Posterior Pituitary Disorders Flashcards
ADH is synthesized in the _______ & then migrates in __________ __________ along the axonal pathways to the _____ pituitary.
hypothalamus, neurosecretory granules, posterior
Pituitary disease alone without hypothalamic involvement does or doesn’t lead to ADH deficiency?
No, it doesn’t lead to ADH deficiency.
Factors that increase ADH/vasopressin release
- increases osmolality
- hypovolemia
- hypotension
- hypothyroidism
- adrenaline (epinephrine)
- cortisol
- nicotine
- angiotensin II
- antidepressants
Factors that decrease ADH/vasopressin
- decreased osmolality
- hypervolemia
- hypertension
- ethanol
- alpha-adrenergic stimulation
3 disorders of ADH secretion
- Cranial diabetes insipidus (DI)
- Nephrogenic DI = renal tubules are insensitive to ADH
- Syndrome of Inappropriate Antidiuretic Hormone (SIADH) = inappropriate excess of ADH
Diabetes Insipidus (DI)
Pathological state in which large amounts of hypotonic, dilute urine are passed (polyuria).
Causes of DI (2)
- Deficiency of ADH secretion (cranial DI)
- An inappropriate renal response to ADH (nephrogenic DI)
- As a result, fluid reabsorption at the kidneys is impaired causing the characteristic signs & symptoms.
Clinical Features of DI
- Polydipsia = deficiency of ADH or insensitivity to its action —– excess excretion of dilute urine with a compensatory increase in thirst.
- Polyuria =up to 20L of water can be passed in a day.
- Severe dehydration = can lead to unconsciousness.
Familial isolated vasopressin deficiency
- causes DI from early childhood
- dominantly inherited
- caused by a mutation in the AVP-NPII gene
DIDMOAD (Wolfram’s) Syndrome
- rare autosomal recessive disorder
- 4 most common features = DI, DM, Optic atrophy & Deafness.
- caused by mutations in the WFS1 gene on c/some 4
- MRI may show an absent or poorly developed posterior pituitary.
Diagnosis of DI
Clinical history + increased plasma osmolality (>300 mOsm/kg) + low urine osmolality (<600 mOsm/kg).
ADH stimulation test is used to?
Distinguish between cranial DI & nephrogenic DI
ADH stimulation test results
- Cranial DI = inability to concentrate urine after fluid restriction alone, but the ability to concentrate urine after administration of ADH.
- Nephrogenic DI = inability to concentrate urine even after administration of ADH.
Osmolality
The concentration of dissolved particles
- normal = 285 - 295 mOsm/kg
- dissolved particles (major) = glucose, sodium, blood urea nitrogen (BUN).
Water Deprivation Test Results
- Normal response
Normal response
- serum osmolality = remains within normal range (275 - 295 mOsm/kg)
- urine osmolality = rises to >600 mOsm/kg
Water Deprivation Test Results
- Diabetes Insipidus (DI)
Diabetes Insipidus (DI)
- serum osmolality = rises above normal without adequate concentration of urine osmolality.
- serum osmolality >300 mOsm/kg
- urine osmolality <600 mOsm/kg
Water Deprivation Test Results
- Nephrogenic DI
If desmopressin doesn’t concentrate urine
Water Deprivation Test Results
- Cranial DI
If urine osmolality rises by >50% after desmopressin.
Nephrogenic DI may be:
(2)
- Inherited
- rare sex-linked recessive, with an abnormality in the vasopressin-2 receptor.
- an autosomal post-receptor defect in aquaporin-2 (ADH-sensitive water channel) - Acquired (more common)
- as a result of renal disease, sickle cell disease, drug ingestion (lithium), hypercalcemia, or hypokalemia.
Syndrome of Inappropriate Anti-diuretic Hormone (SIADH) leads to:
(2)
- Retention of water
- Hyponatremia
Clinical Features of SIADH
Presentation is usually vague, with confusion, nausea, irritability & later, fits & coma.
Mild symptoms of SIADH
Na+ <125 mmol/L
Serious manifestations
Likely Na+ <115 mmol/L
Investigations of SIADH
- dilutional hyponatremia (drinking too much water)
- low plasma osmolality
- euvolemia
- inappropriate urine osmolality >100 mOsm/kg
- continued urinary sodium excretion >30 mmol/L
- absence of hypokalemia (hypotension)
- normal function of renal, adrenal, thyroid.
