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Laboratory Investigations of neurohypophysis
المؤلف:
Marcello Ciaccio
المصدر:
Clinical and Laboratory Medicine Textbook 2021
الجزء والصفحة:
p329-330
2025-09-17
44
The key laboratory tests for diagnosing neurohypophysis disease are listed below.
24-Hour Urine Test
The 24-hour urinalysis assesses urine volume, osmolarity, and specific gravity. Polyuria is the production of a volume of urine >2.5 L/day. Normal values of urine osmolarity are 300–800 mOsm/L. The normal specific gravity of urine is 1005–1020 g/L.
Plasma ADH Assay
The values of the hormone must always be evaluated in relation to plasma and urinary osmolality because, in the normal subject, they change according to the state of hydration. In the presence of good hydration conditions, ADH values are between 1.5 and 6 pg/mL; with free fluid intake, they sup press the assay method’s sensitivity to the lower limit. The determination of ADH, however, is highly complex due to its low molecular weight (~1 kDa), its very short half-life (~20 minutes), and its binding to platelets (>90%). In addition, samples are affected by high centrifugation rates, and ADH levels are not very stable in vitro.
Plasma Osmolality Assessment
Normal plasma osmolality values are between 285 and 295 mOsm/L.
Water Deprivation Test
This test consists of water deprivation for an interval of 7–14 hours during which the patient’s water balance is continuously monitored (hourly) through regular measurements of body weight, plasma osmolality and/or natremia, urinary volume, and osmolality. The test is discontinued in the presence of a weight loss greater than 5% or when a plasma osmolality greater than or equal to 300 mOsm/L is reached. If fluid deprivation does not result in urine concentration by the end of the test, the patient has severe pituitary or nephrogenic DI. In such a case, to make a differential diagnosis, desmopressin is administered at the end of the water deprivation test, and urine osmolality measurement is repeated every hour for two hours; an increase (>300 mOsm/L) is indicative of severe pituitary DI, whereas the absence of change is strongly suggestive of nephrogenic DI (Table 1).
Table1. Water deprivation test
If the water deprivation test results in urine concentrations before plasma osmolality and/or natremia exceed the upper reference limits, in order to differentiate between primary polydipsia, partial pituitary DI, and partial nephrogenic DI, plasma ADH should be measured. Precisely, ADH concentration and plasma osmolality and/or natremia are measured, and fluid deprivation is continued while hypertonic saline (3% sodium chloride) is infused at a rate of 0.05 mL/kg/min. During the infusion, plasma osmolality and/or natremia are measured every 30 minutes; when the values rise above the normal limit, usually 60–90 minutes after the infusion, the ADH assay is performed, and the test is terminated. The results are interpreted using a nomogram depicting the relationship between plasma ADH values and plasma osmolality and/or natremia or urinary osmolality. This method differentiates between primary polydipsia, partial pituitary DI, and partial nephrogenic DI.
MRI of the Hypothalamic-Pituitary Region
MRI of the hypothalamic-pituitary region is an emerging approach that eliminates the need for water deprivation and provides a more straightforward but equally reliable way to differentiate the three major types of DI, regardless of the severity of the underlying defect. In most healthy adults and children, the posterior pituitary gland emits a hyperintense signal in T1-weighted mid-sagittal images. This bright spot is almost always present in primary polydipsia, but it is always absent or reduced in pituitary and nephrogenic DI. Thus, according to this method, the three types of DI can be differentiated in two steps. First, an assay of plasma ADH levels and determination of urinary osmolality without the restriction of fluid intake is performed; if plasma ADH levels are normal or high (>2 pg/mL) and urinary osmolality is low (<300 mOsm/L), the patient has nephrogenic DI. If ADH levels are low or undetectable (<1 pg/mL) and urinary osmolality is also low, an MRI of the brain may differentiate between pituitary DI (no or small T1 signal) or primary polydipsia (normal or enlarged T1 signal). In addition, MRI may also indicate the etiology of both forms of DI.
Copeptin
Another proposed method to the differential DI diagnosis is the measurement of copeptin. This glycoprotein originates from the pre-pro-hormone pre-provasopressin, consisting of ADH, neurophysin II, and copeptin. Pre-provasopressin is synthesized mainly in the paraventricular neurons of the hypothalamus and, during axonal transport, undergoes cleavage followed by the release of the three molecules. The latter are stored in the secretory granules of the neurohypophysis, waiting to be secreted in response to pathophysiological stimuli. The biological function of copeptin is still unclear, although its importance in mediating the correct conformation of ADH has been hypothesized. Copeptin and ADH are secreted in equimolar amounts. However, copeptin, compared to ADH, has a longer half-life, and greater pre- analytical stability, resulting in superior analytical accuracy, precision, and simplicity. The biological sample can be stored for at least 7 days at room temperature and up to 14 days at 4 °C. The assay is performed by immunometric technique. The reference values of copeptin in the general population are 1–14 pmol/L.
Finally, another way to distinguish between the three main types of DI is to closely monitor the effects of antidiuretic therapy on changes in water balance.
Once the diagnosis of the neurohypophysial disease has been made, instrumental investigations can be helpful to identify the underlying cause. MRI can detect tumors, infections, hemorrhages, infarcts, and hydrocephalus. In case of SIADH suspicion, a chest X-ray may reveal any lesions.
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