What Factors Affect the Secretion of Antidiuretic Hormone?

^[1] Syndrome of inappropriate antidiuretic hormone secretion (SIADH) refers to abnormal increase in secretion of endogenous antidiuretic hormone (ADH, arginine vasopressin AVP) due to various reasons, Plasma antidiuretic hormone concentrations are inappropriately high relative to body fluid osmotic pressure, which leads to a group of syndromes related to clinical manifestations such as water retention, increased urinary sodium excretion, and dilute hyponatremia. ^[2]

Antidiuretic hormone dysregulation syndrome

Overview of antidiuretic hormone secretion syndrome

Etiology and pathogenesis of antidiuretic hormone secretion syndrome

(1) Heterologous ADH secretion The parenchymal cells of the following diseased tissues can secrete ADH and its carrier protein, neuropituitary I:

1. The most common malignant tumor is pulmonary oat cell pain, which is caused by about 80% of patients with SIADH. About half of the patients with oat cell carcinoma have increased plasma AVP and water drainage problems, but they do not necessarily have hyponatremia. The presence or absence of SIADH depends on the degree of water load. Other tumors such as pancreatic cancer, lymphosarcoma, Hodgkin's disease, reticulosarcoma, thymic cancer, duodenal cancer, bladder cancer, prostate cancer.

2. Pulmonary infectious diseases such as pneumonia, tuberculosis, pulmonary abscess, and pulmonary aspergillosis can sometimes cause SIADH, which may be due to the synthesis and release of AVP in the lung tissue. In addition, the infected lung tissue can synthesize and release AVP-like peptides. AVP has the same biological characteristics.

(2) Drugs or diseases cause excessive release of ADH 1. Diseases of the central nervous system, traumatic brain injury, subdural hematoma formation, subarachnoid hemorrhage, cerebral thrombosis, cerebral abscess, cerebral atrophy, acute infection of the brain, tuberculosis or other meningitis, can affect hypothalamus-neurohypophysis 1. Promote the release of AVP without being controlled by normal regulation mechanisms such as osmotic pressure, thereby causing SIADH. Drugs that promote or enhance the release of ADH, chlorpromazide, clobetin, tricyclic antidepressants (such as amimidazine), general anesthetics, barbiturates and other drugs can stimulate the release of ADH. Urea can still increase the activity of ADH. Thiazine diuretics due to its sodium excretion and diuresis and GFR decrease, and at the same time trigger ADH secretion, teletubular tubule reabsorption of water increased, and free water clearance rate decreased significantly. Anticancer drugs such as vincristine and cyclophosphamide can also stimulate ADH release.

(3) Other sudden decrease in left atrial pressure stimulates volume receptors, which can increase ADH secretion reflexively. It is seen after mitral stenosis, and SLADH can also be seen in adrenal insufficiency, myxedema, and anterior pituitary hypofunction And other endocrine diseases (due to low blood volume or impaired free water from the kidneys); a few patients have SLADH that cannot be linked to the above etiology, and the sensitivity of renal tubules to ADH may have changed. ^[2]

Antidiuretic hormone secretion syndrome pathophysiology

Due to the excessive release of AVP and is not controlled by the normal regulation mechanism, the reabsorption of water by the renal tubules and collecting ducts increases, urine cannot be diluted, and free water cannot be excreted from the body. Retention, expansion of extracellular fluid volume, blood dilution, decreased serum sodium concentration and osmotic pressure. At the same time, the intracellular fluid is also in a hypotonic state, and the cells swell. When the brain cell function is affected, neurological symptoms can occur. This syndrome generally does not appear edema, because when the extracellular fluid volume expands to a certain degree, it can inhibit the reabsorption of sodium by the proximal tubule, increase the excretion of sodium in the urine, and prevent the water from staying too much in the body. In addition, volume expansion leads to an increase in atrial natriuretic peptide release and further increase in urinary sodium excretion. Therefore, sodium metabolism is in a negative equilibrium state, and hyponatremia and hypotonia are exacerbated. At the same time, volume expansion, increased glomerular filtration rate, and suppressed autograft secretion also increase urinary sodium excretion. Due to the continuous secretion of AVP, although the extracellular fluid is already hypotonic, the osmotic pressure in urine is still higher than the osmotic pressure in plasma. ^[2]

