3. Case Scenario 1.
Twenty two years old university student presents
with 3 months history of excessive thirst. She
consumes about 20-25 glasses of water in a day and
wakes up 5-6 times at night to pass urine and drink
water. She is constipated but her appetite is
normal and she has not lost weight. Her wedding
is scheduled in two months and she is quite
apprehensive about it.
What is differential diagnosis?
6. Diabetes Inspidus
Defined as the passage of large volumes (>3 L/24 hr) of
dilute urine (< 300 mOsm/kg).
Central (neurogenic, pituitary) DI, results from
decreased secretion of antidiuretic hormone ADH
Nephrogenic DI, occurs due to decreased ability to
concentrate urine because of resistance to ADH action
in the kidney
7. Central Diabetes Inspidus (CDI)
Results from any condition that impairs the
synthesis, transport, or release of antidiuretic
hormone (ADH), also known as arginine
vasopressin (AVP).
ADH deficiency may be complete or partial.
8.
9.
10. Vasopressin
Vasopressin normally controls the expression and cell
surface targeting of the apical water channel aquaporin-2
(AQP2) in connecting tubules(CNT) and Connecting ducts
(CD).
The CNT and CD are also the site of amiloride-sensitive
sodium reabsorption via the epithelial sodium channel
(ENaC).
Both AQP2 and ENaC are regulated by vasopressin via V2-
receptor-dependent cAMP production.
Exogenous application of vasopressin efficiently corrects
the reduced AQP2 expression and the urinary
concentration defect in central DI.
11. Diabetes Inspidus
Lack of water reabsorption in the collecting ducts of the
kidneys due to decreased secretion of ADH results in
polyuria.
The urine output can range from 3 L/day in mild partial DI
to over 15 L/day in patients with severe disease.
CDI worsen or first diagnosed during pregnancy since
vasopressinases released from placenta increase ADH
catabolism.
12. Etiology
Idiopathic DI (most common)
Brain trauma
Primary or metastatic brain tumors
Infiltrative diseases
Neurosurgery
Hypoxic or ischemic encephalopathy
Familial DI
Radiation to the brain
Infection such as meningitis or encephalitis
Cerebral edema
Intracranial hemorrhage
13. Etiology
Wolfram syndrome (or DIDMOAD syndrome):
An autosomal recessive disorder with incomplete
penetrance.
DI: Diabetes Inspidus
DM: Diabetes Mellitus
OA: Optic atrophy
D: Deafness.
CDI is due to loss of ADH-secreting neurons in the
hypothalamus and impaired processing of ADH
precursors.
14. Symptoms
Polyuria and Polydipsia.
Urine output of over 3 L/day in adults.
D/D Nocturia/Frequency of micturition,
(Not associated with an increase in total urine output).
The onset of polyuria is usually abrupt in CDI but always
gradual in Nephrogenic DI and Primary or Psychogenic
Polydipsia.
15. Symptoms
Nocturia is often the first sign of CDI.
Urine mostly gets concentrated in the morning due to lack
of fluid ingestion overnight.
Lack of ADH and resulting loss of concentrating ability
results in NOCTURIA.
A relatively dilute urine is excreted, with a urine osmolality
of less than 200 mOsmol/kg.
Dry skin and constipation are other symptoms that may
occur in CDI.
16. Laboratory
Mild Hypernatremia (> 142 mEq/L).
Plasma Osmolality >290 m osm/kg
(Normal 280-295 mOsm/kg).
Why?
Initial loss of water results in concurrent
stimulation of thirst, which minimizes the
degree of net water loss.
17. Diagnosis
Water Deprivation Test:
Helps differentiating central DI from nephrogenic DI
and primary polydipsia.
Water restriction should raise the plasma osmolality
and stimulate ADH secretion and result in concentrated
urine and an increased urinary osmolality to more than
1000-1200 m osmol/L in normal individuals.
Giving exogenous ADH does not raise urinary osmolality
any further.
18. Diagnosis
Stimulation of thirst does not occur, however, when CDI is
due to a central lesion that impairs thirst causing
hypodipsia or adipsia.
In such cases, the plasma sodium concentration can exceed
160 meq/L and the plasma osmolality will rise significantly
also.
This also occurs if a patient has no access to water.
Withholding water in patients with CDI can result in
severe dehydration.
19. Water Restriction Test
Method:
Water restriction lasts 4 to 18 hours.
Overnight fluid restriction should be avoided, as severe
volume depletion and hypernatremia can be induced in
patients with severe polyuria.
Measure the urine volume and osmolality every hour
and serum sodium concentration and osmolality every
two hours.
20. Water Restriction Test
The test should be continued until one of the following
occurs:
The urine osmolality reaches above 600 mOsm/kg, indicating that
both ADH release and effect are intact.
The urine osmolality is stable on 2 or 3 successive measurements
despite a rising plasma osmolality.
The plasma osmolality exceeds 295 to 300 mOsm/kg.
Exogenous ADH is administered (10 microgm of dDAVP nasally or 4
microgm sq).
Urine osmolality is then measured every 30 minutes for the next 3
hours.
21. Water Restriction Test
In patients with complete CDI:
Plasma osmolality is increased but urine osmolality
remains below 290 mOsm/kg and does not increase.
Urine osmolality will increase by approximately 200
mOsm/kg in response to exogenous ADH.
In patients with partial CDI:
Urine osmolality will increase somewhat to 400 to 500
mOsm/kg during water deprivation, but is still well
below that of normal people.
Urine osmolality will increase by approximately 200
mOsm/kg in response to exogenous ADH.
