Diabetes insipidus

1. Central diabetic polydipsia: Any condition that damages the synthesis, secretion, and release of AVP can cause the occurrence of this disease. The etiology of central diabetic polydipsia includes primary, secondary, and genetic types.
(1) Primary: The etiology is unknown in 30% or more. In this type of patient, the number of neurons in the supraoptic nucleus and paraventricular nucleus of the hypothalamus is reduced, and Nissl granules are exhausted. AVP synthase defect, neurohypophysis shrinkage.
(2) Secondary: Central diabetic polydipsia can be secondary to hypothalamic-neurohypophysis damage caused by the following reasons, such as craniocerebral trauma or postoperative, tumors (including primary tumors in the hypothalamus, pituitary, or paranasal area, or intracranial metastases of malignant tumors such as breast cancer, lung cancer, leukemia, carcinoid, etc.); infectious diseases, such as tuberculosis, syphilis, encephalitis, etc.; infiltrative diseases, such as sarcoidosis, granulomatosis (such as Wegener's granulomatosis); cerebrovascular diseases, such as angiomas, etc.
(3) Genetic: The inheritance pattern can be X-linked recessive, autosomal dominant, or autosomal recessive.
2. Renal diabetic polydipsia: Renal diabetic polydipsia is caused by damage to all the steps of AVP production in the kidney, and the etiology includes genetic and secondary types.
(1) Genetic: It is an X-linked recessive inheritance pattern, inherited by women, and men are affected, mostly familial.
(2) Secondary: Renal diabetic polydipsia can be secondary to renal tubular damage caused by various diseases, such as chronic pyelonephritis, obstructive urinary tract disease, renal tubular acidosis, renal tubular necrosis, amyloidosis, myeloma, renal transplantation, and azotemia. Metabolic disorders such as hypokalemia and hypercalcemia can also lead to renal diabetic polydipsia. Various drugs can cause renal diabetic polydipsia, such as gentamicin, cef唑啉钠, norfloxacin, amikacin, streptomycin, high-dose dexamethasone, expired tetracycline, lithium carbonate, etc.
In recent years, due to the wide application of CT and MRI, clinical doctors can discover small brain tumors at an early stage, so the proportion of tumors has increased, while the proportion of idiopathic central diabetic polydipsia has decreased relatively. The etiology of central diabetic polydipsia is also related to age: in children, about 60% of cases are related to brain tumors, and 25% of cases are related to brain degenerative changes.

　　Complications such as hydronephrosis, ureteral dilation, and bladder dilation can be seen.

　　1. Diabetic polydipsia with hypopituitarism: Surgery, tumors, and inflammation in the hypothalamic or pituitary regions can cause diabetic polydipsia and hypopituitarism. Vascular lesions in postpartum pituitary necrosis can also damage the supraoptic nucleus-neurohypophysis system, leading to diabetic polydipsia and Sheehan syndrome. When diabetic polydipsia is accompanied by hypopituitarism, polyuria symptoms are alleviated, and urine osmolality is higher; because glucocorticoids and antidiuretic hormone have antagonistic effects, when glucocorticoids are deficient, the condition of antidiuretic hormone deficiency will be alleviated. In addition, when glucocorticoids and thyroxine decrease, the excretion of urinary solutes decreases, which can also alleviate polyuria symptoms.

　　Diabetes insipidus with decreased thirst syndrome: This syndrome is characterized by a decrease or disappearance of the sensation of thirst at the same time as a deficiency of antidiuretic hormone. The kidneys cannot normally regulate water excretion, and the patient, due to the lack of thirst sensation, cannot increase water intake at any time to meet the body's needs. There is no polydipsia, severe dehydration, and high blood sodium, with body fluids in a hyperosmotic state, accompanied by symptoms of hyperosmolarity, including headache, muscle pain, tachycardia, personality changes, irritability, confusion, delirium, and even coma. It is difficult to adjust the dose of vasopressin during treatment, which is prone to overdose and cause water retention, presenting as a hypoosmotic state or water intoxication. Treatment with chlorpropamide, 250mg/d, can reduce urine output and improve the function of the thirst center.

