PARATHYROID HORMONE,
HYPERPARATHYROIDISM
CKD,
&
PTH ASSAYS
David Plaut
&
Shanti Narayanan
Summer, 2012
Parathyroid Hormone - PTH
PTH is a hormone
secreted by the
Parathyroid gland.
There are four
Parathyroid glands
located behind the
thyroid.
Role of PTH – To Regulate Calcium Levels
The Parathyroid glands have only one
major function – regulate the calcium
level in the body within a very narrow
range (8.5 – 10.2 mg/dL) so that the
nervous and muscular systems can
function properly.
How does PTH regulate Calcium Levels?
Ca 
Parathyroid
Increases
Absorption
of Ca and P
PTH
Calcitriol
Blood
Increases Calcitriol formation
Decreases excretion of Ca
Increases excretion of P
Ca 
P
Causes of Elevated Calcium
In 70% of hypercalcaemia (n = 99), the
cause was unknown.
The second most common diagnosis was
skeletal disorders followed by kidney
disease.
Therefore, PTH analyses should be used
more frequently.
Signs and Symptons
Roughly three in 10,000 persons are affected by 1o HPT
One of the more common causes of hypercalcemia.
“Stones, bones, and groans” 
kidney stones, accelerated bone loss, and GI disomfort.
About 15 percent of patients with hypercalcemia have:
Weakness.
Nausea and vomitting
Weight loss for no known reason.
Being much more thirsty than usual
Frequent urination.
Feeling very tired.
Loss of appetite
Constipation
Trouble thinking clearly
Factors Affecting Prognosis
and Treatment
There are certain issues:
 Whether the calcium level in the blood
can be controlled.
 The stage of the cancer.
 Whether the tumor and the capsule
around the tumor can be completely
removed by surgery.
 The patient’s general health.
Treatment of 1o Hyperparathyroidism
Surgery – remove the diseased
Parathyroid gland and leave
the normal glands.
One bad gland is removed
– 95%
3 or 3 ½ glands are
removed – 5%
Secondary Hyperparathyroidism
Secondary implies that the Parathyroid
glands grew larger and producing excess
PTH in response to kidney disease.
All 4 glands will be enlarged.
Occurs in patients with renal failure.
Occurs in patients who have been on
kidney dialysis for several years.
Levels of PTH in CKD – NKF Guidelines
CKD
Stage
GFR Range
(mL/min./1.73 m2)
I- PTH
Ca / P
Intact PTH
Target Range
(pg/mL)
3
30-59
Every
12 Months
Every
12 Months
35-70
4
15-29
Every
3 Months
Every
3 Months
70-110
5
<15 or dialysis
Every
3 Months
Every
Month
150-300
The NKF/K-DOQI Guidelines are derived from studies that used the
Allegro Intact PTH assay.
NKF / K-DOQI: National Kidney Foundation /Kidney-Dialysis Outcome
Quality Initiative
The PTH Molecule
Peptide consisting of 84 Amino acids.
Breaks into small fragments.
Intact PTH is the whole molecule – 1 to 84.
1
84
1-84
7-84
1-34
13-34
39-84
53-84
PTH Assay Design
Labeled Ab
1-34
39 - 84
1-84
Capture Ab
7-84
1-34
13-34
39-84
53-84
PTH Assays
1st Gen Assays: Not Specific
for Intact PTH.
High cross reaction with
PTH fragments.
2nd Gen Assays: Used
different epitopes for the
N-terminal and C-terminal
fragments.
3rd Gen Assays: Not
commercialized.
Assay
Epitope
of coated
Ab
Epitope
of labeled
Ab
DPC
44-84
1-34
Bayer
39-84
1-34
Roche
26-32
55-64
Allegro
39-84
1-34
Significant variation in assay results between different manufacturers.
Use of different epitopes for antibody binding
Lack of standardization.
Intra-operative PTH: Cost Benefit Analysis
Conventional Surgery
without using
Intra-operative PTH
Standard operation
using Intra-operative
PTH
MIRP using
Intra-operative PTH
Surgery cost : ~ $
4500.
Surgery cost : ~ $
3200.
Surgery cost : ~ $
3200.
Frozen sections:
Frozen sections: $ 0.
Frozen sections: $ 0.
~ $ 1000.
PTH assay: ~ $ 100.
PTH assay: ~ $ 100.
Hospital stay: ~ $
3200.
Hospital stay: ~ $
3200.
Hospital stay: $ 0.
Total cost: ~ $ 8700.
Total cost: ~ $ 6500.
SAVE
$2200
Total cost: ~ $ 3300.
SAVE
$5400
PTH Assays and Parathyroidectomy
Intraoperative PTH measurement
with a decrease of at least 90% in
intra-operative PTH is highly predictive
of successful parathyroidectomy and
normalization of postoperative
calcium and PTH levels.
How Many Samples Are Needed?
The study found that an intraoperative PTH determination
with a > 50% change is an
excellent prognostic marker
of resolution and that only 2
samples are required:
one at baseline
another 10 min. after removal
of the abnormal tissue.
PTH in Renal Patients
Intraoperative decay of PTH
during operation for renal HPT is
somewhat slower in patients with
renal HPT than for patients with
normal renal function.
20 min after resection, a decline
to < 50% of the pre-operative
level predicts cure, while <40%
predicts a failure to cure.
Calcium Assays with PTH Assays?
The mean baseline PTH level dropped by
70% at 5 minutes after removal of the
abnormal glands and by 83% at 10 minutes.
The mean baselines of both TSC and ICa
dropped by 4% at 5 minutes after removal of
the abnormal glands and remained at 4% at
10 minutes. Decreases in TSC and ICa
during parathyroidectomy are minimal.
Unlike PTH levels, TSC and ICa levels do not
consistently decrease at 5 and 10 minutes
after gland resection.
Calcium Levels and Parathyroidism
Doubling the number of serum calcium
analyses did not increase the detected
number of raised calcium levels.
More frequent PTH analyses resulted in a
corresponding increase in detected high
PTH levels. 15% of the patients with
hypercalcaemia were diagnosed with
primary hyperparathyroidism.
Over 40% of patients with primary
hyperparathyroidism in the study had
only slightly raised serum calcium levels.
PTH Assays vs. Other Tools.
The positive predictive values:
sestamibi scanning
81%
radioguided surgery
88%
PTH
99.5%
Perioperative PTH testing has the highest
sensitivity, positive predictive value, and
accuracy.
The inherent variability of sestamibi scanning
and radioguided techniques emphasizes the
critical role of PTH testing during parathyroid
surgery.
Questions ?
Comments
Thank you
THANK YOU
Davidplaut@yahoo.com