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Concept: Desmopressin

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The World Anti-Doping Agency (WADA) has recently added desmopressin, a synthetic analogue of the endogenous peptide hormone arginine vasopressin, to the Prohibited List, owing to the potential masking effects of this drug on hematic parameters useful to detect blood doping. A qualitative method for detection of desmopressin in human urine by high-performance liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated. Desmopressin purification from urine was achieved by means of delipidation with a 60:40 di-isopropyl ether/n-butanol and solid-phase extraction with WCX cartridges. The lower limit of detection was 25 pg/mL. Extraction recovery was determined as 59.3% (SD 29.4), and signal reduction owing to ion suppression was estimated to be 42.7% (SD 12.9). The applicability of the method was proven by the analysis of real urine samples obtained after intravenous, oral and intranasal administration of desmopressin, achieving unambiguous detection of the peptide in all the cases. Copyright © 2012 John Wiley & Sons, Ltd.

Concepts: Mass spectrometry, Hormone, Oxytocin, Vasopressin, Diabetes insipidus, Tandem mass spectrometry, Desmopressin, World Anti-Doping Agency

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Overcorrection of plasma sodium in severe hyponatremia is associated with osmotic demyelination syndrome. Desmopressin (DDAVP) can prevent overcorrection of plasma sodium in hyponatremia. The objective of this study is to compare outcomes in hyponatremia based on DDAVP usage.

Concepts: Neurology, Vasopressin, Sodium, Diabetes insipidus, Hyponatremia, Desmopressin, Central pontine myelinolysis

1

Type 2B von Willebrand disease (VWD) is an inherited bleeding disorder caused by changes in von Willebrand factor (VWF) that enhance binding of VWF to GPIb on platelets. Although this disorder is seemingly well defined due to this single molecular defect, in reality type 2B VWD is a clinically heterogeneous disorder that can be difficult to identify and manage. Diagnostic criteria include a history of mucocutaneous bleeding, laboratory studies showing enhanced VWF binding of platelets and/or a 2B VWD genetic variant, and a family history consistent with autosomal dominant inheritance. Thrombocytopenia, while not always present, is common and can be exacerbated by physiologic stressors such as pregnancy. The mainstay of therapy for type 2B VWD is VWF replacement therapy. Adjunct therapies useful in other types of VWD, such as antifibrinolytics, are also used in type 2B VWD. Desmopressin (DDAVP) is controversial due to exacerbation of thrombocytopenia, but is in practice sometimes used for minor bleeding. Herein we review the available evidence and describe three clinical cases to illustrate the intricacies of diagnosing type 2B VWD, to describe the response to DDAVP and to review the complexities and management during pregnancy.

Concepts: Coagulation, Platelet, Von Willebrand factor, Von Willebrand disease, Bernard-Soulier syndrome, Ristocetin, Heyde's syndrome, Desmopressin

1

Copeptin and arginine vasopressin (AVP) are derived from a common precursor molecule and have equimolar secretion and response to osmotic, haemodynamic and stress-related stimuli. Plasma concentrations of copeptin and AVP in relation to serum osmolality are highly correlated. The physiological functions of AVP with respect to homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response are well known, but the exact function of copeptin is undetermined. Quantification of AVP can be difficult, but copeptin is stable in plasma and can be easily measured with a sandwich immunoassay. For this reason, copeptin has emerged as a promising marker for the diagnosis of AVP-dependent fluid disorders. Copeptin measurements can enable differentiation between various conditions within the polyuria-polydipsia syndrome. In the absence of prior fluid deprivation, baseline copeptin levels >20 pmol/l identify patients with nephrogenic diabetes insipidus. Conversely, copeptin levels measured upon osmotic stimulation differentiate primary polydipsia from partial central diabetes insipidus. In patients with hyponatraemia, low levels of copeptin together with low urine osmolality identify patients with primary polydipsia, and the ratio of copeptin to urinary sodium can distinguish the syndrome of inappropriate antidiuretic hormone secretion from other AVP-dependent forms of hyponatraemia.

Concepts: Diabetes mellitus, Hormone, Endocrinology, Diabetes, Vasopressin, Diabetes insipidus, Hyponatremia, Desmopressin

