diabetes insipidius

1. Farhad Hussain
3/1/2018

2. Definition:
Is due to insufficient ADH activity at the kidneys, and results in the
excessive renal loss of water and electrolytes.

3.  Central or neurogenic DI:
 subnormal levels of ADH caused by hypothalamic-pituitary axis
dysfunction.
 This is the type most often seen by neurosurgeons
 Nephrogenic DI:
 due to relative resistance of the kidney to normal or supra-
normal levels of ADH. Seen with some drugs.

4. a) familial (autosomal dominant)
b) idiopathic
c) postt raumatic (brain injury, including surgery)
d) tumor: craniopharyngioma, metastasis, lymphoma…
e) granuloma: neurosarcoidosis, histiocytosis
f) infectious: meningitis, encephalitis
g) autoimmune
h) vascular: aneurysm, Sheehan’s syndrome (rarely causes DI)

5. a) familial (X-linked recessive)
b) hypokalemia
c) hypercalcemia
d) Sjögren’s syndrome
e) drugs: lithium, demeclocycline, colchicine…
f) chronic renal disease: pyelonephritis, amyloidosis, sickle cell
disease, polycystic kidney disease, sarcoidosis

6.  85% of ADH secretory capacity must be lost before clinical DI
ensues.
Characteristic features:
 High urine output (polyuria) with low urine osmolality, and
(in the conscious patient) craving for water (polydipsia).

7. 1. (neurogenic) diabetes insipidus (true DI)
2. nephrogenic diabetes insipidus
3. psychogenic
a) idiopathic: from resetting of the osmostat
b) psychogenic polydipsia (excess free water intake)
4. osmotic diuresis: e.g. following mannitol, or with renal glucose
spilling
5. diuretic use: furosemide, hydrochlorothiazide.

8. Central DI may be seen in the following situations:
1. following transsphenoidal surgery or removal of
craniopharyngioma:
Patterns:
a) transient DI: supra-normal urine output (UO) and polydipsia which
typically normalizes ≈12–36 hrs post-op
b) “prolonged” DI: UO stays supra-normal for prolonged period (may
be months) or even permanently: only about one–third of these
patients will not return to near-normal at one year post-op

9. c) “triphasic response”: least common
phase 1: injury to pituitary reduces ADH levels for 4–5 days
→DI (polyuria/polydipsia)
phase 2: cell death liberates ADH for the next 4–5 days
→transient normalization or even SIADH-like water retention
phase 3: reduced or absent ADH secretion →either transient
DI (as in “A” above) or a “prolonged”DI (as in “B” above)

10. 2. central herniation : shearing of pituitary stalk may occur
3. brain death: hypothalamic product ion of ADH ceases
4. with certain tumors:
a) pituitary adenomas
b) craniopharyngioma
c) suprasellar germ cell tumors
d) rarely with a colloid cyst
e) hypothalamic tumors: Langerhans cell histiocytosis

11. 5. mass lesions pressing on hypothalamus: e.g. a-comm aneurysm
6. following head injury: primarily with basal (clival) skull fractures
7. with encephalitis or meningitis
8. drug induced:
a) ethanol and phenytoin can inhibit ADH release
b) exogenous steroids may seem to “bring out” DI because they
may correct adrenal insufficiency (below) and they inhibit ADH
release
9. granulomatous diseases

12. The following are usually adequate to make the diagnosis of DI,
especially in the appropriate clinical setting:
1. dilute urine:
a) urine osmolality <200 mOsm/L (usually 50–150) or specific gravity (SG) <1.003
b) or the inability to concentrate urine to >300 mOsm/L in the presence of clinical
dehydration
c) NB: large doses of mannitol as may be used in head trauma can mask this by
producing a more concentrated urine
2. urine output (UO) >250 cc/hr (peds: >3 cc/kg/hr)
3. normal or above-normal serum sodium

13. 4. normal adrenal function: DI cannot occur in primary adrenal
insufficiency because a minimum of mineralocorticoid activity is
needed for the kidney to make free water, thus steroids may“bring
out” underlying DI by correcting adrenal insufficiency

