Diabetes Insipidus

Question 1

DI

general

Answer 1

Condition in which the body is unable to control the balance of water → excretion of large volumes of dilute urine

Affects 1 in 25,000 people
Can affects people of any age, but is mostly seen in adults

Question 2

DI

Types

Answer 2

Types:
Central diabetes insipidus (CDI)
Nephrogenic diabetes insipidus (NDI)
Gestational diabetes insipidus
Dipsogenic diabetes insipidus (primary polydipsia)

Question 3

DI

Potential complications

Answer 3

Severe dehydration
Electrolyte imbalance

Question 4

ADH

normal functioning
Normal osmolality range

Answer 4

Osmoreceptors of the hypothalamus sense changes in osmolality of the blood (Normal: 275 to 295 mOsm/kg)

Osmolality
Concentration of dissolved particles
Major particles include: glucose, sodium, and blood urea nitrogen (BUN)

Increased plasma osmolality (due to dehydration)
Stimulate the sense of thirst
Stimulate the release ADH from the posterior pituitary
ADH acts on the distal tubule to reabsorb water → decrease plasma osmolality (concentrate urine)

Question 5

Question 6

Central Diabetes Insipidus

general

Answer 6

Also referred to as neurogenic diabetes insipidus
Characterized by a decreased production by the hypothalamus or decreased release of antidiuretic hormone (ADH) from the posterior pituitary resulting in a variable degree of polyuria

Question 7

Central Diabetes Insipidus

Causes

Answer 7

Causes:
Idiopathic 30-50%
Assumed to be caused by autoimmune damage to ADH-producing cells

Acquired
Cancerous or noncancerous tumors in the brain or pituitary gland
Head injury
Prior surgery (trans-sphenoidal) or radiation at or around the hypothalamus or pituitary gland
Infections: encephalitis or meningitis
Rare familial (autosomal dominant gene mutation) and congenital diseases

Question 8

Nephrogenic diabetes insipidus

general

Answer 8

Characterized by a decrease in urinary concentrating ability as a result of resistance to the action of ADH

Question 9

Nephrogenic diabetes insipidus

causes
Drug induced

Answer 9

Causes:
Hereditary (children)
X-linked inheritance for a mutation in the vasopressin V2 receptor gene
Mutation in the aquaporin-2 gene
Dysfunction of the aquaporin-2 water channel

Drug-induced
Often reversible
Chronic ingestion of lithium
Leads to dysfunction of the aquaporin-2 water channel

Acute or chronic kidney disease
Reduction in maximum renal concentrating ability due to fewer nephrons or damage to tubules
Examples: pyelonephritis, polycystic kidney disease, amyloidosis

Question 10

Gestational diabetes insipidus

general

Answer 10

Transient ADH resistance in the second half of pregnancy due to release of vasopressinase by the placenta (breaks down vasopressin)

Question 11

Dipsogenic Diabetes Insipidus

general

Answer 11

Also known as psychogenic polydipsia
Cause by drinking excessive amounts of water
Related to a psychologic problem (schizophrenia)
Causes a decreased blood osmolality and the hypothalamus decreases the release of ADH as a normal physiological response and the kidneys produce excessive amount of urine (polyuria)

Question 12

DI

Clin man

Answer 12

Polyuria
Degree of polyuria correlates with the degree of ADH deficiency or resistance
Defined as > 3 L urine output/day in adults (age-specific in children); Severe: 10-15 L/day
Nocturia → daytime sleepiness
Polydipsia (due to ↑ serum sodium and ↑ plasma osmolality)
Hypotension
Dehydration
Headache, dry mucous membranes, light-headed, muscle cramps, confusion, weakness

Question 13

DI

Neurologic symptoms relating to hypernatremia

Answer 13

Irritability
Seizures
Altered mental status → coma

Question 14

DI

volume of urine in 24hr for Dx

Answer 14

24-hour urine volume
> 3 L/day in adults
>2 L/day in children
Rule out DI if < 2 L/day in 24 hours in the absence of hypernatremia

Question 15

central DI ADH lab finding for Dx

Answer 15

↓ serum ADH levels

Question 16

DI

Serum sodium level

Answer 16

Hypernatremia – Either CDI or NDI
Hyponatremia - Dipsogenic diabetes insipidus (primary polydipsia)

Question 17

DI

plasma and urine osmolality values

Answer 17

Plasma osmolality
> 300 mOsm/kg implies CDI or NDI
≤ 280 mOsm/kg implies primarypolydipsia

Urineosmolality
< 300 mOsm/L suggests complete CDI or NDI

Question 18

Water deprivation test/ADH stimulation test

Answer 18

Water deprivation test/ADH stimulation test

Plasma and urine osmolality are measured before water restriction
No water intake for 2–3 hours
Hourly measurements ofplasma andurine osmolality after this interval
If there is no increase inurineosmolality, an ADH analog (desmopressin) is administered

Ifurine osmolalityincreases → CDI (= lack of central ADHsecretion)

Ifurine osmolality stays low → NDI (= defect inkidneys)

Question 19

Central DI

Tx

Answer 19

Central DI
Desmopressin (DDAVP) – 1st line
Synthetic form of ADH/vasopressin
Preferred medication for most patients
Given at the minimum dose to reduce nocturia; administered at bedtime

Risk for hyponatremia – nausea, vomiting, headache, lethargy, seizures, and coma

Question 20

Nephrogenic DI

Tx

Answer 20

Thiazide diuretics - hydrochlorothiazide (HCTZ)
↓ polyuria (↑ proximal tubule sodium and water reabsorption and less water delivered to the ADH-sensitive collecting tubules)

NSAID (indomethacin)
↑ renal concentration of urine by inhibiting renal synthesis of prostaglandins (ADH antagonists)

Question 21

DI

Fluid replacement

Answer 21

Thirst intact – replace water losses orally
Electrolyte abnormalities do not normalize through oral water intake:
IV dextrose and water <500 ml/hour with serum glucose monitoring
Risk for hyperglycemia

Question 22