PTH - Kresser Institute Membership Site

Marker Name: PTH

REFERENCE RANGES FOR PTH:

Laboratory reference range: 15–65 pg/mL

Functional reference range: 15–30 pg/mL (PTH levels >30 pg/mL may be indicative of biological vitamin D deficiency when 25(OH)D levels are low.)

DESCRIPTION:

Parathyroid hormone (PTH) is one of the two hormones, along with calcitriol, that governs calcium and phosphate homeostasis.¹ Under normal circumstances, PTH maintains serum calcium levels within a narrow range. The hormone does this by stimulating calcium resorption in the kidneys and bone resorption.¹ PTH also indirectly helps increase serum calcium by stimulating the production of enzymes in the kidney that convert 25-hydroxyvitamin D to its more active form, 1,25-dihydroxyvitamin D (calcitriol).¹ Calcitriol then increases intestinal absorption of calcium, increases resorption rate of bone, and decreases excretion of calcium and phosphate by the kidneys.² PTH is the main hormone responsible for maintaining serum phosphate levels, which it does by altering renal reabsorption of phosphate and liberating phosphate through bone resorption.³

Calcium in the blood regulates the release, synthesis, and degradation of PTH.¹ Parathyroid cells possess sensitive calcium-sensing surface receptors.¹ Once these receptors sense a drop in serum calcium, parathyroid cells release PTH through exocytosis.⁴ Hypocalcemia, by acting at calcium-sensing receptors on parathyroid cells, can prompt acute and chronic effects of PTH. In addition to exocytosis of PTH, which takes seconds to minutes, hypocalcemia may stimulate PTH gene expression and the proliferation of additional parathyroid cells over the course of days to weeks. Conversely, increases in plasma calcium inhibit PTH secretion. In this way, adequate vitamin D can suppress PTH levels by reducing the need for PTH to increase serum calcium.

PTH is an 84-amino acid polypeptide (PTH (1-84)) that is synthesized, stored, and secreted by the parathyroid glands.¹ However, it is initially produced as a 115-amino acid peptide and cleaved into a 90-amino acid peptide before being cleaved to its most active 84-amino acid form.⁵ Once secreted, the PTH (1-84) is cleared from the bloodstream within two to four minutes, by uptake into the liver and kidney or, to a lesser extent, through proteolytic degradation.¹^,⁶ The 84-amino acid peptide may be further broken down into smaller C-terminal and N-terminal fragments that may be mildly bioactive.⁵ C-terminal fragments have a five- to tenfold longer half-life. As such, the amount of PTH (1-84) may only represent 5 to 30 percent of circulated PTH.

The existence of C- and N-terminal fragments may have implications for PTH hormone assays.⁵ PTH assays are primarily done by two-site immunometric assays, whereas they were formerly measured through radioimmunoassay. Second-generation two-site immunometric assays are called “intact” PTH assays and measure PTH (1-84) and other large C-terminal PTH fragments. Third-generation two-site immunometric assays are called “bioactive” PTH assays and only measure PTH (1-84), not C-terminal PTH fragments.⁵ For most purposes, “intact” and “bioactive” PTH assays provide virtually the same clinical information.⁴ However, there may be instances when third-generation “bioactive” assays may be clinically superior. Examples include PTH measurement in patients with renal failure, intraoperative PTH monitoring, PTH carcinoma, and for patients that have inappropriately “normal” serum PTH concentrations by “intact” PTH assays.⁵

Increased levels of PTH are a normal response to hypocalcemia. However, in a healthy state, the changes in PTH and calcium should rapidly reach equilibrium, driving both values into the normal range. Severe hypocalcemia that cannot be corrected through homeostatic mechanisms, as seen in vitamin D deficiency and chronic kidney failure, may lead to chronic elevations in PTH.¹ This condition is called secondary hyperparathyroidism. Elevated PTH without a concomitant decrease in serum calcium suggests primary hyperparathyroidism.⁷ Primary hyperparathyroidism occurs when the parathyroid glands secrete too much PTH, perhaps due to a nodule in one of the glands itself. Tertiary hyperparathyroidism follows from chronic hypocalcemia and long-standing secondary hyperparathyroidism; hyperplasia in the parathyroid glands leads to increased PTH secretion.⁸

PTH levels should decrease in states of hypercalcemia as a normal homeostatic response.¹

However, chronically elevated calcium will result in decreased PTH secretion as the parathyroid glands attempt to compensate for the hypercalcemia.⁷ If PTH is not responding correctly, such as happens in hypoparathyroidism, both calcium and PTH levels may be abnormally low.⁷ Severe hypomagnesemia causes hypocalcemia by impairing PTH release in hypocalcemic states.^9,10

PTH is virtually always measured along with serum calcium and is often measured along with phosphate, magnesium, 25-hydroxyvitamin D, or 1,25-dihydroxyvitamin D.⁷

Finally, recent research suggests that PTH may be used to determine whether 25(OH)D levels that are borderline low are indicative of biological vitamin D deficiency. According to a meta-analysis studying the suppressive effect of vitamin D on PTH, the effect was greatest with PTH levels over 49 (PTH was suppressed by 21 pg/mL), less significant with PTH levels between 38 and 49 pg/mL (PTH was suppressed by 17 pg/mL), and very small with PTH levels <38 pg/mL (PTH was suppressed by 2 pg/mL).¹¹ These data suggest that PTH levels >30 pg/mL should corroborate concerns about low 25(OH)D in proportion to its upward divergence from 30 pg/mL.

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^7,8

Primary hyperparathyroidism
PTH-secreting tumor
Hypocalcemia (secondary hyperparathyroidism)
- Vitamin D deficiency
- Chronic kidney failure
Tertiary hyperparathyroidism (chronic hypocalcemia and parathyroid gland hyperplasia)
Drugs
- Lithium
- Calcimimetic drugs (e.g., Norcalcin, cinacalcet)
- Non-hypercalcemic vitamin D analogs (e.g., oxacalcitriol, paricalcitol, 1-alpha-hydroxyvitamin D2)

Low in:^7,9,10

Hypercalcemia
Hypoparathyroidism
Congenital hypoparathyroid disorders
Hypomagnesemia

FUNCTIONAL RANGE INDICATIONS:

High in:

Vitamin D deficiency

Low in:

Same as conventional indications

References: