"Establishing the diagnosis of Cushing's syndrome", section on 'CRH after dexamethasone
test'.)

Evaluating for remission of Cushing's disease — Postoperative desmopressin testing may

be useful in individuals who had a strong response preoperatively. In a study of 14 patients
in remission of their Cushing's disease by transsphenoidal microadenomectomy, none
responded to CRH or desmopressin immediately after surgery, but five patients who were
not cured did respond to CRH, desmopressin, or both [57]. Responsiveness to CRH
returned over a period of several months as normal hypothalamic-pituitary-adrenal
function was restored, but the response to desmopressin did not return. A useful approach

https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 5/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

has been suggested in which preoperative desmopressin be performed to inform the use
of desmopressin to monitor patients long term for recurrence [57].

Some studies suggest that in patients who have achieved initial remission after pituitary
surgery, those who have a cortisol response to follow-up desmopressin testing (>193
nmol/L [7 mcg/dL] in one report [58] or >14 percent in another [59]) are more likely to have a
recurrence [58-60]. In one report, there was no concordance between the clinical response
to surgery and the postoperative response to desmopressin [29]. Some studies have
demonstrated that some patients who lacked a response to desmopressin after successful
adenomectomy did subsequently respond, even years before frank hypercortisolism
reappeared [61].

A combined dexamethasone-desmopressin test (CDDT) may also be a predictor of

recurrence after pituitary surgery. Dexamethasone is added to decrease the nonspecific
response of normal corticotrophs to desmopressin. In one report of 38 patients following
successful pituitary surgery for Cushing's disease, 1 mg of dexamethasone was
administered overnight, and 10 mcg desmopressin was injected intravenously on the
following morning. An increase of serum plasma cortisol and ACTH of more than 50 percent
was an early predictor of recurrence (100 percent sensitivity, 89 percent specificity) [62].
Rather than use percent changes, another study found that an increase of cortisol of 7.4
micrograms/dL (204 nmol/L) in response to desmopressin within six months of surgery was
a useful cutoff to predict continued remission versus subsequent recurrence. While late-
night salivary cortisol may best discriminate recurrence [63], desmopressin testing may be
useful when salivary cortisol results are inconsistent or not available [64].

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Diagnosis and
treatment of Cushing's syndrome".)

SUMMARY

● Arginine-vasopressin (AVP) is synthesized in the magnocellular neurons of the

supraoptic and paraventricular nuclei, which project to the neurohypophysis; it is also
co-secreted with corticotropin-releasing hormone (CRH) from single parvocellular
neurons in the paraventricular nuclei, which project their axons to the median
eminence and portal system. AVP has three distinct receptors, which mediate a
number of physiologic effects, including its antidiuretic effect and regulation of
corticotropin (ACTH). (See 'Vasopressin physiology' above.)
https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 6/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

Desmopressin stimulation tests are currently used to:

● Distinguish between the causes of ACTH-dependent Cushing's syndrome (Cushing's

disease and ectopic ACTH syndrome). (See 'Clinical uses' above and 'Identifying the
cause' above.)

● The desmopressin test is used most commonly in countries where CRH is not
available. (See 'Clinical uses' above.)

● Distinguish between Cushing's disease and pseudo-Cushing's syndrome. (See

'Cushing's disease versus pseudo-Cushing's syndrome' above.)

● Stimulate ACTH secretion from corticotroph tumors during petrosal sinus sampling.
Most often, desmopressin is used when CRH is unavailable. Further studies may clarify
whether the combined CRH and desmopressin tests are sufficiently superior to justify
their increased cost. (See 'During petrosal sinus sampling' above.)

● Combined low-dose, overnight dexamethasone followed by desmopressin test on the

following morning appears promising as an early predictor of recurrence of Cushing's
disease following corticotroph tumor resection; long-term assessment of larger
number of patients will be necessary to determine the usefulness of this test. (See
'Evaluating for remission of Cushing's disease' above.)

