A. Calcium is present in serum in three forms. About 50% is
bound to proteins, predominantly albumin. About 10% is
complexed with anions, such as bicarbonate, phosphate,
citrate, etc., and about 40% is in the free, ionized form.
The free, ionized form is the physiologically important
fraction.
Total calcium is routinely measured in serum or urine
specimens by a colorimetric method. The absorption of a dye
(most commonly cresolphthalein complexone) intensifies upon
interacting with calcium from acidified specimens in which
calcium is liberated from bound forms.
Determination of free calcium is not always readily
available, but can be measured by ion specific electrode.
Total serum calcium concentration is generally proportional
to free calcium concentration, so long as albumin
concentration is normal. When albumin concentration is
abnormal, total serum calcium concentration is interpreted
on the basis of what the total calcium concentration would
be if albumin concentration were normal by adding 0.8 mg/dl
to the calcium value for each 1 g/dl that albumin is less
than 4 g/dl, i.e.,
corrected total calcium = measured value +
0.8x(4 g/dl - albumin)mg/dl.
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B. Inorganic Phosphate is routinely measured in serum or
urine specimens by a colorimetric method.
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C. The Alkaline Phosphatase isoenzyme from bone becomes
elevated as a consequence of osteoblast stimulation. Total
serum alkaline phosphatase elevations in metabolic bone
disease are most often only mild, except in Paget's disease
of bone in which cases values are several tens to hundreds
times the upper limit of normal.
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D. Parathyroid Hormone is measured by radioimmunoassay.
Until recently only a few commercial, specialty laboratories
provided reliable results. Interpretation of results is
complicated by the fact that the intact, circulating hormone
is rapidly cleaved by a proteolytic enzyme into N and C
terminal fragments. The circulating half life of the N
terminal fragment is less than an hour. The C terminal
fragment has a longer circulating life time of several
hours. Assays are available for the intact hormone, for the
N terminal fragment and for the C terminal fragment. Values
for the intact hormone are difficult to interpret because
the N and C terminal fragments are also included in the
measurement but with different cross reactivities and is
therefor not clinically useful.
Results from the C terminal assay are useful for deriving
information about the functional status of the parathyroid
gland. PTH results must be interpreted along with serum
calcium results. Elevated PTH values are found in both
primary and secondary hyperparathyroidism. PTH is
appropriately elevated in secondary hyperparathyroidism in
which cases serum calcium values are low or low-normal. PTH
is inappropriately elevated in primary hyperparathyroidism
in which cases serum calcium concentrations are elevated.
Depressed PTH results are found in both primary
hypoparathyroidism and in cases of hypercalcemia from excess
calcium intake and from osteolytic bone destruction.
The N terminal assay is used when blood specimens are drawn
from neck veins draining the glands in order to identify the
location of an autonomously functioning adenoma.
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E. Indirect Indications of PTH Activity
1. % tubular reabsorption of phosphate ( % TPR ) is
decreased as a direct effect of PTH on the kidneys and,
along with the consequently depressed serum phosphate, is
one of the characteristic findings in primary (or ectopic)
hyperparathyroidism. The value is determined from
measurements of phoshate and creatinine on a serum and a
spot urine specimen:
% TPR = 100x[ 1 - (phos.u/phos.s)/(creat.u/creat.s)]
2. The serum Cl-/phosphate ratio increases to 32 - 80 in
cases of primary (or ectopic) hyperparathyroidism.
Decreased serum phosphate, as a consequence of decreased
renal phosphate reabsorption, is one of the characteristic
findings in hyperparathyroidism. A mild to moderate
metabolic acidosis is also typically associated with
hyperparathyroidism. The anion gap is normal so that serum
Cl- is elevated by the amount that HCO3 is depressed. The
ratio provides a simple means to justify a suspicion of
hyperparathytroidism and to conduct more definitive testing.
3. Urine cyclic AMP increases as a consequence of the
interaction of PTH with renal epithelial cell membrane
receptors and its intracellular formation as the "second
messenger". The interaction of PTH-like protein with the
receptors has the same effect.
Cyclic AMP is measured by radioimmunoassay in
a spot urine specimen and along with values for serum and
urine creatinine results are expressed with respect to GFR,
ie:
cyclic AMP excretion rate =
100x(urine cyclic AMP concentraation)/(Cru/Crs)
The test is most useful when PTH is found to not be elevated,
but all other test results are consistent with hyperPTH.
Elevated cyclic AMP excretion rate and depressed or normal
serum PTH concentration strongly suggests ectopic
elaboration of a "PTH-like substance".
Reviewed: April 3, 2000