What is Arginine Vasopressin Disorder (Diabetes Insipidus) (Diabetes Insipidus)?
Arginine vasopressin disorder is a condition related to the production of unusually large amounts of urine that is watered-down (hypotonic) and has no dissolved substances (insipid). This disorder belongs to a group of conditions, either inherited or acquired, that lead to frequent urination and constant thirst (polyuria and polydipsia). It is caused by either a lack of the hormone arginine vasopressin (AVP) or the kidney’s failure to respond to it, resulting in watered-down urine due to excessive thirst. Key symptoms of this disorder include frequent urination, with more than 50 mL produced per kg of body weight, diluted pee, and increased thirst leading to up to 20 L per day of fluid intake. If left untreated, it can cause low body fluid volume (hypovolemia), dehydration, and imbalances in body salts (electrolytes).
In 2022, various Endocrinology and Pituitary Societies around the world proposed changing the name of this disorder from central DI to arginine vasopressin deficiency (AVP-D), and nephrogenic DI to arginine vasopressin resistance (AVP-R).
The main reasoning behind this change is to avoid confusing it with diabetes mellitus, a completely different condition. Despite “mellitus” and “insipidus” differentiating the two, using “diabetes” in both names leads to misunderstandings, especially among non-specialists. This confusion can lead to dangerous consequences, like withholding essential treatment, causing preventable negative effects and even death.
This issue is so significant that safety alerts have been issued, healthcare professional surveys have been conducted, and a global taskforce has been established to deal with it. Additionally, a survey of more than 1000 patients with this disorder revealed that 85% preferred a name change primarily due to encounters with healthcare professionals who lacked understanding of the disease. Specifically, 87% believed their care was negatively affected by this confusion, resulting in unnecessary blood sugar measurements and prescriptions meant for diabetes mellitus.
Lastly, there’s a belief that medical conditions’ names should reflect the physical processes that cause them. For these reasons, the proposed name change to arginine vasopressin deficiency (AVP-D) for central causes and arginine vasopressin resistance (AVP-R) for kidney-related causes has been put forward.
What Causes Arginine Vasopressin Disorder (Diabetes Insipidus) (Diabetes Insipidus)?
1. Arginine Vasopressin Deficiency (AVP-D, formerly known as Central Diabetes Insipidus or CDI)
Arginine Vasopressin Deficiency (AVP-D) is most commonly caused by something we can’t identify, also known as idiopathic causes, as reported in several studies. In some cases, the cause could be a tumor or disease that infiltrates a part of the body.
a) Idiopathic AVP-D
Half of the AVP-D cases are idiopathic and are generally linked most of the time to an immune system disorder. The immune system ends up causing inflammation in the pituitary gland, particularly in specific areas like the pituitary stalk and the back of the gland. Various studies have shown that antibodies targeting vasopressin cells are present in patients with endocrine abnormalities.
b) Familial and Congenital Disease
Other conditions that could cause AVP-D include genetic and congenital diseases such as familial AVP-D, Wolfram syndrome, and Proprotein convertase subtilisin/kexin type 1 (PCSK1) gene deficiency among others.
c) Neurosurgery or Trauma
Trauma to the hypothalamus and back of the pituitary or neurosurgery can induce AVP-D.
d) Cancer
Certain types of cancer can also cause AVP-D.
e) Adipsic DI
Some people develop what’s known as adipsic DI. This illness occurs if the same lesion that caused AVP-D also affects the brain’s osmoreceptors.
f) Hypoxic encephalopathy
AVP-D can be caused by hypoxic encephalopathy or severe ischemia (such as during cardiac arrest or shock).
g) Infiltrative disorders
Some infiltrative disorders are also linked to AVP-D.
2. Arginine Vasopressin Resistance (AVP-R, formerly known as Nephrogenic Diabetes Insipidus or NDI)
AVP-R happens when the kidney becomes resistant to an antidiuretic hormone, reducing its ability to concentrate urine. It can result from either a genetic disorder or as a side effect of certain drugs or disorders such as lithium toxicity or hypercalcemia (high levels of Calcium) among others.
3. Pregnancy-Induced/Gestational form of Arginine Vasopressin disorder (gAVP-d)
Pregnancy can cause an increase in vasopressin metabolism due to a placental enzyme. However, this is usually balanced with increased fluid intake.
