What Are Diabetes Insipidus Symptoms?

Diabetes insipidus (DI) is a deficiency of arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), due to hypothalamus-neurohypophyseal lesions, or a deficiency in the sensitivity of the kidney to AVP due to multiple lesions. A group of clinical syndromes that cause renal tubules to reabsorb water dysfunction. The former is central diabetes insipidus (CDI) and the latter is renal diabetes insipidus (NDI). Its clinical features are polyuria, irritability, low specific gravity or hypotonic urine. Diabetes insipidus is common in young adults, with a male to female ratio of 2: 1, and hereditary NDI is more common in children.

Basic Information

English name

diabetes insipidus

Visiting department

Department of Endocrinology, Nephrology

Multiple groups

Young male

Common causes

Tumor, trauma, infection, vascular disease

Common symptoms

Thirst, drink more, pee

Contagious

no

Diabetes insipidus : the cause

Central diabetes insipidus

Any condition that leads to impaired AVP synthesis and release can cause CDI. The etiology is divided into three types: primary, secondary and hereditary.

(1) The primary cause is unknown, accounting for 30% -50% of diabetes insipidus. In some patients, the hypothalamus supraoptic nucleus and paraventricular nucleus cells can be significantly reduced or disappeared.

(2) Secondary

1) Head trauma and hypothalamic-pituitary surgery are common causes of CDI. Among them, transient CDI is most common after pituitary surgery. If surgery causes damage to the pituitary stalk above the median carina, permanent CDI can result.

2) Tumor Diabetes insipidus may be the earliest clinical symptom of a tumor on the sphenoid. The primary intracranial tumors are mainly eustachian tube tumors or pineal tumors. The secondary tumors are the most common intracranial metastases of lung cancer or breast cancer.

3) Granulomatous sarcoidosis, histiocytosis, sarcoma, xanthomas, etc.

4) Infectious diseases Encephalitis, meningitis, tuberculosis, syphilis, etc.

5) Vascular lesions Aneurysms, arterial embolisms, etc.

6) Autoimmune diseases can cause CDI, and anti-AVP cell antibodies are present in the serum.

7) Mild diabetes insipidus can occur in women during late pregnancy and puerperium , which is associated with increased AVP-degrading enzymes in the blood.

(3) Heritability It can be X-linked recessive, autosomal dominant, or autosomal recessive. X-linked recessive inheritance is transmitted by females, males are affected, and heterozygous children may have poor urine concentration, and the general symptoms are mild, without significant drinking and polyuria. Autosomal dominant inheritance can be caused by mutation of AVP precursor gene or AVP carrier protein gene. Autosomal recessive inheritance, often in familial cases, patients with polyuria since childhood, may be due to defects in osmotic receptors.

2. Diabetes insipidus

Because the kidney does not respond to AVP or weakens the response, there are two types of hereditary and secondary causes.

(1) 90% of hereditary patients with DNI are X-linked, and at least 90% of them can detect AVP receptor type 2 (AVPR2) gene mutations; the remaining 10% are autosomal and their mutant genes are aquaporins 2 (AQP2), 9% of which is dominant and 1% is recessive.

(2) Secondary

1) Tubulointerstitial lesions such as chronic pyelonephritis, obstructive urinary tract disease, renal tubular acidosis, tubular necrosis, amyloidosis, etc.

2) Metabolic diseases such as hypokalemia and hypercalcemia.

3) Drugs such as antibiotics, antifungal drugs, antitumor drugs, antiviral drugs, etc. Among them, lithium carbonate may cause NDI due to impaired cell cAMP production and interfere with renal reabsorption of water.

Clinical manifestations of diabetes insipidus

Hypotonic polyuria

Polyuria is the most significant symptom in patients with DI, and patients with CDI are generally more acute and have a clear date. Urine volume exceeds 2500ml / d or 50ml / (kg.d)], accompanied by thirst and excessive drinking. Nocturia is significantly increased, and urine output is generally above 4L / d, and very few can exceed 10L / d, but it has also been reported to reach 40L / d. The specific gravity of urine is 1.0001 1.0005, and the osmotic pressure of urine is 50 200mOsm / L, which is obviously lower than that of plasma. Long-term polyuria can lead to increased bladder capacity, so the frequency of urination has decreased. Partial diabetes insipidus patients have relatively mild symptoms with a urine output of 2.4 to 5 L / d. If severe dehydration is caused by restricting water intake, the specific gravity of urine can reach 1.010 to 1.016, and the urine osmotic pressure can exceed the plasma osmotic pressure by 290 to 600 mOsm / L. If the patient's thirst center is not affected and drinking water is not restricted, it generally only affects sleep, is weak, and is not easy to endanger life. If the patient's thirst is diminished or disappeared, failure to replenish water in time can cause severe dehydration, a significant increase in plasma osmotic pressure and serum sodium levels, extreme weakness, fever, mental symptoms, and even death. Once diabetes insipidus is combined with hypohypophysis, diabetes insipidus can be reduced, and symptoms can be recurred or exacerbated after glucocorticoid replacement therapy.

