Diabetes Insipidus
In the presence of frequent urination, enuresis (involuntary emission of urine), nocturia (repeated need to urinate during the night), and/or persistent thirst, a 24-hour urine test should be performed; if the volume is >50 cc/kg/day, corresponding to a volume of 2.5 L/day, the diagnosis of polyuria is established. After excluding the most common causes of polyuria (antidiuretic drugs and metabolic causes such as diabetes mellitus) through appropriate laboratory investigations, a baseline copeptin measurement or the water deprivation test is performed (Fig. 1). In the case of the water deprivation test, if fluid deprivation does not lead to urine concentration (urinary osmolality <300 mOsm/L), the patient has severe pituitary or nephrogenic DI; to make a differential diagnosis, desmopressin is administered. If fluid deprivation results in the production of concentrated urine, the patient may have partial pituitary DI, partial nephrogenic DI, or primary polydipsia; to make the differential diagnosis, plasma ADH is measured before and after infusion of hypertonic saline, evaluating its values in relation to plasma osmolality/natremia and urinary osmolality (Fig. 2).
Fig1. Diagnostic algorithm for the evaluation of polyuria. (Copyright EDISES 2021. Reproduced with permission)
Fig2. Algorithm for the differential diagnosis of diabetes insipidus by water deprivation test. Na + natremia, PO plasma osmolality, UO urinary osmolality, DI diabetes insipidus. (Copyright EDISES 2021. Reproduced with permission)
Figure 3 shows Timper’s algorithm for differential diagnosis of DI by determination of baseline copeptin levels and/or after fluid deprivation. It has been shown that copeptin determination makes water deprivation testing unnecessary in cases of nephrogenic DI, correctly identifying all patients with reduced or absent peripheral sensitivity to ADH. In contrast, an 8-hour (overnight) fluid deprivation resulting in a copeptin value <2.6 pmol/L is suggestive of complete central DI. Finally, a baseline copeptin value <21.4 pmol/L in the absence of water deprivation requires evaluation of the pep tide response to an osmotic stimulus that induces an increase in plasma sodium levels >147 mmol/L, such as infusion of 3% hypertonic saline; following the stimulus, copeptin values <4.9 pmol/L are suggestive of partial central DI; conversely, values ≥4.9 pmol/L indicate the presence of primary polydipsia. The algorithm proposed by Timper represents an evolution of the one proposed by Fenske (Fig. 4), which involves the calculation of the ratio of copeptin to serum sodium concentrations during an appropriate osmotic stimulus (fluid deprivation).
Fig3. Timper et al. algorithm for the differential diagnosis of diabetes insipidus by copeptin, in association or not with the liquids deprivation. (Copyright EDISES 2021. Reproduced with permission)
Fig4. Fenske et al. algorithm for the differential diagnosis of diabetes insipidus. (Copyright EDISES 2021. Reproduced with permission).
Alternatively, a differential diagnosis of diabetes insipidus can be made based on plasma ADH and MRI values without water restriction (Fig. 5).
Fig5. Algorithm for the differential diagnosis of diabetes insipidus by ADH and magnetic resonance imaging. (Copyright EDISES 2021. Reproduced with permission)
Signs and symptoms of uncomplicated pituitary DI can be treated with desmopressin, which selectively acts on ADH receptors, increasing the urine concentration and reducing urine f low dose-dependently. On the other hand, signs and symptoms of nephrogenic DI can be treated with a thiazide diuretic and/or amiloride in combination with a low-sodium diet.
Inappropriate ADH Secretion Syndrome
The diagnosis is made by exclusion, based on clinical history, laboratory data, and physical examination.
SIADH should be suspected in patients presenting with hypotonic hyponatremia associated with euvolemia, defined as the absence of clinical signs of hypovolemia (tachycardia, mucosal dryness) or hypervolemia (subcutaneous edema, ascites).
Table 1 shows the laboratory tests for the preliminary diagnosis of SIADH.
Table1. Laboratory parameters for SIADH diagnosis
Other laboratory tests helpful for SIADH diagnosis are:
• Inability to eliminate a water load with urine (healthy sub jects eliminate with urine more than 80% of the water load within 4 hours, with urinary osmolality <100 mOsm/L).
• Hypouricemia due to volume expansion and the action of ADH on renal ADH receptors that increases uric acid clearance. Recently, an algorithm based on assessing copeptin levels has been proposed to detect SIADH (Fig. 6).
Fig6. Algorithm for the differential diagnosis of hyponatremia based on copeptin. (Copyright EDISES 2021. Reproduced with permission)
Treatment of SIADH depends on the underlying cause. Hyponatremia is corrected by continuous infusion of hyper tonic saline (NaCl 3%), which may be combined with loop diuretics. If the cause removal is not possible or has been followed by resolution of the SIADH, permanent treatment is indicated. The treatment of the first choice is fluid restriction.
