Which hormone lowers plasma levels of ionized calcium: Calcineurin, Calcitonin, Parathyroid Hormone (PTH), or PTH-related peptide?

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Calcitonin Lowers Plasma Ionized Calcium

The correct answer is #2: Calcitonin. Calcitonin is the hormone that lowers plasma levels of ionized calcium by inhibiting bone resorption and increasing renal calcium excretion 1, 2, 3.

Mechanism of Action

Calcitonin rapidly decreases serum calcium through two primary mechanisms:

  • Inhibition of osteoclast activity: Calcitonin has an immediate effect on decreasing osteoclast-mediated bone resorption, which reduces calcium efflux from bone into the bloodstream 2, 3, 4

  • Increased renal calcium excretion: Calcitonin produces a calciuric effect, promoting calcium loss through the kidneys 3

  • Secretion trigger: Calcitonin secretion is stimulated by increases in serum calcium concentration, serving as a protective mechanism against hypercalcemia 2

Why the Other Options Are Incorrect

Calcineurin (#1) is not a hormone—it is an intracellular phosphatase enzyme involved in T-cell activation and has no direct role in calcium homeostasis 1.

Parathyroid Hormone (PTH) (#3) has the opposite effect: it raises plasma calcium levels through multiple mechanisms including stimulating bone resorption, increasing renal calcium reabsorption, and enhancing intestinal calcium absorption via vitamin D activation 1, 5.

PTH-related peptide (PTHrP) (#4) mimics PTH action and also raises plasma calcium, commonly seen in malignancy-associated hypercalcemia 6.

Clinical Relevance

  • Calcitonin is used therapeutically for acute hypercalcemia management due to its rapid calcium-lowering effect 3, 4

  • The hormone is secreted by C-cells of the thyroid gland and represents a phylogenetically ancient calcium regulatory mechanism 2, 7

  • Despite its clear pharmacological effects, the precise physiological role of calcitonin in humans remains somewhat unclear, as calcitonin deficiency (post-thyroidectomy) does not produce obvious clinical abnormalities 2, 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Calcitonin as a drug.

Annals of internal medicine, 1981

Guideline

Phosphate Excretion and PTH

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Diagnostic Approach for Hypercalcemia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

[Physiology of parathyroid hormone and calcitonin].

Padiatrie und Padologie, 1983

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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