Clinical manifestations of antidiuretic hormone secretion syndrome

1. A history of primary symptoms or medication.

2. Hyponatremia:

The severity of clinical symptoms is related to the degree of ADH secretion and water load. Most patients do not show typical symptoms when they limit their water. However, if water load is applied, water poisoning and hyponatremia can occur, progressive weakness, fatigue, and faintness may occur when the blood sodium is less than 125mmol / L. When the blood sodium drops below 110mmol / L, There may be medulla paralysis, a stiff state, positive cone tract signs, and even coma and convulsions, which can be fatal in severe cases. Although the water in the patient's body is retained in the cells, it generally does not exceed 3 to 4L, so although there is weight gain without edema. ^[2]

Antidiuretic hormone secretion syndrome laboratory and other tests

1. Plasma osmotic pressure decreases with the decrease of blood sodium;

2. While blood sodium <125mmol / L, urine sodium> 20mmol / L, up to 80mmol / L or more, urine osmotic pressure increased;

3. Mild decrease in serum chloride and BUN.

4. Water load ADH inhibition test: Drink a lot of water in a short time (drink at 20ml / kg body weight within half an hour). Normal people should urinate a lot because of the release of ADH, and 80% of the water can be excreted within 5 hours Osmotic pressure can be lower than 100mOsm / kg H2O (below plasma osmotic pressure), while patients with SLADH urinate <40% of drinking water, urine osmotic pressure> plasma osmotic pressure. This test has certain risks and should be carried out selectively (with blood sodium> 125 mmol / L without obvious symptoms). ^[2]

Diagnosis of antidiuretic hormone secretion syndrome

Diagnosis: serum sodium is reduced (usually below 130mmoi / L);

The increase of urinary sodium often exceeds 30mmol / L;

lower plasma osmotic pressure (often below 270mOsm / L);

urine osmotic pressure exceeds plasma osmotic pressure;

History of primary disease or medication;

Increased plasma AVP is of great significance for the diagnosis of SIADH. Under normal circumstances, when the extracellular fluid is in a hypotonic state, the release of AVP is suppressed, and plasma AVP is often significantly reduced or cannot be measured; but in patients with SIADH, plasma AVP is often Improperly increased.

No edema, normal renal function and adrenal function.

Etiology diagnosis should first consider malignant tumors, and secondly exclude factors such as central system diseases and lung infection drugs. ^[2]

Differential diagnosis of antidiuretic hormone secretion syndrome

(1) Hyponatremia caused by renal sodium loss, especially adrenal insufficiency, salt-losing nephropathy, hypoaldosteronism, Fmconi syndrome, diuretic treatment, etc., can lead to decreased renal reabsorption of sodium and excretion of sodium Increased and caused hyponatremia. There are often primary diseases and dehydration, and blood urea nitrogen often increases. In SIADH patients, blood volume is usually normal or increased, and blood urea nitrogen is often decreased. For suspicious cases, diagnostic treatment can be made, limiting the daily water intake to 0.6 ~ 0.8L, such as weight loss of 2 ~ 3kg in 2 ~ 3 days, hyponatremia and hypotonia are corrected, urine sodium Excretion is significantly reduced, which has diagnostic significance for SIADH. If the body weight is reduced and hyponatremia is not corrected, and urine sodium is still excreted, it is consistent with hyponatremia due to renal sodium loss.

(2) Gastrointestinal fluid loss such as diarrhea, vomiting, gastrointestinal, biliary tract, membrane gland osteogenesis, or gastrointestinal decompression can cause loss of large amounts of digestive fluid and cause hyponatremia, often with a history of primary disease, and Urine sodium is often below 30mmol / L.