DISCLOSURE

The views expressed in this topic are those of the author(s) and do not reflect the official
views or policy of the United States Government or its components.

Use of UpToDate is subject to the Terms of Use.

REFERENCES

1. Findling JW, Raff H. DIAGNOSIS OF ENDOCRINE DISEASE: Differentiation of

pathologic/neoplastic hypercortisolism (Cushing's syndrome) from physiologic/non-
neoplastic hypercortisolism (formerly known as pseudo-Cushing's syndrome). Eur J
Endocrinol 2017; 176:R205.
2. Zimmerman EA, Nilaver G, Hou-Yu A, Silverman AJ. Vasopressinergic and oxytocinergic
pathways in the central nervous system. Fed Proc 1984; 43:91.
3. Sugimoto T, Saito M, Mochizuki S, et al. Molecular cloning and functional expression of
a cDNA encoding the human V1b vasopressin receptor. J Biol Chem 1994; 269:27088.

https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 7/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

4. Raff H. Glucocorticoid inhibition of neurohypophysial vasopressin secretion. Am J

Physiol 1987; 252:R635.
5. Zimmerman EA, Ma LY, Nilaver G. Anatomical basis of thirst and vasopressin secretion.
Kidney Int Suppl 1987; 21:S14.

6. Deen PM, Verdijk MA, Knoers NV, et al. Requirement of human renal water channel
aquaporin-2 for vasopressin-dependent concentration of urine. Science 1994; 264:92.

7. Bichet DG, Razi M, Lonergan M, et al. Hemodynamic and coagulation responses to 1-

desamino[8-D-arginine] vasopressin in patients with congenital nephrogenic diabetes
insipidus. N Engl J Med 1988; 318:881.
8. Thibonnier M, Auzan C, Madhun Z, et al. Molecular cloning, sequencing, and functional
expression of a cDNA encoding the human V1a vasopressin receptor. J Biol Chem 1994;
269:3304.

9. de Keyzer Y, Auzan C, Lenne F, et al. Cloning and characterization of the human V3

pituitary vasopressin receptor. FEBS Lett 1994; 356:215.
10. Birnbaumer M, Seibold A, Gilbert S, et al. Molecular cloning of the receptor for human
antidiuretic hormone. Nature 1992; 357:333.
11. Lolait SJ, O'Carroll AM, McBride OW, et al. Cloning and characterization of a vasopressin
V2 receptor and possible link to nephrogenic diabetes insipidus. Nature 1992; 357:336.
12. Ferrante E, Barbot M, Serban AL, et al. Indication to dynamic and invasive testing in
Cushing's disease according to different neuroradiological findings. J Endocrinol Invest
2022; 45:629.

13. Malerbi DA, Mendonça BB, Liberman B, et al. The desmopressin stimulation test in the
differential diagnosis of Cushing's syndrome. Clin Endocrinol (Oxf) 1993; 38:463.
14. Scott LV, Medbak S, Dinan TG. ACTH and cortisol release following intravenous
desmopressin: a dose-response study. Clin Endocrinol (Oxf) 1999; 51:653.
15. Terzolo M, Reimondo G, Alì A, et al. The limited value of the desmopressin test in the
diagnostic approach to Cushing's syndrome. Clin Endocrinol (Oxf) 2001; 54:609.
16. Malerbi DA, Fragoso MC, Vieira Filho AH, et al. Cortisol and adrenocorticotropin
response to desmopressin in women with Cushing's disease compared with
depressive illness. J Clin Endocrinol Metab 1996; 81:2233.
17. Sakai Y, Horiba N, Tozawa F, et al. Desmopressin stimulation test for diagnosis of ACTH-
dependent Cushing's syndrome. Endocr J 1997; 44:687.

18. Rollin GA, Costenaro F, Gerchman F, et al. Evaluation of the DDAVP test in the diagnosis
of Cushing's Disease. Clin Endocrinol (Oxf) 2015; 82:793.
19. Le Marc'hadour P, Muller M, Albarel F, et al. Postoperative follow-up of Cushing's
disease using cortisol, desmopressin and coupled dexamethasone-desmopressin tests:

https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 8/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

a head-to-head comparison. Clin Endocrinol (Oxf) 2015; 83:216.

