Arginine vasopressin (AVP) deficiency is a rare neuroendocrine disorder caused by the loss or impaired function of vasopressinergic neurons in the hypothalamus and posterior pituitary gland. This results in impaired synthesis and secretion of AVP. A deficiency of AVP causes the inability to concentrate urine and excessive renal water loss, leading to hypotonic polyuria.
AVP deficiency has previously been called central diabetes insipidus (CDI).
Etiology
AVP deficiency is caused by various etiologies, all with the commonality of neuronal destruction. Most cases of acquired AVP deficiency develop as a result of 3 pathophysiological mechanisms:
- anatomical destruction of vasopressinergic neurons by neoplasms,
- traumatic damage, as result of traumatic brain injury (TBI) or neurosurgical intervention,
- autoimmune destruction of the AVP-secreting neurons.
Additionally, inherited forms of the disease are caused by mutations in the AVP gene, usually present in childhood. These are usually monogenic disorders, caused by single mutations in the AVP gene.
Signs and Symptoms
The primary symptoms of AVP deficiency are polydipsia, polyuria, and nocturia. Additional symptoms may include weakness, lethargy, fatigue, and myalgias. Patients may also develop decreased bone mineral density at the lumbar spine and femoral neck. In patients with central nervous system involvement, headaches and visual defects are common.
In children, symptoms may include:
- Severe dehydration
- Constipation
- Vomiting
- Fevers
- Irritability
- Failure to thrive
- Delayed growth
Diagnosis
The first step in diagnosing AVP deficiency is confirming the presence of hypotonic polyuria through measuring daily urine volume. Generally, a daily volume of greater than 2.5 to 3 L may be investigated further. Once polyuria is confirmed, ruling out other possible causes (i.e., diabetes mellitus, renal impairment, hyperglycemia, hypercalcemia, and hyperkalemia) should occur through laboratory testing. Following this, a series of tests may be conducted to diagnose the disease such as:
- Water deprivation test
- AVP measurement
- Hypertonic saline infusion
- Plasma copeptin measurement
- Thirst measurement
Management Strategies and Treatment
Management of AVP deficiency involves fluid intake management to replace renal water loss and medication. Desmopressin, or deamino D-arginine vasopressin (DDAVP) is a selective vasopressin V2 receptor agonist. When these receptors are activated, there is a cascading effect that leads to an increase in cyclic adenosine monophosphate (cAMP). This results in increased water permeability which decreases urine volume and increases urine osmolality. DDAVP is available in parenteral, oral, and nasal forms.
Clinical Trials and Studies
For a full list of clinical trials relating to AVP deficiency, click here.
Resources
The Pituitary Foundation: AVP Deficiency
References
Tomkins M et al. Diagnosis and Management of Central Diabetes Insipidus in Adults. In: The Journal of Clinical Endocrinology and Metabolism. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516129/
McCarty TS, Patel P. Desmopressin. [Updated 2023]. In: StatPearls [Internet]. Available at https://www.ncbi.nlm.nih.gov/books/NBK554582/#:~:text=Desmopressin%20
For more information on rare endocrine disorders, visit https://checkrare.com/diseases/endocrine-disorders/