(3) Hyponatremia may also occur in hypothyroidism, which may be caused by excessive release of AVP or by the inability of the kidneys to excrete diluted urine. However, severe hypothyroidism is accompanied by myxedema and other manifestations, and it is not difficult to judge it in combination with thyroid function tests.

(4) Dilute hyponatremia may occur in refractory heart failure, advanced liver cirrhosis with ascites, or nephrotic syndrome, but these patients have their own characteristics of the original disease, and are often accompanied by obvious edema, ascites, and sodium reduce.

(5) Excessive drinking water can cause hyponatremia and lower plasma osmotic pressure, but the urine osmotic pressure is significantly reduced, which can be easily distinguished from SIADH.

(6) Cerebral salt wasting syndrome (CSWS)

This disease is caused by the inability of the kidney to preserve sodium during the course of intracranial disease, leading to a large loss of sodium from the urine, and taking away too much water, leading to hyponatremia and a decrease in extracellular fluid volume. The main clinical manifestations of CSWS are hyponatremia, increased urine sodium, and hypovolemia; while HADH is normal blood volume or a slight increase in blood volume, which is the main difference from CSWS. In addition, CSWS is effective in supplementing sodium and blood volume, but water-restrictive treatment is ineffective, which worsens the condition. ^[2]

Antidiuretic hormone secretion syndrome treatment

First, the etiology treatment early treatment of the primary disease. The drug cause should be stopped immediately, and SIADH can disappear quickly after stopping. SIADH due to central nervous system disease is often transient and disappears as the underlying disease improves. After treatment for tuberculosis or pneumonia, SIADH often recovers. In patients with SIADH due to malignant tumors, SIADH can be reduced or disappeared after surgical resection, radiation therapy, or chemotherapy. The disappearance of SIADH can also be used as evidence for the thoroughness of tumor treatment.

Second, correct excessive water load and hyponatremia

1. Restricting water intake is very important for controlling symptoms. For generally mild SIADH, strictly restricting water intake (approximately 800-1000ml of daily water supply) can eliminate symptoms.

2. If you have severe symptoms of water poisoning, you can use furosemide or diuretic acid (myelin diuretic drainage more than urination), and instill hypertonic saline (0.1ml / kg? Min), and intravenous infusion of 3% chloride Sodium solution, drip rate is 1-2ml / kg per hour, which will gradually increase serum sodium and improve symptoms. Control the blood sodium elevation rate not more than 1 ~ 2mmol / Lh, generally return to about 125mmol / L, and the patient's condition improves, that is, stop hypertonic saline drip (note to prevent pulmonary edema and maintain electrolyte balance, do not use 5% glucose solution drip Note).

3.20% mannitol 250ml, once every 4 to 6 hours, which is good for water drainage and can be applied as appropriate.

3. Antidiuretic hormone secretion inhibition or (and) activity antagonist drug demeclmyeline can antagonize the effect of AVP on renal tubular epithelial cell receptor adenylate cyclase and inhibit renal tubular reabsorption of water. It has been tried in patients with SIADH caused by lung cancer, 900 ~ 1200mg daily, orally divided into 3 times. It can cause isotonic or hypotonic diuresis and hyponatremia. The drug can cause azotemia, but it can disappear after stopping the drug. For those who are difficult to control the restriction of water, this drug can be used for treatment. Lithium salts can also hinder the effect of AVP on renal tubules, but they are more toxic and should be used with caution. Phenytoin can inhibit the release of vasopressin and is effective for some patients. Fludrocortisone (0.1-0.2mg, three times a day) may have a sodium stagnation effect, which can be treated with intravenous injection of furosemide and sodium chloride solution. ^[2]

Prognosis of antidiuretic hormone dysregulation syndrome

The prognosis of SIADH depends on the underlying disease. Caused by drugs, lung infections, and reversible diseases of the central nervous system are often transient and have a good prognosis. The prognosis is caused by malignant tumors such as lung cancer and membrane adenocarcinoma. ^[2]