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2 BACKGROUND A variety of disorders are associated with plasma ADH concentrations Thus, water retention accompanies normal water intake, leading to hyponatremia and hypo-osmolality. The urine is usually more concentrated than plasma. Termed the syndrome of inappropriate secretion of antidiuretic hormone, or SIADH. The clinical picture can be produced experimentally by giving high doses of vasopressin to a healthy subject receiving normal to high fluid intake. Water restriction in patients suspected of having SIADH will result in plasma osmolality and sodium concentration returning to normal.

3 The diagnostic criteria The diagnostic criteria for SIADH include (1) hyponatremia with corresponding plasma hypo- osmolality (< 280 mosm/kg); (2) urine less than maximally dilute, ie, inappropriately concentrated (> 100 mosm/kg); (3) euvolemia (including absence of congestive heart failure, cirrhosis, and nephrotic syndrome); (4) absence of renal, adrenal or thyroid insufficiency. Urinary sodium is usually > 20 mmol/d, probably a consequence of increased atrial natriuretic factor. Dynamic testing and plasma ADH levels are usually unnecessary in diagnosis.

4 Causes of SIADH - Malignant lung disease, particularly bronchogenic carcinoma - Nonmalignant lung disease, eg, tuberculosis - Tumors at other sites (especially lymphoma, sarcoma), eg, duodenum, pancreas, brain, prostate, thymus - Central nervous system trauma and infections - Drugs that stimulate vasopressin release, eg, clofibrate, chlorpropamide, and other drugs such as thiazides, carbamazepine, phenothiazines, vincristine, cyclophosphamide SSRIs (eg, fluoxetine, sertraline) - Endocrine diseases: adrenal insufficiency, myxedema, anterior pituitary insufficiency - HIV infection


6 Types of Osmoregulatory Defects Type A: - Found in 20% of patients, - Characterized by large irregular changes in plasma ADH completely unrelated to serum osmolality. - Associated with both malignant and nonmalignant disease.

7 Types of Osmoregulatory Defects Type B: - Found in about 35% of patients - Associated with secretion of ADH that is excessive but proportionate to osmolality. - In these patients, the osmotic control of ADH secretion appears to be either set at a low level or abnormally sensitive to changes in serum osmolality.

8 Types of Osmoregulatory Defects Type C: - Found in 35% of patients, - Characterized by a high basal level of ADH that rises even higher with a rise in serum osmolality.

9 Types of Osmoregulatory Defects Type D: - Found in only 10% of patients, represents a different type of problem. - ADH is normally suppressed in hypovolemic states and rises normally with increase in osmolality. - Thus, the SIADH in these patients may be associated with a change in renal sensitivity to serum arginine vasopressin.

10 LÂM SÀNG SIADH là nguyên nhân thường gặp của hạ Na máu TCLS của hạ Na máu liên hệ đến TKTU TCLS sớm của hạ Natri máu là chán ăn, buồn ói, lơ mơ và vô cảm, Nặng hơn là mất định hướng, kích động,kinh giật,giảm PX,TC thiểu năng TKVĐ và đôi khi có nhịp thở Cheyne-Stocks Hôn mê và động kinh khi Na<120mEq/L Hạ Na máu mãn,Na>125mEq/L ít có TCLS Na<105mEq/L: ½ số BN sẽ chết TCLS ít liên quan với nồng độ Na, nhưng liên quan nhiều với tốc độ giảm Na máu

11 LÂM SÀNG Khi áp lực thẩm thấu HT trở lại bình thường TC sẽ đảo ngược Tuy nhiên, nếu điều trị quá nhanh có thể gây ly giải myelin vùng cầu của TKTU  liệt mềm, nói khó, nuốt khó



14 Treatment The treatment of SIADH depends upon the underlying cause. A patient with drug-induced SIADH is treated by withholding the drug. The treatment of SIADH in a patient with bronchogenic carcinoma is more complicated, however, and the prognosis is poor. Treatment aims to return plasma osmolality to normal without causing further expansion of the extracellular fluid compartment, as would occur following infusion of hyperosmotic solutions.

15 Treatment A. FLUID RESTRICTION The simplest form of treatment is fluid restriction, although in the long term the excessive thirst associated with this treatment may be difficult to manage

16 Treatment B. DIURETICS If plasma osmolality is low  loop diuretics such as furosemide can be employed. These agents limit free water generation in the loop of Henle and reduce the concentration gradient in the renal medulla Because diuresis is accompanied by significant urinary losses of potassium, calcium, and magnesium, these electrolytes should be replaced by intravenous infusion

17 Treatment C. OTHER METHODS Severe hyponatremia: hypertonic saline, ie, 3% saline IV 0.1 mL/kg/min. However  fluid overload may precipitate heart failure or circulatory collapse, and overly rapid correction may lead to central pontine myelinolysis. Drugs that reduce the effect of vasopressin on the kidney may be useful. - Demeclocycline, 1-2 g/d orally, causes a reversible form of nephrogenic diabetes insipidus. However, it is nephrotoxic, and renal function (blood urea nitrogen and serum creatinine) must be monitored carefully. - Lithium carbonate has a similar effect, but therapeutic doses are so close to the toxic dose that this drug is rarely useful

18 Tài liệu tham khảo 1. Nội tiết học đại cương – Mai Thế Trạch, Nguyễn Thy Khuê 2. Williams Textbook of Endocrinology, 11th 3. Basic & Clinical Endocrinology, 7th Edition


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