Hypocalcaemia

• Often defined as calcium of <2.1 mmol/l
• Calcium< 1.9 mmol/l can be considered an emergency

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Clinical features

• Paraesthesia (perioral, digital)
• Tetany
• Seizures
• Laryngospasm (may be stridor and cough)
• Depression
• AV-block or cardiac arrest
• Two eponymous signs
  • • Trousseau’s sign – application of a BP cuff causes carpopedal spasm
    • Chvostek’s sign – facial twitching on tapping the cheek
    • However these  are not always helpful, and can occur in patients with normal or even raised calcium who also have epilepsy or migraine
    • Can be useful if patients have had the signs before, and wondering if hypocalcaemia has recurred

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ECG features

• Prolonged QT-interval
• T wave inversion
• Heart block
• VF, VT, PEA and asystole

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Causes

• Post thyroidectomy / parathyroidectomy
  • • After thyroidectomy – 20% develop temporary hypocalcaemia, 3% permanent
    • After parathyroidectomy it’s usually temporary
• Vitamin D deficiency with secondary hyperparathyroidism (you may see a low phosphate and elevated alkaline phosphatase)
• Magnesium deficiency (eg in PPI use or alcoholism) or hyperphosphatemia
• Chronic Kidney Disease
• Acute pancreatitis
• Hypoparathyroidism
  • • Can be associated with
      • • DiGeorge syndrome
        • APECED (type 1 autoimmune polygladular syndrome) – can be Addisons, chronic mucocutaneous candida, vitiligo, enamel hypoplasia, eye problems, alopecia and nail dystrophy, enteritis/hepatitis, other autoimmunity
        • Sanjad-Sakati and Kenny Caffey syndromes
        • X linked, or familial isolated
        • HDR syndrome
    • Can be acquired – infiltration (iron, copper, sarcoid, cancer), neck irradiation, autoimmune
• PTH resistance – rare, childhood onset, may be a family history
• Drugs
  • Calcium channel blocker overdose
  • Chemotherapy
  • Bisphosphonates
    • • Especially if the patient is vitamin D deficient
      • Make sure vitamin D well replaced before giving bisphosphonates or denosumab for osteoporosis or surgery – risk of crashing hypocalcaemia
  • Calcium binders
• Other – toxic shock syndrome, large volume blood transfusion, rhabdomyolysis, tumour lysis syndrome

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Investigations

• Always check PTH, bone profile, Vitamin D level and magnesium
• Ionised calcium may be better guide if there’s significant acid-base disturbance
• Genetic panel if suspected congenital/familial cause of hypoparathyroidism
• If PTH low / normal – consider hypomagnesaemia, hypoparathyroidism, autoimmune
• If PTH high – lots of causes. Phosphate and vitamin D levels can help in diagnosis.

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Acute treatment

• In a peri-arrest situation treat with:
  • • 30ml 10% calcium gluconate diluted in 100 ml 5% dextrose IV over 10 minutes (if not in extremis, give 10ml 10% calcium gluconate in 100ml 5% dextrose over 10 mins).
    • If calcium gluconate is not available – 10 mL 10% calcium chloride IV over 10 minutes can be given
    • Then can give an infusion – 100ml calcium gluconate in 1L fluid, 50-100ml/hour (caution in renal failure)
    • Treatment can be repeated until the patient is asymptomatic but if more than four doses are required pause treatment, seek expert advice and review the cause of the patient’s instability
    • Also give Magnesium sulphate 50% 4-8 mmol IV if peri-arrest
    • Ensure they remain on a cardiac monitor
• If calcium level < 1.9 mmol/l but not peri-arrest
  • • Urgent replacement (unless there’s a history of chronic hypoparathyroidism and they’re already on alfacalcidol)
    • Consider a cardiac monitor (and especially if history of arrhythmias or on digoxin)
    • Give 10-20ml 10% calcium gluconate over 10 minutes (in 100ml 5% dextrose) with ECG monitoring
    • Then give an infusion (10 x the initial dose) – 100ml 10% made up to 1L (saline or dextrose) over 10-20 hours (50-100ml/hour). Side effects include thrombophlebitis, cardiotoxicity, hypotension, flushing, N&V, sweating
    • Treat the underlying cause
    • If post-op, can give alfacalcidol or calcitriol therapy
• If mild hypocalcaemia (ie >1.9 mmol/l)
  • • Often don’t need to admit the patient
    • Can treat with supplements (adcal, calichew etc)
    • Sandocal 1000, two tablets BD might be a good option (discuss if on PPI – it can impact absorption)
    • Can give vitamin D 100,000 units if significantly low levels (or 300,000 units over 6-10 weeks)
    • Repeat calcium level in 24 hours and then in one week. If remains < 2.1, can increase sandocal to three times daily
    • If low Mg2+… consider replacing magnesium IV and stop any drugs contributing (diuretics, PPIs), or try to reduce GI losses

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Notes on causes

• Vitamin D deficiency
  • • Very common especially in malnutrition, vegan diets, low sunlight exposure, CKD, CLD, anti-seizure medication
    • Defined as < 50
    • Typically high PTH and low phosphate
    • Treat with a total loading dose 300,000 units of cholecalciferol over 6-10 weeks (eg 50,000 units per week for 6 weeks). Not suitable for vegans, derived from animal wool
    • See vitamin D deficiency for a more detailed overview of causes and management
• Hypomagnesaemia – at very low Mg2+ levels, PTH is suppressed
• Secondary hyperparathyroidism
  • • Can be caused by vitamin D deficiency
    • Most commonly caused by CKD
    • Also caused by malabsorption eg pancreatic disease
    • Can lead to tertiary hyperparathyroidism with high calcium if not treated
    • Treat with vitamin D if kidneys ok (100,000 units orally OD for 3 days, then maintenance)
• Hypoparathyroidism
  • • Usually acquired post thyroidectomy
    • Can be autoimmune
    • Can be caused by immunotherapies
    • Rarely part of a syndrome (eg Di Georges)
    • Treat with activated 1.25 vit D (alfacalcidol/calcitriol) and oral calcium (citrate rather than carbonate if on PPI). Better to give calcium BD than OD, and take with meals
    • Aim calcium 2-2.2 (does not need to be normal). Aim to reduce symptoms.
    • Ensure vitamin D replete
    • Occasionally a patient needs parathyroid hormone replacement, especially if risk of hypercalciuria/stones eg teriparatide (off license). Sometimes pumps are used. Palopeg is coming.
    • Monitor bloods, urinary calcium excretion. DEXA not required routinely
    • To lower urinary calcium – could reduce calcium supplements, sodium restrict diet, thiazides, and consider renal imaging especially if eGFR decreasing
    • In pregnancy – can be complicated
      • • Hypercalcaemia increases risk of PET and foetal hypocalcaemia, whilst hypocalcaemia increases risk of foetal loss and infant skeletal abnormalities.
        • Continue vit D and calcium but monitor more closely.
        • Avoid PTH replacement and thiazides
        • Abrupt stopping of breastfeeding can cause hypocalcaemia
• Pseudohypoparathyroidism
  • • Low calcium due to PTH resistance (elevated PTH levels, elevated phosphate)
    • Genetic, rare
    • Different types. Can get Albrights hereditary osteodystrophy and Achibalds sign (no knuckles 4^th and 5^th digits).
    • Other types have normal hands but low calcium
• Pseudopseudohypoparathyroidism – phenotype (ie hand changes), but normal biochemistry