　　Diabetes insipidus with pregnancy: When diabetes insipidus patients are pregnant, the condition of diabetes insipidus may worsen due to increased secretion of adrenal cortical hormones in pregnant women, which can counteract the antidiuretic effect of antidiuretic hormone, or inhibit the secretion of antidiuretic hormone. Moreover, during pregnancy, there is an increase in adrenal cortical hormones and thyroid hormones, an increase in the excretion of solutes in urine, leading to increased urine output. Throughout pregnancy, especially in the middle period, the need for antidiuretic hormone increases, often exacerbating the condition of diabetes insipidus. After delivery, the condition of diabetes insipidus improves.

This disease often starts slowly and is often progressive, with the condition gradually becoming apparent over several days. A few cases may be sudden, with a clear onset date.
Polyuria, thirst, and polydipsia are the most prominent clinical symptoms. Polyuria is characterized by increased frequency of urination and increased urine volume, with 24-hour urine volume reaching 5-10L or more. Generally, it does not exceed 18L. Patients usually prefer cold drinks and cold water. The specific gravity of urine is usually below 1.005.
Dry skin and mucous membranes, emaciation, and weakness. If water is not supplemented in time, symptoms of hyperosmolarity may occur, which are neurological symptoms caused by brain cell dehydration, including headache, changes in consciousness, irritability, delirium, and eventually leading to coma.
Secondary patients may have primary clinical manifestations. Diabetes insipidus caused by different etiologies may have different clinical characteristics. Hereditary diabetes insipidus often starts in childhood. Diabetes insipidus caused by craniocerebral trauma or surgery may manifest as a triphasic change of polyuria-antidiuretic-polyuria. Renal diabetes insipidus is relatively rare.

　　Avoid high-protein, high-fat, spicy, and high-sodium foods, as well as smoking and drinking. These can increase plasma osmotic pressure, thus exciting the thirst center in the brain; and they are prone to generate heat, dryness, and damage to Yin, aggravating symptoms such as thirst in this disease.

　　Long-term mental stimulation (such as fear, sadness, anxiety, or mental tension) can cause dysfunction of the cerebral cortex and lead to endocrine disorders. This makes the secretion of antidiuretic hormone more abundant, resulting in increased urine output and exacerbating the condition.

　　3. Avoid drinking tea and coffee. Tea and coffee contain caffeine and theophylline, which can excite the central nervous system, enhance myocardial contraction force, dilate renal and peripheral blood vessels, and have a diuretic effect, increasing urine volume and aggravating the condition.

1. Urine examination, the urine specific gravity is usually between 1.001 and 1.005, and the corresponding urine osmolality is 50-200mOsm/L (the normal value is 600-800mOsm/L), which is significantly lower than plasma osmolality. If water intake is restricted, urine specific gravity can rise to 1.010, and urine osmolality can rise to 300mOsm/L.
2. The level of antidiuretic hormone in plasma decreases (the normal baseline value is 1-1.5pg/ml), especially when water deprivation and hypotonic saline infusion cannot increase, indicating a decrease in the reserve capacity of pituitary antidiuretic hormone.
3. Water deprivation vasopressin test is the most commonly used functional test to help diagnose pituitary diabetes insipidus.
Method: Measure body weight, blood pressure, heart rate, urine volume, urine specific gravity, urine osmolality, and blood osmolality before water deprivation. Continue to fast for 8-12 hours, measure the above indicators every 2 hours, until urine volume does not change, and urine specific gravity and urine osmolality no longer increase for two consecutive times. At this time, 5U of antidiuretic hormone is injected subcutaneously, and urine volume is collected again 1 hour and 2 hours after injection, and urine specific gravity and urine osmolality are measured.
In normal people or people with spiritual thirst, after water deprivation, urine volume decreases, urine specific gravity and urine osmolality increase, so blood pressure and body weight usually do not change significantly, and plasma osmolality will not exceed 300mmol/L. After injection of antidiuretic hormone, urine volume will not continue to decrease, and urine specific gravity and urine osmolality will no longer continue to increase.
After water deprivation, the decrease in urine volume in diabetes insipidus is not significant, and there is no significant increase in urine specific gravity and urine osmolality. Body weight and blood pressure decrease significantly, plasma osmolality increases (greater than 300mmol/L), and after injection of antidiuretic hormone, urine volume decreases significantly, and urine specific gravity and urine osmolality increase several times. Water deprivation and intramuscular injection of antidiuretic hormone in renal diabetes insipidus patients cannot reduce urine volume and concentrate urine.
4. Magnetic Resonance Imaging High-resolution MRI can detect the following lesions related to central diabetes insipidus:
(1) The pituitary volume is small.
(2) The pituitary stalk is thickened.
(3) The pituitary stalk is interrupted.
(4) The upper margin of the pituitary is slightly convex.
(5) High signal disappearance of the neurohypophysis. The disappearance of high signal in the neurohypophysis is related to hypofunction of the neurohypophysis and reduced secretion granules of posterior pituitary ADH, which is a MRI feature of central diabetes insipidus.
5. Gene probes for the renal diabetes insipidus gene on the X chromosome can be used for prenatal diagnosis of hereditary renal diabetes insipidus during the late pregnancy of mothers, with 96% reliability.

