Endocrine Disease III Flashcards
How much Ca does the average person have?
1kg - 99% of skeleton
Functions of calcium?
Cofactor in coagulation
Skeletal mineralisation
Membrane stabilisation
How is Ca homeostasis achieved?
Ca is transported to and from the kidney, intestine and bone
Decreased serum Ca = increase PTH
= Increased bone resorption, increase Ca reabsorption and increase Ca absorption
= negative feedback - returns sCa conc to 1.1mmol/l
What does the PTH also do?
Reduce phosphate reabsorption
Increase 1apha- hydroxylation of 25-OH vit D
What is calcium homeostasis and example of?
Neg feedback = return serum ionised calcium back to 1.1mmol/l
Why can abnormalities in PTH occur?
Appropriate: to maintain Ca balance
Inappropriate: cause calcium imbalance
How does sCa conc impact PTH conc?
High sCa = low PTH
Low sCa = high PTH
If normal = equal concs
What is hypocalcaemia?
Low serum calcium
Causes of hypocalcaemia?
• Vitamin D deficiency/Osteomalacia • Hypoparathyroidism – post surgery, radiation, autoimmune disease – Hereditary (Autosomal dominant hypocalcaemia) – Syndromes (Di George, HDR [hypopara, deafness, renal dysplasia] etc) – Infiltration (Wilson’s disease, haemochromatosis) • Chronic renal failure • Magnesium deficiency • Pseudohypoparathyroidism • Acute pancreatitis • Multiple citrated blood transfusions
Consequences of hypocalcaemia?
• Paresthesia (burning sensation) • Muscle spasm – Hands and feet – Larynx – Premature labour • Seizures • Basal ganglia calcification • Cataracts • Dental hypoplasia • ECG abnormalities – Long QT interval
How to look for clues relating to hypocalcaemia?
History of neck surgery Presence of other autoimmune conditions History of congenital defects and immunodeficiency Family history = genetic cause Neck scar Growth failure, hearing loss
PTH, Ca and phosphate levels in vitamin D deficiency? (2ndry hyperparathyroidism)
Increased PTH, decreased CA and phosphate
PTH appropriate
How does hypoparathyroidism cause low sCa levels?
Low PTH
= Low renal ca reab = increase ca excretion
= Low renal phosphate reab = high serum phosphate
= Decreased bone resorption
= Increased formation of 1,25(OH)2D = decreased intestinal ca reab
= Low sCa
What is Pseudohypoparathyroidism?
Resistance to parathyroid hormone:
Type 1 - mutation with deficient Galpha subunit
1a Albright hereditary osteodystrophy
Clinical features of Pseudohypoparathyroidism?
- Short stature
- Obesity
- Round facies
- Mild learning difficulties
- Subcutaneous ossification
- Short fourth metacarpals
- Other hormone resistance
PTH, Ca and phosphate levels in hypoparathyroidism?
Low PTH and Ca, high phosphate
Inappropriate PTH
PTH, Ca and phosphate levels in Pseudohypoparathyroidism?
High PTH, low Ca, high Phosphate
Appropriate PTH
How to manage hypocalcaemia?
If symptomatic or Ca less than 1.9mmol/l:
- IV Ca gluconate for 10 mins (10% soln 10mins)
OR
- Vitamin D tx
Causes of hypercalcaemia?
Malignancy - bone mets, myeloma, PTHrP, lymphoma = 90% causes Primary hyperparathyroidism Benign hypercalcaemia Thiazides Sarcoidosis Immobilisation Adrenal insufficiency
Symptoms and consequences of hypercalcaemia?
• Thirst, polyuria • Nausea • Constipation • Confusion coma • Pancreatitis • Gastric ulcer • Renal stones • ECG abnormalities - Short QT
Signs of hypercalaemia?
• Confusion, hypotonia, hyporeflexic • Dehydration • Signs of malignancy (enlarged liver, clubbing, thyroid mass, breast lump, lymph nodes) • Faecal impaction • Irregular pulse (arrhythmia)
Approach to hypercalcaemia?
Identify drugs causing it (thiazides, vit D)
Identify presence of renal failure? - Tertiary hyperparathyroidism
Check serum PTH and 24hr urine Ca excretion
If PTH high or normal and urine calcium excretion > 0.01 mmol/l – Primary
Hyperparathyroidism
• If PTH high or normal and urine calcium excretion < 0.01 mmol/l – FHH
• If PTH low or suppressed – exclude malignancy,
hyperthyroidism, Addison’s, sarcoidosis, granulomatous
disorders
What occurs to sCa when there is a malignancy causing hypercalcaemia?
increase sCa
= decrease PTH
= decrease bone resorption, ca absorption and ca reab
Hypercalcaemia of malignancy?
About 20 to 30% of patients with cancer
• 80% are due to bony metastases (breast, thyroid , kidney,
lung, prostate)
• 20% due to PTHrP release (others secrete Vitamin D,
ectopic PTH)
• Osteoclastic Hypercalcaemia
