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?
Increases Calcitriol formation
Decreases excretion of Ca
Increases excretion of P

Calcitriol
Ca 
Blood

Parathyroid

PTH

P

Increases
Ca  Absorption
of Ca and 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. Feeling very tired.

Nausea and vomitting Loss of appetite
Weight loss for no known reason. Constipation
Being much more thirsty than usual Trouble thinking clearly
Frequent urination.
 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

Intact PTH
CKD GFR Range
I- PTH Ca / P Target Range
Stage (mL/min./1.73 m2)
(pg/mL)

Every Every
3 30-59 35-70
12 Months 12 Months

Every Every
4 15-29 70-110
3 Months 3 Months

Every Every
5 <15 or dialysis 150-300
3 Months Month

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. Epitope Epitope
High cross reaction with Assay of coated of labeled
PTH fragments. Ab Ab

2nd Gen Assays: Used DPC 44-84 1-34

different epitopes for the
N-terminal and C-terminal Bayer 39-84 1-34
fragments.
Roche 26-32 55-64
3rd Gen Assays: Not
commercialized. 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 Standard operation MIRP using

without using using Intra-operative Intra-operative PTH
Intra-operative PTH PTH

Surgery cost : ~ $ Surgery cost : ~ $ Surgery cost : ~ $

4500. 3200. 3200.
Frozen sections: Frozen sections: $ 0. Frozen sections: $ 0.
~ $ 1000. PTH assay: ~ $ 100. PTH assay: ~ $ 100.
Hospital stay: ~ $ Hospital stay: ~ $ Hospital stay: $ 0.
3200. 3200. Total cost: ~ $ 3300.
Total cost: ~ $ 8700. Total cost: ~ $ 6500.

SAVE
SAVE $5400
$2200
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 intra-

operative 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