Parathyroid Hormone (PTH) and clinical implications:

By SWA

Parathyroid Hormone (PTH) is a hormone produced by the parathyroid glands, which are four small glands located behind the thyroid gland in the neck. PTH plays a crucial role in regulating calcium and phosphate levels in the blood, which are essential for nerve function, muscle contraction, bone health, and other bodily processes. When blood calcium levels drop, PTH is released to restore balance, thus maintaining a stable environment for cellular function.

How PTH Regulates Calcium Levels

PTH regulates blood calcium levels through several mechanisms:

  1. Bone Resorption: PTH stimulates osteoclasts (bone-resorbing cells) to break down bone tissue, releasing calcium and phosphate into the bloodstream. This process, called bone resorption, increases blood calcium but can lead to bone weakening if PTH levels are excessively high over time.

  2. Kidney Reabsorption: In the kidneys, PTH promotes calcium reabsorption in the renal tubules, reducing calcium excretion in urine. This helps conserve calcium in the body and maintain blood levels.

  3. Activation of Vitamin D: PTH stimulates the kidneys to produce active Vitamin D (calcitriol), which increases calcium absorption from the intestines. This is a key mechanism for raising blood calcium levels, especially when dietary calcium is low.

  4. Phosphate Excretion: PTH reduces phosphate reabsorption in the kidneys, causing more phosphate to be excreted in the urine. This is important because high levels of both calcium and phosphate in the blood can lead to calcium-phosphate crystal formation, potentially damaging tissues.

Effect of PTH on the Larynx and Trachea

While the larynx and trachea are not direct targets of PTH, abnormal calcium levels resulting from excessive or deficient PTH can have indirect effects on these structures, especially in cases of hypocalcemia (low calcium).

  1. Laryngospasm: In cases of hypoparathyroidism or low PTH, blood calcium levels can fall dangerously low, leading to hypocalcemia. Severe hypocalcemia can cause laryngospasm, an involuntary and sudden contraction of the vocal cords that can obstruct breathing. This condition is life-threatening and requires immediate treatment with calcium to relax the muscles around the larynx.

  2. Muscle Cramps and Spasms: Hypocalcemia from low PTH levels can also lead to tetany, a condition characterized by muscle cramps and spasms. Tetany can affect the laryngeal muscles, potentially leading to a sensation of tightness or constriction in the throat. In extreme cases, it can cause spasms severe enough to affect breathing through the trachea.

  3. Hoarseness and Voice Changes: Chronic calcium imbalance, especially in hypoparathyroidism, can impact the muscles involved in voice production, leading to hoarseness or changes in voice quality. This is due to the impact of low calcium on the neuromuscular function of the vocal cords.

PTH Regulation

The secretion of PTH is tightly controlled by calcium-sensing receptors (CaSR) on the surface of parathyroid cells. These receptors monitor blood calcium levels and adjust PTH secretion accordingly:

  • Low blood calcium stimulates the parathyroid glands to release more PTH.
  • High blood calcium suppresses PTH release, preventing excessive calcium buildup in the blood.

This feedback mechanism maintains calcium within a narrow, optimal range, essential for cellular function and muscle activity.

Conditions Associated with Abnormal PTH Levels

  1. Primary Hyperparathyroidism

    • In primary hyperparathyroidism, one or more of the parathyroid glands become overactive and produce excessive PTH, leading to high blood calcium (hypercalcemia). This is often due to a benign tumor called a parathyroid adenoma.
    • Symptoms of primary hyperparathyroidism include fatigue, bone pain, kidney stones, frequent urination, nausea, mood changes, and, in severe cases, muscle weakness and cardiac arrhythmias.

  2. Secondary Hyperparathyroidism

    • In secondary hyperparathyroidism, the parathyroid glands secrete high levels of PTH in response to low blood calcium caused by factors outside the glands. Common causes include chronic kidney disease (CKD) and Vitamin D deficiency.
    • Chronic kidney disease impairs Vitamin D activation and calcium retention, leading to continuous stimulation of the parathyroid glands. Over time, this causes the glands to enlarge and become hyperactive.