4. Primary Polydipsia
Primary Polydipsia is a common condition in people with psychiatric disorders, where people drink excessive amounts of water. Some medications and certain conditions like brain tumors or meningitis can also increase water intake.
Risk Factors and Frequency for Arginine Vasopressin Disorder (Diabetes Insipidus) (Diabetes Insipidus)
Arginine vasopressin disorder (AVP-D) is an unusual hormone-related condition that affects around 1 in 25,000 people worldwide. It doesn’t favor any gender, meaning both men and women can develop it. It can occur at any age; however, inherited types tend to appear earlier in life. Because it’s relatively rare, it can sometimes be overlooked in medical settings, which could lead to complications.
Signs and Symptoms of Arginine Vasopressin Disorder (Diabetes Insipidus) (Diabetes Insipidus)
When it comes to AVP-D and AVP-R, the two conditions share common symptoms. This includes excessive thirst (polydipsia), increased urine output (polyuria), and frequent urination during the night (nocturia). In adults, polyuria is classified as producing over 3 liters of urine per day or over 2 liters per square meter in children. People without these conditions usually have more concentrated urine in the morning because they haven’t been drinking fluids overnight and because AVP levels rise during the latter part of the sleep period. If one’s ability to concentrate urine becomes slightly impaired, one of the first signs can be nocturia. But nocturia can also be influenced by other factors and is, therefore, a little non-specific.
In children, the symptoms may not directly indicate the condition. For instance, they could have serious dehydration, constipation, nausea and vomiting, fever outbreaks, irritability, and difficulty growing or developing at an expected pace. Among patients with AVP-D who possess tumors in the central nervous system, the classic symptoms may appear alongside headaches and vision problems.
Another symptom of AVP-D can be a reduction in bone mineral density in the lower spine and the top section of the thigh bone near the hip. It’s currently not fully understood why this happens. Other symptoms that AVP-D patients might have include weakness, feeling tired or lethargic, and muscle pain (myalgias).
Testing for Arginine Vasopressin Disorder (Diabetes Insipidus) (Diabetes Insipidus)
Correctly diagnosing the type of AVP-D (a condition related to excessive thirst) is vital for appropriate treatment. Misdiagnosis can lead to serious health implications. For example, incorrect treatment due to misdiagnosis could lead to significantly low sodium levels in the blood. The overlapping symptoms of different polyuria (excessive urine production) and polydipsia (excessive thirst) syndromes can make accurately diagnosing AVP-D challenging. To help tell these conditions apart, doctors use tests like the water deprivation test, which checks how well your body retains water.
Correctly diagnosing AVP-D involves some key steps: confirming the presence of hypotonic polyuria (producing large amounts of diluted urine), determining the specific type of polyuria-polydipsia syndrome, and identifying the underlying cause. This step-by-step approach can help guide the appropriate diagnostic tests and refine treatment choices.
Blood tests and urine analyses are vital. For instance, in hypotonic polyuria confirmation, doctors calculate the 24-hour urine volume and assess baseline values of blood electrolytes and the concentration of solutes in the blood and urine. It is necessary to rule out other potential causes of the patient’s symptoms during this stage. Understanding a patient’s urine concentration also plays a critical role in differentiating between AVP-D and AVP-R or primary polydipsia.
Specialized tests such as the water deprivation test and desmopressin trial also come into play, helping distinguish between different forms of AVP-D and primary polydipsia. These tests work based on the body’s normal response to dehydration, which is to reabsorb water to concentrate the urine. Patients with AVP-D or AVP-R do not show this normal response.
Identifying the cause of the disorder is the next crucial step. This involves a detailed history and physical exam, checking for hormonal imbalances, and potentially an MRI scan to check for any disruptions in the brain’s anatomy. A review of the patient’s medication list is important, as some medications can cause AVP-R. Other tests may be necessary to identify any underlying kidney disease or genetic abnormalities.
In conclusion, diagnosing AVP-D involves a careful investigation and the use of several types of diagnostic tests. This comprehensive approach helps to ensure accurate diagnosis and appropriate treatment for the patients.
Treatment Options for Arginine Vasopressin Disorder (Diabetes Insipidus) (Diabetes Insipidus)
DDAVP, a medication that mimics the hormone ADH, can be given in many ways: either orally, intranasally, subcutaneously, or intravenously. In adults, a typical dose might be 10 mcg if it’s given nasally or 4 mcg when it’s administered either under the skin or directly into a vein. For newborns or young infants, usually 1 mcg is given via the same routes, however, it is usually given slowly (over 20 minutes), and the dose must not exceed 0.4 mcg per kilogram of body weight.
