Year 2: Neurohypophysial disorders

Question 1

What two types of diabetes inspipdus are there?

How do they differ?

Answer 1

Cranial (central) DI

• No adequate secretion of VP

Nephrogenic

• kidneys can’t response to secreted ADH

Question 2

What are possible causes of cranial Diabetes insipidus?

Answer 2

Most of the: aquired

Damage to the neurohyophysal system

• traumatic brain injury
• pituitary surgery
• pituitary tumors, metastisis spreading to pituitary
• Granulomatous infiltration of median eminence (i.e. inflammation)

Can be congenital (very rare)

Question 3

What are possible causes of nephrogenic diabetis inspidus?

Answer 3

Congenital causes

• rare e.g. mutation in V2 receptors or aquaporin channels

Aquired

• drugs (e.g. lithium used in treatment of depression etc.)

Question 4

What are the biochemical signs and symptoms of Diabetis inspidus?

Answer 4

Symptoms/Signs

• Polydipsia
• Polyuria
• Hypoosmolar urine
• Dehydration

Biochemical markers

• Hypernatraemia
• raised urea
  
  • –> Both signs for dehydration
• High plasma osmolarity

Question 5

Which tests would you do with someone you suspect to have diabetis insipidus?

Answer 5

Next to biochemical markers (HIgh NA+. high plasma osmolarity, high urea)

Water deprivation test

• Deprive people from water and regularly measure urine production, concentration, plasma osmolality, and body weight
• In the end: Administer ADH analogue (DDAVP)
• When loosind >3% of body weight : end of test (dehydreation)

Findings:

• When water deprived: DI patients no concentration of urine, in other patients (normal, psychogenic polydipsia) urine will be concentrated
• Administering DDAVP: nephrogenic and cranial can be differentiated

Question 6

What is psychogenic polydipsia?

What are the consequences?

Answer 6

• Seen in psychiatric patients (might be due to anti-cholinergic drugs causing dry mouth)
• People who are told to “drink plenty”

–> Nothing wrong with body function, people just drink to much (–> pee a lot)

Leading to:

• Low plasma osmololity
• Low NA+
• Dilute urine

Question 7

Which conditions could you suspect when a patient comes to you with polyuria and polydipsia?

What are the differential diagnosis

Answer 7

1. Most common: Diabetis Mellitus
   
   • rule out by test, glucose etc
2. If not DM:
   
   • Diabetis insipidus
   • Psychogenic polydipsia

Question 8

How could you treat cranial Diabetis inspipdus?

What is important after treatment?

Answer 8

Selective V2 agonst: Desmopressin (DDAVP) (ADH analogue)

• nasal administration (majority) (–> might be considered less important medication in hospital –> easity forgotton –> might cause death)
• Can also be orally or subcutaneous

Important:

• Tell patients to not drink that much anymore! Otherwise risk of hyponatraemia!

Question 9

How could you treat nephrogenic diabetis inspidus?

Answer 9

Rhiazide diuretics

–> noone knows how and why this works

Possible mechanism:

High plasma osmolarity

Question 10

How do you call a disease that casues too much ADH secretion?

What is its definition/characteristic?

Answer 10

Syndrome of Inappropriate ADH (SIADH)

the plasma vasopressin concentration is inappropriately high for the existing plasma osmolality

Question 11

What are the symptoms and characteristics of SIADH?

Answer 11

• •can be symptomless
• •however if p[Na+] <120 mM: generalised weakness, poor mental function, nausea –> Na+ essential to maintain depolerisation etc. in neurones
• •if p[Na+] <110 mM: CONFUSION leading to COMA and ultimately DEATH

Biochemical characteristics:

• Hyerosmolar urine
• Hypoosmolar plasma
• Hyponatraemia

Question 12

What are causes of SIADH?

Answer 12

CNS causes:

• stroke, tumor, trauma, sub-arrachnoid haemorrhage

Pulmonary disease

• Pneumonia, bronchiectasis

Malignancy

• ectopic ADH e.g. by small cell lung carcinoma

Drug-related

• Carbamazepine (seizure control) , SSRI (Selective Serotonin Reuptake Inhibitor)

Ideopathic

Question 13

How would you treat SIADH?

Answer 13

1. Appropriate treatment (e.g. surgery for tumour)
2. To reduce immediate concern, i.e. hyponatraemia
3. Immediate: fluid restriction
4. Longer-term: use drugs which prevent vasopressin action in kidneys
   
   • e.g. induce nephrogenic DI ie reduce renal water reabsorption - demeclocyline

• inhibit action of ADH - V2 receptor antagonists (VAPTANS)

Question 14

Explain the use of Vaptans in SIADH

Answer 14

Non-competitive V2 antagonist

• inhibts AQP2 production and transport
• causing aquaresis: electrolyte sparing diuretic (only water)

–> very expensive is limiting current use

Question 15

Which test should you always perform after diagnosing a patient with Diabetis insipidus?

Why?

Answer 15

Always perform imaging:

About 1/2 of cases: metastasis of systemic tumor spreading to neurohypophysis)

to rule out cancer cause