20. Araya AV, Romero C, Lemp M. Combined dexamethasone and desmopressin test in the
differential diagnosis of ACTH-dependent Cushing's syndrome and pseudo-cushing's
states. Pituitary 2017; 20:602.
21. Wang FF, Tang KT, Yen YS, et al. Plasma corticotrophin response to desmopressin in
patients with Cushing's disease correlates with the expression of vasopressin receptor
2, but not with that of vasopressin receptor 1 or 3, in their pituitary tumours. Clin
Endocrinol (Oxf) 2012; 76:253.
22. Vassiliadi DA, Tsagarakis S. DIAGNOSIS OF ENDOCRINE DISEASE: The role of the
desmopressin test in the diagnosis and follow-up of Cushing's syndrome. Eur J
Endocrinol 2018; 178:R201.

23. Nieman LK. Recent Updates on the Diagnosis and Management of Cushing's
Syndrome. Endocrinol Metab (Seoul) 2018; 33:139.

24. Nieman LK. Diagnosis of Cushing's Syndrome in the Modern Era. Endocrinol Metab Clin
North Am 2018; 47:259.
25. Gaillard RC, Riondel AM, Ling N, Muller AF. Corticotropin releasing factor activity of CRF
41 in normal man is potentiated by angiotensin II and vasopressin but not by
desmopressin. Life Sci 1988; 43:1935.

26. Scott LV, Medbak S, Dinan TG. Desmopressin augments pituitary-adrenal responsivity
to corticotropin-releasing hormone in subjects with chronic fatigue syndrome and in
healthy volunteers. Biol Psychiatry 1999; 45:1447.
27. Colombo P, Passini E, Re T, et al. Effect of desmopressin on ACTH and cortisol secretion
in states of ACTH excess. Clin Endocrinol (Oxf) 1997; 46:661.
28. Tsagarakis S, Tsigos C, Vasiliou V, et al. The desmopressin and combined CRH-
desmopressin tests in the differential diagnosis of ACTH-dependent Cushing's
syndrome: constraints imposed by the expression of V2 vasopressin receptors in
tumors with ectopic ACTH secretion. J Clin Endocrinol Metab 2002; 87:1646.
29. Losa M, Mortini P, Dylgjeri S, et al. Desmopressin stimulation test before and after
pituitary surgery in patients with Cushing's disease. Clin Endocrinol (Oxf) 2001; 55:61.
30. Moro M, Putignano P, Losa M, et al. The desmopressin test in the differential diagnosis
between Cushing's disease and pseudo-Cushing states. J Clin Endocrinol Metab 2000;
85:3569.

31. Tsagarakis S, Vasiliou V, Kokkoris P, et al. Assessment of cortisol and ACTH responses to
the desmopressin test in patients with Cushing's syndrome and simple obesity. Clin
Endocrinol (Oxf) 1999; 51:473.
32. Newell-Price J, Perry L, Medbak S, et al. A combined test using desmopressin and
corticotropin-releasing hormone in the differential diagnosis of Cushing's syndrome. J
https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 9/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

Clin Endocrinol Metab 1997; 82:176.

33. Dahia PL, Ahmed-Shuaib A, Jacobs RA, et al. Vasopressin receptor expression and
mutation analysis in corticotropin-secreting tumors. J Clin Endocrinol Metab 1996;
81:1768.

34. Arlt W, Dahia PL, Callies F, et al. Ectopic ACTH production by a bronchial carcinoid
tumour responsive to desmopressin in vivo and in vitro. Clin Endocrinol (Oxf) 1997;
47:623.

