Normal PTH levels by Age

Parathyroid Hormone (PTH) Blood Test

Parathyroid hormone (PTH) is an 84–amino-acid peptide secreted predominantly by two pairs of parathyroid glands, located behind or adjacent to the thyroid gland in the neck. Occasionally, ectopic parathyroid glands may be found along their developmental route from the mediastinum to the neck. The 84-amino-acid PTH is packaged into dense secretory granules for regulated secretion.

Figure 1. Structure of Parathyroid hormone (1-84)

Clinically, measurement of PTH in serum or plasma is vital for the evaluation and management of:

• Thyroid disorders (e.g., in the context of thyroid surgery),
• Kidney disorders (particularly chronic renal failure [CRF] and secondary Hyperparathyroidism),
• Various causes of hyper- or hypocalcemia (to differentiate parathyroid vs. nonparathyroid etiologies).

Since PTH directly influences calcium and phosphate homeostasis, this assay is routinely monitored in patients with chronic renal failure and in suspected or established primary Hyperparathyroidism.

Reference Ranges of PTH by Age

Because PTH assays measure different fragments of the hormone (or the intact molecule), reference ranges may vary based on the methodology. Standard reported ranges include:

1. Adults (Serum)
   • C-terminal : 50–330 pg/mL (50–330 ng/L)
   • N-terminal: 8–24 pg/mL (8–24 ng/L)
   • Intact PTH: 10–65 pg/mL (10–65 ng/L)
2. Adults (Plasma)
   • C-terminal : <50 microLEq/mL (<50 mLEq/L)
   • N-terminal: <6.1 pmol/L
   • Intact PTH: 1–5 pmol/L
3. Pediatrics
   • C-terminal (ages 1–16): 51–217 pg/mL (51–217 ng/L)
   • N-terminal (ages 2–13): 14–21 pg/mL (14–21 ng/L)
   • Intact PTH (ages 2–20): 9–52 pg/mL (9–52 ng/L)

Table 1. Laboratory ranges for fractions of the PTH molecule

Physiology and Secretory Regulation of PTH

Parathyroid Glands and PTH Synthesis

• PTH is synthesized as a 115-amino-acid pre-pro-peptide but 84–amino-acid PTH is the primary secreted form.
• The major regulatory signal for PTH secretion is serum calcium. When ionized calcium rises, PTH secretion falls. When calcium levels drop, PTH levels increase.

Calcium-Sensing Receptor (CaSR)

• The parathyroid glands express a cell-surface calcium-sensing receptor (CaSR), which detects extracellular calcium.
• Gain-of-function mutations of the CaSR can lead to autosomal dominant hypocalcemia (ADH), while loss-of-function mutations cause familial hypocalciuric hypercalcemia (FHH).
• Calcimimetics (e.g., cinacalcet, etelcalcetide) activate the CaSR to reduce PTH secretion, useful in secondary Hyperparathyroidism (CKD) and certain severe primary hyperparathyroid cases.

Magnesium and Vitamin D Impact

• Magnesium also plays a role: severe or prolonged hypomagnesemia can blunt PTH secretion.
• 1,25-Dihydroxyvitamin D (1,25-D) also inhibits PTH gene transcription.
• Serum phosphate may directly or indirectly modulate PTH, although data are somewhat mixed.

Metabolism and Clearance of PTH

• PTH has a circulating half-life of about <5 minutes.
• Hormone fragments (N-terminal, midregion, C-terminal) are produced mainly in the liver and kidney.
• C-terminal fragments are cleared by glomerular filtration, so they accumulate in renal failure.
• Only the amino terminus (PTH 1–34) has full biological activity.
• Intact PTH assays measure PTH 1–84 plus certain fragments (e.g., 7–84). “Whole” or “bio-intact” assays aim to detect only PTH 1–84, but many labs still use the intact PTH test.

