Dear Sir,
We thank the authors for their letter entitled, "Caution during use
of DDAVP in IPSS," by Drs. Pecori Giraldi, Federici, and Cavagnini. The
authors suggest that because of the hypercoagulable state that
characterizes Cushing disease, DDAVP may not be safe since it has been
shown to increase the level of von Willebrand factor (vWF) and could
therefore lead to platelet adhesion and cause thromboembolism. The authors
point to their own published work suggesting this effect (1). In this
paper, the authors show that not only vWF levels increase, but also t-PA,
likely to achieve a balance by activating fibrinolytic pathways.
Therefore, increased risk of thromboembolic events in Cushing disease
patients in the context of DDAVP administration is a theoretical
consideration.
Thromboembolism is a rare complication of BIPSS and when reported,
has been linked to lack of prophylaxis with IV heparin (2, 3). In our
practice, we routinely heparinize patients undergoing BIPSS, whether they
receive CRH or DDAVP to stimulate the pituitary (4). The case series
previously reported where DDAVP was used rather than CRH do not indicate
an increased risk of thromboembolic events (5-8). As the increased risk of
thromboembolism is only a theoretical consideration, we can only use this
available clinical data. Because the sensitivity of BIPSS is significantly
increased by the use of CRH or DDAVP, the benefits of using DDAVP appear
at this point to outweigh the theoretical risks. One possible positive
outcome of the CRH shortage is that more data will be accumulated to
determine whether there are unexpected negative effects of using DDAVP.
1. Pecori Giraldi F, Ambrogio AG, Fatti LM, Rubini V, Cozzi G,
Scacchi M et al. Von Willebrand factor and fibrinolytic parameters during
the desmopressin test in patients with Cushing's disease. Br.J.Pharmacol.
2011;71:132-6.
2. Blevins LS Jr, Clark RV, Owens DS. Thromboembolic complications
after inferior petrosal sinus sampling in patients with Cushing's
syndrome. Endocr Pract 1998; 4:365-367.
3. Obuobie K, Davies JS, Ogunko A, Scanlon MF. Venous thrombo-
embolism following inferior petrosal sinus sampling in Cushing's disease.
J Endocrinol Invest 2000; 23:542-544.
4. Deipolyi...Oklu et al. The role of bilateral inferior petrosal
sinus sampling in the diagnostic evaluation of Cushing syndrome. Diagn
Interv Radiol 2012; 18:132-138
5. Castinetti F, Morange I, Dufour H, et al. Desmopressin test during
petrosal sinus sampling: a valuable tool to discriminate pituitary or
ectopic ACTH-dependent Cushing's syndrome. Eur J Endocrinol 2007;157:271-
7.
6. 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;66:136-42.
7. Malerbi DA, Mendonca BB, Liberman B, et al. The desmopressin
stimulation test in the differential diagnosis of Cushing's syndrome. Clin
Endocrinol (Oxf) 1993;38:463-72.
8. Salgado LR, Mendon??a BB, Pereira MAA, et al. Use of Desmopressin
in Bilateral and Simultaneous Inferior Petrosal Sinus Sampling for
Differential Diagnosis of ACTH-Dependent Cushing's Syndrome. The
Endocrinologist 1997;7:135-40.
Conflict of Interest:
None declared
Dear Sir,
We thank the authors for their letter entitled, "Caution during use of DDAVP in IPSS," by Drs. Pecori Giraldi, Federici, and Cavagnini. The authors suggest that because of the hypercoagulable state that characterizes Cushing disease, DDAVP may not be safe since it has been shown to increase the level of von Willebrand factor (vWF) and could therefore lead to platelet adhesion and cause thromboembolism. The authors point to their own published work suggesting this effect (1). In this paper, the authors show that not only vWF levels increase, but also t-PA, likely to achieve a balance by activating fibrinolytic pathways. Therefore, increased risk of thromboembolic events in Cushing disease patients in the context of DDAVP administration is a theoretical consideration.
Thromboembolism is a rare complication of BIPSS and when reported, has been linked to lack of prophylaxis with IV heparin (2, 3). In our practice, we routinely heparinize patients undergoing BIPSS, whether they receive CRH or DDAVP to stimulate the pituitary (4). The case series previously reported where DDAVP was used rather than CRH do not indicate an increased risk of thromboembolic events (5-8). As the increased risk of thromboembolism is only a theoretical consideration, we can only use this available clinical data. Because the sensitivity of BIPSS is significantly increased by the use of CRH or DDAVP, the benefits of using DDAVP appear at this point to outweigh the theoretical risks. One possible positive outcome of the CRH shortage is that more data will be accumulated to determine whether there are unexpected negative effects of using DDAVP.
1. Pecori Giraldi F, Ambrogio AG, Fatti LM, Rubini V, Cozzi G, Scacchi M et al. Von Willebrand factor and fibrinolytic parameters during the desmopressin test in patients with Cushing's disease. Br.J.Pharmacol. 2011;71:132-6.
2. Blevins LS Jr, Clark RV, Owens DS. Thromboembolic complications after inferior petrosal sinus sampling in patients with Cushing's syndrome. Endocr Pract 1998; 4:365-367.
3. Obuobie K, Davies JS, Ogunko A, Scanlon MF. Venous thrombo- embolism following inferior petrosal sinus sampling in Cushing's disease. J Endocrinol Invest 2000; 23:542-544.
4. Deipolyi...Oklu et al. The role of bilateral inferior petrosal sinus sampling in the diagnostic evaluation of Cushing syndrome. Diagn Interv Radiol 2012; 18:132-138
5. Castinetti F, Morange I, Dufour H, et al. Desmopressin test during petrosal sinus sampling: a valuable tool to discriminate pituitary or ectopic ACTH-dependent Cushing's syndrome. Eur J Endocrinol 2007;157:271- 7.
6. 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;66:136-42.
7. Malerbi DA, Mendonca BB, Liberman B, et al. The desmopressin stimulation test in the differential diagnosis of Cushing's syndrome. Clin Endocrinol (Oxf) 1993;38:463-72.
8. Salgado LR, Mendon??a BB, Pereira MAA, et al. Use of Desmopressin in Bilateral and Simultaneous Inferior Petrosal Sinus Sampling for Differential Diagnosis of ACTH-Dependent Cushing's Syndrome. The Endocrinologist 1997;7:135-40.
Conflict of Interest:
None declared