35. Antoni FA. Novel ligand specificity of pituitary vasopressin receptors in the rat.
Neuroendocrinology 1984; 39:186.
36. Arnaldi G, de Keyzer Y, Gasc JM, et al. Vasopressin receptors modulate the
pharmacological phenotypes of Cushing's syndrome. Endocr Res 1998; 24:807.
37. Pecori Giraldi F, Marini E, Torchiana E, et al. Corticotrophin-releasing activity of
desmopressin in Cushing's disease: lack of correlation between in vivo and in vitro
responsiveness. J Endocrinol 2003; 177:373.
38. Dickstein G, DeBold CR, Gaitan D, et al. Plasma corticotropin and cortisol responses to
ovine corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), CRH plus AVP,
and CRH plus metyrapone in patients with Cushing's disease. J Clin Endocrinol Metab
1996; 81:2934.
39. Tsagarakis S, Kaskarelis IS, Kokkoris P, et al. The application of a combined stimulation
with CRH and desmopressin during bilateral inferior petrosal sinus sampling in
patients with Cushing's syndrome. Clin Endocrinol (Oxf) 2000; 52:355.
40. Pasquali R, Gagliardi L, Vicennati V, et al. ACTH and cortisol response to combined
corticotropin releasing hormone-arginine vasopressin stimulation in obese males and
its relationship to body weight, fat distribution and parameters of the metabolic
syndrome. Int J Obes Relat Metab Disord 1999; 23:419.

41. Kaltsas GA, Giannulis MG, Newell-Price JD, et al. A critical analysis of the value of
simultaneous inferior petrosal sinus sampling in Cushing's disease and the occult
ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 1999; 84:487.
42. Booth GL, Redelmeier DA, Grosman H, et al. Improved diagnostic accuracy of inferior
petrosal sinus sampling over imaging for localizing pituitary pathology in patients with
Cushing's disease. J Clin Endocrinol Metab 1998; 83:2291.
43. Machado MC, de Sa SV, Domenice S, et al. The role of desmopressin in bilateral and
simultaneous inferior petrosal sinus sampling for differential diagnosis of ACTH-
dependent Cushing's syndrome. Clin Endocrinol (Oxf) 2007; 66:136.
44. Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing's syndrome. Lancet 2015;
386:913.

https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 10/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

45. Tsagarakis S, Vassiliadi D, Kaskarelis IS, et al. The application of the combined
corticotropin-releasing hormone plus desmopressin stimulation during petrosal sinus
sampling is both sensitive and specific in differentiating patients with Cushing's
disease from patients with the occult ectopic adrenocorticotropin syndrome. J Clin
Endocrinol Metab 2007; 92:2080.

46. Findling JW, Raff H. Newer diagnostic techniques and problems in Cushing's disease.
Endocrinol Metab Clin North Am 1999; 28:191.

47. Deipolyi AR, Alexander B, Rho J, et al. Bilateral inferior petrosal sinus sampling using
desmopressin or corticotropic-releasing hormone: a single-center experience. J
Neurointerv Surg 2015; 7:690.
48. Feng M, Liu Z, Liu X, et al. Tumour lateralization in Cushing's disease by inferior petrosal
sinus sampling with desmopressin. Clin Endocrinol (Oxf) 2018; 88:251.
49. Wind JJ, Lonser RR, Nieman LK, et al. The lateralization accuracy of inferior petrosal
sinus sampling in 501 patients with Cushing's disease. J Clin Endocrinol Metab 2013;
98:2285.
50. Mulligan GB, Faiman C, Gupta M, et al. Prolactin measurement during inferior petrosal
sinus sampling improves the localization of pituitary adenomas in Cushing's disease.
Clin Endocrinol (Oxf) 2012; 77:268.
51. Sharma ST, Raff H, Nieman LK. Prolactin as a marker of successful catheterization
during IPSS in patients with ACTH-dependent Cushing's syndrome. J Clin Endocrinol
Metab 2011; 96:3687.

52. Findling JW, Kehoe ME, Raff H. 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. J Clin Endocrinol Metab
2004; 89:6005.

53. Qiao X, Ye H, Zhang X, et al. The value of prolactin in inferior petrosal sinus sampling
with desmopressin stimulation in Cushing's disease. Endocrine 2015; 48:644.