In all types of diabetes insipidus (DI), it is extremely important to replace the fluids the patient loses. This is because some patients with DI might also have a malfunctioning thirst mechanism, meaning they won’t drink enough water to compensate for the fluid loss through urine. In these patients, dehydration can lead to high sodium levels in the blood.
The treatment for Arginine Vasopressin Deficiency (AVP-D), previously known as Central Diabetes Insipidus, is usually DDAVP. AVP-D patients require ongoing treatment, and the amount of DDAVP needed can vary depending on what’s causing the condition. The key is to find the lowest dose that effectively controls excessive urination. It’s also vital for patients and their families to watch for signs of low sodium levels (hyponatremia), such as nausea, vomiting, drowsiness, headache, confusion, seizures, and even coma, as the condition can lead to brain injury. Other possible treatments for AVP-D include a diet low in salt and protein, medications like thiazide diuretics, chlorpropamide, carbamazepine, and non-steroidal anti-inflammatory drugs (NSAID). DDAVP is considered safe for pregnant women.
For Arginine Vasopressin Resistance (AVP-R), previously known as Nephrogenic Diabetes Insipidus, the first step is to deal with the root cause. This might involve stopping a medication that’s causing the problem, such as lithium. A diet low in solutes (things like salt and protein) may help reduce urine output. The less of these substances you consume, the less urine your body will produce. Thiazide diuretics may also be useful when combined with dietary changes. These medications reduce urine output by triggering the release of a hormone (aldosterone) that makes your body produce less urine. Lastly, DDAVP and NSAIDs can be used as they inhibit the production of a compound (prostaglandin), which can interfere with the effects of ADH.
What else can Arginine Vasopressin Disorder (Diabetes Insipidus) (Diabetes Insipidus) be?
Possible causes of polyuria (producing large volumes of urine) might include:
- Drinking too much water (primary polydipsia)
- High sugar levels in urine due to uncontrolled diabetes
- Increased urination after eating a high-protein diet (urea diuresis)
- Polyuria can also occur after receiving large quantities of intravenous
sugar water (dextrose) or other IV fluids. - Body tissue breakdown that results in urea production can also lead to increased urination
- Use of mannitol, a type of sugar used in medicine
- An overactive bladder syndrome
Additionally, frequent urination at night (nocturia) could also be due to:
- Drinking a lot of water or other fluids before bedtime
- Enlarged prostate (prostatic hypertrophy) in men
- Diabetes
What to expect with Arginine Vasopressin Disorder (Diabetes Insipidus) (Diabetes Insipidus)
The outlook for patients with AVP-D often depends on the root cause, which could be things like brain tumors, disease spread, sarcoidosis, infiltrative disease, or other medical conditions. Genetic disorders like Wolfram Syndrome and septo-optic dysplasia often result in particularly poor outcomes.
On the flip side, patients with AVP-R usually have an excellent outlook if the main cause can be treated. Stopping the intake of lithium can return kidney function to normal, but in some cases, AVP-R might remain. Those with g-AVP-D generally have a good outlook, as long as they stay properly hydrated.
Death can be avoided as long as the person has access to water. However, the condition can lead to a cardiovascular collapse, fever, and high sodium levels in the blood, especially in children and older patients.
Possible Complications When Diagnosed with Arginine Vasopressin Disorder (Diabetes Insipidus) (Diabetes Insipidus)
If Diabetes Insipidus (DI) is not treated, it can lead to various complications. These complications include:
- Constant dehydration
- Rapid heart rate
- Decreased body temperature
- Low blood pressure
- Weight loss
- Feeling extremely tired
- Headaches
- Damage to the kidneys
- Damage to the brain
Preventing Arginine Vasopressin Disorder (Diabetes Insipidus) (Diabetes Insipidus)
Patients hold an essential role in managing their health. There are several important things they should understand and remember:
* Sticking to their prescribed medication is crucial, particularly when they are prescribed water pills or if they are using DDAVP.
* Cutting down on the intake of salt and protein can help in reducing excessive urination.
* It’s important to stay hydrated. In some cases, carrying water everywhere may be necessary.
* Knowing the signs of dehydration is critical. These can include feeling dizziness, light-headedness, confusion, or a difficulty in clear thinking.