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Toronto Notes 2019 Calcium Homeostasis
Approach to Hypercalcemia
1. Is the patient hypercalcemic? (correct for albumin – see sidebar)
2. Is the PTH high/normal or low?
3. If PTH is low, is phosphate high/normal or low?
4. If phosphate is high/normal, is the level of vitamin D metabolites high or low?
Clinical Features
• symptoms depend on the absolute Ca2+ value and the rate of its rise (may be asymptomatic)
Endocrinology E39
Table 29. Symptoms of Hypercalcemia
The symptoms and signs of hypercalcemia include:
“Bones, stones, groans, and psychiatric overtones”
The most common cause of hypercalcemia in hospital is malignancy-associated hypercalcemia
• Usually occurs in the later stages of
disease
• Most commonly seen in lung, renal, breast,
ovarian, and squamous tumours, as well as lymphoma and multiple myeloma
Mechanisms:
• Secretion of parathyroid hormone-related
protein (PTHrP) which mimics PTH action by preventing renal calcium excretion and activating osteoclast-induced bone resorption
• Cytokines in multiple myeloma
• Calcitriol production by lymphoma
• Osteolytic bone metastases direct effect
• Excess PTH in parathyroid cancer
Before prescribing Calcitonin, remember to ask about fish allergies
Differential Diagnosis of Hypercalcemia
• Primary hyperparathyroidism
• Malignancy: hematologic, humoral, skeletal
metastases
(>90% from 1 or 2)
• Renal disease: tertiary hyperparathyroidism • Drugs: calcium carbonate, milk alkali
syndrome, thiazide, lithium, theophylline,
vitamin A/D intoxication
• Familial hypocalciuric hypercalcemia
• Granulomatous disease: sarcoidosis, TB,
Hodgkin’s lymphoma
• Thyroid disease: thyrotoxicosis
• Adrenal disease: adrenal insufficiency,
pheochromocytoma • Immobilization
Signs and Symptoms of Acute Hypocalcemia
• Paresthesias: perioral, hands, and feet • Chvostek’s sign: percussion of the facial
nerve just anterior to the external auditory meatus elicits ipsilateral spasm of the orbicularis oculi or orbicularis oris muscles
• Trousseau’s sign: inflation of a blood pressure cuff above systolic pressure for 3 min elicits carpal spasm and paresthesia
Hypomagnesmia can impair PTH secretion and action
Watch Out for:
• Volume depletion via diuresis • Arrhythmias
Cardiovascular
HTN
Arrhythmia
Short QT Deposition of Ca2+ on valves, coronary arteries, myocardial fibres
GI
Constipation Anorexia Nausea Vomiting (groans) PUD pancreatitis
Renal
Polyuria (Nephrogenic DI) Polydipsia Nephrolithiasis (stones)
Renal failure (irreversible) Dehydration
Rheumatological MSK
Gout Weakness Pseudogout Bone pain Chondrocalcinosis (bones)
Psychiatric
>3 mmol/L (12 mg/dL) Increased alertness Anxiety
Depression
Cognitive dysfunction Organic brain syndromes >4 mmol/L (16 mg/dL) Psychosis (moans)
Neurologic
Hypotonia Hyporeflexia Myopathy Paresis
** Hypercalcemic crisis (usually >4 mmol/L or 16 mg/dL): primary symptoms include oliguria/anuria and mental status changes including somnolence and eventually comagthis is a medical emergency and should be treated immediately!
Treatment
• treatment depends on the Ca2+ level and the symptoms
• treattheunderlyingcauseofthehypercalcemia
• treatacute,symptomatichypercalcemiaaggressively
• mild asymptomatic hypercalcemia; monitor, avoid: thiazide, volume depletion, high Ca2+ diet, lithium,
bed rest
Table 30. Treatment of Acute Hypercalcemia/Hypercalcemic Crisis
Increase Urinary Ca2+ Excretion
Diminish Bone Resorption
Decrease GI Ca2+ Absorption
Dialysis
Isotonic saline (4-5 L) over 24 h ± loop diuretic (e.g. furosemide) but only if hypervolemic (urine output >200mL/h)
Calcitonin:
4 IU/kg IM/SC q12h
8 IU/kg IM/SC q6h
Only works for 48 h, can develop tachyphylaxis
Rapid onset within 4-6 h
Before prescribing Calcitonin, remember to ask about fish allergies
Bisphosphonates (treatment of choice)
Inhibits osteoclastic bone resorption, preventing calcium release from bone
Effects on calcium levels are typically seen at 24-48 h after administration
Calcitonin often given in conjunction with bisphosphonate, given rapid onset of effect Indicated in malignancy-related hypercalcemia (IV pamidronate or zoledronic acid used)
Corticosteroids can be used in hypercalcemia mediated by 1,25 Vitamin D. Corticosteroids are potent inhibitors of 1a-hydroxylase and therefore, decrease calcitriol production by activated mononuclear cells (e.g. in lymphoma, granuloma)
Effects will be seen in 2-5 d
Treatment of last resort
Indication: severe malignancy-associated hypercalcemia and renal insufficiency or heart failure
Hypocalcemia
Definition
• total corrected serum Ca2+ <2.2 mmol/L
Table 31. Clinical Features of Hypocalcemia
Acute Hypocalcemia
Paresthesia
Laryngospasm (with stridor)
Hyperreflexia
Tetany
Chvostek’s sign (tap CN VII)
Trousseau’s sign (carpal spasm)
ECG changes
Delirium
Psychiatric Sx: emotional instability, anxiety, and depression
Note: Tetany is a hallmark of hypocalcemia – can be mild or severe
Mild: perioral numbness, parastheisa of hands and feet, muscle spasm
Severe: carpopaedal spasm, laryngospasm, focal/generalized seizures
Chronic Hypocalcemia
CNS: lethargy, seizures, psychosis, basal ganglia calcification, Parkinson’s, dystonia, hemiballismus, papilledema, pseudotumour cerebri
CVS: prolonged QT interval → Torsades de pointes (ventricular tachycardia)
GI: steatorrhea
ENDO: impaired insulin release
SKIN: dry, scaling, alopecia, brittle and transversely fissured nails, candidiasis, abnormal dentition
OCULAR: cataracts
MSK: generalized muscle weakness and wasting