1. Posterior pituitary hormones: The posterior pituitary hormones, vasopressin (ADH) and oxytocin. These hormones are synthesized in the hypothalamus and pass down nerve axons in to the circulation.oxytocin is involved in thecontrol of uterine contractility and of milk release from the lactating breast. Diorders of its secretion are probably uncommon and are not clinically important. in contrast, vasopressin is essential to life and disorders of its secretion are well recognized.

2. Vasopressin Has a vital role in the control of the tonicity of the extracellular fluid, and hence indirectly of the intracellular fluid, and water balance. Excessive secretion results in dilutional hypernatremia, with risk of water intoxication, decreased secretion result in diabetes insipidus, a condition in which there is uncontrolled excretion of water with a tendency to severe dehydration. The syndromes of excessive secretion of vasopressin are discussed on p 25, they are frequently seen in conditions which do not affect the pituitary directly, diabetes insipidus, on other hand is usually due to pituitary or hypothalamic disease, fig 7.11.

4. Although it can also be due to a failure of the kidney to respond to the vasopressin (nephrogenic diabetes insipidus). IN diabetes insipidus, the lack of vasopressin result in polyuria and thirst.Unless the hypothalamic thirst center is damaged, thirst leads to increased fluid intake (polydipsia) the differential diagnosis includes other conditions causing polyuria and polydipsia. For example diabetes mellitus, chronic renal failure, hypocalcaemia, and hypokalemia. Simple tests will eliminate these possibilities. Children with diabetes insipidus may present with enuresis.

5. Compulsive desire to drink (psychogenic or primary polydipsia) also causes polyuria. However, in this case polyuria is secondary to increased fluid intake, while in D.I the opposite applies, polydipsia being a response to polyuria. In both conditions the urine is dilute. If a random urine osmolality is greater than 750 mmol/kg, D.I is excluded. Plasma sodium concentration and osmolality are usually normal in both conditions although they may be high-normal in D.I (and frankly elevated if patients are denied water) and low- normal in primary polydipsia.

6. IF THERE IS ANY DOUBT ABOUT THE DIAGNOSIS, A FLUID DEPRIVATION TEST SHOULD BE PERFORMED. This is effectively abiological assay for vasopressin. Patients with D.I may become dangerously dehydrated if denied access to fluid they may also exercise considerable ingenuity to abtain fluid. Close supervision is therefore required and the test must always be performed by day not overnight.

7. In normal subject, the urine becomes concentrated in response to fluid deprivation and plasma osmolality does not exceed (295mmol/kg). in D,I. the urine does not become concentrated and plasma osmolality rises.in patients who are water over loaded before the test is started, the urine become concentrated, plasma osmolality is usually low and may remain so since vasopressin secretion is only stimulated if it rises above (285mmol/kg) thus urine becomes concentrated only if the plasma osmolality exceeds this level.

8. At the end of the eight-hour period, the patient is allowed to drink the water and is given (1-desamino-D- arginine –vasopressin) desmopressin, Asynthetic analogue of vasopressin. In cranial diabetes insipidus the urine should become concentrated; in patient whose kidneys are insensitive to vasopressin (nephrogenic diabetes insipidus) it remains dilute. If the water deprivation test is to be carried out on a patient with anterior pituitary disease, adequate cortisol replacement must be provided.

9. If the results of a fluid deprivation test are equivocal, the plasma vasopressin response to hypertonic saline infusion should be assessed. The response is normal in patients with nephrogenic diabetes insipidus or primary polydipsia, but decreased in patients with cranial diabetes insipidus. The former two conditions can be distinguished by comparing plasma vasopressin concentration with urine osmolality after a period of fluid deprivation (Fig. 7.14).

10. In nephrogenic diabetes insipidus, plasma vasopressin is much higher than normal. Alternatively, since vasopressin measurements are not widely available, a closely supervised therapeutic trial of desmopressin treatment can be used. This causes an improvement in cranial diabetes insipidus, has no effect in the nephrogenic type and causes increasing hyponatraemia in primary polydipsia. An algorithm for the investigation polyuria is given in Fig. 7.15.

11. Fluid deprivation test Procedure Allow fluids overnight before test and give light breakfast with no fluid; no smoking permitted Weigh patient Allow no fluid for 8 h.; patient must be under constant supervision during this time Every 2h: Weigh patient (Stop test if weight falls by >5% initial body weight*) Patient empties bladder: measure urine volume and osmolality Measure plasma osmolality ( stop test if osmolality >300 mmol/Kg*) After 8h allow patient to drink and give 20 g desmopressin intranasally Measure urine osmolality every 4h for a further 16h *end-point diagnostic of diabetes insipidus; allow access to fluid and assess response to desmopressin Interpretation of results: see Fig. 7.15. Fig. 7.14