14.  the diagnosis of DI is confirmed by a water deprivation test
CAUTION: perform only under close supervision as rapid and
potentially fatal dehydration may ensue in DI).
 This test is rarely necessary if serum osmolality >298 mOsm/L

15. Stop IVs and make the patient NPO
 Monitoring:
 check urine osmolality q hr
 check patient weight q 1 hr
continue the test until one of the following occurs:
 normal response occurs: urine output decreases, and urine
osmolality rises to 600–850 mOsm/L
 6–8 hours lapse
 urine osmolality plateaus (i.e. changes <30 mOsm in 3
consecutive hours)
 patient loses 3% of body weight

16. if the patient fails to demonstrate the normal response, then:
 give exogenous ADH (5 U aqueous Pitressin® SQ), which normally
increases urine osmolality to >300 mOsm/L
 check urine osmolality 30 and 60 minutes later
 compare highest urine osmolality after Pitressin® to the
osmolality just before Pitressin

18. In conscious ambulatory patient
 If DI is mild, and the patient’s natural thirst mechanism is intact,
instruct patient to drink only when thirsty and they usually “keep
up” with losses and will not become overhydrated.
 If severe, the patient may not be able to maintain adequate intake
of fluid or tolerate the frequent trips to bathroom. In these cases,
treatment typically involves a vasopressin analogue. Start with
either:

19. 1. desmopressin (DDAVP®)
a) PO: 0.1 mg PO BID, adjust up or down PRN urine output
(typical dosage range: 0.1–0.8 mg/d in divided doses)
b) nasal spray: 2.5 mcg (0.025 ml) by nasal insu ation BID, titrate
up to 20 mcg BID as needed (the nasal spray may be used for
doses that are multiples of 10 mcg)

20. 2. ADH enhancing medications (works primarily in chronic partial
ADH deficiency. Will not work in total absence of ADH)
 chlorpropramide: increases renal sensitivity to ADH
 hydrochlorothiazide: thiazide diuretics may act by depleting
Na+ which increases reabsorption in proximal tubules and
shifting fluid away from distal tubules which is where ADH
works. e.g. Dyazide® 1 PO q d (may increase up to 2 per day
PRN)

21. In conscious ambulatory patient with impaired thirst mechanisms
 If thirst mechanisms are not in tact in conscious ambulatory
patient, they run the risk of dehydration or fluid overload. For
these patients:
1. have patient follow UO and daily weights, balance fluid intake and
output using antidiuretic medication as needed to keep UO
reasonable
2. check serial labs (approximately q weekly) including serum sodium,
BUN

22. In non -ambulatory, comatose/stuporous, or brain -dead patient;
1. follow I’s & O’s q 1 hr, with urine specific gravity (SG) q 4 hrs and
whenever urine output (UO) >250 ml/hr
2. labs: serum electrolytes with osmolality q 6 hrs

23. 3. IV fluid management:
 BASE IV: D5 1/2 NS + 20 mEq KCl/L at appropriate rate (75–100
ml/hr)
 PLUS: replace UO above base IV rate ml for ml with 1/2 NS
 NB: for post-op patients, if the patient received significant
intraoperative fluids, then they may
 have an appropriate post-op diuresis, in this case use 1/2 NS to
replace only ≈ 2/3 of UO that
 exceeds the basal IV rate

24. 4. if unable to keep up with fluid loss with IV (or NG) replacement
(usually with UO>300 ml/hr),
 then EITHER
 5 U arginine vasopressin (aqueous Pitressin®) IVP/IM/SQ q 4–6
hrs (avoid tannate oil suspension due to erratic absorption and
variable duration)
OR
 vasopressin IV drip: start at 0.2 U/min & titrate (max: 0.9 U/min)
OR
 desmopressin injection SQ/IV titrated to UO, usual adult dose:
0.5–1 ml (2–4 mcg) daily in 2 divided doses

25.  Due to low levels of ADH (or, rarely, renal insensitivity to ADH)
 High output of dilute urine (<200 mOsmol/L or SG<1.003) with
normal or high serum osmolality and high serum sodium often
accompanied by craving for water.
 Danger of severe dehydration if not managed carefully