Hypercalcaemia

There are 3 subtypes of hypercalcaemia:

• Primary
• Secondary
• Tertiary

Primary hyperparathyroidism:

• Caused by single (>80%) parathyroid adenomas or by diffuse hyperplasia of all the glands (15-20%)
• Multiple parathyroid adenomas are rare and parathyroid carcinoma is even less common (<1%), although it usually causes severe hypercalcaemia

Secondary hyperparathyroidism:

• Is physiological compensatory hypertrophy of all parathyroids due to hypocalcaemia (such as occurs in vitamin D deficiency or renal failure)
• PTH levels are raised but Ca²⁺ levels are low or normal
• PTH falls to normal after correction of the cause of hypocalcaemia (if possible)

Tertiary hyperparathyroidism:

• Is the development of apparently autonomous parathyroid hyperplasia after longstanding secondary hyperparathyroidism (most often in renal failure)
• Plasma Ca²⁺ and PO₄^3- are both raised, the latter often grossly so
• Parathyroidectomy is necessary at this stage

Causes of hypercalcaemia:

Excessive PTH secretion:

• Primary hyperparathyroidism (commonest by far)
• Tertiary hyperparathyroidism
• Ectopic PTH secretion (very rare)

Excess action of vitamin D:

• Iatrogenic or self-administered excess
• Granulomatous diseases (e.g. sarcoidosis, TB)
• Lymphoma

Excessive calcium intake:

• ‘Milk-alkali’ syndrome

Malignant disease (second most common cause):

• Secondary deposits in bone
• Production of osteoclastic factors by tumours
• Myeloma

Other endocrine disease (mild hypercalcaemia only):

Thyrotoxicosis

Addison’s disease

Drugs:

• Thiazide diuretics
• Vitamin D analogues
• Lithium administration (chronic)
• Vitamin A

Miscellaneous:

• Long-term immobility
• Familial hypocalciuric hypercalcaemia

Symptoms and signs:

General features:

• Malaise
• Tiredness
• Depression

Renal features (20-40% of patients):

• Renal colic (caused by calculi)
• Polyuria
• Nocturia
• Haematuria
• HT

Bone pain

Abdominal pain (sometimes due to PUD)

Chondrocalcinosis (a form of pseudogout)

Ectopic calcification

Corneal calcification (a marker of longstanding hypercalcaemia, but causes no symptoms)

Investigations:

Biochemistry:

• Several fasting serum calcium/phosphate should be taken. The hallmark of primary hyperparathyroidism is hypercalcaemia and hypophosphataemia, with detectable intact PTH levels during hypercalcaemia
• A mild hyperchloraemic acidosis
• Renal function is usually normal, but should be measured as a baseline
• Protein electrophoresis (to exclude myeloma)
• Serum TSH and T₃ (to exclude thyrotoxicosis)

Imaging:

• Abdominal X-rays may show renal calculi or nephrocalcinosis

Medical management of primary hyperparathyroidism:

• No effective medical interventions at present
• Should maintain a high fluid intake
• Avoid a high intake of calcium or vitamin D
• Encourage exercise

Surgical management of primary hyperparathyroidism:

Surgery is indicated for:

• Patients with renal calculi or impaired renal function
• Bone involvement or marked reduction in cortical bone density
• Unequivocal marked hypercalcaemia (>2.9mmol/L)
• The uncommon younger patient, under 50 yrs
• A previous episode of severe acute hypercalcaemia

Complications of surgery:

Postoperative hypocalcaemia:

• Most common in patients with significant bone disease (the ‘hungry bone’ syndrome)
• A mild, transient hypoparathyroidism often continues for 1-2 weeks

Other (rarer) complications – as for thyroid surgery:

• Laryngeal nerve palsy
• Haemorrhage

Acute hypercalcaemia and its treatment:

Often presents with:

• Dehydration
• Nausea
• Vomiting
• Nocturia
• Polyuria
• Drowsiness/altered consciousness

The serum Ca²⁺ is over 3mmol/L and sometimes as high as 5mmol/L

Whilst investigation of the cause is under way, immediate treatment is mandatory:

• Adequate rehydration is essential (usually 4-6L of saline on day 1 and 3-4L for several days thereafter)
• Intravenous bisphosphonates are now the treatment of choice. Give pamidronate 15-60mg IV in 0.9% saline/dextrose over 2-8 hours
• Calcitonin (200U IV 6-hourly)
• Prednisolone (30-60mg daily) is effective in some instances (e.g. sarcoidosis, myeloma and vitamin D excess) but in most cases is ineffective
• Oral phosphate (sodium cellulose phosphate 5g TID). Side-effects include diarrhoea

Familial hypocalciuric hypercalcaemia:

• Uncommon, autosomal dominant
• Usually asymptomatic
• Demonstrates increased Ca²⁺ reabsorption, despite hypercalcaemia
• PTH levels are normal or slightly raised
• Urinary Ca²⁺ is low
• Surgery is NOT indicated as the course appears benign