Hereditary NDI often starts in infancy and most have a family history. Mostly transmitted by women, men develop disease. After birth, he had polyuria and drink more. If he didn't find it in time, he often died because of severe dehydration, hypernatremia and high permeability coma. If you can survive, there may be slow growth, symptoms reduced or disappeared in adulthood. Recurrent dehydration and hypertonicity in infants can cause mental retardation and damage to vascular endothelium, and diffuse calcifications in the skull and blood vessels.

2. Clinical manifestations of primary disease

Patients with secondary diabetes insipidus also have symptoms and signs of primary disease. Patients with traumatic CDI may present with transient diabetes insipidus and trisomy diabetes insipidus. Three-phase diabetes insipidus can be divided into acute phase, intermediate phase and sustained phase. The acute phase is manifested as polyuria, which occurs after injury, usually lasting 4 to 5 days, mainly because the injury causes neuronal shock, and cannot release AVP or release non-biologically active precursor substances. The middle stage manifests as oliguria and increased urine osmotic pressure, which is caused by the sudden increase of AVP in the circulation due to AVP overflowing from degenerating neurons. The duration is persistent polyuria, the appearance of which is uncertain, and the large cell neurons in the supra-nucleus and paraventricular nucleus disappear> 90% or irreversible damage of the pituitary stem> 85%.

Diabetes insipidus during pregnancy (GDI): It refers to a group of symptoms that are mainly manifested in the third trimester of pregnancy with polyuria, low specific gravity urine, polydipsia, polydipsia, and electrolyte disturbance. Among the various factors that cause GDI, the role of vasopressin secreted by the placenta is the most important. It increases the degradation of AVP. When the balance between AVP degradation in the human body and increased pituitary compensation AVP secretion is hit Disturbance, the remaining AVP levels cannot maintain sufficient antidiuretic activity, which causes diabetes insipidus. The level of this enzyme decreased rapidly after delivery, and its activity was no longer detectable in plasma after 4 weeks.

Diabetes insipidus test

Urine output

More than 2500ml / d is called polyuria. The urine output of patients with diabetes insipidus can reach 4-20L / d, and the specific gravity is usually below 1.005. The urine specific gravity of some patients with diabetes insipidus sometimes reaches 1.010.

2. Blood and urine osmotic pressure

The patient's blood osmotic pressure is normal or slightly higher (normal blood osmotic pressure is 290 to 310 mOsm / L), and the urine osmotic pressure is generally lower than 300 mOsm / L (normal urine osmotic pressure is 600 to 800 mOsm / L). 60 70mOsm / L.

3. Plasma AVP determination

Normal people's plasma AVP (free drinking water) is 2.3-7.4pmol / L (radioimmunoassay), which can be significantly increased after water abstinence. The plasma AVP concentration in patients with complete CDI is undetectable; the plasma AVP level in some patients with CDI is lower than the normal range; the plasma AVP level in patients with NDI rises or is normal; patients with mental thirst are in the normal range or decrease.

4. Water forbidden-vasopressin test

Changes in urine osmotic pressure before and after water abstinence and before and after vasopressin were compared.

Method: 6 to 16 hours of water ban (normally 8 hours of water ban, depending on the severity of the disease). Body weight, blood pressure, plasma osmotic pressure and urine specific gravity were measured before the test, and urine volume, urine specific gravity and urine osmotic pressure were measured every hour afterwards. When the urine osmotic pressure reaches a peak, the urine osmotic pressure difference is less than 30mOsm / L for two consecutive times, and the urine osmotic pressure is no longer increased when the water is not allowed to continue. Urine volume and urine osmotic pressure were measured once or twice.

The results showed that the weight, blood pressure and plasma osmotic pressure of normal people did not change much (<295mOsm / L), the urine osmotic pressure was greater than 800mOsm / L, and the urine osmotic pressure did not increase by more than 9% after vasopressin injection. People with mental thirst are similar to normal people. In patients with complete diabetes insipidus, the peak plasma osmotic pressure is greater than 300mOsm / L, urine osmotic pressure is lower than blood osmotic pressure, and the urine osmotic pressure rises by more than 50% after vasopressin injection; Above 300mOsm / L, the urine osmotic pressure may slightly exceed the plasma osmotic pressure, and the urine osmotic pressure increases between 9% and 50% after injection. NDI patients did not respond after vasopressin injection. This test should be performed under close observation. If the patient's weight drops more than 3% to 5% after entering the water, or if there is a significant decrease in blood pressure, irritability, etc., the test should be stopped immediately and water should be added in time.

5. Other

Secondary CDI requires measurement of vision, visual field, saddle radiography, skull CT, or MRI to determine the cause. Genetic mutation analysis can help identify the molecular etiology of hereditary DI.