Biologic Effects of PTH

• Bone: In high levels (as in Hyperparathyroidism), PTH increases osteoclastic bone resorption. Intermittent low-dose PTH can increase osteoblastic bone formation (used therapeutically for osteoporosis, e.g., teriparatide).
• Kidney: PTH increases calcium reabsorption in the distal tubule and decreases phosphate reabsorption in the proximal tubule, contributing to hypercalcemia and hypophosphatemia.
• Intestine: PTH indirectly enhances calcium and phosphate absorption via increased renal synthesis of 1,25-dihydroxyvitamin D.
• Major Receptor: PTH/PTHrP receptor, activating cAMP and phospholipase C pathways.

Indications & Uses

1. Parathyroidectomy for Primary Hyperparathyroidism
   • Intraoperative PTH monitoring: a drop of >50% post-resection suggests surgical success.
   • Long-term cure is also linked to normal serum calcium (<10.2 mg/dL) within six months after surgery.
2. Hypocalcemia Secondary to Thyroidectomy
   • A single intraoperative or postoperative intact PTH measurement can predict development of symptomatic hypocalcemia and guide vitamin D supplementation.
3. Suspected Hypercalcemia due to Hyperparathyroidism
   • Mild hypercalcemia + high-normal or elevated PTH suggests primary Hyperparathyroidism.
   • Decreased PTH is typical in nonparathyroid hypercalcemic disorders (e.g., malignancy).
4. Chronic Kidney Disease (CKD)
   • Elevated PTH and secondary Hyperparathyroidism are common, especially in stage 3 or worse (GFR <60 mL/min/1.73 m^2).
   • Target ranges of intact PTH vary by CKD stage. For example:
     • Stage 3: 35–70 pg/mL
     • Stage 4: 70–110 pg/mL
   • Patients with repeated iPTH >800 pg/mL who fail standard interventions may be candidates for parathyroidectomy.
5. Hypocalcemia
   • Elevated PTH in the face of low serum calcium can be seen with intestinal malabsorption, vitamin D deficiency, renal failure, or hereditary vitamin D resistance.
   • If PTH is not elevated in hypocalcemia, consider primary parathyroid failure.
6. Suspected or Known Bone Disease
   • Elevated PTH is associated with hyperparathyroid bone disease.
   • CKD patients often require 2–3 times normal PTH for normal bone turnover.

Chronic Kidney Disease and PTH Monitoring

• In CKD, the test helps distinguish secondary Hyperparathyroidism, especially in:
  • Stage 3: GFR 30–59 mL/min/1.73 m^2 → measure PTH every 12 months
  • Stage 4: GFR 15–29 mL/min/1.73 m^2 → measure PTH every 3 months
  • Stage 5: GFR <15 or on dialysis → measure PTH every 3 months
• Dietary phosphorus restriction (800–1,000 mg/day) is recommended if iPTH levels exceed target.
• Elevated iPTH (>500–600 pg/mL) can indicate moderate/severe secondary Hyperparathyroidism.

Clinical Application Of pTH monitoring

• PTH is secreted in response to hypocalcemia, returning serum calcium to normal. When serum calcium normalizes, PTH secretion diminishes.
• This test is critical for diagnosing Hyperparathyroidism and differentiating parathyroid vs. nonparathyroid causes of hypercalcemia.
• Simultaneous measurement of serum calcium is essential for interpretation. Many labs provide PTH/calcium nomograms.

In patients with secondary or tertiary hyperparathyroidism (HPT), especially those with chronic renal failure (CRF) or post–renal transplant, intraoperative parathyroid hormone (IOPTH) monitoring offers a valuable tool for guiding surgical management. By measuring the drop in PTH levels immediately after resecting hyperfunctioning parathyroid tissue, clinicians can confirm adequate gland removal and reduce the likelihood of missed or supernumerary glands.