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Desmopressin, a synthetic vasopressin analog, is used to treat central diabetes insipidus, hemostatic disorders such as von Willebrand’s disease, and nocturnal enuresis. We present the case of a 69-year-old man who developed severe hyponatremia during treatment with intranasal desmopressin at 10 µg twice daily for chronic polyuria and nocturia thought to be due to central diabetes insipidus. After 5 months of therapy, the patient noticed progressive fatigue, anorexia, dizziness, weakness, light-headedness, decreased concentration, and new-onset falls. At 6 months of therapy, the patient was brought to the emergency department for altered mental status and was found to be severely hyponatremic with a serum sodium level of 96 mmol/L, down from a value of 134 mmol/L at the initiation of therapy. The intranasal desmopressin was discontinued and the patient was admitted to the intensive care unit where the hyponatremia was slowly corrected over the next week to 132 mmol/L, never increasing by more than 8 mmol/L a day, with careful fluid management. This included infusion of over 11 L of 5% dextrose to account for a high urine output, which peaked at 7.4 L in 1 day. However, while the recommended rate for sodium correction was followed, the patient’s magnetic resonance imaging of the brain obtained after discharge displayed evidence of central pontine myelinolysis. Despite this finding, the patient eventually returned to his baseline mental status with no permanent neurologic deficits.

Concepts: Brain, Diabetes mellitus, Magnetic resonance imaging, Vasopressin, Von Willebrand disease, Diabetes insipidus, Hyponatremia, Desmopressin

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Abnormal Uterine Bleeding (AUB) is a frequent cause of visits to the emergency department and a major reason for concern among adolescents and their families. The most common cause of AUB, in otherwise healthy adolescents, is ovulatory dysfunction, although 5-36% of adolescents who present with heavy menstrual bleeding, have an underlying bleeding disorder (BD). The most common form of BDs is von Willebrand Disease, reflecting 13% of adolescents with AUB. Management of AUB depends on the underlying etiology, the bleeding severity, as well as the need for hospitalization. Treatment of adolescents with an underlying coagulopathy depends on the severity of the BD, while therapeutic interventions are summarized in supportive measures, hormonal treatments (e.g. Combined Oral Contraceptives), non-hormonal treatments (e.g. tranexamic acid and desmopressin), surgical options (e.g. dilatation & curettage) and treatment options in specific conditions.

Concepts: Hormonal contraception, Combined oral contraceptive pill, Menstrual cycle, Von Willebrand factor, Von Willebrand disease, Bernard-Soulier syndrome, Menorrhagia, Desmopressin

0

The role of desmopressin (DDAVP) to prevent or treat rapid serum sodium concentration ([Na]s) correction during hyponatremia management remains unclear.

Concepts: Vasopressin, Sodium, Serum sodium, Diabetes insipidus, Hypovolemia, Hyponatremia, Desmopressin

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Development of compounds with therapeutic application requires the interaction of different disciplines. Several tumors express vasopressin (AVP; arginine vasopressin) receptors with contrasting effects depending on receptor subtype. Desmopressin (dDAVP) is an AVP-selective analog with antiproliferative properties. In this work, an evolutionary approach and a rational strategy were applied in order to design novel AVP analogs.

Concepts: Cancer, Metastasis, Lung cancer, Hormone, Carcinoma, Vasopressin, Diabetes insipidus, Desmopressin

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von Willebrand disease (vWD) is the most common inherited coagulopathy in dogs, particularly in Doberman Pinschers. We developed a pyrosequencing-based assay to estimate the frequency of the c.7437G>A mutation associated with vWD type 1 in the Doberman Pinscher population of Buenos Aires, Argentina. We found a 0.41 frequency for the mutated allele, which varied significantly within families (family 1 = 0.43, family 2 = 0.58, unrelated animals = 0.35). The use of a popular founder male carrier of mutant allele A increased vWD incidence within a family and in the general population. The mode of inheritance was confirmed as autosomal dominant with incomplete penetrance. No differences were found between sexes and coat colors. Pyrosequencing was a good complement to clinical and coagulation tests for vWD type 1 diagnosis and a useful alternative for detecting the c.7437G>A mutation.

Concepts: Genetics, Evolution, Coagulation, Platelet, Von Willebrand factor, Von Willebrand disease, Desmopressin, Doberman Pinscher

0

Diabetes insipidus, characterized by polyuria and polydipsia, is a rare disease during pregnancy. Nevertheless, its recognition is important to avoid complications due to dehydration and hypernatremia. Its manifestation during pregnancy ranges from exacerbation of pre-existing central or nephrogenic diabetes insipidus to transient pregnancy-induced diabetes insipidus due to the increased metabolism of the antidiuretic hormone vasopressin by the placental vasopressinase. Diagnosis can be challenging, as urinary frequency is common during pregnancy and primary polydipsia also needs to be excluded. Also the standard water deprivation test is not recommended during pregnancy due to the increased risk of complications. Treatment depends upon the final diagnosis, with desmopressin (DDAVP) being the medication of choice in AVP-deficient diabetes insipidus, whereas nephrogenic diabetes insipidus requires treatment of the underlying disease and supportive measures.

Concepts: Diabetes mellitus, Endocrinology, Vasopressin, Diabetes insipidus, Polyuria, Desmopressin, Polydipsia, Hypernatremia