　　The rational diet for patients with diabetes insipidus includes the following four types:

　　1. Due to polyuria and polydipsia, patients should be advised to have enough warm water on hand. However, they should also pay attention not to drink too much.

　　2. Avoid water intoxication.

　　3. Pay attention to supplementing salt in moderation.

　　Diarrhea patients can take more roughage foods, such as celery, etc.

　　Primary pituitary diabetes insipidus is treated with two methods: substitution therapy and drug therapy. Substitution therapy is used for complete pituitary diabetes insipidus, and the formulations of vasopressin preparations include the following types:

　　1. Vasopressin Solution for subcutaneous injection, 5-10U per time, with an action time of only 4-6 hours, suitable for the diagnosis and temporary treatment of diabetes insipidus.

　　2. Long-acting Diabetes Insipidus Stop: An oily injection, 5U per mL, starting from 0.1ml and gradually increasing to 0.5-0.7ml per time. A deep intramuscular injection once can last for 3-5 days, but do not take more than the recommended dose to avoid water intoxication.

　　3. Powdered Diabetes Insipidus Stop: 20-50mg per nasal inhalation, once every 4-6 hours. Long-term use may cause chronic rhinitis and affect absorption.

　　4. Artificially synthesized DDAVP (1-deamino-8-dextroarginine vasopressin) has strong antidiuretic effects, long-lasting action, and no pressor side effects. It can be inhaled through the nasal mucosa, twice a day, 10-20μg each time. It can be used for gestational diabetes insipidus.

　　5. New Antidiuretic Tablets containing 10μg of ADH, which can be dissolved sublingually during the day or before bedtime, with some efficacy.

　　Oral medications are suitable for partial diabetes insipidus, and the options include:

　　(1) Hydrochlorothiazide: 25mg per time, three times a day. As a salt diuretic, it can cause mild salt loss. It may reduce blood volume, stimulating ADH secretion and release on one hand, and increase the reabsorption of water in the proximal tubules on the other hand, but the exact mechanism is not yet clear. It is also effective for nephrogenic diabetes insipidus. It is recommended to eat a low-salt diet and avoid coffee and cocoa drinks when taking the medicine.

　　(2) Chlorpropamide: In vitro tests can increase the peripheral effect of antidiuretic hormone. It may increase the formation of cAMP in the distal tubules and may increase the release of ADH, but it is ineffective for nephrogenic diabetes insipidus. The dosage is 0.125-0.25g, once or twice a day, and it starts to take effect 24 hours after taking the medicine, with a decrease in urine output. Side effects include hypoglycemia, leukopenia, or liver function damage, and when used with hydrochlorothiazide, it can reduce hypoglycemic reactions.

　　(3) Anturin: The pharmacological effect may be to increase ADH release. When used with DDAVP, it can counteract resistance. The dosage is 0.2-0.5g per time, three times a day. Long-term use may cause liver damage, myositis, and gastrointestinal reactions as side effects.