Endocrinology Flashcards
If a patient with hypercalcaemia has an elevated PTH what is the most likely diagnosis?
Primary (or tertiary) hyperparathyroidism
If a patient with hypercalcaemia has a normal PTH level, what diagnoses do you have to consider?
Primary hyperparthyroidism
Tertiary hyperparathyroidism
Familial hypocalciuric hypercalcaemia
In a patient with hypercalcaemia and a low (or low normal) PTH, what further investigations should you undertake?
PTHrp
25-hydroxyvitamin D (25[OH]D, calcidiol)
1,25-dihydroxyvitamin D (calcitriol)
TFTs
Consider multiple myeloma screen
Consider vitamin A level
What does an elevated 25-hydroxyvitamin D (25[OH]D, calcidiol) level in the setting of hypercalcaemia Indicate?
Vitamin D intoxication
What next tests should you order in a patient with hypercalcaemia, a low PTH and elevated levels of 1,25-dihydroxyvitamin D (calcitriol)
Chest imaging to look for evidence of granulomatous disease (eg sarcoidosis) or malignancy (eg lymphoma)
What biochemical markers are consistent with hypercalcaemia of malignancy?
Hypercalcaemia (usually greater elevation that in hyperparathyroidism)
Low or low-normal PTH
Elevated PTHrP
Low calcitriol level
What biochemical markers are consistent with hypercalcaemia of malignancy?
Hypercalcaemia (usually greater elevation that in hyperparathyroidism)
Low or low-normal PTH
Elevated PTHrP
Low calcitriol level
In hypercalcaemia, what 3 disorders are associated with hypocalciuria?
Familial hypocalciuric hypercalcaemia
Thiazide diuretics
Milk-alkali syndrome
If evaluation for hypercalcaemia does not suggest primary hyperparathyroidism, hypercalcaemia of malignancy or vitamin D intoxication (ie low PTH, low PTHrP, low or normal calcitriol level), what other conditions are most likely?
Conditions associated with unsuspected stimulation of bone resorption including:
multiple myeloma
thyrotoxicosis
immobilization
vitamin A toxicity
Or unrecognized calcium intake in the face of renal insufficiency (as in the milk-alkali syndrome)
What is the milk-alkali syndrome?
The milk-alkali syndrome consists of the triad of:
hypercalcemia +
metabolic alkalosis +
acute kidney injury
associated with the ingestion of large amounts of calcium and absorbable alkali
What is osmotic demyelination syndrome and when does it occur?
Occurs with overly rapid correction of SEVERE (<120mmol/L)
CHRONIC (ie >2 days)
HYPOTONIC
hyponatraemia
Almost exclusively occurs in those with serum sodiums less than 120 (and majority less than 105)
Other risk factors (including for patients who develop ODS at less severe degrees of hyponatraemia and slower rates of correction) include:
- alcohol use disorder
- malnutrition
- liver disease
- hypokalaemia
- hypophosphataemia
What is the pathophysiology of osmotic demyelination syndrome?
In response to systemic serum hypotonicity (the serum sodium concentration is the primary determinant of serum tonicity) water flows across the blood-brain barrier thereby increasing brain water content and causing brain cells (primarily astrocytes) to swell (ie cerebral oedema). These cells surround brain capillaries and protect neurons from swelling via a cell-to-cell transfer of cellular solutes and water.
However the brain adapts almost immediately (adaptation is completed within 2 days) to return brain volume toward normal by:
Firstly, the initial cerebral oedema raises interstitial hydraulic pressure which creates a gradient forcing interstitial sodium and water out of the brain and into CSF,
Secondly, astrocytes lose intracellular solutes (osmlytes incl potassium, amino acids such as glutamine/glutamate etc) thereby shedding excess water so it has the same tonicity as plasma
Because of this adaption, hyponatraemia that develops over more than 2-3 days is not associated with severe brain swelling and is therefore less likely to be complicated by seizures, coma and brain herniation.
HOWEVER once the brain has adapted to the hypotonicity (ie patients without acute hyponatraemia), the rate of correction of hyponatraemia becomes important - overly rapid correction in patients with chronic hyponatraemia may lead to ODS.
The exact pathogenesis of ODS is incompletely understood.
It is thought that in ODS, rapid correction of hyponatraemia (which increases serum sodium and therefore serum tonicity) causes excess water to flow out of the brain (across BBB) to the systemic circulation but the reuptake of osmolytes into brain cells occurs more slowly - this results in an acute fall in brain cell volume which causes direct injury to astrocytes/oligodendrocytes that are crucial for normal myelination and maintenance of BBB. As well, the initial movement of potassium and sodium back into brain cells leads to an increase in cell cation concentration BEFORE the organic osmolytes can be replaced which leads to protein aggregation, DNA fragmentation and apoptosis leading astrocytes and oligodendrocytes to die in regions of the brain affected by demylelination.
The end result is that ODS causes demyelination, often diffusely of which central pontine involvement may or may not be present
Patients with hyponatraemia >120mmol can rarely suffer ODS - under what two clinical situations can this occur?
1) Patients with severe liver disease and moderate hyponatraemia whose sodium levels increase after liver transplantation
2) Patients with AVP disorders (formerly diabetes insipidus) who develop moderate hyponatraemia as complication of desmopressin therapy then have desmopressin discontinued
What is the maximum rate of sodium correction you should not exceed in a patient with risk factors for ODS?
You should not exceed 6 to 8 mmol/L in any 24-hour period
Goal 4-6mmol/L
When do symptoms of ODS typically occur?
Delayed for 2-6 days after overly rapid correction of serum sodium has occurred