Diagnosis of diabetes insipidus

Those with thirst, polydipsia, polyuria, and low specific gravity should consider this disease, and if necessary, can perform hematuria osmolarity measurement and water-pressure-pressin test, which can often clear the diagnosis of diabetes insipidus and help Assess the extent and classification of diabetes insipidus.

1. Diagnosis points of CDI

(1) Large urine output, up to 8-10L / d or more;

(2) Hypotonic urine, urine osmotic pressure is lower than plasma osmotic pressure, generally lower than 20mOsm / L; urine specific gravity is low, mostly below 1.005;

(3) When drinking water is insufficient, hypernatremia is often accompanied by hyperuricemia, suggesting the lack of AVP, and the decrease of uric acid clearance leads to an increase in blood uric acid;

(4) Application of stimulus tests (such as water test, hypertonic saline test, etc.) that release excited AVP can not reduce urine volume, and can not significantly increase urine specific gravity and urine osmotic pressure;

(5) The application of AVP treatment has obvious effects, the urine output decreases, the urine specific gravity and urine osmotic pressure increase.

2. Key points in the diagnosis of partial CDI

(1) After banning drinking at least twice, the specific gravity of urine is 1.012 1.016;

(2) The urine osmotic pressure / blood osmotic pressure ratio when the urine osmotic pressure reaches a peak after water cessation is greater than 1, but less than 1.5;

(3) Sensitive to the vasopressin test.

3. Diagnosis points of NDI

(1) Have a family history, or a history of excessive amniotic fluid during the pregnancy of the patient's mother, or a history of primary diseases that can cause secondary NDI;

(2) Excessive symptoms after birth, frequent diaper changes during infancy, frequent drinking, slow development or fever of unknown cause, and children and adulthood with symptoms of polyuria, thirst, and drinking

(3) The urine concentration function is reduced, the daily urine volume is significantly increased, the specific gravity is less than 1.010, and the urine osmotic pressure is low, which is usually less than 300mOsm / L;

(4) The water-pressure and vasopressin tests generally do not reduce urine output, increase urine specific gravity and urine osmotic pressure, and the urine osmotic pressure / blood osmotic pressure ratio is <1. In patients with secondary NDI, in addition to decreased urine concentration, other kidneys Function is also impaired.

Differential diagnosis of diabetes insipidus

Mental thirst

The clinical manifestations are very similar to diabetes insipidus, but AVP is not lacking, mainly due to mental factors causing thirst and drinking more, which leads to polyuria and low specific gravity urine. These symptoms can fluctuate with emotions and are accompanied by other neurotic symptoms. The water-inhibiting vasopressin test helps to distinguish between the two.

2. Diabetes

There are symptoms of polyuria, thirst, and drinking, but the urine specific gravity and urine osmotic pressure are increased, and the blood sugar is elevated. The urine glucose is positive, which is easy to identify.

3. Chronic kidney disease

In particular, renal tubular disease, hypokalemia, hypercalcemia, etc., can affect renal condensing function and cause symptoms such as polyuria and thirst, but there are corresponding clinical manifestations of the primary disease, and the degree of polyuria is also relatively light.

Diabetes insipidus treatment

Alternative therapy

AVP replacement therapy is mainly used for complete CDI. Partial CDI can also be used for AVP replacement therapy when the oral medication is not effective. Alternatives include: vasopressin solution: the effect is only maintained for 3-6 hours, multiple injections per day are required, and long-term application is inconvenient. It is mainly used for the treatment of diabetes insipidus after brain injury or neurosurgery. Diabetes powder: lysine vasopressin is a nasal spray. Long-term application can cause chronic rhinitis and affect absorption. Tannin vasopressin injection: also known as long-acting urinary insipidation. It can be maintained for 3-5 days after injection. It can be thoroughly mixed before injection. Excess can cause water poisoning. 1-Deamin-8-d-Arginine vasopressin (DDAVP or desmopressin): is a synthetic AVP analog. DDAVP enhances the anti-diuretic effect, while the vasoconstrictive effect is only 1/400 of AVP, the ratio of anti-diuretic and pressurizing effects is 4000: 1, and the action time is 12 to 24 hours. determine.

2. Other anti-diuretic drugs

(1) Chlorpromide This drug can stimulate the pituitary to release AVP and enhance the water absorption of AVP, which can increase the production of cAMP in the renal tubules, but it is not effective for NDI. Can cause severe hypoglycemia, can also cause water poisoning, attention should be paid.

(2) Hydrochlorothiazide can reduce urine output by half. The mechanism of action may be due to increased sodium excretion in the urine, sodium deficiency in the body, increased reabsorption of the proximal tubules in the kidney, and reduced urine output to the distal tubules, thus reducing urine output. Long-term use can cause potassium deficiency, hyperuricemia, etc., potassium salts should be added appropriately.

(3) Carbamazepine can stimulate the release of AVP and reduce the amount of urine, but its effect is less than that of chlorpromide.

3. Etiology treatment

For patients with secondary diabetes insipidus, the primary disease should be treated as much as possible. If it cannot be cured, it can also be treated based on the above drugs.