DI - Causes

Question 1

DI causes

Answer 1

Primary polydipsia

Central DI / Neurohypophyseal or neurogenic DI

Nephrogenic DI

Question 2

DX TEST:

Answer 2

_ Urine osmolality low: typically 2 liters per day.

Strong sign if >3 liters per 24 hours - Serum BUN Elevated in patients with volume depletion. normal or elevated - Serum glucose Order as baseline, and to exclude diabetes mellitus (DM) as a cause of polyuria.

However, it should be recognized that DM and DI (central or nephrogenic) can coexist, and that DM may be a risk factor for central DI.

Question 3

Primary polydipsia

Answer 3

• psychogenic polydipsia: primary increase in water intake middle-aged women w psychiatric illnesses- including those taking a phenothiazine
• Could be hypothalamic lesions - as may occur with an infiltrative disease such as sarcoidosis

Question 4

Central DI / Neurohypophyseal or neurogenic DI:

Answer 4

• deficient secretion of antidiuretic hormone (ADH).
• idiopathic / induced by trauma, pituitary surgery, or hypoxic or ischemic encephalopathy.
• Rare familial cases

Question 5

Nephrogenic DI

Answer 5

Nephrogenic DI — normal ADH secretion but renal resistance to its water-retaining effect / most patients who are elderly or who have underlying renal disease have a reduction in maximum concentrating ability.

Symptomatic polyuria due ADH-resistance is seen primarily in four settings

• Nephrogenic DI presenting in childhood is almost always due to inherited defects. The most common are X-linked hereditary nephrogenic DI due to mutations in the AVPR2 gene encoding the ADH receptor V2, and autosomal recessive and dominant nephrogenic DI due to mutations in the aquaporin-2 (water channel) gene.
• Nephrogenic DI presenting in adults is almost always acquired with chronic lithium use and hypercalcemia being the most common causes of a defect severe enough to produce polyuria.

Question 6

DI other tests

Answer 6

_ Water deprivation test Used to confirm DI. Patients are deprived of fluids for 8 hours or until 3% loss of their body weight is reached. Serum osmolality, urine volume and osmolality are measured hourly. If urine osmolality is less than the serum osmolality following dehydration, this confirms DI. urine osmolality < serum osmolality following _ AVP (desmopressin) stimulation test Desmopressin 2 micrograms subcutaneously, and serum osmolality, urine osmolality, and urine volumes are measured hourly over the next 4 hours. Central DI kidneys respond to desmopressin with a reduction in urine output and an increase in urine osmolality of >50%. Nephrogenic DI, there is a lack of response _ 3% hypertonic saline infusion test Used to differentiate partial central and nephrogenic DI and primary polydipsia. _Cranial CT/MRI (contrast enhanced) On T1-weighted images, the posterior pituitary may show up as a bright spot due to stored hormone in neurosecretory granules; these granules are present in 80% of normal subjects, but absent in nearly all patients with central DI. _ Serum TSH and free T4 Central DI is associated with polyendocrine autoimmune disorders, including Hashimoto thyroiditis. Patients with central DI are often at risk for secondary hypothyroidism, in which case TSH is normal or low, rather than high for primary hypothyroidism. Elevated TSH and low free T4 in Hashimoto thyroiditis _ Antithyroid peroxidase autoantibodies Should be considered if there is a clinical suspicion of hypothyroidism. Central DI is associated with polyendocrine autoimmune disorders, including Hashimoto thyroiditis positive in Hashimoto thyroiditis _ Genetic studies Central DI: the WFS1 gene or AVP-neurophysin gene Nephrogenic DI: mutation in AVP receptor AVP-V2 receptor MC