Hypercalcaemia/parathyroid disease and hypocalcaemia

Question 1

How many parathyroid glands are there and where are they?

When is parathyroid hormone secreted?

What does it do?

Answer 1

• There are 4 parathyroid glands, lying posteriorly to the thyroid
• The chief cells are responsible for secreting parathyroid hormone (PTH)
  
  • PTH is secreted when plasma calcium levels are low
  • PTH can also be secreted in response to low vitamin D, or high phosphate levels
• PTH works to increase plasma calcium reabsorption from bone by:
  
  • Directly stimulating calcium resabsorption from bone
  • Directly increasing renal tubular calcium reabsorption
  • Indirectly stimulating increased GI calcium absorption
    
    • By increasing vitamin D activation in the kidney
  • PTH has a secondary effect of increasing renal phosphate excretion

Question 2

What is the role of vitamin D?

How is ‘active’ vitamin D formed?

Answer 2

Vitamin D acts to sustain plasma calcium and phosphate levels by increasing their inflow from the GI tract

• It i also required for normal bone formation
• Endogenously it is synthesized in the skin, forming D₃, cholecalciferol
• Exogenously it is ingested as D_2, ergocalciferol (common in fish, liver and dairy products)
• ‘Active’ vitamin D is then formed by a second hydroxylation in the kidney, to produce to 1,25-(OH)₂-D_2/3

Question 3

What are causes of vitamin D deficiency?

Answer 3

Most commonly occur in people with inadequate sunlight exposure, malabsorptive conditions and liver/kidney disease

Question 4

Where is calitonin secreted from?

What is its function?

Answer 4

• Calcitonin is secreted by parafollicular/’C’ cells of the thyroid gland in response to increased plasma calcium levels
• It acts to decrease plasma calcium levels, by antagonism of the effect of PTH on the bone

Question 5

Why is the importance of calcitonin in humans is controversial?

Answer 5

• Removal of thyroid, and complete calcitonin deficiency does not lead to overt hypercalcemia
• Extreme hypersecretion of calcitonin by tumours rarely produces hypocalcaemia
• It is likely that PTH/Vitamin D levels are adjusted in response to calcitonin changes

Question 6

Give an overview of the normal control of serum calcium

Answer 6

• Intestinal uptake of calcium depends on the amount of ionized calcium in the lumen, and the presence of activated vitamin D
• 90% of renal excretion of calcium is related to sodium reabsorption in the proximal tubule, with 10% regulated by PTH in the distal tubule

Question 8

What are the common causes of raised serum calcium?

Answer 8

In a patient with hypercalcaemia, 97% of cases are due to primary hyperparathyroidism or malignacy (PTH high in hyperparathyroidism, low in malignancy)

Causes:

• Excessive PTH secretion
  
  • Primary hyperparathyroidism
  • Tertiary hyperparathyroidism
  • Ectopic PTH secretion (very rare)
• Malignancy
  
  • Myeloma
  • Metastatic deposits in bone
  • Paraneoplastic
    
    • PTHrp secretion: e.g. SCC (of lung or other tissues)
    • Production of osteoclastic factors
• Excess Vitamin D
  
  • Exogenous excess
  • Granulomatous disease: TB/sarcoid
  • Lymphoma
• Excess calcium intake
  
  • ‘Milk-alkali’ syndrome (antacids + large amounts of calcium lead to excessive absorption
• Other endocrine disease
  
  • Thyrotoxicosis
  • Addison’s
• Renal disease
  
  • Severe AKI
• Drugs
  
  • Thiazide diuretics
  • Lithium
• Hereditary
  
  • Familial hypocalciuric hypercalcaemia

Question 9

What are the symptoms of hypocalcaemia?

Answer 9

• Peripheral irritability:
  
  • Tetany/cramps
  • Carpo-pedal spasm
    
    • Wrist flexion and fingers drawn together
    • Happens especially after occulusion of brachial artery, e.g. with a blood pressure cuff: Trosseau’s sign
    • Tapping over the facial nerve causes twitches: Chvostek’s sign
• Central irritability
  
  • Seizures
• Depression/anxiety
• Perioral paraesthesia
• Cataracts

Question 10

What the common causes of hypocalaemia?

Answer 10

With low PTH (hypoparathyroidism)

• Idiopathic/primary hypoparathyroidism (autoimmune)
• Post thyroid/parathyroid surgery
• Post neck irradiation
• Infiltration: sarcoid/malignancy
• Congential absence of the gland: Digeorge syndrome
• Severe hypomagnesia: impairs PTH secretion

With high PTH

• Vitamin D deficiency
• Acute pancreatitis
• Alkalosis
• Acute hyperphosphataemia
  
  • renal failure
  • rhabdomyolysis
  • tumour lysis
• Drugs: bisphosphonates, calcitonin