54. Tirabassi G, Papa R, Faloia E, et al. Corticotrophin-releasing hormone and

desmopressin tests in the differential diagnosis between Cushing's disease and
pseudo-Cushing state: a comparative study. Clin Endocrinol (Oxf) 2011; 75:666.
55. Coiro V, Volpi R, Capretti L, et al. Desmopressin and hexarelin tests in alcohol-induced
pseudo-Cushing's syndrome. J Intern Med 2000; 247:667.

56. Pecori Giraldi F, Pivonello R, Ambrogio AG, et al. The dexamethasone-suppressed

corticotropin-releasing hormone stimulation test and the desmopressin test to
distinguish Cushing's syndrome from pseudo-Cushing's states. Clin Endocrinol (Oxf)
2007; 66:251.

https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 11/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

57. Colombo P, Dall'Asta C, Barbetta L, et al. Usefulness of the desmopressin test in the
postoperative evaluation of patients with Cushing's disease. Eur J Endocrinol 2000;
143:227.

58. Romanholi DJ, Machado MC, Pereira CC, et al. Role for postoperative cortisol response
to desmopressin in predicting the risk for recurrent Cushing's disease. Clin Endocrinol
(Oxf) 2008; 69:117.
59. Valéro R, Vallette-Kasic S, Conte-Devolx B, et al. The desmopressin test as a predictive
factor of outcome after pituitary surgery for Cushing's disease. Eur J Endocrinol 2004;
151:727.
60. Dall'Asta C, Barbetta L, Bonavina L, et al. Recurrence of Cushing's disease preceded by
the reappearance of ACTH and cortisol responses to desmopressin test. Pituitary 2004;
7:183.

61. Ambrogio AG, Andrioli M, De Martin M, et al. Usefulness of desmopressin testing to

predict relapse during long-term follow-up in patients in remission from Cushing's
disease. Endocr Connect 2017; 6:791.

62. Castinetti F, Martinie M, Morange I, et al. A combined dexamethasone desmopressin

test as an early marker of postsurgical recurrence in Cushing's disease. J Clin
Endocrinol Metab 2009; 94:1897.

63. Danet-Lamasou M, Asselineau J, Perez P, et al. Accuracy of repeated measurements of

late-night salivary cortisol to screen for early-stage recurrence of Cushing's disease
following pituitary surgery. Clin Endocrinol (Oxf) 2015; 82:260.
64. Vassiliadi DA, Balomenaki M, Asimakopoulou A, et al. The Desmopressin Test Predicts
Better Than Basal Cortisol the Long-Term Surgical Outcome of Cushing's Disease. J Clin
Endocrinol Metab 2016; 101:4878.
Topic 158 Version 16.0

Contributor Disclosures
André Lacroix, MD Grant/Research/Clinical Trial Support: Corcept Therapeutics [Cushing's
syndrome];Novartis [Pituitary tumors, Cushing's syndrome].
Consultant/Advisory Boards: Ipsen
[Pituitary tumors];Novartis [Pituitary tumors, Cushing's syndrome];Pfizer [Pituitary tumors];Recordati
[Cushing's syndrome].
Speaker's Bureau: Novartis [Cushing's syndrome];Recordati [Cushing's
syndrome].
Other Financial Interest: European Journal of Endocrinology [Senior editor].
All of the
relevant financial relationships listed have been mitigated. Hershel Raff, PhD Consultant/Advisory
Boards: Cerium [Therapeutic ACTH formulations]; Corcept [Laboratory testing for HPA axis disorders].
All of the relevant financial relationships listed have been mitigated. Lynnette K Nieman, MD No
relevant financial relationship(s) with ineligible companies to disclose. Kathryn A Martin, MD No
relevant financial relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for

https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 12/13
9/26/22, 8:30 PM Desmopressin (DDAVP) stimulation test - UpToDate

references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

https://www.uptodate.com/contents/desmopressin-ddavp-stimulation-test/print 13/13