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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. - PowerPoint PPT Presentation
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PARATHYROID HORMONE,HYPERPARATHYROIDISM
CKD,&
PTH ASSAYS
David PlautDavid Plaut
&&
Shanti NarayananShanti Narayanan
Summer, 2012Summer, 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?
Par
ath
yro
id
Blo
oB
loo
dd
Ca Ca
Store House of Store House of
Ca & P Ca & P
Increases Absorption of Ca and P
Increases Calcitriol formationDecreases excretion of CaIncreases excretion of P
PTHPTH
PTHPTH
PTHPTH
Calcitriol
Calc
itriol
Calc
itriol
Ca Ca
P P
Bones
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 HPTOne 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 excessPTH 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 CKD StagStag
ee
GFR RangeGFR Range(mL/min./1.73 (mL/min./1.73
mm22))I- PTHI- PTH Ca / PCa / P
Intact PTH Intact PTH Target Range Target Range
(pg/mL)(pg/mL)
33 30-5930-59 EveryEvery12 Months12 Months
EveryEvery12 Months12 Months 35-7035-70
44 15-2915-29 EveryEvery3 Months3 Months
EveryEvery3 Months3 Months 70-11070-110
55 <15 or dialysis<15 or dialysis EveryEvery3 Months3 Months
EveryEveryMonthMonth 150-300150-300
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 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.Peptide consisting of 84 Amino acids.
Breaks into small fragments.Breaks into small fragments.
Intact PTH is the whole molecule – 1 to Intact PTH is the whole molecule – 1 to
84.84.1-84
7-847-84
1-341-34
13-34
39-84
53-84
1 84
PTH Assay Design
7-847-84
1-341-34
13-3413-34
39-8439-84
53-8453-84
1-841-8439 - 8439 - 841-341-34
Capture Ab
Labeled Ab
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.
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
Conventional Surgery without using Intra-operative PTH
Surgery cost : ~ $ 3200.
Frozen sections: $ 0.
PTH assay: ~ $ 100.
Hospital stay: ~ $ 3200.
Total cost: ~ $ 6500.
Surgery cost : ~ $ 3200.
Frozen sections: $ 0.
PTH assay: ~ $ 100.
Hospital stay: ~ $ 3200.
Total cost: ~ $ 6500.
MIRP using Intra-operative PTH
MIRP using Intra-operative PTH
Standard operation using Intra-operative PTH
Standard operation using Intra-operative PTH
Surgery cost : ~ $ 4500.
Frozen sections:
~ $ 1000.
Hospital stay: ~ $ 3200.
Total cost: ~ $ 8700.
Surgery cost : ~ $ 4500.
Frozen sections:
~ $ 1000.
Hospital stay: ~ $ 3200.
Total cost: ~ $ 8700.
Surgery cost : ~ $ 3200.
Frozen sections: $ 0.
PTH assay: ~ $ 100.
Hospital stay: $ 0.
Total cost: ~ $ 3300.
Surgery cost : ~ $ 3200.
Frozen sections: $ 0.
PTH assay: ~ $ 100.
Hospital stay: $ 0.
Total cost: ~ $ 3300.
SAVESAVE$2200$2200SAVESAVE$2200$2200
SAVESAVE$5400$5400SAVESAVE$5400$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 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 avi
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