  3. Tertiary Hyperparathyroidism

    • Tertiary hyperparathyroidism can develop in patients with long-standing secondary hyperparathyroidism, typically due to chronic kidney disease. After prolonged overstimulation, the parathyroid glands may become autonomous and continue to secrete PTH even when blood calcium levels are normal or high.
    • This condition often requires surgical removal of some or all of the parathyroid glands to control PTH and calcium levels.

  4. Hypoparathyroidism

    • Hypoparathyroidism occurs when the parathyroid glands produce insufficient PTH, resulting in low blood calcium levels (hypocalcemia). Causes include autoimmune diseases, surgical removal of the glands (e.g., during thyroid surgery), or genetic conditions.
    • Symptoms of hypoparathyroidism include tingling in the fingers, muscle cramps, spasms, seizures, and laryngospasm, which can affect breathing if severe. Chronic hypocalcemia can also affect heart and brain function, making this a serious condition if untreated.

The PTH Test

A PTH blood test is often used to assess parathyroid function and determine the cause of abnormal calcium levels.

  • When to Order a PTH Test: A PTH test is typically ordered if blood calcium levels are abnormally high or low, or if symptoms like muscle cramps, bone pain, or kidney stones are present. It’s also useful in cases of suspected osteoporosis or chronic kidney disease.

  • Interpreting PTH Levels:

    • High PTH with High Calcium: Suggests primary hyperparathyroidism or possibly tertiary hyperparathyroidism in patients with chronic kidney disease.
    • High PTH with Low or Normal Calcium: Indicates secondary hyperparathyroidism, often due to Vitamin D deficiency or chronic kidney disease.
    • Low PTH with High Calcium: Suggests hypercalcemia of malignancy, where high calcium is typically due to factors unrelated to PTH, such as PTHrP secretion by certain cancers.
    • Low PTH with Low Calcium: Indicates hypoparathyroidism, potentially due to autoimmune conditions or surgical removal of the parathyroid glands.

For more information on PTH testing, visit the Lab Tests Online guide on PTH.

How PTH and PTHrP Differ

While PTHrP (Parathyroid Hormone-related Protein) and PTH both raise blood calcium, PTHrP is usually produced in small amounts by tissues throughout the body, while PTH is only made by the parathyroid glands. Certain cancers (e.g., lung, breast) can secrete high levels of PTHrP, mimicking PTH’s effects and leading to hypercalcemia. Measuring both PTH and PTHrP can help distinguish between a parathyroid condition and cancer-related hypercalcemia.

Summary

Parathyroid Hormone (PTH) plays a vital role in regulating blood calcium, impacting bones, kidneys, and the intestines. It’s essential for proper muscle and nerve function, including in the larynx and trachea. Imbalances in PTH can lead to significant health issues, from bone weakening and kidney stones in hyperparathyroidism to severe muscle spasms and laryngospasm in hypoparathyroidism.

A PTH test is critical for diagnosing and understanding calcium imbalances. Elevated PTH with high calcium typically points to primary hyperparathyroidism, while low PTH with high calcium may suggest malignancy. Careful interpretation of PTH levels, alongside calcium and PTHrP tests, provides essential insights into the underlying causes and helps guide appropriate treatment.

For further reading, see Endocrine Society’s resource on Hyperparathyroidism.

For further information on PTH and its clinical implications, visit Endocrine Society’s resource on Hyperparathyroidism. https://www.endocrine.org/journals/journal-of-the-endocrine-society/the-eucalcemic-patient-with-elevated-parathyroid-hormone-levels

Anatomical illustration of the parathyroid glands:

  1. Parathyroid Gland Placement: The parathyroid glands should be positioned on the back of the thyroid gland, typically with two glands on each side, located in the neck area.

  2. Size and Shape: The parathyroid glands should appear as small, oval structures, usually around the size of a grain of rice.

  3. Anatomical Context: Ensure the surrounding structures are correctly labeled:

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right.
Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9 

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