Endocrinology 3- Neurohypophysial Disorders

Question 1

How does vasopressin increase water reabsorption?

Answer 1

• Binds to V2 receptor which results in aquaporin 2 synthesis
• Aquaporin 2 is inserted in the apical membrane, water travels in the cell.

Question 2

How is vasopressin release regulated?

Answer 2

• By osmoreceptors in the organum vasculosum (project to paraventricular nucleus and supraoptic nucleus
• Osmoreceptors shrink in hypertonic solution (as high Na+ conc in extracellular fluid has lower water potential). This stimulates osmoreceptor firing (PVN and SON)

Question 3

What is diabetes insipidus and what are the two types?

Answer 3

• Absense or lack of circulating vasopressin is cranial

- Kidney resistance is nephrogenic (very rare)

Question 4

List the causes of cranial diabetes insipidis

Answer 4

• Usually acquired
• Damage to the neurohypophysial system
• Traumatic brain inury
• Pituitary surgery
• Pituitary tumours
• Metastasis of pituitary gland
• Granulomatous infiltration of median eminence (TB or sarcoidosis)
• Can be congenital

Question 5

List the signs and symptoms of diabetes insipidus

Answer 5

• Polyurea (lots of wee)
• Urine very dilute - hypo-osmolar
• Thirst and increased drinking (polydipsia)
• Dehydration if fluid intake is not maintained - can lead to death
• Disruption of sleep

Question 6

What is psychogenic polydipsia?

Answer 6

• Seen in psychiatric patients
• Also called primary polydipsia
• Patients have excess fluid intake (polydipsia) and excess urine input (polyuria) but vasopressin is normal
• Patients told to drink plenty by healthcare professionals, and drugs cause a dry mouth

Question 7

List the biochemical features of diabetes insipidus

Answer 7

• Hypernatraemia
• Raised urea
• Increased plasma osmolality
• Low urine osmolality

Question 8

List the biochemical features of psychogenic polydipsia

Answer 8

• Mild hyponatraemia (excess water)
• Low plasma osmolality
• Dilute urine

Question 9

What are the selective vasopressin receptor agonists?

Answer 9

Terlipressin binds to V1 (blood vessels)

Desmopressin (DDAVP) binds to V2 (kidney)

(Vasopressin will bind to both so is useless)

Question 10

Describe the administration and effect of desmopressin

Answer 10

• Administered orally, nasally or subcutaneous
• Reduced urine volume and concentration in cranial diabetes insipidus
• Patients shouldn’t continue to drink large amounts of fluid (hyponatraemia)

Question 11

How are thiazides effective in treatment of nephrogenic diabetes insipidus?

Answer 11

• Inhibits Na+/CL- transport in distal convoluted tubule (diuretic)
• Volume depletion
• Compensatory increase in Na+ reabsorption from proximal tubule, and increased water reabsorption
• Decreased fluid reaches the collecting duct

Question 12

What is syndrome of innapropriate ADH?

Answer 12

• ADH levels are inappropriately high for the plasma osmolality
• Results in increased ECF volume, atrial natriuretic peptide production and as a result hyponatraemia

Question 13

List the signs of SIADH

Answer 13

• High urine osmolality
• Decreased urine volume
• Decreased sodium (hyponatraemia) mainly due to increased water reabsorption

Question 14

List the symptoms of SIADH

Answer 14

• Symptomless
• Sodium concentration below 120mM results in weakness, poor mental function and nausea
• Below 110mM confusion leading to coma and then death

Question 15

List the causes of SIDAH

Answer 15

• SAH, stroke, tumour or TBI
• Pulmonary diseases such as pneumonia
• Lung cancer (small cell)
• Can be drug related (carbemazepine, selective serotonin reuptake inhibitor)
• Can be idiopathic

Question 16

List the treatments of SIADH

Answer 16

• Immediately fluid restriction is used
• Treat the underlying cause (eg. surgery for a tumour)
• Longer term drugs that suppress vasopressin activity are used (demeclcyline or V2 receptor antagonists)

Question 17

What are vaptans?

Answer 17

• Non competitive V2 receptor antagonists
• Inhibit aquaporin 2 synthesis and transport and transport to the collecting duct apical membrane, preventing renal water reabsorption
• Aquaresis - renal excreton of water with no elecrolyte loss
• Very expensive drug

Question 18

How is the posterior pituitary seen on MRI?

Answer 18

As a bright spot

Question 19

Which hormones are produced by the posterior pituitary?

Answer 19

Vasopressin (ADH) and oxytocin

Question 20

List the causes of nephrogenic diabetes insipidus

Answer 20

• Congenital (mutation in gene encoding V2 or aquaporin type 2)
• Acquired (lithium)

Question 21

How can diabetes insipidus lead to death?

Answer 21

• Inadequate production/response to vasopressin
• Large volumes of hypotonic urine
• Increase in plasma osmolarity
• Reduction in EC fluid volume resulting in thirst (polydipsia)
• Drinking results in increase in EC fluid volume
• However, if a patient has undiagnosed diabetes insipidus has no access to water (eg. if they had a stroke and couldn’t drink) then they will die.

Question 22

How is diabetes insipidus diagnosed?

Answer 22

• Water deprivation test
• Normal fluid deprived people and psychogenic polydipsia patients will have little or no concentrated urine
• In diabetes insipidus, urine will continue to be produced in large volumes and very dilute (central and nephrogenic)
• Bodyweight needs to be measured regularly (3% reduction means dehydration)
• Vasopressin test then distinguishes between cranial and nephrogenic - central will then concentrate urine, nephrogenic will not

Question 23

How is nephrogenic diabetes insipidus treated?

Answer 23

Thiazides (diuretic)