Clinical Pearls:

1. Indicator of Surgical Success
   • A significant decline in IOPTH (for example, >50–80% at 10 to 20 minutes) strongly predicts operative cure in both secondary (CRF-related) and tertiary (post-transplant) HPT.
   • In some studies, a ≥90% drop has been associated with nearly 100% specificity, indicating near-certain success if that threshold is met.
2. Practical Advantages
   • Prevents Reoperation: Rapid IOPTH feedback helps detect any remaining hyperfunctioning parathyroid tissue, reducing the risk of persistent or recurrent disease.
   • Flexible Cutoffs: Different thresholds (e.g., 70%–80% at 20 minutes versus >90% at 40 minutes) can be tailored to the clinical setting, surgical timing, and renal clearance considerations.
3. Role in Renal HPT
   • Patients with CKD often accumulate inactive PTH fragments, affecting standard assays. Despite this, IOPTH still improves the overall cure rate when thresholds are adjusted for delayed PTH clearance.
   • Total parathyroidectomy with autotransplantation, guided by IOPTH, remains a mainstay for refractory secondary/tertiary HPT.

Overall, IOPTH monitoring allows surgeons to confirm complete parathyroid resection intraoperatively, thus minimizing failure rates and improving outcomes for renal HPT patients whose disease is resistant to medical therapy.

Test Procedure & Specimen Requirements

For the 12 hours preceding specimen collection, the patient should avoid taking any multivitamins or dietary supplements (including hair, skin, and nail supplements) that contain biotin (vitamin B7). The patient should also remain fasting for 12 hours before providing the specimen.

The recommended supply is the Sarstedt Aliquot Tube (5 mL; T914). The preferred collection container is a serum gel tube, although a red-top tube is also acceptable. For submission, a plastic vial is required with a specimen volume of 1 mL. After collection, centrifuge the sample and transfer the serum to the plastic vial for final submission.

1. Sample Tube
   • Red top or serum separator tube for serum PTH.
   • Plasma samples often drawn in EDTA tubes (check lab protocol).
2. Drawing the Sample
   • Typically, an 8 AM fasting sample is drawn.
   • PTH has a diurnal variation: highest ~2 AM, lowest ~2 PM. Adjust if the patient works nights.
   • Obtain a serum calcium level simultaneously, if ordered.
3. Patient Instructions
   • Explain the procedure.
   • Generally, the patient is NPO (nothing by mouth except water) after midnight.
   • Apply pressure/pressure dressing to the site post-venipuncture.

Additional Insights from Research

1. Regulation of PTH Secretion
   • CaSR (calcium-sensing receptor) is pivotal in familial hypocalciuric hypercalcemia and other genetic variants.
   • Calcimimetics (e.g., cinacalcet, etelcalcetide) are helpful in CKD-related Hyperparathyroidism or parathyroid carcinoma.
2. Metabolism and Clearance
   • The liver and kidney degrade PTH, producing multiple fragments with varying half-lives.
   • In renal failure, C-terminal fragments accumulate, which can affect certain PTH assays.
3. Biologic Activity
   • The N-terminal region (especially residues 1–34) has the main biologic effect.
   • The C-terminal portion may have a minor or antagonistic action.
4. Bone Effects
   • High PTH => osteoclastic bone resorption (hyperparathyroid bone disease).
   • Intermittent, low-dose => osteoblastic bone formation (therapeutic usage in osteoporosis).
5. Clinical Relevance
   • Hyperparathyroidism: elevated PTH with hypercalcemia.
   • Hypoparathyroidism: low or inappropriately normal PTH with hypocalcemia.
   • Secondary Hyperparathyroidism in CKD: often very high PTH with hypercortical bone changes and electrolyte derangements.

Reference

Einbinder Y, Benchetrit S, Golan E, Zitman-Gal T. Comparison of Intact PTH and Bio-Intact PTH Assays Among Non-Dialysis Dependent Chronic Kidney Disease Patients. Ann Lab Med. 2017 Sep;37(5):381-387. doi: 10.3343/alm.2017.37.5.381. PMID: 28643486; PMCID: PMC5500736.