Manifestations
Neurologic Symptoms
Cardiovascular Symptoms
Gastrointestinal Symptoms
Renal Symptoms
Bone Symptoms
There is little correlation between the presenting symptoms of hypercalcemia
and serum calcium concentrations. Rapid diagnosis of hypercalcemia may be
complicated because symptoms associated with hypercalcemia are
characteristically nonspecific and are easily attributed to chronic or terminal
illness.[1,2] Symptom severity may be caused in part by confounding factors such
as previous cancer treatment, drug disease-state interactions, or comorbid
pathologies.
Few patients experience all the symptoms that have been associated with
hypercalcemia (see the table on Symptom Prevalence Among Patients Treated for Hypercalcemia
of Malignancy Stratified by Corrected Serum Total Calcium
Concentrations at Presentation, below), and some patients may not experience any symptoms.
Patients with corrected total serum calcium concentrations higher than 14
mg/dL (>7.0 mEq/L or 3.49 mmol/L) are generally symptomatic.[1] It must be
emphasized that clinical manifestations are closely related to the rapidity of
hypercalcemia onset. Some patients develop signs and symptoms when calcium is
only slightly elevated, while others with long-standing hypercalcemia may
tolerate serum calcium levels higher than 13 mg/dL (>6.5 mEq/L or 3.24 mmol/L)
with few symptoms. Neuromuscular manifestations are generally more marked in
older patients than in young patients.
One author observed that malaise and fatigue were the most common complaints at
patient presentation, followed by (in order of decreasing prevalence rate)
varying degrees of obtundation, anorexia, pain, polyuria-polydipsia,
constipation, nausea, and vomiting.[3]
Symptom Prevalence Among Patients Treated for Hypercalcemia
of Malignancy Stratified by Corrected Serum Total Calcium
Concentrations at Presentation*
Symptoms
|
Prevalence (%) by Serum Calcium
Concentration
|
*Adapted from Ralston et al.[3]
|
|
<3.5 mmol/L
|
≥3.5 mmol/L
|
Central nervous system symptoms |
41 |
80 |
Constipation |
21 |
25 |
Malaise-fatigue |
65 |
50 |
Anorexia |
47 |
59 |
Nausea and/or vomiting |
22 |
30 |
Polyuria and/or polydipsia |
34 |
35 |
Pain |
51 |
35 |
Clinical manifestations can be categorized according to body systems and
functions.
Neurologic Symptoms
Calcium ions have a major role in neurotransmission. Increased calcium levels
decrease neuromuscular excitability, which leads to hypotonicity in smooth and
striated muscle. Symptom severity correlates directly with the magnitude of
serum-ionized calcium concentrations and inversely with their rate of change.
Neuromuscular symptoms include weakness and diminished deep-tendon reflexes.
Muscle strength is impaired, and respiratory muscular capacity may be
decreased. Central nervous system impairment may manifest as delirium with
prominent symptoms of personality change, cognitive dysfunction,
disorientation, incoherent speech, and psychotic symptoms such as
hallucinations and delusions. Obtundation is progressive as serum calcium
concentrations increase and may progress to stupor or coma.[1,2] Local
neurologic signs are not common, but hypercalcemia has been documented to
increase cerebrospinal fluid protein, which may be associated with headache.
Headache can be exacerbated by vomiting and dehydration.[2] Abnormal
electroencephalograms are seen in patients with marked hypercalcemia.[1]
Cardiovascular Symptoms
Hypercalcemia is associated with increased myocardial contractility and
irritability. Electrocardiographic changes are characterized by slowed
conduction, including prolonged P-R interval, widened QRS complex, shortened
Q-T interval, shortened or absent S-T segments, and possibly abrupt sloping and early peaking of the proximal limb of
T waves. Hypercalcemia enhances patients’
sensitivity to the pharmacologic effects of digitalis glycosides (e.g.,
digoxin). When serum calcium concentrations exceed 16 mg/dL (>8.0 mEq/L or
3.99 mmol/L), T waves widen, secondarily increasing the Q-T interval. As
calcium concentrations increase, bradyarrhythmias and bundle branch block may
develop. Incomplete or complete atrioventricular block may develop at serum concentrations
around 18 mg/dL (9.0 mEq/L or 4.49 mmol/L) and may progress to complete heart
block, asystole, and cardiac arrest.[1,2]
Gastrointestinal Symptoms
Gastrointestinal symptoms are probably related to the depressive action of
hypercalcemia on the autonomic nervous system and resulting smooth-muscle
hypotonicity. Increased gastric acid secretion often accompanies hypercalcemia
and may intensify gastrointestinal manifestations. Anorexia, nausea, and
vomiting are intensified by increased gastric residual volume. Constipation is
aggravated by dehydration that accompanies hypercalcemia. Abdominal pain may
progress to obstipation and can be confused with acute abdominal obstruction.
Renal Symptoms
Hypercalcemia causes a reversible tubular defect in the kidney, resulting in the
loss of urinary concentrating ability and polyuria. Decreased fluid intake and
polyuria lead to symptoms associated with dehydration, including thirst, dry
mucosa, diminished or absent sweating, poor skin turgor, and concentrated
urine. Decreased proximal reabsorption of sodium, magnesium, and potassium
occur as a result of salt and water depletion that is caused by cellular
dehydration and hypotension. Renal insufficiency may occur as a result of
diminished glomerular filtration, a complication observed most often in
patients with myeloma.
Although nephrolithiasis and nephrocalcinosis are usually not associated with
hypercalcemia of malignancy, calcium phosphate crystals can precipitate within
renal tubules to form renal calculi as a consequence of long-standing
hypercalciuria. When they occur, coexisting primary hyperparathyroidism should
be considered.
Bone Symptoms
Hypercalcemia of malignancy can result from osteolytic metastases or
humerally mediated bone resorption with secondary fractures, skeletal
deformities, and pain.
References
-
Bajorunas DR: Clinical manifestations of cancer-related hypercalcemia. Semin Oncol 17 (2 Suppl 5): 16-25, 1990.
[PUBMED Abstract]
-
Mahon SM: Signs and symptoms associated with malignancy-induced hypercalcemia. Cancer Nurs 12 (3): 153-60, 1989.
[PUBMED Abstract]
-
Ralston SH, Gallacher SJ, Patel U, et al.: Cancer-associated hypercalcemia: morbidity and mortality. Clinical experience in 126 treated patients. Ann Intern Med 112 (7): 499-504, 1990.
[PUBMED Abstract]
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