Clinical Significance Of Diseases Of the Posterior Pituitary: Diabetes Insipidus
Diabetes Insipidus Manifestation
Normally, antidiuretic hormone (ADH) is secreted in response to physiological stimuli such as osmolality, hypovolemia, hypotension, and psychological stress. This hormone (ADH) plays a great role in maintaining serum osmolality within a narrow range. Failure of secretion of ADH from the supraoptic nucleus leads to the development of central diabetes insipidus. The clinical abnormality becomes evident when about 99% of the neurons in this region are lost. This may result from the destruction of these cells by secondary neoplasms from breast, lung, thyroid or malignant melanoma, infiltrative disorders like sarcoidosis, leukemia and histocytosis, infections such as tuberculosis and syphilis, brain injury and irradiation of the skull. Rarely ADH secreting cells may be absent congenitally.
Increased Thirst In Diabetes Insipidus
Polyuria In Diabetes Insipidus
Diabetes insipidus presents with gross polyuria, thirst and polydipsia. The urine volume may vary from 2.5 to 10 liters in 24 hours. Majority of these patients have normal thirst mechanisms and they make up the fluid loss by taking in adequate quantity of water and salt and thus prevent the development of dehydration and hyponatremia. When the free intake of water and salt is diminished as in coma or due to other causes, severe dehydration and hypovolemia develop. In moderately severe cases, the osmolality of urine ranges from 40 to 600 mosm/Kg. In well compensated patients, apart from the history and the gross polyuria with dilute urine (specific gravity around 1004), no other abnormality may be evident. In those subjects in whom the disease is secondary to other disease processes, the primary abnormality may be evident.
Diabetes insipidus should be diagnosed by the history and the presence of polyuria with low specific gravity of urine. The urine volume does not fall and the specific gravity does not rise with fluid deprivation. Since fluid restriction may be hazardous in these subjects, it has to be done only under close supervision. Other conditions producing polyuria with low specific gravity of the urine such as nephrogenic diabetes insipidus and psychogenic polydipsia have to be differentiated.
Nephrogenic diabetes insipidus
The renal tubules are refractory to the action of normal levels of circulating ADH. This may be congenital as in primary nephrogenic diabetes insipidus or secondary to diseases such as chronic renal failure, diabetes mellitus, hypercalcemia, hypokalemia and sickle cell anemia.
Also know as psychogenic polydipsia involves compulsory water drinking in its complex psychiatric disturbances in which the patient drinks large amounts of water. The disorder may show remission and exacerbation.
Central diabetes insipidus can be distinguished from nephrogenic diabetes insipidus and primary polydipsia by simple laboratory tests.
- Measurement of 24-hour urine volume: If the urine volume is less than 2 liters, diabetes insipidus is unlikely. It is to be remembered that mild cases may present with lower urine volumes, but in times of stress such as diarrhea or excessive sweating, hypovolumic shock and hyponatremia ensues.
- If the osmolality of early morning urine exceeds 800 mosm/Kg, it almost rules out diabetes insipidus.
- Water deprivation test and vasopressin administration: Fluid deprivation for 6 to 18 hours is done under medical supervision. Since this is hazardous, it should not be continued if the body weight falls by 5% or 2 Kg. Urine osmolality is measured hourly till steady values are obtained in three consecutive samples. Then 5 units of aqueous vasopressin is given parenterally. Osmolality of plasma and urine is determined hourly for further three hours. In central diabetes insipidus, urine osmolality increases by 50% whereas in parents with nephrogenic diabetes insipidus the rise is less than 10%. Patients with psychogenic polydipsia require longer periods of fluid deprivation for obtaining steady urine osmolality, since they tend to be fluid overloaded. Fluid deprivation results in rise of urine osmolality.
X-ray of the skull is a rewarding procedure in many cases of diabetes insipidus, since destructive lesions such as secondaries, calcified areas or bony defects as in histiocytosis may be evident.
Dehydration In Diabetes Insipidus
Cases with moderate or severe disease require specific therapy.
Vasopressin analogues: Though vasopressin was used originally, at present the synthetic analogue DDAVP (desmopressin) is used. It is given as nasal spray or instillation. It has a duration of action for 12 to 14 hours and many cases require only one or two doses daily. Morever, DDAVP is devoid of the pressor activity. It is absorbed even in the presence of nasal congestion. Parenteral preparations are available for use in more severe cases or in emergencies.
Agents probably potentiating endogenous ADH: Drugs like chlorpropamide (250 to 500 mg/day), clofibrate and carbamazepine bring about reduction in urine volume in mild and moderate cases.
Thiazide diuretics are effective in bringing down urine volume but the mechanism of action is different. These drugs, being cheaper and more easily available, may be tried and the dosage adjusted to maintain clinical normalcy.
The prognosis of diabetes insipidus depends upon the primary causes. As such, diabetes insipidus does not shorten life expectancy, if it is identified and promptly managed.
© 2014 Funom Theophilus Makama