22. Water Restriction Tests
Interpretation:
Normal subjects and primary polydipsia:
Urine osms are greater than plasma Osms after water restriction.
Urine osms increase minimally (<10%) after exogenous ADH.
Central Diabetes Insipidus:
Urine osms remain less than plasma osms after water restriction.
After ADH is given, urine osms increase 100% in complete CDI
and over 50% in partial CDI.
Nephrogenic Diabetes Insipidus:
Urine osms remain less than plasma osms.
After ADH, urine osms increase by less than 50%.
23. Treatment
Fluid Replacement is most important.
Encourage oral water intake
IV Fluids such as D5W if the patient is unable to take fluids
by mouth.
Why not 0.9% Normal Saline?
Why not IV Sterile water?
24. Treatment.
Desmopressin is the drug of choice for long-term therapy
of CDI to control polyuria.
Available in subcutaneous, IV, intranasal, and oral
preparations. Generally, it can be administered 2-3 times
per day.
It is safe during pregnancy for both the mother and the
fetus.
25. Monitoring & Follow up
Monitor for fluid retention and hyponatremia during
initial therapy.
Keep record of volume of water intake and the
frequency and volume of urination, and inquire about
thirst
Monitor serum sodium, 24-hour urinary volumes, and
specific gravity.
Follow-up visits with the patient every 6-12 months
27. Antidiuretic effect of Diuretics
Thiazide diuretics inhibit the NaCl co-transporter
(NCC/TSC) in the renal distal convoluted tubule (DCT).
The DCT is water impermeable and considered to be part
of the diluting segment
28. Antidiuretic effect of Diuretics
The antidiuretic action of thiazides is secondary to
increased renal sodium excretion. The renal sodium
loss causes extracellular volume contraction leading to
lowered GFR and increased proximal tubular sodium
and water reabsorption. Hence, less water and solutes
are delivered to the distal tubule and collecting duct
and are lost as urine.
30. o Mr. A 54 years old man underwent transsphenoidal
surgery, following a history of tonic-clonic seizures
and a diagnosis of pituitary tumor.
o 6 month later he reported to his GP C/O of fatigue,
lethargy, decreased exercise capacity, dry skin,
decreased sweating, depressive mood, impaired social
function and low self-esteem
o A diagnosis of Depression was made and SNRI were
started.
31. Case Scenario:2 ………contd
Three months later he reported decreased libido,
impotence and decreased body hair .
Next one year he complained of cold intolerance, dry
skin, mental dullness, constipation, hoarseness.
In next few months he developed weakness, nausea,
vomiting, anorexia, weight loss, low grade fever,
postural hypotension, frequent hypoglycemic spells,
and noticed fairness of his complexion.
32. Physical Examination
Slightly overweight fine, pale, and smooth skin with
fine wrinkling on the face deficient or absent body and
pubic hair,
Atrophy of genitalia decreased muscle strength,
Postural hypotension,
Bradycardia,
Delayed deep tendon reflexes
36. Etiology
• Head injuries
• Brain tumor
• Brain surgery
• Radiation treatment
• Autoimmune inflammation (hypophysitis)
• Stroke
• Infections of the brain, such as meningitis
• Tuberculosis
37. Signs and Symptoms
Hypopituitarism is often
progressive. Although the signs
and symptoms can occur
suddenly, usually they tend to
develop gradually. They are
sometimes vague and subtle
and may be overlooked for
many months or even years.
38. Signs & Symptoms
• Depend on which pituitary hormones are
deficient.
• Fatigue
• Headaches
• Low tolerance for stress
• Muscle weakness
• Nausea
• Constipation
• Weight loss or gain
• A decline in appetite
39. Symptoms
• Abdominal discomfort
• Sensitivity to cold or difficulty staying warm
• Visual disturbances
• Loss of underarm and pubic hair
• Joint stiffness
• Hoarseness
• Facial puffiness
• Thirst and excess urination
• Low blood pressure
• Lightheadedness when standing
40.
41. DEPEND ON HORMONES LOST
1. Lack of FSH LH :
1. Hypogonadim: amenorrhea
2. Lack of TSH: hypothyroidism
3. Lack of ACTH: adrenocortical insufficiency
4. Prolactin deficiency: FAILURE OF POSTPARTUM LACTATION
5. If all of the above: PANHYPOPITUITARISM
6. In children: GH: short stature
44. 1. Remove cause
2. REPLACEMENT THERAPY; depends on hormone lost
3. THYROXINE in 2° hypothyroidism
4. Hydrocortisone for 2° hypoadrenalism
20 mg at AM
10 mg at PM
5. Growth hormone : for children
6. Testosterone: monthly injections
7. Estrogen + progesterone
8. For induction of ovulation FSH + LH
45. Follow up
Mr. A is currently on
1. Thyroxine 200 microgram daily
2. Prednisolone 7.5 mg/day
Inj testosterone 250 mg IM every month
He also developed DM three years ago and is on Pre-
mix insulin.
He needs dose adjustments whenever he has URTI.
He is under follow up for past 12 years.
Last month he underwent laparoscopic
cholecystectomy under GA and is doing fine.
46. Case Scenario 3
A 30 years old lady reports failure to conceive after her
first childbirth that was 5 years ago.
Her mother in law reports heavy postpartum bleeding
after her previous delivery and that she did not have
lactation and her baby had to be started on formula
feed.
She also describes multiple episodes of fainting on
standing from sitting, has become isolated and
uninterested, lost 8 Kg of her weight, and has
amenorrhea since last child birth.
DIAGNOSIS??